Podcasts about Myc

In this episode of Hema Now, Jonathan Sackier is joined by John Riches, Clinical Reader in Cancer Immunometabolism at the Barts Cancer Institute and Honorary Consultant Haemato-oncologist. They explore how metabolic shifts drive lymphoma progression, the potential of immunotherapy, and what the future holds for treating lymphoid malignancies.  Timestamps:      00:00 – Introduction  01:46 – Riches' journey into haematology  03:42 – What is T cell exhaustion?  07:06 – The key role of metabolism in lymphoma  09:33 - Richter's syndrome  13:17 – Breakthroughs in immunotherapy  20:27 – The challenges of translational research  25:39 – B cells in autoimmune diseases  28:16 – The potential of breath biopsy  32:58 – Riches' three wishes for healthcare 

Do you feel like to-do lists don't work for you? In this video, I share why to-do lists might be the #1 organizing mistake you're making and give you a better system! I'll guide you through structuring tasks, prioritizing effectively, and scheduling tasks while making time for personal needs. Learn how to finally get organized, reduce stress, and achieve your goals with a system that actually works by using the E-Pillar of my C.L.E.A.R. Framework. Want to stop feeling overwhelmed? Listen to this episode! Enjoy - XO - Dianne The episode at a glance: [0:00 -1:21] Intro & welcome [1:22 - 1:54]  What this episode is about [1:55 - 2:40]  How we got to believing To-Do Lists actually help [2:41 - 2:57]  If to-do lists worked [2:58 - 3:30]  Never-ending to-do lists  [3:31 - 4:00]  Steps to staying more organized [4:01 - 4:36]  My C.L.E.A.R. Framework [4:37 - 5:14]  Connect with me and outro   P.S. Referenced in this episode C.L.E.A.R. Framework can be found on my site https://diannejimenez.com DianneJimenez.com/contact P.P.S.  When it comes to getting organized or getting the kids involved, where do you struggle the most?  DM me on Instagram — The post (episode #68: To-Do Lists Don't Work? The System That Does) appeared first onDianne Jimenez | Professional Organizer website. To read the blog post of this episode, head to https://diannejimenez.com/68 If you loved this episode, please consider Rating it or giving it a Review on your preferred platform - it would mean the world to me and help other parents needing to discover my podcast   * USA:  https://podcasts.apple.com/us/podcast/the-organized-ish-parent-podcast/id1606051910 * CANADA: https://podcasts.apple.com/ca/podcast/the-organized-ish-parent-podcast/id1606051910 * SPOTIFY:  https://open.spotify.com/show/60AVuZmF4iIl43aoWz5Xyh?si=e4ba1060574040a4 *YOUTUBE: https://www.youtube.com/channel/UCsLq1WtSo-VG0aUJEfDKdPQ *AMAZON MUSIC: https://music.amazon.ca/podcasts/ebe904c1-eece-469b-8dd5-7144e6b798ab/the-organized-ish-parent-podcast —

The first Ishara open  House Challenge .Book 3 in 18 parts, By FinalStand. Listen to the ► Podcast at Explicit Novels.Odd Happenings{8:58 am, Wednesday, Sept. 3rd ~ 5 Days to go; the Final Salvo ~ at this time}I had deposited my Mother in the place I felt was safest for her   with OT (Oyuun T m rbaatar) at the Kazakhstan's UN mission. Her being my family was what mattered to them most. I picked her up on my way to work, which made my entrance into the lobby all that much more cataclysmic.I was traveling light with only Wiesława Živa providing me with security. Chaz, Pamela and Juanita were catching up with their sleep, with a promise of taking me out for a late lunch. That was really them telling me to not leave JIKIT until they came for me around 2:00 pm.So anyway, me, Mom and Wiesława walked into the ground floor of the Mil Ma Towers to find eleven people waiting on us. We were in downtown Manhattan in a part of town the NYPD paid particular attention to. What could go wrong, right? Two of the people were Amazons from Havenstone. With them were two fine young men from the US 'don't make me kill you' Department. By this time in my life I was sure they had one   which no one talked about.Five of my expectant visitors were of the same mold as those who protected Hana for me. Not the Ghost Tigers   that would have put me at ease. Sure, they were a gang of assassin and in this circumstance; I would have preferred them. As it was, ten sets of highly-trained Illuminati operative eyes kept me, my party and the four guardians of JIKIT in their overlapping fields of vision.The last two, were doing an impromptu family reunion. They were Aunts 'X' and 'Y', and neither of them smelled like fish, or crab."Aunt Deidre," I tossed out there. "What brings you here today?"It looked like clobbering time! No. Wait. Neither Mom, nor my aunts, were saying anything and they were normally so verbose."Sibeal.""Imogen.""Sibeal, you are looking surprisingly well for a dead woman," the other one said."Deidre, you are looking surprisingly alive for someone who deserves to be dead," Mom bantered back."How long have you known about this?" Imogen's eyes flickered my way."Not long, a while, more than a day, ah, take your pick," I mumbled. I decided to turn that frown aka 'my gut wrenching terror that my Mother was about to die' upside down aka ramped up my sexy, 'glad to see you in a totally incestuous way'."So, what brings you here today and why aren't you waiting upstairs with the rest of my band of cutthroats, malcontents and ne'er do-wells? Oh, and I'm happy to see both of you." Karma was about to bitch-slap the shit out of me and it was so well deserved."I'm pregnant," Imogen studied my reaction. Yeah, I had banged her after Deidre, but before Baibre because I am a fucking reprehensible human being and sometimes, I feel I am utterly irredeemable."Great news," I exhaled. I so wanted to ask 'so, who is the father?' except that was too cruel, even for an O'Shea.No one stopped me from stepping up and hugging her. Everyone in the lobby had heard her loud and clear. Anyone who knew me, or even about me, knew she wasn't passing on the information because Imogen liked sharing good news. I kept my hands on her hips while I leaned my torso back until we could make eye contact."Does Granddad know?" It occurred to me in that second that Pamela was going to kick herself for missing this and the opportunity to kick me as well."I told him over the phone. His reaction was neutral," she responded."Whoa, girl? Boy? How are you doing? When are we going to sit down and figure out a name? Is there anything I can do for you?""Come home with me," she suggested."No," Mom snapped. "Next time he steps into your custody, we all know you won't let him get away." She meant the plane trip to Ireland."No, Mom," I countered. "I'm a grown man now and I make my own decisions. That being said   no, I'm not going home with you.""Not only am I still in love with the concept of my personal freedom, I have important work to do. People are counting on me.""We are counting on you too," Deidre stated. "In fact, that is the other reason we came here. We need you.""Why do I feel that has to do with something besides sex?""Can we talk to you in private?" Imogen requested. There were a thousand and one reasons to say 'no'. Things like 'common sense', bad behavior   they had murdered my homicidal uncle   and the fact they were as morally twisted as their creator. Oh   and they were hot and I hadn't been laid in forever."Sure. Let's go upstairs. You can have your people sweep the room to ensure our privacy then the four of us can sit down and have a family chat," I offered."We don't want her in the room," Deidre indicated Mom."We are a package deal," I denied her. "Like her, or not, she is as much family to me as you both are."They consented far too fast. Either I was falling into their masterful trap, or something horrible had happened. Neither options was palatable to me. The bodyguards departed, Wiesława last of all."What's gone wrong?" Mom preempted me. Her sisters glared."Father's body is not his own," Imogen told us. I was trying to figure out the relevance of that when Mom gasped."Oh fuck," she said in a small voice. "No serum?" Oh yeah, the refinement of those addictive pheromones Grandpa Cáel had gifted me with. Whatever flesh-form he currently inhabited wasn't one containing his genetic make-up meaning,"Oh shit," I mumbled. "What can I do?""Yes," Deidre replied to Mom."Let them die," Mom insisted (to me). Less I forget, she was raised by Grandpa Cáel too. Her being a loving mother to me didn't translate over to her being a humanitarian of any kind."The Hell you say," I jumped up and stared down at Mom. "You hate them. I don't. Letting them die makes me worse than him." Grandpa."So you will help us?" Deidre moved to the edge of her seat."Okay. This is the point where I threaten you into making some concessions, we argue then you eventually cave in because no matter how terrible your futures look, you aren't willing to give up on living. None of that is going to happen. What do you need from me?""Come back with us to Ireland so we can finish our experiments," Imogen joined me in standing. Unwilling to give her sister any physical advantage, Mom stood as well."No. That isn't even a believable lie," I scolded her. "You don't need to blackmail me into helping you. I'll do it gladly. That doesn't mean I'll let you trick me into doing something stupid. I do 'stupid' all the time. I'm accustomed to it and I know it when its ugly head rises up before me. Try again.""We could pick a neutral location," Deidre suggested."How about Havenstone?" They didn't look like that plan was even worthy of their consideration. "Imogen, inside you is growing a possible heir to House Ishara. An attack on you would be an attack on Ishara. Barring you betraying the Amazons, you would be perfectly safe.""Wonderful," Mom's sarcasm dripped off every word. "I'm going to be a grandmother to my nephew while my son is bringing a child into the world that can double as his cousin.""That sound pretty horrible, Mom. It is the truth, but it still sounds pretty terrible."While those words tumbled out of my mouth, I did a little soul back-searching. How in the fuck was   outside of the actual fucking   was Imogen pregnant? My existence was a freaking fluke of nature. A few words were bandied about the room while I was lost in deductive reasoning and turning hunches into assumptions and turning those into reasonable mystic hypotheses.I created the Mojo-Little Engine that thought it could. Specifically, the legacy of Vranus. Legions of little Vranusian sperm had been jumping hurdle after hurdle to keep the faith alive   that Vranus would meet his Ancestors with his mission accomplished. I was already half way there.Still, the legacy of Vranus and the hopes of Dot Ishara hadn't stopped in their struggle just because I had been born. They were still trying to restore the mortal descendants of a Dead House. They were also still spiritually pushing me on to fulfill his last command   to save the Arinniti sons.I was halfway there by returning the offspring of Bolu, Vranus' fellow guardian, back to the fold. It remained for me to round up the purpose of the whole mission in the first place. My semen weren't taking a chance that I could get gakked before that was accomplished. Having knocked up an augur despite the toxic soup she called blood should have been a dire warning to me, I'm an idiot.When the curse of Sarrat Irkalli clashed with the actions of Dot Ishara, Ishara had won. Sarrat Irkalli sought to deny Alal any children of his own. Dot was insisting the male line of Vranus Ishara continue on. The end result was Alal received his long-denied grandson, who just happened to also want him dead because of a feud that stretched back over two millennia.As an added insult, his grandson then knocked up one of Alal's genetically manipulated daughters, again giving him something he couldn't accomplish on his own   heirs   grand-sons and  daughters, most who would also want to kill him, being Amazons and members of the 9 Clans after all. Why? Cause Goddesses are bitches, that's why.That got me to wondering when would be the next time I was going to meet Ishara. I hadn't suffered severe head trauma in while and she was overdue for some snuggle time, witty banter and a fortune cookie. I'd try to be careful. It wouldn't do any good, but I had to try."Why are you crying?" Mom touched my arm."No reason," I lied."Why don't we make plans for tonight?" Deidre insinuated herself next to me. "We'd like to meet Hana. From what I understand, Father likes her.""No can-do," I sniffled. "I've got an orgy with 159 women at 8 o'clock, except there won't be any sex, or fun of any kind. Basically, I have to convince a roomful of women to not beat me up and take my stuff.""You don't have to go," Imogen had finished boxing me in   I had a chair behind me and Momma-clones all around."For the same reason I'm going to take care of our child, Imogen, I have to go to this meeting. People are counting on me to do the right thing without telling me what the right thing to do is.""That's unfair," Deidre empathized by stroking my chest."Not so. This is just another day in the life of a new hire at Havenstone Commercial Investments. Every day is like this and in five more days, the real fun beings." That wasn't entirely accurate. I had one good, stress-free week. It was when Carrig put me in a coma. That week I had done pretty well for myself.{9:28 am, Wednesday, Sept. 3rd ~ 5 Days to go}I trundled my latest 'Assistant-in-Charge of keeping the hopes of future Isharans alive' (I didn't want to call Aunt Imogen, or any other woman, my 'Baby-Mamma'), along with Mom and Deidre, for a meet-and-greet with Buffy. I had spelled out in no uncertain terms that Buffy was the power behind the Ishara Throne and thus making 'her' believe they were playing on the up-and-up was their best hope for easing relations between the O'Shea and the Amazon Host.After they left me (with the assurance we'd be getting back together for lunch, with Hana), I made three calls. I needed to make a formal request to Katrina (any Illuminati member(s) entering any Amazon facility was her purview) and another to Elsa (as a sign of respect) that Aunt Imogen and two unarmed bodyguards, max, needed to see our medicos about a delicate issue.The third call was to Buffy to enlighten her as to both the arrival of another one of my aunts (so we needed to get along peacefully with her) and that Aunt Imogen was carrying yet another potential heir to House Ishara. I suggested it would be a symbolic gesture if a member of House Ishara could hang around for the visit, as it might impress upon Imogen our House had a vested interest in keeping her alive."Another one?" Buffy sizzled. "And this one is your aunt?""It is a date then," I stumped her."You are going to take your pregnant aunt out on a date?" Buffy's sizzle meter was rapidly climbing to Krakatoa proportions."Nope. I'm setting up a date for us. You, me and a quiet location at 12:01 am Tuesday morning, my First. Later in the morning, I'll be heading out to wherever they have stored Felix so we can work on some cooperative strategy.""And if I say 'no'?" She was terribly grumpy."Ugh, I guess I'll go bar-crawling with Odette and Timothy, Gay and Lesbian bars only. That way I know I'll behave.""And if they say 'no'?" she was slightly less hostile."I'll know you threatened their lives, and then you and I will finally find out who is better on the mats. Trust me, it will not be an experience you will enjoy.""I don't know. I think I'd like that.""No. You start threatening the other people I love and you will not be happy; I guarantee that, Buffy."She realized I was both serious and angry. She had stepped out of bounds, the 'bounds' I had set up two hours earlier during our elevator ride."Is the meeting still on for the night?" she evaded my disappointment."Yes. Will you be there?""Of course," she grumped."Buffy, don't bother showing up if you can't separate 'us' as friends, 'us' as Wakko Ishara and my First, and you as my apprentice."Making me miserable in the first relationship doesn't help the latter two one bit. I try not to be an irresponsible asshole as House Head. More than anyone else, you know what I will sacrifice to be Ishara and one with my Isharans. I'll also step out and be plain ole 'Cáel Nyilas' when events permit.""But I am sick and tired of people not taking my desire to be foolish and care-free seriously. Being a dogmatic ass-hat isn't in me, but if you can't work with that, from here on out we are Wakko Ishara and Buffy Ishara and nothing more. I will still trust you as an Isharan, but not as a friend. Your choice.""Don't be such an asshole!" she snapped."Screw you!" I fired back. "I made a fucking effort to plan out some personal time with you, disguised as a joke; you knew it and you still decided to be a ball-buster. Like I need another fucking ball-buster right now, with all the other shit on my plate. You know better!" I was screaming. The people in JIKIT were working overtime at not staring at me."I'm under a ton of stress here too," she snarled. "I have to deal with the Council, keep our House growing and fulfill my obligations with Executive Services.""Do you want to quit? No longer by my 'apprentice'? Go back to working for Katrina full time?""Really?" she whispered."Of course the fuck not!" I shouted. "I didn't pick you for the job because of your sterling personality, or your bedroom excellence. I picked you because I had, and still have, utter faith in your ability to do whatever is necessary to overcome the landfill-sized colossal ill-fortune the Ancestors have dumped in our lap.""I'm just asking you to stop being a whiny, over-sensitive cunt and remember: it was the psychotic bitch who I chose for the top spot," I rumbled."I'm going to kick your ass," she seethed."Nice to know. We on for Monday night?"Pause."Yes," and she hung up. Two seconds later my phone rang again. "Buffy?" I answered. "And don't be late!" she menaced, then hung up again."So," Addison turned my way, "are you praying for World Peace to break out, or Nuclear War?""Hardy-har-har," I griped."Now that your personal drama is temporarily derailed, we have something for you to look at," Mehmet motioned for my attention. "Ever heard of Kōfuku no Kagaku?" I shook my head. "It translates over as 'Happy Science' and it is a cult-like organization in Japan.""Cool beans. Why do I have a sinking impression it is not a front for the Ninja?""That is what we want you to find out," Addison took over. "Of critical importance is the news conference their leader, Ryuho Okawa, gave earlier this afternoon/morning (~ 3:17 pm Tokyo time = 2:17 am East Coast time ~), especially a very relevant part of his interesting public announcement."He claims to be the Earthly manifestation of the Supreme Being. That is old news. Today he claimed that Temujin of the Khanate was the reincarnation of the original Genghis Khan and, with him, Ryuho, as the unifier of theological forces and therefore serving as spiritual advisor to Temujin, they would usher in a new period of Peace throughout Asia.""I'm waiting for the other shoe to drop," I exhaled."He also claims that Japan is in the midst of an epic struggle, both spiritually and in the physical sense. The 'ancient guardians' of Japanese purity, the 6 Ninja Families, are at war with the depth of all Evil, the Chinese Seven Pillars of Heaven by name, who are determined to drag all of Asia away from the Light and into the Darkness of pain, degradation and slavery."In fact I quote: 'Alone among the nations of the Earth, only the Japanese cultural identity can stand firm against this global menace. Only the Japanese can keep the torch of true Enlightenment aloft. Only the Japanese can guide the development of the Khanate into the Supreme Empire it is meant to be'.""I'm going to go out on a limb here and say this guy is pseudo-religious, a Japanese ultra-nationalist as well as anti 'all things Sino'," came out of my mouth."Correct.""None of the Secret Societies would do something so public. Temujin's background is a mystery, but no one in the Khanate is calling him a reincarnated spirit, and they know the truth," I continued."This guy is pretty nutty," Mehmet confirmed. "He also claims to channel Buddha, Mohammed, Christ and Confucius. His followers worship him as the Earthly manifestation of the 'Supreme Being' named El Cantare, which is yet another name for any number of ancient supreme deities. And he claims to consult with the 'spirit guardians' of national leaders and aids in their mystic defense, with the aid of the Five Sacred Sisters' Spirits."Clearly this man was insane. Unfortunately, insane didn't make someone wrong,"Ah Hell," I muttered.Mehmet and Addison perked up; after all, figuring out the bizarre was my position on the team."He probably is insane, and I can't blame him," I sighed. "He isn't El Cantare; he is in touch with the Weave.""I have a feeling this is 'not good'," Addison murmured. "How bad is it?""The Five Sacred Spirit Sisters are most likely the five augurs who died in order to save Temujin, which, in turn, allies the 9 Clans with the E&S and Amazons to 'save' Japan, though it is not 'saved' yet.""Technically, the Weave IS the Supreme Being. It's largely indifferent, yet capable of doing both good and ill in response to outside (aka mortal) stimuli. If you can observe the Weave, you might be able to see the most likely path destiny is taking as well as the key players screwing with that destiny."That would include the Gong Tau sorcerers and the ninjas use of their own brand of magic; and God only knows what other mystic tricks the others have been attempting.""How do we get them to stop?" Captain Delilah Faircloth muttered."Not that easy Delilah. Everyone in this room has intersected because of a magic experiment that happened before any of us were born (Mom).""The fight at Summer Camp was flipped on its head because I saw the ghost the 7 Pillars sent to scout the area. My freeing of one of those trapped and tortured souls led to the calamity at the Barbeque Pit. I didn't use magic. I countered it. Still, my actions were interfering with the Weave."All four people the augurs, those Five Sisters, told me about had been dead at some point in time, some for thousands of years. Ajax didn't kill anyone using magic. Neither has Saku, yet both of them are products of disruptions in the Weave. 'Me' being alive and breathing is yet another disruption, since I shouldn't exist because of another mystic curse from five thousand years ago."Being alive and killing people means I've killed people who shouldn't be dead. Do we need to go into all the millions that have died in the Khanate war? Which was a combination of a resurrected Temujin and the 7 Pillars hunger for World Domination, if we do nothing, the rippled of those other disruption will still carry on."Except for me, no one on this taskforce has used an iota of magic, yet we are all dedicated to combatting mystical forces," I related to the group. I wondered where Rikki (Martin) and Beatrice (Ya Konan) had gotten off to. Lady Yum-Yum being absent only made my 'Scooby' senses tingle more."You use magic?" Agent-86 tilted his head in curiosity."I talk to a Goddess on a semi-regular business. I see ghosts. I've been the conveyer of messages from dead people and I've killed an un-killable man. Do we need to go back over my kidnapping by the 7 Pillars? The memories of my undead Grandfather floating around in my head?""I'm not calling thunderbolts out of the sky and shooting fireballs out my ass, but what I am doing is magical, nonetheless.""So, what do we recommend to our allies and benefactors (i.e., our sovereign governments)?" Mehmet inquired."Hmm, we tell our governments this crackpot is a Prophet of Doom who could be turned into an asset," I rubbed my brow with all four fingers and a thumb. Rikki, Beatrice and Lady Worthington-Burke quietly entered the room. They were all highly pleased in a 'I just won the lottery' kind of way. I was curious, but had to carry on with my train of thought."Quietly start seeking out other mystic societies, preferably low-key, quiet types who avoid the limelight, and start looking into other forms of magical insight and, quite frankly, protection. If the Weave has let this happen, we can expect worse. Lastly, I'll ask my 'Brother' to meet with this guy and get a feel for his personality.""That will only increase the believability of his ramblings," Addison protested."The boat called 'Denial' has already sailed. The World is in crisis. People are going to look for non-conventional answers. It is better to get ahead of this and bring Ryuho Okawa on board as a 'consultant'. Don't give him the whole picture by any means. The guy is definitely a loose cannon. Even worse, he is also a loose cannon the Weave has touched.""Besides, the Seven Pillars are going to figure this out pretty quick, their Weave sensitivity, ya know, and either kidnap him to be their own spiritual seismic sensor, or kill him for being both a loose cannon and yet another person screwing with their 'best laid plans'. Keeping him alive has the added benefit of making the Seven Pillars expend resources trying to get at him. Japan needs every bit diversion they can get."Let's not forget to tell our Secret Society allies of our plans, lest they kill him too. His babblings aren't going to make the 9 Clans or the E&S happy with him. They both have an established habit of making perceived enemies dead. Let's keep him alive and utilize this opportunity.""I like this plan," Addison nodded. Mehmet was clearly on board as well. Agent-86 clearly was playing the best on-line mystic MMORPG ever! (And with the added bonus that his team's action had real-world consequences.) The three 'ladies' new to the room received an abbreviated version of our discussion and my 'suggestions'. They weren't really suggestions. Barring a few insanely criminal endeavors, JIKIT treated me like a true asset."Something else big?" Addison looked to her British counterpart (Yum-Yum)."The Japanese Diet has voted for a public referendum on a Constitutional Amendment to repeal/revise Article 96 of the Japanese Constitution.""Oh fuck," was echoed, either verbally or subliminally, by everyone in the room except for me, Delilah and Agent-86.'Cáel' knew Jack and Shit about the Japanese Constitution. Hell, I barely knew about the US one and I was a native. However, Alal did know it, and knew both what Article 96 was and what its amendment really meant. Good-old 96 was the rolling dark cloud across the political Great Plains that heralded a swarm of tornados. Clouds were clouds and their arrival could mean anything.Article 96 dictated how the Japanese Constitution could be amended. The current process was a 2/3rd vote in both the House of Councilors (the 'Upper House', roughly equivalent to our Senate) and the House of Representatives (the 'Lower' House) followed by a public referendum. The proposed amendment to Article 96 would transform the process to a mere majority vote in both Houses.Imagine the shit-storm which would be unleashed if the US Congress tried to pull that shit. The biggest political issue was that the Japanese Liberal Democratic Party (LDP) held 294 of the 475 seats in the lower house (a clear majority) and 115 of the 242 in the Upper House (7 seats short of a majority). If the amendment passed next month (October 14th to be precise), the LDP could pretty much do as they pleased.And what was the first thing they were going to do? They were going to put to rest another part of the Constitution, namely the far more globally important Article 9. And what was that?Real World Stuff: WarningsArticle 9:(1)Aspiring sincerely to an international peace based on justice and order, the Japanese people forever renounce war as a sovereign right of the nation and the threat or use of force as means of settling international disputes.(2)To accomplish the aim of the preceding paragraph, land, sea, and air forces, as well as other war potential, will never be maintained. The right of belligerency of the state will not be recognized.If Article 9 was repealed, the Japanese nation could exercise diplomacy by military means, aka declaring an offensive war against a foreign power. Currently Japan had a modest budget military budget of $48 Billion a year (Earth's 10th largest). It was modest when you considered it was a mere 1% of the Japanese GDP. Great Britain, France and South Korea's smaller economies all functioned nicely with double that percentage for their military budget.Regionally, every other nation was increasing their military expenditures, except Japan's protector, the US and (perhaps) North Korea, who's spending on anything was a closely guarded state secret. Right now, China and the Khanate's military expenditures were running roughly even at $180 billion each, but this was an arm's race the PRC would eventually win, they had too great an advantage in the size of their workforce and a far larger industrial base.The truth was, if the PRC couldn't win this race fast, she was facing a long, grinding war reminiscent of the Communists' Long Rise to Power that wrecked their country a century ago. The monetary dynamic was shifting badly against them because the Khanate wasn't alone.India, Taiwan and Vietnam were also ramping up their war spending to a combined tune of $34 billion and now allied with the Khanate, equating to an additional $90 billion the PRC had to overcome. South Korea was already adding $8 billion to their military and Russia was taxing the fuck out of Manchuria to both pay for their 'Peaceful Intervention' and to increase the 'Readiness' of their other forces.All of this military spending was bad for both the regional and global economies (unless you were Israel who was turning out hardware 24/7/365 for the Khanate and Indian war machines). So at this point, Japan doing 'nothing' was possibly more disastrous than doing 'something' else.They were already spending $50 fucking billion on glorified policemen while the future of East Asia was being decided without them. Doubling the military budget would place a huge burden on the largely pacifistic population. It would also put Japan in the position of deciding the Fate of Nations.With the repeal of Article 9, Japan could utilize 'proactive means' to keep the naval supply routes to China open, not even the Indian's had the naval presence to confront the Japanese. Such a policy was a nice, friendly gesture to the Asian Colossus, who wasn't likely to show a shred of appreciation for their efforts.No, China had spent the last 60 years stoking the hatred of the Land of the Rising Sun among their people. (Many Japanese forgot current Chinese hatred was based on the Japanese butchering their way across China for nearly a decade between 1937 to 1945).(The Cornerstone) There was a truism which had guided American, Chinese, Japanese and Russian political thought for 150 years: 'There could only be one supreme power in East Asia and the Eastern Pacific'. Japan had followed the logical expression of that paradigm by invading Taiwan (1895), Korea (1910), beating up on Imperial Russia (1904), taking Manchuria (1931) and going to war with China (1937) while that country was trapped in a bloody civil war.To stop the Empire of Japan's rise, the US had attempted to cripple the Japanese economy before the Empire could harvest their just-acquired Asian natural resources. In response, Japan had thrown its soldiers and sailors into a futile effort against the British Empire, the United States and China and lost.With Imperial Japan crushed and the Soviet Union preoccupied in Europe, China had risen. The irresistible force of China's rapidly increasing population, natural resources exploitation and extensive land mass took hold. Japan couldn't compete in a 'fair' fight. Since 1945, the Japanese government had lived with the fear of aggression from Russia and/or China aimed their way.The US felt the same way, or they had. The fear produced by the broad acceptance of 'Only-One-Shall-Rule-Asia' had led to the Korean War, the half-century cease-fire along the Demilitarized Zone in Korea and the Vietnamese Civil War. The Communists in China and Russia had feuded until the Soviet Union collapsed under its own economic inadequacies.A reborn Russia, even with the ultra-nationalist Putin at the helm, couldn't stop China's growing domination. Asia was China's for the taking, until the Khanate rose up like some desert mirage in the Western Steppe, one that turned into the Mother of All Storms. So now, miraculously, the dominion of Asia was up for grabs once more.Japan could not overcome China; that was a given. The Dragon had more people, more resources and an almost three-fold larger economy. Given a decade, the PRC would grind the Khanate down. Once more it was the tyranny of numbers. Even India, Taiwan and Vietnam could only slow down the inevitable.India's subpar economic output marginalized the power of their citizenry. Taiwan had the proportional economy, but not nearly enough people. Vietnam had neither and had always had a rough time defending themselves, much less been successful confronting powers beyond her homeland. Putin's Mother Russia had a host of other problems, internal and external, so she had already contributed as much as Putin dared.Until Thursday morning, Tokyo Time, the undeniable Destiny of Asia remained in the hands of those men in Beijing. The dominoes were falling in a way those rulers had not foreseen and now fumed over. But on Wednesday night, there was no industrial power (with the population to back it up) which could threaten the People's Republic of China.Europe and the US wouldn't intervene. Much like the leadership in Japan, the Communist Chinese Politburo believed Putin had wagered as much as dared. No other nation on Earth mattered. Japan? That was laughable. Their Constitution bound the hands off their military behind their backs with a pledge of eternal pacifism.The Chinese weren't blind to the 250,000 men and women of the Japanese Self Defense Force. Without the political will, those troops might have well have been in Brazil. A hostile Brazil was actually a greater worry because Brazil was the powerhouse of South America, a G-8 economy and hungered for a Permanent Seat on the UN Security Council. The PRC was dedicated to denying their desire as it would have diluted the PRC's burgeoning diplomatic power.Japan? Ha.Thursday morning, in what was essentially an undetected (by anyone except the Ninja and JIKIT) coup d' tat, pacifism was sacrificed on the Altar of Nationalism. Article 96's demise was pre-ordained. A poll taken on July 1st, 42% of Japanese felt positively about the repeal of Article 96 while 46% opposed it.The same agency took a new poll on August 28th. The economic-political situation of Japan was going through a titanic tidal shift. If Buddhism moved you toward devout pacifist, the Khanate had liberated Tibet and was clearly withdrawing as the UN troops' boots hit the ground.If you were a Nationalist of any kind, you were seeing a whole lot more people at your rallies, accessing your websites and signing up to join your formerly fringe parties. If you were a Socialist, you were scared. Why? The PRC was in the process of nationalizing all of Japan's (and South Korea's and Taiwan's) business interests in China, for the 'Duration of the Emergency', or so they said.That meant plenty of Japanese workers were losing their jobs and looking to blame someone. You couldn't blame the centrist LDP. The LDP had been working alongside the Japanese Communist Party for months. They had done nothing wrong and had worked tirelessly for a peaceful diplomatic solution. It was their 'comrades' in China, their Marxist confederates, who were costing the hard-working Japanese workers their jobs.If you were in the Establishment, all of the above worried the crap out of you. Japan's economy had been limping along at barely-positive growth for a decade. Your aging population needed more and more from their public services and, worst of all, you had nothing in your political and economic tool box to escape the obvious oncoming national catastrophe.The possibility of a Global Recession loomed on the horizon, if they were lucky. Highly respected economists in Japan and elsewhere were examining all the key indicators over the past three months and were suggesting hording as a viable policy for middle class households to consider. If you were in the Developing World, worse was heading your way.The word being bandied about on those esteemed academic internet websites wasn't 'recession', it was depression. Global prosperity thrived on nations investing in both their own economy and the economies of other nations. The governments representing a third of the World's population were not investing in their economies.Unless you were a war profiteer, you could expect fewer consumer goods on the shelves; and what was there would cost more. Your income wasn't going up; your expenses were. If you were an Atheistic homeowner in the Western World with a secured 3.25% fixed rate home loan, you took up religion. The prime interest rate would be racing for the 20% mark and that was only if your economy was stable.If you lived in a country in the Developing World, your trade goods didn't compete with those created in the G-20. Your competition was with other Developing World businesses and the prize was the pocketbooks of those consumers in the G-20, which was a shrinking purse.It wasn't like you were being paid all that much to begin with; and now those once poor-paying, but at least plentiful, jobs were drying up. You needed your government to help you out. It wasn't like those governments could raise money by taxing the unemployed and under-employed. They didn't have money. And the rich in most of those same nations had a long and successful legacy of avoiding paying.Those growing economies had a few tried and tested 'solutions' for getting their countries through these rough stretches.The IMF? 'We are out to make 'positive' capital investments and your economic outlook doesn't look promising. We suggest 'austerity'.'The BRICS? Since India and China were basically in an undeclared state of war: 'we won't be loaning anyone anything for a while.'The BIS? 'As soon as the People' Bank of China, the Reserve Bank of India, the Central Bank of Ireland, the Bank of Israel and the Central Bank of the Republic of Turkey get back to us about their sudden, serious lack of transparency, we'll call you back.'World Bank? Holy Shit! 'The world's going down the toilet, we will do what we can.'F Y I, I (as in Cáel) had been wrong. The 6 Elders of the Ninja families didn't talk to Japanese Prime Minister, Shinzō Awbee. They talked with another, far more immediately important man. So sue me (Cáel) for not knowing the inner workings of various world governments, and creatively interpreting events surrounding all those people I (Cáel) didn't. I'm a freaking Liberal Arts major with a fertile imagination, not a superspy, or even a competent Intelligence Analyst!}The Japanese government had appealed to the U.S., U.N., P.R.C., A.S.E.A.N., India; and (through back channels aka JIKIT) the Khanate for an end to this madness; all with typical results:The U.S.A: We are working on it (without letting them know what precisely they were working on)Japan: Well, do something fast. Our Government Bonds are about to be more useful as wallpaper.The U.N.: We are working on it (with their long-established tradition of not doing anything until the crisis had passed)Japan: You are preparing to pass a Resolution to move this matter from the First Committee to the Fourth Committee, gee, thanks guys. Will they be meeting sometime before Christmas?The PRC: We are too busy right now, so shut up, keep the trade lanes open, and was that your submarine we detected sneaking into our territorial waters?Japan: What? What do you mean you are 'too busy?' You are one of our biggest trading partners, your economy is going down the toilet, and, No! That was not our submarine in your territorial waters. That accusation is absurd.(Note from Japanese Prime Minister, Shinzō Awbee, to Admiral Katsutoshi Kawano, head of the JMSDF {the de facto Japanese Navy}), The PRC has made this outrageous claim that one of our submarines has been sneaking around their territorial waters. There is no truth to that rumor, right?Kawano: Which time?Prime Minister: Oh My God! What have you people been doing and why is this the first time I'm hearing about it?Kawano: Sir, if you are just now getting around to asking us, you don't want to know.Prime Minister: What do you mean 'I don't want to know?' I'm the head of the damn government and, you are right. Fine. There is no way I'm going back to the Chinese Ambassador and apologizing for any this. Is there any way this can come back to screw us over?Kawano: With all these US and British submarines helping us out, not very likely, Prime Minister.Prime Minister: Oh, very good. You are correct, I don't want to know what you 'haven't' been doing. I am ordering you to destroy all transcripts and recordings of this conversation.Kawano: It has been my distinct honor not having this conversation with you, Prime Minister. Sayōnara.ASEAN, What do you expect us to do about this? Have you seen the unimpressive combined sizes of our members' air forces and navies? Did you see the smack-down the Khanate has inflicted on the PLAN's South China Sea Fleet?Besides, the PRC is claiming that the Khanate launched covert attacks against the Parcels and Spratly islands which originated from Indonesian and Filipino waters. We are investigating the issue. If you are asking us for help, you are truly screwed. Don't call us. We will call you.Japan, {muttering} Investigating the attacks that came from your territory, bullshit! You are covering your own asses, damn it!(Note from Prime Minister, Shinzō Awbee, to Shotaro Yachi, Japanese National Security Advisor), I've heard an ugly rumor that the Khanate has forces secreted in the Philippines and Indonesia. Do you happen to know anything about it?Yachi: Yes Sir. We had advance notice of the organization, composition and destination of those forces.Awbee (while muttering 'no one tells me anything anymore'): What the! Would you please tell me what is going on.Yachi: We have made critical steps toward future alliances which will guarantee Japanese security for decades to come.Awbee What does that mean, and since when have you been creating and implementing foreign policy? We have a Minister for that, in case you somehow over-looked him at the last cabinet meeting. Wait! Does he know about this too?Yachi: No Sir, Foreign Minister Kishida is currently unaware of the Kinkyū tokushu sakusen tasukufōsu (Emergency Special Operations Task Force). Admiral Katsutoshi knows the basics of our operational policy, since we need to borrow some of his assets from time to time. Director-General Kitada (of the Public Security Intelligence Agency) and key personnel from the Foreign Ministry's Intelligence & Analysis Service and Security Bureau make up the majority of the task force's operatives.Awbee: What have you been doing?Yachi: You don't want to know, Mr. Prime Minister. It would make things, awkward.Awbee: 'You don't want to know', of course, I don't. I'm only the elected head of this government. Why would I possibly want to know what acts of espionage and war my deputies are executing?Yachi: I am glad we are on the same page, Sir. Will there be anything else?Awbee: No, wait. Do you have any intelligence on what the Khanate is up to?Yachi: Yes Sir. Is there anything in particular you want to know?Analysis Services: Can you contact someone in their leadership willing to discuss regional affairs?Yachi: I can put you in touch with the Great Khan himself if necessary.AS: What!Yachi: Sir, I would hardly be acting in our nation's best interests if I couldn't divine the intentions of the key players on the stage. Shall I initiate the necessary communications to facilitate that level of clandestine diplomatic contact?AS: No. Yes. No, I need to think about this. Hmm, have you been conducting any domestic espionage missions?Yachi: You don't want me to answer that, Sir.Awbee: of course I don't, I'm only the damn Prime Minister. Shotaro, I'm still Prime Minister, aren't I?Yachi: Yes Sir. We have been working overtime to ensure that. We've foiled two enemy assassination attempts and one attempted kidnapping so far. We remain vigilant.AS: How come this is the first I'm hearing about it? Is the head of my security in on this conspiracy of yours too?Yachi: No Sir. These particular guardians wish to avoid notoriety at all costs.Awbee: Okay. Good to know. Ah, keep up the good work and destroy any trace of this conversation.Yachi: Way ahead of you, Sir. Have a good night.India, Yes, we are more than willing to work with you toward regional stability. Care to acknowledge the Khanate's legitimacy first? We'd really appreciate it. Sure, get back to us when you've done that. Until then, the South China Sea Awaits! Yes, we plan to keep what we've earned. Later now. We think there is going to be further instability in Southeast Asia.Japan, Ya think? It is your damn warships sailing around the freaking South China Sea enforcing your utterly un-secret alliance with the Khanate. Why are you doing this to us? What have we ever done to you?The Khanate, We are not out to damage your national interests. We apologize, but there is now way we will call off this war with the Communist Chinese. It is them, or us, to the death. We have already received and agreed to your request to allow all Japanese flagged ships safe transit through the South China Sea. We really wish to be your friends this time, to make up for those two invasion attempts seven hundred years ago.(Note from  Prime Minister to Self) Great. The only reasonable people who aren't out to kick me in the nuts are also the ones I can't acknowledge talking to. I've got to do something a

Tadifi's legendBook 3 in 18 parts, By FinalStand. Listen to the ► Podcast at Explicit Novels.Meanwhile, Elsa was quietly amused. It wasn't like I could request the SD to force my House Guard to not do something they had been told to do by someone in my hierarchy. That would lead to chaos, and it was unfair to Juanita."Fine," I decided. "Get us three some water. Elsa and I will be practicing."Now Juanita was stuck. I wasn't asking her to leave the room, just leave me alone. I was technically her leader, respect notwithstanding."It is good to see you have not become drunk with power," Elsa smirked once Juanita had left on her errand."Your mockery is unappreciated," I glared back. I was only kidding. "I haven't seen you around recently. It is good to see you.""It is good to see you too," Elsa said in a voice far softer and compassionate than I would have preferred. After all, she had me drugged, beaten, then beaten me up again in the not so distant past.Of course, I had also sexed her up, bringing her to orgasm with my fingers alone. We had also exchanged a burning French kiss in Katrina's office that Buffy was aware of. Then there was the Buffy-Elsa personal feud and the Elsa-Rhada family feud. Balancing that was Elsa's super-hot body and intriguing personality. Sex with her promised to be memorable, more memorable than normal."What have you been up to? I'd like to say I've been behaving myself, but I don't want to advance our relationship by lying (right now, about this).""You are largely responsible for what I've been up to the past two weeks," she stepped back. She tossed her spear aside and entered her fighting stance. How nice of her to warn me, and get rid of her weapon. How erotically odd of her to give me the illusion of a chance."I deny everything," I rocked back. She was blindingly fast. The fact that I was able to block most of the blow was a testament to how much I had learned in the past two and a half months."Watashi wa nihongo o hanashimasu', 'Wǒ shuō pǔtōnghu ', 'Wǒ shuō guǎngdōng hu ' and 'Aku isa basa jawa'," she lectured me as she maneuvered me into a corner with a series of kicks and feints. She spoke Japanese, Mandarin, Cantonese and Javanese. That was nice to know."Wait," then she kicked me off the mat."Amazons don't have a 'time out'," she smiled. I cautiously worked my way back onto the practice area."What part did you play?" I readied myself. This time, I went on the offensive. I used my greater strength and reach to compensate (rather poorly) for her superior reflexes."Someone had to ride herd on those disparate forces. My status was respected by the Amazons, I had experience dealing with outsiders, plus your person Addison nominated me, and Katrina suggested that you and I were close. That was enough for the Khanate. Your embassy and earlier aid to the Seven Families brought the 9 Clans along.""And you stole the carrier?""It was an once-in-a-lifetime opportunity to humiliate the Seven Pillars," she grinned. "Riding in a nuclear submarine was interesting, right up there with running around, spray painting translations next to all the markings onboard the captured vessel. Herding regular civilians wasn't nearly as much fun.""In the annals of the SD, that is going to be a victory hard to surpass," I got out right before my legs were swept out from under me. Before I could roll over, she landed on top of me. She didn't go for a pin. Elsa simply sat there, straddling my hips and looking down at me. We were both breathing heavily."I owe you for that," she patted me on my bare chest."Is that a good thing, or a bad thing?""I'll let you figure that out during the Great Hunt," she gave a sliver of a smile."Not you too," I groaned."Who else are you worried about?""You and twenty-nine other Amazons. By name, Rachel. She's pretty upbeat about her chances and believes she has a score to settle.""Rachel will be a tough one," Elsa acknowledged."Comfortable?" Juanita muttered."Yes, I am," Elsa grinned her way. "Thank you for asking." Juanita gave me a look that suggested I do something like protest, or actually try to fight her off."Why are you being nice to me?" I wondered."I've learned to appreciate your numerous qualities," Elsa enlightened me. "I am also honest enough to admit I was completely wrong about you. You make a good Amazon." That was huge praise indeed and more importantly, it was to a public audience. I was double fortunate that no one was close enough to see Elsa's camel toe resting against my lightly covered hard-on."Thank you. Is there anything I can do for you?""Aren't you engaged to someone?" Juanita reminded me. What she was really saying was 'don't you know you belong to the maidens of House Ishara?' Trust me, I know these things. Had she meant Hana, she would have said Hana."She has the patience of Job," I reasoned. "Oh, Elsa, Job is a figure in the Old Testament of the Bible." I doubted she knew."Oh. Is he a bloody-handed butcher, raging misogynist, or one of those pacifistic wimps?""He's a nice guy who gets swallowed by a whale.""That's Jonah," Juanita corrected me. "Job is the one who was tested by God. Job accepted God taking away all his family, wealth and health, only to be rewarded for his loyalty to God with more than he ever had before.""Wimp.""I would never turn away from Ishara," Juanita rumbled."Zorja would never feel the need to test my loyalty so," Elsa riposted."Oh look," I thrust my hips up. "I seem to need a shower." Elsa's expression was of superiority and lust combined into a lethal cocktail of my demise."Let's go. You can wash my back," she said as she rose over me. She even offered me a hand up. That was unexpected and accepted warily."Is there some battle wound that makes you incapable of bathing yourself?" Juanita got feisty. Holy Hell, she was my Caribbean Buffy-twin."None," Elsa smugly commented. "I like the feel of his hands on my body. He possesses non-threatening masculinity wed with sisterly solidarity. It is a unique experience that you seem woefully unaware of.""Yippee!" I whispered."You really are a man-whore," Juanita declared under her breath."Check," I gave her a thumbs-up. Sadly, Elsa gave me enough respect to walk at my side, not in front of me (so I could have been mesmerized by her buttocks.) As I was stripping down in the locker room, I noticed Juanita hovering close by. "Are you going to follow me into the shower?""Yes.""Why? I am not going to be in danger in the middle of Havenstone.""I'll be the judge of that," she insisted."You do realize I've had sex with an audience before, don't you?""I've been warned about that and know proper counter-measures.""What? What kind of measures?" I was now naked and, towel in hand, was making my way to the communal showers."Charlie horses, trips, stun-gun if applicable," she informed me with relish."You are threatening to damage my prestige," I enlightened her."Cáel, I was chosen for more than my martial skills. I was selected because I will not wilt before your childish ways.""Are you a lesbian?""No. Why would a woman have to be a lesbian to withstand your wiles?""You'll figure it out eventually," I chuckled. Actually, knowing what a playboy-cad I was turned out to be a counter-intuitive edge for me. Expecting me to be a letch just meant I totally ignored the woman. Then the doubt would set in. 'Why wasn't I hitting on her?' she would think. She'd go through the phase of her not being good enough for me to knowing that wasn't the case, definitely, and would come at me to prove herself right. Wham-bam, another one in the can. Oink.Step One: reduce the amount of time talking to her as a fellow human traveler of life. From here on out, I would address her by her name when I wanted something and otherwise treat her like furniture ~ furniture I was comfortable with. In this case, I treated her like a towel rack. She promptly dropped it. That was okay, I was planning to get dressed wet anyway.I rinsed off my hair quickly as Elsa settled underneath the showerhead beside me. As soon as I finished, she handled me a bottle of (scentless) body soap. It was probably one of those the jaguar will smell me coming ten miles away excuses Amazons used to avoid being girlie. I got my hands all sudsy and began working on her shoulders and neck from behind.Wordlessly, Elsa followed my physical directions, allowing me to wash her arms before working my way down her back in languid, amorous circles. Around the 10th thoracic vertebrae, Elsa gave me a deep, cleansing exhalation. I dug my fingers into her taut back muscles, racking them down to her buttocks, deftly ran them along the sides of her glutes and finished up caressing them along the line between her thighs and ass.I worked her buttocks apart, worked my fingers along her perineum, tickling the back of her labia then up, across her anus and back to her tailbone and the small of her back. A crazy idea came to me: maybe I could talk her into a tramp stamp; something like If you are reading this, know I'll kill you next. That would be so Elsa.I lathered her ass up for another half-minute before working my way down to her thighs, starting with the hip joints and then coaxing of her parted lips. I knelt down so that I was resting on the balls of my feet. Elsa obliged me by parting her legs, standing on her toes with her feet over a foot apart, then placing her hands against the shower stall while arching her back so that her hips were thrust back."Oh, come on," Juanita protested. "What kind of bath is this?""Did you hear something?" Elsa looked down at me."Nope. I was focusing all of my attention on you," I smiled up at her. I was really liking the way her muscles were stressed through her exertions. I couldn't seem to pay enough attention to her robust calves. I didn't pass up the opportunity to plant gentle kisses on each cheek either.Elsa's ankles and feet happened all too fast and the pretense of a bath was complete. She looked at me while she soaped up her breasts then let the water cascade all over her body."Thank you, Cáel," she gave me a regal nod of her damp head, turned and left. "Train harder for the Hunt. You are going to need every edge you can get.""I'm stalking oysters over the weekend. They are cunning and stealthy adversaries," I replied sagely. Elsa snorted, then started toweling off as she left, going toward her own locker. I walked past my soaked towel on the floor without a single glance. Juanita stalked behind me, clearly with a lot on her mind she was now waiting for the proper moment to share. I got dressed."Not going to dry off?" she grumbled."I never use towels," I lied. "I like the rain-washed feel." By ignoring her act of defiance, I really steamed her. I wasn't done. As we headed toward the elevator, I opened up with my next jibe. Buffy really shouldn't challenge me so. I'm a past-master of dealing with clingy, bossy women."Regretting you made that bet?" I mused while we waited."What bet?" she simmered."The bet where you assured Buffy and whomever else was in the room that you wouldn't break down and physically harm me ~ punishing me for my wicked ways?""What? How did," she groused then, "You are playing me.""Yep.""You really are full of yourself," she seared me with her gaze."No, but I know what I'm good at and I'm good at frustrating women. I've been working at it for the past four years and I've got over 200 women who would agree that I'm very good at doing it.""Why are you doing this to me? I'm on your side," she turned all pouty and hurtful."Because if I don't, I'll go mad, Juanita," I enlightened her. "You want to protect me, right?""Yes," she sensed a verbal trap. The elevator opened and we stepped in."See, I don't want to be protected," I started."That's,""Let me finish, please," I stopped her. She gave me the visual 'go-ahead'. "I don't want to live a life where I need to be protected. I don't want to worry that women I hang out with could be cornered by some unsavory types at an eatery because those women happen to know and like me.""I admire what you are doing, I really do. This is not the life I wanted, though. This is not what I wanted to be doing four months after leaving college. I wanted to be some corporate worm, barely scraping by on my work reviews and being, as you said, 'a man-whore'.""You don't have that luxury," she pointed out."Am I not doing my job?" I countered."I guess you are," she grudgingly admitted."Yet you feel you have the right to critique my personal life and how I approach it," I related. "I'm not beating you up by playing the I am Ishara bullshit. I certainly don't expect anyone to be grateful to me for the opportunity to be in a House. I don't because I believe that every member of House Ishara has already proven they belong here before I ever meet them. I believe in you. Sometimes I would appreciate it if my sisters would give me the same respect."She looked away because my harpoon had struck home."Unlike the rest of you, I inherited my place in this madhouse. Unlike every other Amazon here, I am only a part of House Ishara because I am the choice of a thousand ancestors to be our leader. Notice that no one asked me if I wanted to do this. And I don't think I ask too much of you because frankly, there are times when I feel unworthy to be in your company.""You are still Ishara and I must still be your guardian," she held her ground. I glared at her. She glared back. I coughed. She kept glaring."What's my name?""Oh," she shrugged. "Cáel Wakko Ishara.""That may sound silly you to, but I have chosen the designations for myself, my First Ancestor and the Goddess for a good reason."We rode in silence. When we got to the ground floor, we made our way to our bikes and got ready to head home."What is the reason?""To never take ourselves too seriously. The worst thing I can think to befall my House is we become as humorless as the rest of the bitches around here. 'Laugh at Death' should be our motto.""Isn't that a bit childish?""Of course it is," I groaned. "You clearly haven't been paying attention to a damn thing I've been saying. I swear I'm thinking about bringing back 'National Clown Nose Day'.""We had a 'National Clown Nose Day'?" she pedaled to keep up."God help me," I muttered.(Where is my Serge?)"You are not going to let me go through my door first?" I sighed in exasperation. Juanita insisted that she go through every door first, because today was so very different than yesterday, when I had Pamela, perhaps I protest too much."You have a gun," a somewhat familiar voice said from inside my/Timothy's apartment. Oh, fuck. Ya know, because Juanita was as pretty as she was lethal, which is to say 'too much for the given company'."Don't make any sudden moves unless you want to see it," Juanita cautioned her."Oh, it's okay," Odette intervened. "This is Anais Saint-Armour. She's a Mountie.""Oh, she's on the List too," Juanita grumbled. "What has he done wrong this time?""Why don't you tell me who you are first?" Anais growled at Juanita while I pushed my way into the room."I don't like your attitude," Juanita glared."Anais, this is Juanita Leya Antonio Garza; she's my latest bodyguard. Juanita, this is Anais, a good friend of mine who helped save my life in Hungary when the 'terrorists' were closing in," I somewhat exaggerated,, she had helped me catch up with the rest of the team when Pamela and I got sidetracked."Why did he chose you?" Anais fumed. Did I mention she's insanely jealous with an aching need to know why I was marrying anyone else, but her."What list?" Odette proved to be on the ball."He didn't chose me. I volunteered for the spot.""Buffy made an anti-girlfriend list. Elsa is on it too," I mumbled."I bet you did," Anais (responding to Juanita)."It is not like that," I moved to interpose myself between my Mountie and my non-mounted (for now) guardian. "I'm on the board of directors for Havenstone now and,""How did that happen?" Anais turned 'The Force' on me. (That's Canadian for the Royal Canadian Mounted Police, really) "You insisted (reference back in the days we were seeing one another) you were impoverished.""I inherited it from my Father,""He's poor too. I ran a background check when we first started dating," Anais kept up the pressure."My Mother?""She's dead.""Okay, it was my Father through a convoluted meandering of genetics," I went back to attempting the truth (shame on me)."Which is it?" she glowered."My Father, but it's too complicated to get into now," I tried to touch her. She recoiled. She was still pissed with me."He's telling the truth this time," Odette rose to my defense."Why didn't you tell me this when you were in Hungary? For that matter, if you are rich, why didn't you use those resources to get yourself out of trouble instead of involving me?" She really was a great cop."I had to make a call to someone I trusted and who couldn't be traced back to me, or Havenstone, or the Irish Embassy," I fibbed."What have you gotten yourself into?" Anais thawed somewhat."I believe I promised you dinner," I reminded her."You did.""Where are we going?" Juanita stressed our lack of privacy."'We' aren't going anywhere. Ms. Anais Saint-Armour and I are going to a restaurant of her choosing. Don't worry about it. She carries a gun.""I'm not carrying a gun," Anais torpedoed my plan."Where are we going?" Juanita repeated herself. I had to switch mental gears quickly to take in the new looks I was getting from Anais. I shouldn't have ignored those cues."I can't get around my personal security service," I sighed. Why did I give in? Anais was all about gathering evidence and then drawing conclusions from the facts in available.I had been involved in some significant bad-assery in Europe that was way beyond anything she would have associated with the old me. Terrorist cells duking it out with me (and others) in a Budapest metro station? A rustic inn being reduced to ashes after a suspected firefight? Bomb threats? A full-scale military operation in Romania?I had been kidnapped with a resultant massive manhunt for me then returned under highly mysterious circumstances. There had been a young girl with me, we were close for reasons not really gone into and I had saved her despite all forms of parenthood had been anathema to me.I was a man who others deemed necessary to protect, thus a man making secretive phone calls, getting snippets of information and being involved in the deaths of way too many people to be the old, playboy me. Who had I become?I therefore might be a man who 'needed' to marry a billionairess due to some unspeakable political reasons, not out of any romantic/sexual desire of my own. Anais knew that I was a commitment-phobe, not a gold-digger. That meant she could be involved with me without it really being cheating. I needed her help, I had reached out to her when I was in crisis and she was in the people-helping business, right?There was clearly more evidence out there for her to discover and she had the good fortune to be able to have me in a spot where I could be interrogated."Where do you want to go?" I disengaged and went to my room. The door was only partially shut as I changed."Eleven Madison West," I was told."Oh," Odette cooed, "that place is expensive.""I know," Anais remarked."Why did you pick it?" Odette inquired."To remind Cáel that meals can be very expensive." That was my 'date' reminded me that I'd cheated with her over the course of a home-cooked meal, cooked not-by-her in someone else's home. I wondered how Maya was doing.Eleven Madison West meant I pulled out one of my Havenstone suits. They were tailored after all and I suspected that getting into this place at this time of night was going to take some charisma and finagling. Dressing as causal-me wouldn't do. When I stepped out, jaws dropped ~ I do look good all gussied up. Odette dispelled the shock by jumping into my arms."You look hot," she squealed. "Too bad I'm not going out with you.""You might want to remember that," Anais griped."We need to stop by Havenstone so I can attempt to dress up for this affair," Juanita stated."How about we call in a replacement? Give you the night off?" I suggested."Who?""Chaz?""You want that British SSR non-commissioned officer to be your personal bodyguard for tonight? You've got balls," Juanita coughed. I took out my phone and got ready to give him a call."Hey, Anais, why didn't you call me to tell me you were coming over?" I carefully avoided the word 'warned' as she would take that the wrong way."I don't have your personal phone number. I called your home phone and got the answering service, last night and again this morning," she narrowed her eyes."Odette, did Timothy get lucky last night?" I looked past the Mountie."No. A good friend of his rolled his motorcycle and he went to the hospital to help him out," Odette shook her head. Poor Timothy. My roomie/fuck-buddy misinterpreted Anais's pique. "Timothy is gay, not a sexual enabler.""Huh?" Juanita wondered."Wingman," I translated. "Sometimes the three of us go to gay clubs where I act as his wingman,""And they feed me to lesbians," Odette sounded enthusiastic. Thanks to me she was hardly a same-sex virgin."If there are three people living here and two bedrooms, who sleeps on the sofa?" Anais skewered Odette with her eyes."If Cáel has company and isn't sharing, I sleep with Timothy," Odette refused to wilt, or cut me some slack with Anais."Isn't sharing?" those ocular death orbs flicked my way."Hmm, if we are going to Elven Madison West, I had better make that call," I evaded. I rang Chaz."Nyilas," he answered. "How are you doing this evening?""I'm good. I have an ex-girlfriend from out of town visiting, she wants to go to a swanky place and Juanita isn't dressed for the detail so,""You want me to double date?""No, I need a bodyguard.""You are assuming I have something appropriate to wear.""You are British!" I protested. "Even your chicks have tuxedos.""Very well. Will this be a personal protection detail, or close support?""Aahhh,""Close support," said Anais."Personal Protection," countered Juanita."The one most likely to save me from being stabbed with a steak knife," I muttered."I am not going to physically attack you," Anais simmered. Yeah, right, I had heard that one before, and not just from her."Personal Protection it is," Chaz informed me."Oh, and she's a Mountie.""Is she armed?""No," I thanked the goddesses."Does she want to be?""Huh? Are you going to arm her?" I panicked."No. You have a NYPD liaison. Give Officer Kutuzov a call and make a formal request. If she is a law enforcement officer in good standing, it shouldn't be a problem.""Oh, I can do that?, I'm not sure that's the best idea," I prevaricated."Man up, Nyilas," he chided me. "You should work on making it so women don't want to shoot you instead of thinking of ways to disarm them.""Spoken like a man who wisely prefers the company of other men," I grumbled."Good use of the word 'wisely'. Next question: what are we using as a means of conveyance?""Umm,""I have my motorcycle," Anais was less than helpful."If you weren't one of the bravest human beings I'd ever met, I would determine at this moment that you are a dolt. Call Havenstone and arrange for one of those Mercedes Armored GL550s. Bring your license. I drive on the correct side of the road and I'm not keen on having a distraught paramour driving into a storefront at 80 kph.""Man, I like the way you speak," I joked."I took advantage of a proper English education.""I was joking with you.""I know.""Can I date your sister?" I didn't know if he had a sister, but he'd hinted there were multiple Tomorrow's out there. Anais' mood didn't improve."Yes. I like you. You are a good bloke.""Does your sister know how to kill people?""Yes. I'd say she's relatively proficient with a variety of small arms and hand-to-hand techniques," he enlightened me."Just checking.""Cáel, every woman you are interested knows how to kill people, or how to have people killed," Chaz reminded me."What about Odette? She's neither well connected nor lethal.""Odette is indeed an enigma. She counters that by being well liked by people who are capable of killing others who hurt her, except where you are concerned. You live a treasured life.""Have you made dinner reservations? If you need me for a black tie event it has to be, what is the American for it, swanky.""That's more of a Cael/Pamela thing," I corrected him. "American's say 'high class', expensive, or 'hot spot'.""Thanks for the update. Make those calls.""O-kay. Will do. I'll meet you at Havenstone in thirty minutes. Does that work for you?""Yes. Make those calls. I'll see you at, 7:52 pm, EDT. Mark.""Huh?""Goodbye Cáel," and he hung up."Who is this 'Chaz' character?" Anais questioned me."He is Color Sergeant Charles Tomorrow of the British Army's Special Reconnaissance Regiment, he's a badass and he's delicious," Odette answered for me."How do you know him, either of you?" came next."He was with," Odette began blabbing 'National Security' stuff."Odette, don't. Anais, he is member of the Joint International Khanate Interim Taskforce along with me. Odette helps out in an auxiliary role," I answered."Cáel, how did you end up doing this kind of work?" she was perplexed. "You were devoid of anything approaching civic responsibility when we were last together. Quite frankly, I didn't think you cared for anyone but yourself.""Hey now," Odette got feisty. She was my friend after all."We can talk about that over dinner?" I suggested. She didn't like that answer, so I lied. "I grew up," which was what she wanted to hear. I was spared any more interrogation at the moment by the necessity of making those three phone calls. Nikita liked hearing from me again, though she was less pleased that it was official business. She did agree to contact the appropriate agency for me, despite me making it for a different female law enforcement agent.I'd wised up about Havenstone. I called Executive services to have the car delivered to my door step. I cautioned the operative that, in my neighborhood, they might be stopped on suspicion of purchasing guns, drugs, and/or a good time. I would have the car in fifteen minutes and agreed to take the delivery driver back to work afterwards. I'd have done it even if I wasn't meeting Chaz.At Eleven Madison West, I got a snooty 'exactly who do you think you are?' followed by 'you will be placed on the waiting list, a spot may open up around 9:50'. Was I going to inform Chaz and Anais of this? Of course not. I planned to beg like a big dog, suggest that while I was a nameless face, I actually knew people, a person, and we'd see how far that got me.While waiting for the S U V to arrive and on the drive back to Havenstone, this is pretty much what followed:"Do you know who was behind your father's murder yet?""Yes, but I can't talk about it.""Was that the reason people are trying to kill you?""Yes. That and other reasons.""What other reasons?""Things I can't talk about.""Why can't you talk about it?""Secret society stuff ~ decoder rings, secret handshakes, writing in cyphers, holding clandestine meetings in public places after dark, and various other things world governments don't want me talking about.""Are you pulling my leg?" I wished I was running my hands over her legs. This wasn't the time for that revelation."No. Most of what I am telling you is the truth.""Were you in a shootout at the Chicago Medical Examiner's morgue?""Yes. I was unarmed at the time.""Was your life in danger?""It depends on what you mean by 'danger'. My allies had guns and were expert shots. I was shot at, but they missed me, so I not sure how much my life was at risk.""Can you please be serious?""I'm trying. You scare me.""You don't need to be afraid of me. I only want to help." That was mostly true. She was a diligent, hard-working incorruptible public servant,well, as long as you overlooked her charging me with bestiality when she was truly pissed with me."I'm not afraid of you hurting me. I'm afraid for you. You are an excellent peace officer and I'm worried that you will learn too much. Then your life will be as screwed up as mine.""I can take care of myself.""The reality that you are going out with me unarmed speaks volumes about what you don't know, Anais.""Don't think this line of questioning is over, Cáel.""Don't worry. I know you are not done.""Very well. How is your aunt?" The crab-fisherwoman, not the Irish menagerie."Happy as a clam, working a real job and living life on her own terms.""Where did you go wrong?" That was a loaded question. I had to tread carefully."A girl humiliated me in high school. I decided to take control of my life and somehow, despite my best intentions to be an unreliable lothario, I've ended up with people closer to me than family,and this constant need for physical protection.""Why are you engaged?" Finally, the real reason she was here. Had she come by to pick up her accoutrements, she would have been gone by the time I came home. She wanted answers, answers that allowed her to be in charge of our relationship again. It was the double-barreled impact of exceptional sex and wondering why she wasn't 'the one'.(Me) "Are you seeing somebody?""You didn't answer my question.""I've answered plenty of your questions. Answer mine.""No. Men expect too much from a career woman." Translation: 'I'm a bitch that, regardless of my dynamite looks and raunchy sex drive, repels men because I'm a compulsive control freak with abysmal trust issues.'"You do put your career first." Translation: 'I've totally forgotten that you are a compulsive control freak with abysmal trust issues.' It was what she wanted to hear."Your turn.""Put on your tin-foil hat. I did it to save lives in Central Asia when the anthrax strikes were going on. I have this friend over there that people listen to.""Who? The Great Khan?"I didn't respond which wasn't the answer she was expecting."How?" as in how could I possibly be good friends with the master of arguably the third or fourth most powerful nation on the face of the Earth"That's one of those things I can't talk about.""Do you love her?""I don't know. I'm lousy at relationships. I get along with her daughter. Her father wants to bury me alive in the Nevada desert. The rest of the family seems to be coming around to the idea that I might be one of them.""That isn't a 'yes'.""No, it isn't.""Do you think you can ever love someone?" If you need translated, sigh, okay, 'why don't you love me?'"Do you mean 'when am I going to stop stumbling from botched relationship to botched relationship and make something constructive of my personal life?'""Yes.""Did I mention that I've discovered I have a grandfather?""No. That isn't answering my question.""It is in a way. Did I mention that Mom had ten sisters I wasn't aware of? I had an uncle, but he died in my arms.""No. My condolences on your uncle. What does this have to do with you becoming more of an adult and becoming accountable for your life?""Did I mention I have an adopted grandmother who is my spiritual twin?""No.""Don't worry about my uncle. He died trying to kill me. My aunts murdered him, though I can never prove it.""Oh.""My grandfather? He was the one who sent those terrorists to kill me. It was his litmus test to see if I was worthy of being in his family. I passed.""Are you serious?""Yes. My spiritual grandma? She's a retired professional assassin. Daily I interact with a half-dozen people who have killed multiple human beings in their lifetimes. You want to know why I'm not behaving responsibly? I am acting responsibly. I'm trying to not get the decent civilians around me killed."She took awhile digesting that. By that time, we had returned to Havenstone and picked up Chaz. I made introductions."So, are you really with the SRR?" she asked him."Yes.""Why are you with Cáel?""My mandate contains multiple answers. Suffice it to say, since my RAF contemporary will not be returning from the UK until tomorrow, I am presently chief liaison officer for Her Majesty's government with JIKIT.""Why are you coming along as Cáel's bodyguard? Don't you have something better to do with your Friday evenings?" Subtle and polite, Anais ain't. Why was I putting up with her? She was a sexual tornado who would try anything once. She was a real prize."First question: Cáel is a friend, his life is in perpetual danger and I consider it my duty to keep him alive. He would do the same for me. Second question: the nature of my present assignment doesn't leave much room for any meaningful romantic associations.""Hmm," I contemplated what wasn't being said. "Chaz, you are nailing one of my security chicks, aren't you?""Yes.""Which one?""A man of character doesn't brag about such things."Chaz was getting some Amazon nookie. I had to find a way to tell him how dangerous that was. She might decide he's make good father material, not a good thing where Amazons were concerned."Are all of his security personnel women?" Anais pressed."Miss Saint-Amour, Havenstone is a corporation that employs over ten thousand people. There are precisely five men currently on their payroll. All their security personnel are woman. Cáel has very limited, if any, input on the matter.""Are you sure about that?""Yes, Miss Saint-Amour. Who would trust a man of Cáel's dubious experience with his own security?" Chaz pointed out."Oh." She hadn't thought of that."Can you tell me why you think his life is in danger?""He is far more likely to be kidnapped than murdered. He possess certain sensitive data that powerful entities would like to access, thus I am his bodyguard tonight. Considering the quality of the women who normally guard him, I consider it an honor.""To guard Cáel, on a date?""He was kidnapped visiting a child at a playground. Yes, we believe his life is in constant peril. The training and experience of his security service is top flight and it has been a pleasure to serve among them.""Were you with him in Budapest and Romania?""The metro station?""Yes.""Yes.""Romania?""Do you mean the counterterrorism action south of Miercurea Ciuc?""Yes.""Yes."Wow, these two were lousy communicators. I could imagine Chaz propositioning one of my Amazons.Chaz: 'You have a superior feminine physique which I find appealing. Want to fuck?'Amazon: 'You look like you have the prerequisite stamina and battle scars to be part of the New Directive. Sure.'"Were you involved in the actual combat? The SRR is normally an intelligence gathering unit.""I was gathering battlefield intelligence, Miss. That required my close proximity to armed and actively hostile enemy aliens (as in they were in Romania illegally, not that they were all supernatural beings). My involvement resulted in two KIA's and one WIA.""Damn Chaz, you rock.""I am a professional.""How many did Pamela gak?""One KIA.""Just one? Whoa, that's so unlike her.""She kept trying to bracket the cell leader (aka Ajax). He had the Devil's Own Luck.""Cáel, why are you making light of all those deaths?" Anais chastised me. "How many terrorists did you wound, or kill?""I wounded one guy.""That is disingenuous," Chaz chided me. "You orchestrated the operation, showed tactical expertise in seizing the most critical terrain feature and engineered the death of the terrorist leader.""My Cáel did that? When I knew him, he was adverse to violence," Anais shook her head."Considering the considerable number of people he's killed, he's still adverse to physical confrontation where his own life is involved. But God help you if you threaten someone he is close to, though. He's the man who can get things done when the team is in a pinch.""Cáel, what happened to you?" she didn't sound upset at all."I learned to care for people beyond my immediate interest, you know, actual long-term relationships," with the unspoken 'as opposed to women I'm currently having sex with'."It took you long enough," she snipped. Reference her being a compulsive control freak with abysmal trust issues.The interrogation was put on hold while we entered the restaurant and,"Mr. Nyilas?" the maytre dee greeted me."Yes.""We will get you a table right away," he nodded obsequiously. What the hell was up with that? Where was my two hour wait time? Oh yeah, I was a minor, fifteen seconds of fame celebrity."Will Ms. Sulkanen be joining you this evening?""No. She had to oversee a packaged Erythrosine-monosaccharides explosion in Boca Raton. Flaming plastic pink flamingo bits were raining down everywhere. I imagine it is taking an Everest-sized load of hush money to keep this out of the media," I replied. I was so eerily sincere, he bought it and a look of horror snuck over his face. I had become the public face of corporate malfeasance."Your table (gulp) is ready, Sir," he began to sweat. He took us to our table for four then beat a hasty retreat. Undoubtedly his civic-mindedness would have him calling up TMZ within a minute. After all, it was unlikely he owned any plastic pink flamingos, or invested in their construction. Once he was gone, Chaz let a thin smile break through his hard-earned military unfazed-ability."What exactly are packaged Erythrosine-monosaccharides?" he inquired."Packaged is self-explanatory. Erythrosine is pink food coloring and monosaccharides are,""Sugar," Anais frowned."Exploding pixie sticks, I have nieces and nephews. You are a genius at misdirection, Mr. Nyilas," he nodded."Thank you, Color Sergeant Tomorrow. It is nice to be appreciated for my bizarre and useless preoccupation," I grinned."You practice lying?" Anais' view of me dimmed."Miss, he excels at extraneous, outrageous utterances. No harm is intended.""Things like I was helping her find her contact lenses?" That had been my excuse when caught coming out of Maya's apartment. Sadly, Anais is highly perceptive and knew the lady didn't wear contacts. The copious female aroma wafting off me certainly hadn't helped."That's unfair," I countered. "Back then, I was a college nitwit suffering from undiagnosed nymphomania. I'd like to think I'm getting better."" tes-vous mieux?" she retorted in French."Je suis assez intelligent pour aller vers vous lorsque des vies  taient sur la ligne." That's right, Anais. When my life and the lives of others were on the line, she was the first one I thought to call. Letting a woman know that you admire her profession, professionalism and reliability never hurts."Are you really a nymphomaniac?" she returned to English. French is the language of sex, as is any derivative of Sanskrit, Farsi and Portuguese. Reference the multitude of Indians, the hotness of Persian women and the outpouring of lust that is Brazil."I had a magnetoencephalography recently. The neuroscientists didn't know what to make of my brain patterns. I appear to be somewhat unique in my madness."She didn't believe me. I didn't blame her. No one really likes hearing a truth they don't want to accept."Here," I leaned forward and pointed to the tiny divot in my forehead. "I was stabbed with a needle in the skull. That is why they looked at me, not because of my sexual malfunction."She touched it to makes sure. We were interrupted by the waiter stopping by to see if we were ready to order yet."We will have three of the most expensive appetizers, dinners, deserts and wines," Anais preempted us. Ugh. I was either a millionaire by the wonders of Havenstone accounting, or broke. I foolishly never looked into such things, never having had much money before. I needed a distraction."Hey Chaz, nice suit," was what came to mind. It was a swell masterpiece of the tailoring arts I hadn't expect from a ground-pounder from a family of ground-pounders serving Queen and Country for generations."Thank you. Pamela picked it out for me, suspecting an event such as this would transpire. She told me you paid for it," Chaz answered."I did?""I made the reasonable deduction that she forged your signature on whatever medium was used for payment," he shrugged, "in the same way she exhibits a criminal tendency toward every other aspect of her life.""What does Pamela look like?" Anais glowered."She's his grandmother," Chaz responded politely. "They make quite the pair. Normally we don't let them alone in the same room. Bad things happen.""Bad things?""Things like that scenic hostel being reduced to ruin," he enlightened her."This is the supposed assassin?""Retired assassin," Chaz corrected her. "So far she's only, what is the term you two use?" he looked at me."Sending a Get-Well card to their next of kin? Pumping up the volume? Making a critical attitude adjustment? Retroactively revoking their lease on life? We have a few.""Yes, those. Pamela has assured the team director that she no longer accepts assignments of a murderous nature. These days she only practices her skills on those we determine are a threat to the greater endeavor," he explained."She murders people? You all murder people?" Anais furrowed her brow. "Cáel, do you engage in these activities?""What? Who? Me? No!" I waved off any conspiratorial associations. "The vast majority of people I've killed was totally by accident.""How do you accidently kill people?" she pierced my soul with her voice."Okay, I let them kill themselves because warning them would have resulted in me and some friends meeting very immediate violent ends," I pleaded."Miss Saint-Amour, I've talked to trustworthy people who were on the scene when this happened. It was a paramilitary action with the lives of children on the line. Cáel acted to save the lives of innocents," Chaz defended me. That is what Anais wanted to believe; that I was basically a decent human being. I was a pig, but a courageous one. I had confronted her after my infidelity, on the other side of the US/Canadian border where her jurisdiction didn't apply.I knew my revelations were hideously hard to believe. In my favor, I had been in dangerous places doing dangerous things. The Metro firefight had been captured on the place's security system (which had been leaked to the public thus leading to some delusional admirers into thinking I would make a great new King of Hungary even though they hadn't had a monarch since 1918 nor was I from the right (Hapsburg) family. In case this whole Havenstone thing came crashing down in flames, I needed to keep my options open).There had been a bomb threat at Mindszent which I had reputable sources call in (and where I had admittedly hung out with a few of the women who saved me from an earlier disaster) and Miercurea Ciuc had made the international news. Well over 100 people had died and some of the terrorists were still at large. The Romanian government declared I had been 'instrumental' in the confrontation without saying what 'instrumental' meant.I was heroically vague, more mature than where we left off and clearly incited pussy-twitching memories. We'd once fucked so continuously hard and long one weekend that neither one of us could stand until an hour after we stopped. Anais was well worth the pain I was contemplating. Sex with her wasn't the pain I was worried about. It was dodging all her calls afterwards. Once again reference her being a compulsive control freak with abysmal trust issues.Oh, how did I know she was reveling in our past coital moments? She hadn't walked out on me yet. She hadn't walked out when she found Odette in my domicile, when she met Juanita, or when she found out that I worked with highly experienced killers as part of my new daily routine.Normally Anais was smarter than this and had a career in law enforcement to contemplate. Lastly, she hadn't asked to be armed, despite getting permission from the NYPD. Had she decided to get a gun, Anais was sure in her hormonally-cascading mindset she would have shot me by now. I incite all kinds of passion in women. It is a curse.The rest of dinner was unremarkable. Anais continued to interrogate Chaz who proved that he was both skilled in counter-interrogation techniques and not willing to spill anymore secrets about what anyone at JIKIT did. However he had provided her with every logical reason to beat feet back across the Canadian border and she hadn't taken the hints about what a disaster sleeping with me could be.We drove Anais back to her motel, then Chaz and I headed home in silence. Despite his earlier declarations, he knew how to drive the 'right' way all along. As he was letting me out in front of my building, he gave me this pleasant warning."I'm not going to lecture you about not going back there, or avoiding the crazy ones. You already know better and are going back by her place anyway. I do advise that whatever you do, don't let her restrict your movements in any way. She's likely to make you pay double for your past indiscretions and take payment out on your cock. Good luck, Mate.""Wait," I stopped him. "Can you help me hotwire her bike? I can use that as an excuse to darken her doorway.""Dolt," he muttered. He helped me anyway because that's what really good friends do ~ assisting you in your self-destruction so we could joke about it later. At least that was what I hoped was going on. Chaz being a closet sadist was an unsettling idea. I didn't get to immediately pursue my plan because,(We work for you, don't we?)At 9 am, the President of the United States of America, after a late night briefing and a good night's sleep, decided that for the sake of world peace he had to intervene in Southeast Asia ~ Thailand to be specific, though he had some vague notion that a summit of regional leaders was in the offing and the US needed to establish some sort of game plan instead of looking impotent and disinterested.Based on carefully selected bits of information supplied to him by us (JIKIT), he ordered two carrier taskforces to move to the Gulf of Thailand to enforce an anticipated UN arms embargo and 'No-Fly Zone'. It would take four days (September 3rd) for Carrier Strike Group Nine (built around the USS Ronald Reagan) and the 11th Marine Expeditionary Unit (2,200 souls) to take up a position in the South China Sea close to the Gulf of Thailand. By fortuitous circumstance, 500 Marines and sailors were already deployed to Malaysia on a joint training mission with the Malaysian Marines.The second one, the USS Carl Vinson's Carrier Strike Group One wouldn't arrive until the 9th, six days later. What the US government wanted to know was what the Khanate and Vietnam would do in those long, lonely six days. The Khanate had as many modern, up-to-date combat aircraft on Woody Island as the Reagan could send up. The Vietnamese could add another 48 planes worth worrying about.There was the added complication that Thailand hadn't asked for help yet. His experts (us again) were suggesting that he was about to wake up one morning and find Khanate tanks rolling down the streets of Bangkok, which

Featuring an interview with Ms Robin Klebig, including the following topics: Overview of the natural history and treatment landscapes of lymphoma subtypes (0:00) Structure and mechanisms of action of bispecific antibodies (23:41) Similarities and differences among the various approved and investigational CD20 x CD3 bispecific antibodies for non-Hodgkin lymphoma (28:14) Case: A man in his early 50s with multiagent/multiregimen-refractory follicular lymphoma who experienced disease progression with chimeric antigen receptor T-cell therapy now receives mosunetuzumab (39:14) Case: A woman in her mid 60s with relapsed/refractory (R/R) diffuse large B-cell lymphoma receives glofitamab (49:08) Case: A man in his mid 60s with R/R high-grade B-cell lymphoma with MYC and Bcl-2 rearrangements receives epcoritamab (52:57) Case: A man in his early 60s with composite lymphoma receives epcoritamab (56:55) NCPD information and select publications

Dr. Shannon Westin and her guest, Dr. Breelyn Wilky, discuss the JCO article, "“Botensilimab (Fc-enhanced anti-cytotoxic lymphocyte-association protein-4 antibody) Plus Balstilimab (anti-PD-1 antibody) in Patients With Relapsed/Refractory Metastatic Sarcomas." TRANSCRIPT  Shannon Westin: Hello, everyone, and welcome to another episode of JCO After Hours, the podcast where we get in depth on research that has been published in the Journal of Clinical Oncology. I am your host, Gynecologic Oncologist and Social Media Consultant Editor of the JCO, Shannon Westin. I serve here from the University of Texas MD Anderson Cancer Center. And I am so excited to welcome Dr. Breelyn Wilky. She's an Associate Professor and the Director of Sarcoma Medical Oncology in the Department of Medicine Division of Medical Oncology, and the Cheryl Bennett & McNeilly family endowed chair in Sarcoma Research, the Deputy Associate Director of Clinical research at the University of Colorado Cancer Center. Welcome. Dr. Breelyn Wilky: Thank you so much. I'm delighted to be here. Shannon Westin: And with all those titles, I'm super impressed that she was able to complete the manuscript that we're going to discuss today, which is “Botensilimab (Fc-enhanced anti-cytotoxic lymphocyte-association protein-4 antibody) Plus Balstilimab (anti-PD-1 antibody) in Patients With Relapsed/Refractory Metastatic Sarcomas.” And this was published in the JCO on January 27, 2025. And please note, our participants do not have any conflicts of interest. So this is exciting. Let's first level set. Can you review with us just the current state of sarcoma incidents, survival outcomes, that kind of thing so we all know where we're starting? Dr. Breelyn Wilky: Yes. So, you know, sarcomas are really, I like to call them the black box cancer type. And the big thing is that there's really more than a hundred different kinds of sarcomas, which collectively altogether make up only 1% of adult cancers. And so we talk about these as being bone and soft tissue tumors, but really, the heterogeneity is just incredible. You're talking maybe 10,000 to 12,000 new cases of soft tissue sarcoma per year, which is pretty rare in the grand scheme of things. And the trouble with these is that while you can cure sarcomas if you find them early and they're localized, when they metastasize and spread and are not resectable, we're looking at median overall survivals of really only 12 to 18 months, even, you know, with our best therapies that we have. So, really there's just a dire need for new treatments for this really tough group of diseases. Shannon Westin: Yeah, I agree. I'm a gynecologic oncologist, and we have our little subset of sarcomas that I know there's a little bit out of every one. So I'm really excited to pull this manuscript as one of our podcasts offerings because I think we're all seeing these patients in the clinic and certainly our listeners that have sarcoma or have family members with sarcoma, this is so good to have a real focus on a rare group of tumors that have been a little bit lumped together. Now, with that being said, I know this is such a heterogeneous population, but can you briefly overview a little bit around the standard of care for treatment of recurrent sarcomas? Dr. Breelyn Wilky: We have actually been using the same drugs really since about the 1970s, and up until very recently, nothing had really challenged doxorubicin, the old ‘red devil', like we used to call it. And this has been the mainstay of treatment for metastatic sarcomas and really used across the board. In the GYN literature, for uterine leiomyosarcoma, we did see some promising activity with the combination of doxorubicin and trabectedin coming out of the French group. But, except for that study, no combination therapy or new drug has been proven better in terms of overall survival compared to doxorubicin monotherapy, really over 40, 50 years. So it's definitely a tough situation. Now, we do have other drugs that we use, so most patients will wind up getting doxorubicin-based therapy. There's a couple of other regimens that we'll reach to, like gemcitabine docetaxel. And once you get into the specific subtypes, we have some approvals in liposarcomas and leiomyosarcomas for some other drugs. But really the median progression for survival for most of these regimens is somewhere four to six months. And response rates typically are somewhere like 10%, 15% for most of these. So it's really just a very tough field and a tough group of patients to try to make an impact for. Shannon Westin: So let's talk a little bit more kind of getting focused on what you've studied here. What's been the role of immunotherapy thus far in the treatment of sarcomas maybe prior to this particular study? Dr. Breelyn Wilky: Clearly, we all know that immune therapy has just changed cancer care forever over the last few years for so many different types of cancers and diseases like melanoma and renal cell and lung cancer have just been transformed by checkpoint inhibitors specifically directed against PD-1 or CTLA-4 or both. And so, of course, you know, sarcoma docs we're super excited to try to see if these might potentially have activity in our tumors as well. I never had seen myself in my career getting into immunotherapy until I was able to run an investigator-initiated study during my role in Miami, where we combined pembrolizumab, so PD-1 inhibitor, with axitinib which was a pan-VEGF inhibitor. And lo and behold, like I had patients that I was seeing responses when other treatments, all those chemotherapies I was just talking about had failed. And one of my first patients I treated was about a 60-year-old lady with something called cutaneous angiosarcoma. So this is a blood vessel sarcoma all over her face. And we had treated her with 10 different therapies, all the chemotherapy regimens, targeted therapies, clinical trials, and nothing was working. But I put her on a phase 1 trial with a baby dose of CTLA-4 and this woman had a complete response. And so for me, once I saw it work in even just those couple of patients, like that was nothing that we'd ever seen with our chemotherapy regimens. And so that sort of shifted my career towards really focusing on this, and this is about the time where some of the studies started to come out for sarcomas. And the take home with sarcoma is about 20% of sarcomas have this sort of immune hot physiology. So what that basically means is if you look at gene expression of immune related gene signatures, or you look for infiltrating T-cells, sort of the SWAT team of our immune system, like you can find those in the tumors. And it's sort of evidence that the immune system had some clue for that 20% of patients that this was a foreign tumor and that it should be attacking it and maybe just needed a little help. But globally, about 80% of sarcomas are these immune cold tumors, which means the immune system has no clue that these things are even a threat. And there's almost no immune activation, very, very few antigens. In other cancer types, high neoantigens or tumor antigens help the immune system work better. And so that basically goes with what we've seen with trials of PD-1 or CTLA-4 blockade. About 20% of sarcomas, with some exceptions, can respond. But really 80% across the board, you're stuck, you just can't get them to be recognized. And so that's where I think this data is so interesting is there's some signals of activity in these immune cold tumors which, at least historically with the trials we've done so far, we really haven't seen that with sort of the traditional checkpoints. Shannon Westin: So I think now this is a great time to maybe talk about the study design in general, the eligibility and just give us kind of a run through of that. Dr. Breelyn Wilky: So this trial was a phase 1 trial of a drug called botensilimab, which is a next generation CTLA-4 directed immune modulator. So what makes botensilimab different is that the CTLA-4 end is very similar to other CTLA-4 inhibitors that are out there, but it's been engineered on the back end of the molecule that binds to Fc gamma receptors to basically bind tighter with higher affinity. And what this translates to in laboratory models and increasingly now in patients is it does a better job of priming, of educating our T cells, our, again, these highly intelligent antigen specific cells, but also natural killer cells. It does a better job of sort of educating those. It helps to activate macrophages and other supporting actors in the immune response. And so the idea here is that there's evidence that botensilimab may do a better job at creating new responses in immune cold tumors. The study combined either botensilimab as monotherapy or in combination with a PD-1 inhibitor called balstilimab. And this was all comers, really a variety of tumor types. And to date I think we're close to about 500 patients with a variety of solid tumors that have been accrued to this study, this C-800-01 phase 1 trial. This paper reports on the sarcoma patients that were enrolled as part of this study. And so, again, given what I've told you about sarcomas being really immune cold, we were just so excited to have the opportunity to enroll on a next generation immune therapy for these tumors that really we were running into roadblocks trying to use immunotherapy previously. Shannon Westin: It's a very compelling idea and I'm so excited for you to tell people what you found. I think first things first, it was an early phase trial. So why don't we talk a little bit about the safety of the regimen. Was there anything that you didn't expect? Dr. Breelyn Wilky: Right. So similar to other checkpoint inhibitors, you know, the idea is that these drugs can cause immune mediated toxicities, right? So essentially you're revving up the immune system and it can sometimes get a bit confused and start attacking our normal cells, our normal organs, leading to essentially any number of toxicities of basically head to toe, something can get inflamed and you can develop a toxicity from that. So the key take homes with this particular drug with, botensilimab with balstilimab, we saw colitis was sort of the primary immune mediated toxicity and it was about a third of patients, give or take. It happens and it can be aggressive and needs to be managed aggressively. And you know, one of the things that we learned very quickly taking part in this study is how important it is that as soon as patients start to get diarrhea, immunosuppression gets on board. So steroids, early use of TNF alpha blockade, so infliximab for example, if we jumped on it quickly and we recognized it and we got the patients treated, it would resolve fairly quickly and even some patients could remain on treatment. So I think that was sort of the first take home is “Okay if you get colitis, you treat it fast, you treat it early and you can still have patients not only recover, which essentially everybody recovered from this colitis and then being able to continue on treatment and still have their anti-tumor responses.” So that's the first point. The second thing that was really interesting is part of the engineering of botensilimab on the back end of the molecule, it's been designed to decrease complement binding and it's thought that that triggers some of these other toxicities that we've seen with prior CTLA-4 inhibitors like pneumonitis or hypophysitis. We actually don't see that with botensilimab. So there's sort of this selective toxicity that may reflect the design of the molecule. But overall the treatment was, we didn't see any new safety signals that were outside of what we would expect in class. And colitis was sort of the dominant thing that we had to be ready for and ready to manage. Shannon Westin: We've been doing it for a while now, so we kind of know what to do and we can act quickly and really try to mitigate and avoid some of the major toxicities. So that's great that that was what was reflected in what you found. And then of course I think: What about the efficacy?” Right. This is what we care about as practitioners, as patients. Does it work and are there any subtypes that seem to benefit the most from this combination? Dr. Breelyn Wilky: Right. So for the sarcoma patients, we treated 64 patients and 52 of those patients were evaluable for efficacy. So a decent size group of patients in sarcomas, where, you know, typically our trials are pretty small, they're very rare, but we had 52 evaluable with at least one post baseline scan. So that was our criteria. And basically we saw across all of the patients, and keep in mind, these are heavily pre-treated patients, as you mentioned, so a median of 3 prior lines of therapy, so most of these patients had had chemotherapies and then about 20% had also had prior immunotherapy as well. So PD-1 treatments or so on. The overall response rate by RECIST was 19.2% for all of the evaluable patients. And then with iRECIST, which is sort of that immune adapted response criteria that allows for early pseudo progression, we actually had another patient who did have that. And so that response rate was 21.2%. Overall, we were really excited to see this in a heavily pre-treated group of patients. But what was really exciting to me was when we looked at the subset of patients that had angiosarcoma, that blood vessel tumor I was talking about earlier with my other patient. So angios come in two flavors. One is this sort of cutaneous type, or meaning involving the skin that has a UV signature, a UV damage signature, very similar to melanoma. So these tumors tend to have a high mutation burden. And oftentimes there is a track record that we've seen responses with immunotherapy in cutaneous angiosarcomas. But the other group that we deal with is called visceral angiosarcomas. And so these are totally different biologically. These are often driven by mutations in MYC or KDR amplification, and they arise in organs, so primary breast angiosarcoma, not associated with radiation, or they can arise in the liver or the spleen or an extremity. So these are very, very different tumors, and the visceral ones almost never historically have responded to checkpoint inhibitors. So we had 18 patients with angio split - 9 with cutaneous, 9 with visceral. And we were just blown away because the response rate for that group was 27.8%. And if you looked at the responses between the hot ones and the cold ones, it was almost equal and a little bit better in the visceral. So we had a 33% response rate in visceral angiosarcoma, which is crazy, historically speaking, and about 20% again in the cutaneous angios. So for a disease where visceral angio gets treated with chemotherapy, might respond initially, but then rapidly progresses - like these people go through multiple lines of therapy - to have a third of patients responding, and then some of those responses were durable. Our median duration of response for the study was 21.7 months, which is just nuts for sarcomas where we just don't see those sorts of long term benefits with the drugs that we have. So I think those are kind of the two main things. There were other subtypes that had clinical benefit and responses as well in d-diff liposarcoma, soft tissue leiomyosarcoma, which are again thought to be fairly cold immune subtypes. So just really exciting to kind of see responses we hadn't expected in a very challenging group of tumors. Shannon Westin: We see all these patients and we have patients that respond so well to immunotherapy with other histotypes. And so it's so exciting to see an option for these really hard to treat tumors that our patients struggle with. So this is so, so very exciting. I wanted to make mention, you know, I was really impressed with the amount of translational work you were able to do in this early phase study. So do you want to review just maybe a few of the key findings that you guys discovered? Dr. Breelyn Wilky: It's always great. I'm a translational researcher at heart and we do a lot of immune correlative work. And I think the reason I got so excited about this field to begin with was trying to learn why it works for some patients and why it doesn't work for other patients. So I'm a huge believer in learning from every patient that we can. So it's such a testament to the company, Agenus, who sponsored this trial to invest their time and resources into correlative studies at this phase. It's huge. So we learned a couple of things. IL-6 or interleukin 6 is a cytokine that basically has, in other tumor types, been associated with worse outcomes. And what we were interested in this group is we saw the same thing. And again, sarcomas have very, very little correlative biology that's done. We're really in infancy and understanding the microenvironment and how that milieu balances out in our tumors. So we were really excited to see again that lower peripheral interleukin 6 associated with improved overall survival. So again, kind of sorting out a group of patients that might be immunologically favorable when it comes to this type of therapy. The other thing that's important to know about sarcoma is so the other tumor types are lucky and have PD-L1 expression and the tumor is a biomarker, but we never have PD-L1 expression. We can find it in sarcomas and it can be loosely correlated with a chance of benefit with immunotherapy. But I've had patients respond that were PD-L1 negative, and I've had patients that were loaded with PD-L1 that didn't seem to make a difference. And that's not just in this study. So we saw in this trial a trend towards improved overall survival with PD-L1 expression that wasn't significant, but there was like this trend. And it's really interesting because, again, this is largely a CTLA-4 directed therapy. And so what we wondered is if PD-L1 expression is an index of sort of this underlying potential immunogenicity. And actually PD-1 works very late in the whole immune process. That's really at the very end where you've got the T cell that's facing the tumor cell and it's just activating that T cell that's already grown up and already educated and ready to go. Whereas CTLA-4 is really educating in early immune responses and expanding the T cells that have potential to kill. So I'm interested to look into this in more depth in the future to see if this is actually the biomarker for CTLA-4 directed therapy that we've been looking for, because we really don't have a great sense about that. And then the last piece just to note is that in this trial, like most others, very, very few sarcomas had high mutational burden. Everybody was very low, which reflects the population. And it's just really more encouragement than an immune cold tumor with very crappy neoantigens can still respond to immunotherapy if we get them the right agents. Shannon Westin: Yeah, I mean, I'm taking notes because we have such a struggle with this across the gynecologic tumors. I'm like, “Okay, maybe this is finally it.” So hopefully your work will go on to really inspire us across a number of solid tumors that have been traditionally cold. So, so very exciting. And I would just say for my last question, obviously, congratulations on this successful study. What do you think are the next steps for this combination in sarcomas? Dr. Breelyn Wilky: So, again, just to your point, this trial enrolled a bunch of different subtypes, and sarcomas are not the only immune cold tumor that this combo has looked really promising for, microsatellite stable colorectal cancer, ovarian cancer that was platinum refractory, non-small cell lungs. So I think the future is really bright for immune cold tumors kind of across the board. So, yes, lots of hope for not just sarcomas but in terms of our patients, I just have to be so grateful to Agenus for their interest in a rare disease. Sometimes it's hard to get that interest for a very challenging group of patients that are all heterogeneous, they are not all the same and our big clinical trials are a few hundred patients. It's just a very different environment. But they have been so supportive and involved in making sure that sarcomas are represented in their priorities. So there are ongoing discussions about what the optimal way to explore this further in sarcomas is going to be and I cannot wait to have the official plans in place. But my hope is this will not be the last that we see of these drugs for our patients. Shannon Westin: Well, I support that and my vote is on your side. So, thank you so much again, Dr. Wilky. This time just flew by. This was such a great discussion and I mean, I think it's, again, a testament to your exciting data. And thank you to all of our listeners. This has been JCO After Hours' discussion of “Botensilimab (Fc-enhanced anti-cytotoxic lymphocyte-association protein-4 antibody) Plus Balstilimab (anti-PD-1 antibody) in Patients With Relapsed/Refractory Metastatic Sarcomas,” published in the JCO on January 27, 2025. So be sure to check out the full manuscript. And we hope that you enjoyed this podcast. And if you want to hear more about research published in the JCO, check this out on our ASCO JCO website or wherever you get your podcasts. Have an awesome day.   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement. Dr. Wilky Disclosures  Consulting or Advisory Role: SpringWorks Therapeutics, Deciphera, Epizyme, Adcendo, Polaris, Boehringer Ingelheim, AADi, InhibRx Research Funding: Exelixis Travel, Accommodations, Expenses: Agenus    

La guerre de Troie, immortalisée par Homère dans l'Iliade, fascine depuis des siècles. Mais s'agit-il d'un mythe littéraire ou d'un véritable conflit historique ? Depuis longtemps, les historiens et archéologues tentent de démêler la réalité de la légende.Les sources antiques : mythe ou réalité ?L'Iliade, écrite au VIIIe siècle avant J.-C., raconte une guerre entre les Grecs et les Troyens, déclenchée par l'enlèvement d'Hélène par Pâris. Mais ce récit épique, empli d'interventions divines, semble davantage relever de la mythologie que d'un compte rendu historique fiable.Toutefois, d'autres auteurs antiques, comme Hérodote et Thucydide, considéraient que la guerre de Troie avait bien eu lieu, mais sous une forme moins spectaculaire. Ils suggéraient que derrière le mythe, un véritable affrontement avait opposé des cités de la mer Égée à Troie, située en Anatolie (l'actuelle Turquie).Les découvertes archéologiquesAu XIXe siècle, Heinrich Schliemann, un archéologue allemand, met au jour les ruines de Troie sur le site de Hisarlik, en Turquie. Il découvre plusieurs strates de cités superposées, indiquant que Troie a été détruite et reconstruite à plusieurs reprises. Parmi elles, Troie VII, datée autour de 1200 avant J.-C., semble correspondre à la période présumée de la guerre de Troie.Les fouilles ont révélé des traces de destruction par le feu et des armes, suggérant un conflit. Mais qui étaient les assaillants ? Une coalition de cités grecques, comme dans l'Iliade, ou d'autres peuples de la région ? L'absence de preuves directes empêche de trancher définitivement.Une guerre plausible ?À l'époque du Bronze récent, les tensions entre royaumes étaient courantes en Méditerranée. Troie, située près des Détroits des Dardanelles, contrôlait un point stratégique pour le commerce entre l'Europe et l'Asie. Un conflit entre les Mycéniens et les Troyens pour le contrôle de cette route commerciale est donc plausible.Conclusion : mythe ou réalité ?Si l'existence d'une guerre impliquant Troie autour de 1200 avant J.-C. semble probable, rien ne prouve qu'elle s'est déroulée exactement comme dans l'Iliade. L'histoire d'Achille, du cheval de Troie et des dieux reste une légende embellie par les poètes. Mais comme souvent, derrière un mythe, il y a une part de vérité. Hébergé par Acast. Visitez acast.com/privacy pour plus d'informations.

La guerre de Troie, immortalisée par Homère dans l'Iliade, fascine depuis des siècles. Mais s'agit-il d'un mythe littéraire ou d'un véritable conflit historique ? Depuis longtemps, les historiens et archéologues tentent de démêler la réalité de la légende.Les sources antiques : mythe ou réalité ?L'Iliade, écrite au VIIIe siècle avant J.-C., raconte une guerre entre les Grecs et les Troyens, déclenchée par l'enlèvement d'Hélène par Pâris. Mais ce récit épique, empli d'interventions divines, semble davantage relever de la mythologie que d'un compte rendu historique fiable.Toutefois, d'autres auteurs antiques, comme Hérodote et Thucydide, considéraient que la guerre de Troie avait bien eu lieu, mais sous une forme moins spectaculaire. Ils suggéraient que derrière le mythe, un véritable affrontement avait opposé des cités de la mer Égée à Troie, située en Anatolie (l'actuelle Turquie).Les découvertes archéologiquesAu XIXe siècle, Heinrich Schliemann, un archéologue allemand, met au jour les ruines de Troie sur le site de Hisarlik, en Turquie. Il découvre plusieurs strates de cités superposées, indiquant que Troie a été détruite et reconstruite à plusieurs reprises. Parmi elles, Troie VII, datée autour de 1200 avant J.-C., semble correspondre à la période présumée de la guerre de Troie.Les fouilles ont révélé des traces de destruction par le feu et des armes, suggérant un conflit. Mais qui étaient les assaillants ? Une coalition de cités grecques, comme dans l'Iliade, ou d'autres peuples de la région ? L'absence de preuves directes empêche de trancher définitivement.Une guerre plausible ?À l'époque du Bronze récent, les tensions entre royaumes étaient courantes en Méditerranée. Troie, située près des Détroits des Dardanelles, contrôlait un point stratégique pour le commerce entre l'Europe et l'Asie. Un conflit entre les Mycéniens et les Troyens pour le contrôle de cette route commerciale est donc plausible.Conclusion : mythe ou réalité ?Si l'existence d'une guerre impliquant Troie autour de 1200 avant J.-C. semble probable, rien ne prouve qu'elle s'est déroulée exactement comme dans l'Iliade. L'histoire d'Achille, du cheval de Troie et des dieux reste une légende embellie par les poètes. Mais comme souvent, derrière un mythe, il y a une part de vérité. Hébergé par Acast. Visitez acast.com/privacy pour plus d'informations.

GDP Script/ Top Stories for January 30th Publish Date: January 30th From the BG AD Group Studio Welcome to the Gwinnett Daily Post Podcast. Today is Thursday, January 30th and Happy birthday to ***01.30.24 - BIRTHDAY – FRANKLIN D ROOSEVELT*** I’m Keith Ippolito and here are your top stories presented by KIA Mall of Georgia. City of Duluth Honored With 2025 Visionary City Award For Rogers Bridge Project Stephen Aaron running for 9th District GOP Chair Best Beer Festival: Here's How You Can Vote For Suwanee Beer Fest Plus, Leah McGrath from Ingles Markets on healthy alternatives All of this and more is coming up on the Gwinnett Daily Post podcast, and if you are looking for community news, we encourage you to listen daily and subscribe! Break 1: 07.14.22 KIA MOG STORY 1: City of Duluth Honored With 2025 Visionary City Award For Rogers Bridge Project The City of Duluth has received the 2025 Visionary City Award from the Georgia Municipal Association and Georgia Trend Magazine for its Rogers Bridge Project. Recognized in the Large Cities Category, the project connects Rogers Bridge Park in Duluth to Cauley Creek Park in Johns Creek, enhancing regional accessibility and sustainability. The pedestrian and cyclist bridge promotes active lifestyles and community collaboration. Duluth Mayor Greg Whitlock celebrated the honor, highlighting the city’s commitment to enriching lives and fostering unity. The award was presented at GMA’s Cities United Summit on Jan. 26. STORY 2: Stephen Aaron running for 9th District GOP Chair Ellijay resident Stephen Aaron has announced his candidacy for chairman of the 9th District Republican Party, which includes northern Gwinnett County. Currently serving as 1st Vice Chairman, Aaron aims to strengthen the party through leadership training, fundraising, and membership growth ahead of the 2026 election cycle. With 20 years of GOP involvement and experience on over 20 campaigns across eight states, Aaron emphasizes the importance of proactive efforts to maintain the district’s conservative values. The election will take place during the 9th District Convention on April 26. STORY 3: Best Beer Festival: Here's How You Can Vote For Suwanee Beer Fest The Suwanee American Craft Beer Fest has been nominated for the USA TODAY 10Best Readers’ Choice Award for Best Beer Festival. After winning in 2022 and placing runner-up the past two years, the festival is once again vying for the top spot. Known for its lively atmosphere, diverse craft beer selection, and community spirit, the event attracts beer enthusiasts from across the region. Voting is open daily until Feb. 24, with winners announced on March 5. Event Manager Tiffany Belflower expressed excitement about the nomination, highlighting the team’s dedication and attendee passion. We have opportunities for sponsors to get great engagement on these shows. Call 770.874.3200 for more info. We’ll be right back Break 2: 08.05.24 OBITS_FINAL STORY 4: Brightside Cafe Brightside Café, located at 554 West Main Street in Buford, has transformed a historic building into a community-focused coffee shop with a mission. Founded by Jennifer Elinburg and Carrie Walton, the café employs 22 special-needs individuals, offering them opportunities to build confidence and success. Open since December, the café serves coffee, smoothies, and baked goods while fostering meaningful interactions between employees and customers. A nonprofit, Brightside Forever Foundation, supports its operations and plans for a mobile trailer. With growing community support, the café continues to thrive, creating a space of inclusion and joy. STORY 5: Paul Duke STEM Senior Makes List Of Top Teen Scientists Chloe Au, a senior at Paul Duke STEM High School, has been named one of the top 300 scholars in the prestigious Regeneron Science Talent Search (STS) competition by the Society for Science. Her research, “The Role of Myc in Tunicate Central Nervous System Development,” earned her this recognition, along with a $2,000 award for herself and her school. Chloe, who interned with Georgia Tech’s Neuroscience Department, is passionate about neurodegeneration research inspired by personal experiences. Principal Dr. Jonathon Wetherington praised her achievement, highlighting the potential of high school students when given advanced research opportunities. Break 3: And now here is Leah McGrath from Ingles Markets on healthy alternatives ***INGLES ASK LEAH 2 HEALTHY ALTERNATIVES*** We’ll have closing comments after this Break 4: Ingles Markets 2 Signoff – Thanks again for hanging out with us on today’s Gwinnett Daily Post Podcast. If you enjoy these shows, we encourage you to check out our other offerings, like the Cherokee Tribune Ledger Podcast, the Marietta Daily Journal, or the Community Podcast for Rockdale Newton and Morgan Counties. Read more about all our stories and get other great content at www.gwinnettdailypost.com Did you know over 50% of Americans listen to podcasts weekly? Giving you important news about our community and telling great stories are what we do. Make sure you join us for our next episode and be sure to share this podcast on social media with your friends and family. Add us to your Alexa Flash Briefing or your Google Home Briefing and be sure to like, follow, and subscribe wherever you get your podcasts. Produced by the BG Podcast Network Show Sponsors: www.ingles-markets.com www.wagesfuneralhome.com www.kiamallofga.com #NewsPodcast #CurrentEvents #TopHeadlines #BreakingNews #PodcastDiscussion #PodcastNews #InDepthAnalysis #NewsAnalysis #PodcastTrending #WorldNews #LocalNews #GlobalNews #PodcastInsights #NewsBrief #PodcastUpdate #NewsRoundup #WeeklyNews #DailyNews #PodcastInterviews #HotTopics #PodcastOpinions #InvestigativeJournalism #BehindTheHeadlines #PodcastMedia #NewsStories #PodcastReports #JournalismMatters #PodcastPerspectives #NewsCommentary #PodcastListeners #NewsPodcastCommunity #NewsSource #PodcastCuration #WorldAffairs #PodcastUpdates #AudioNews #PodcastJournalism #EmergingStories #NewsFlash #PodcastConversations See omnystudio.com/listener for privacy information.

Joining us from Texas today is Caitlin and it is her birthday!Caitlin's first baby was born at 34 weeks via an emergency C-section due to elevated blood pressure and fetal distress. Though she was scared, it was not a traumatic experience and her recovery went well. She just knew that moving forward for future births, she wanted to experience labor and she wanted something different. Caitlin talks about the importance of knowing not just your provider's general stance on VBAC, but their specific policies surrounding it. At 39 weeks, she went to the hospital with preeclamptic symptoms. Still counting on her provider to support her VBAC, Caitlin started to face things she wasn't comfortable with. Her symptoms were under control, but she could tell that her baby wasn't yet ready to come. She knew she needed to sign an AMA and go home. When the time came, Caitlin was able to advocate for the birth she wanted, declined the interventions she knew she didn't truly need, and leaned on those who felt safe in her space. “Having the VBAC made me so proud and confident in myself and any future births that I'm blessed with.” Happy Birthday, Caitlin!!How to VBAC: The Ultimate Prep Course for ParentsFull Transcript under Episode Details Meagan: Hello, hello Women of Strength. You guys, I am so excited for today's episode. We have our friend, Caitlin, from– are you from Texas? Where are you from?Caitlin: I'm from Texas, yes. Meagan: Texas. Yes. I wanted to say that then I started questioning myself. She is from Texas and we just went over a quick rough draft of all the things that happened in her birth and there are so many points I feel like to her birth. One, she's a VBAC. She had preeclampsia with her first and her second. This is her second baby during her VBAC and with her first, she signed an AMA so we are going to talk about that and what that looks like. We're going to talk more about preeclampsia. We're going to talk about switching providers. One, switching providers but two, maybe trying to set ourselves up to not have to switch in the future and setting up ourselves to have a supportive provider from the beginning because she definitely had that and so much more. I'm really, really excited to get into the story. I do have a Review of the Week. This review is– I don't actually know how to say the name. Sidsie, maybe? It says, “Such an amazing resource for VBAC-hopeful mamas and others preparing for birth who haven't had a previous Cesarean. Their podcast has amazing birth stories and their blog has amazing articles. They have a ton of resources to find doulas and providers and are excited and happy to help support VBAC mamas. I recommend their podcast to my doula clients and I listen to each episode as it comes out. Definitely check it out.” I love that. This is a birth worker. Birth workers, we love you and we love your reviews. As you know, we do have a doula directory so if you are looking for a doula, these doulas are absolutely incredible. Go to thevbaclink.com and click on “Find a Doula”, search your area, and find out which doulas are close to you. Also, if you haven't had a chance, I'm requesting a specific place for reviews today. If you would not mind, head over to Google at “The VBAC Link” and click on it then leave a review. I would absolutely love it. Meagan: Okay, Caitlin. I'm already so excited that I just am going to turn the time over to you but before I do, I have to say one thing. Caitlin: I'm excited too. Do it. Meagan: Happy birthday. Caitlin: Thank you. Meagan: It's not your birthday the day you are recording, but we have determined it will be the day your episode comes out which we didn't do on purpose. Happy birthday. Caitlin: Thank you so much. I appreciate it. Meagan: You're welcome. You are welcome. All right. Well go ahead and share your stories. Caitlin: Okay, well I guess we should start with my first birth which was August 18, 2021. I was 34 weeks pregnant. I had lingering high blood pressure for about a week and it was elevating over time. My doctor was like, “Let's look at the baby.” With that check, baby was showing signs of distress and it was pretty immediate and quick. We went in for an emergency C-section. In the moment, I was so scared. It was my first child. I know what that meant. I didn't really care what that meant for my future births. I didn't really think of what that might mean for my future birthing experience. My main concern was that my current baby isn't doing well and let's do what we need to do to keep him and myself safe. That's how that went. I do want to say that my C-section was not traumatic. I didn't have a terrible recovery. It really was all good. I just knew that moving forward for future births that I wanted to experience labor. I had never experienced labor. I wanted to have more children than just two so I knew moving forward from that the risks that come with it. That's how my first kiddo was born. It was an emergency C-section. He was healthy. He was in the NICU for a little bit but that's just because he was so little at 34 weeks. Meagan: You actually had a preterm. That was another thing I forgot I wrote down. You had a preterm Cesarean. Caitlin: I did. Yes. It was very quick. We were at my doctor's appointment at 10:00 and got to the hospital and baby was born within an hour or two. It was a quick turnaround. It was a very high stress situation but it all worked out okay. Now my 3-year-old is wonderful. I'm grateful for how that all worked out and I'm glad that he was safe and that I was safe.That was my first birth. For my second, I knew that I wanted to try for a VBAC. I did extensive research and when I say extensive research, I mean I went crazy a little bit. No. there's never too much research. I did obtain all of the information I could find. I was listening to podcasts 24/7. I looked at studies and articles and the actual science behind it all. I just dove headfirst into it and I knew that this was what I wanted to try for. I wasn't scared of a repeat Cesarean. Again, I wasn't like, I can't do that again. I just knew this was the route I wanted to try to take. My due date for my second was August 19, 2023, so literally 2 years and a day after my first was born. I told my doctor at every single appointment even as early as it gets at the appointment where you hear the heartbeat and the appointment before they could even find the heartbeat, I was like, “I want a VBAC. I want a VBAC. I want a VBAC.” He was extremely receptive. He said, “You're a perfect candidate.” He was super receptive so I felt really good about it. I was thinking about this last night with my husband as I was running through all of the little details and I think my provider being so on board made me feel like I didn't need to do the little additional prodding questions to make sure that it was going to work out. It just seemed like every time I brought it up that it was a no-brainer. It was going to be VBAC fine. That's kind of your caveat for later but I felt like it was all going to be great. My provider was on board and that's the number-one checklist. But the thing I didn't do was ask him specifics. I didn't ask if I needed an induction, what does that look like? I didn't ask him, how many successful VBACs have you done? What is your approach if x, y, and z happens? I didn't get details because it just seemed so positive the whole time. Meagan: And that's the hard thing. It can be so easy to be like, “Hey, I want a VBAC. Do you support that?” “Yeah. Cool, no problem. Yep. Of course, we do. No worries.” Or like you said where he was like, “Yes, I know you want a VBAC. Let's move on,” instead of talking about that VBAC. I feel like that was maybe a little bit of a flag in ways. Caitlin: Yes. I should have picked up on it because it got to the point where I would walk into an appointment and the first words were, “I know you want a VBAC. We've got that.” I'm like, “Okay, great. We've got it.” I think I was a little naive that that was him checking that off the appointment list maybe and being like, I don't actually need to give this girl a VBAC when push comes to shove. Meagan: Or tell her anything, yeah. I really encourage people to ask open-ended questions like you said like, “How many VBACs do you support? How do you feel about VBAC and what does it look like? For some reason if I have to be induced, do you induce them and what does it look like then?” and all of those types of things. Caitlin: Definitely. Definitely. I started to feel all of this pressure because toward the end, we didn't really talk about a plan. Then the language changed to, “We can't really make a plan because we just have to wait and see if you're going to go into labor.” So then I was like, “Oh dang, then I really need to go into labor.” Then we got to 36-37 weeks and I'm getting more and more in my head, “What if I don't go into labor? What happens next? We still don't have a plan.” We started to do membrane sweeps. I got three membrane sweeps and I did them on the time period– I don't remember what it was. I think if you do two within 48 hours or something like that, people say– I don't know who people are. I was just a maniac with my research and they were like, “Maybe that will increase your chances of your body going into labor on its own.” I did three membrane sweeps trying to get the ball rolling. I stayed at 1 the whole time. No changes. I was doing all of the things at home up to week 39. I was eating dates, curb walking, drinking raspberry leaf tea, bouncing on the ball. I was pumping colostrum. My baby is 9 months old and I still have colostrum in her freezer. Meagan: Holy cow, girl. Caitlin: I was doing everything begging my body to please do this for me. Please. There were no changes. Meagan: It wasn't listening. It wasn't ready. Caitlin: It wasn't. I was also forgetting to consider the fact that my body with my first did not go into labor. This was my first real experience with childbirth and labor. Do you know what I mean? My C-section grew and changed me in so many ways and like I said, I don't regret that at all, but in my head I kind of counted that like, my body should be going into labor, when in reality, my body wasn't going to go into labor. At least not as early as I was trying to make it. So moving on from that, I did all of the things. I kept doing the things. I felt frustrated doing the things because the things weren't thinging and I couldn't but I tried and all I kept doing was being positive. My blood pressure was fine my entire pregnancy so we got past that 34-week mark which with my first, my high blood pressure started at week 33 and we got past that point. I felt really good about it. There were no high readings then on August 4th, I was 38 weeks. It was a Friday. I had felt kind of off during the day but I was also like, I'm 38 weeks pregnant. I'm probably going to feel off for the next however many weeks I'm pregnant. Then later that night, I noticed major swelling in my hands and my feet. I was like, this is something I am familiar with. I am not familiar with other things that are coming, but this is something that I am. We didn't have a blood pressure cuff so husband had me go to a CVS or Walgreens or something like that and take it in one of those machines and it was extremely high. I was apprehensive. I was like, I don't want to rush right in. I called my on-call person and obviously their response was to go to the hospital. They can't guide you through anything when it comes to high blood pressure over the phone. I go to the hospital. I was planning on going there for my VBAC even though I'm 39 weeks now and still at a 1 but I'm like, It's going to be fine. My doctor's on board. The bummer with that was that it was a Friday night and it was probably closer to the middle of the night and early Saturday morning. The nurse who had us at intake was actually– we recognized her and couldn't figure it out then she was like, When did you have your last baby? It was the same nurse who helped us prep for the emergency delivery of my first son. She was super sweet and super comforting. It was nice to have somebody who had seen what we went through previously. My blood pressure was still high at the hospital. They started some IV fluids and I was just resting. They checked on baby and he looked great. No issues with him which from my prior experience, that's what changed everything for me was that he was fine. So I kept asking throughout our time sitting and watching our blood pressure, I was like, “Baby is fine?” They were like, “He's doing great.” That was super, super– and that was completely different from my first time around. Then finally, the doctor came in who was working for that night and the first words out of her mouth were, “We'll do a C-section first thing in the morning. We'll get you on the calendar.” I was like, “Oh, well my plans were to try for a VBAC,” and that was basically met with an eye roll. She was like, “You can talk to the doctor who is in for your doctor this weekend because he's not the doctor over the weekend. You can talk to her and see what she thinks.” I was like, “No, yeah. I'll be happy to talk to her. Do you want me to call her right now? Because I'm not going to stay here. Don't put me on the schedule for tomorrow morning.” She actually did. She called the doctor who was in for the weekend from my doctor's practice and I mean, basically what I kept getting was, “Protocol is when you have high blood pressure this late in pregnancy, we just do a C-section.” Then every time I asked, “Why?” I was like, “If my baby is fine, why do we do a C-section? If my baby is doing okay,” and my blood pressure at that point was getting lower. We were managing it. I think the fluids helped, elevating my legs, resting, and all of those things. My blood pressure was lowering and my baby was fine. I was like, “Why?” They didn't really have an answer every time I asked that. I got on the phone with the doctor who was in for my doctor over the weekend and the one who would be doing the C-section the following morning. I'm telling you. We were on the phone for– I had her on speakerphone so my husband could hear what she was saying and what I was saying. My husband knew I did all of this research but as I was debating with this doctor, I could see on his face that he was learning things. He was like, “Oh, that's a good point. Oh, really? Okay. Okay. You're not that crazy, Caitlin. I see it. You know?” So I could see him learning through what I was saying to her about my why and why I wanted to do it this way. She was basically saying, “I can have a baby in your arms by lunch tomorrow. You could be walking around.” I was like, “That's really not my goal. That's not what I'm trying to do.” Finally, I was like, “Hey, look. Based on what I have found, I know that a good induction method would be a balloon Foley. Can you come do that? I'm not going to say yes to a C-section tomorrow with my baby doing fine and my blood pressure dropping. It's getting better.” She was like, “Okay.” She was like, “I can do it.” I was like, “Have you done it before?” She was like, “Yes I have. I will come in and do one tonight. We can see how you progress overnight and so on and so forth.” They put us in our room and my blood pressure was looking good. They take monitors off of me. They don't need to be watching baby anymore. All is good. We're sitting in the room. We are waiting for the doctor to come to start the balloon. Finally, I asked the nurse. I'm like, “Hey, is the doctor coming? She said she wanted to give me time to progress overnight so we could see how we were doing in the morning.” I'm aware of the fact that this could take a long time. I told the doctor that. I said, “I'm very patient. I'm not trying to rush this.” She's like, “I'll go check on the doctor and see where she's at.” She comes back in the room and said the doctor was asleep at home. The doctor said she was going to come do the balloon Foley first thing in the morning. I was like, “That's not what we talked about on the phone. The doctor told me she was going to come do it tonight so we could progress overnight and all that stuff.”Me and my husband are sitting in this room. Our kid is at home, our other child and they are not even checking me anymore. They're not monitoring anything. My blood pressure is good. The baby is healthy. I'm like, “Why is there no urgency?” If this was something that needed to be done, why are we not doing anything? I guess that was my concern. As I'm verbally processing this with my husband, the nurse was extremely professional but I felt a vibe. I asked my husband, “Did you feel the same thing when she was affirming what we were discussing verbally?” Just between him and I but I felt like she was like, “Yes. You're not wrong.” The second I said to my husband, “I think we should leave. I feel like this isn't right,” the nurse was like, “I can get you those papers whenever you want them.”She went and I was like, “I think I want them. I don't know. I'm a rule follower. I don't want to risk anything.” My husband was like, “Caitlin, I don't know. I don't know if this is safe,” but I just felt like if there was no urgency to get things moving now, then what's the urgency in waiting until Monday when I could talk to my provider who had encouraged me and said that the VBAC was possible the whole time? So we left against medical advice. It was very intimidating for somebody who was a rule follower. We felt like we were going to be dogs with our tails tucked between our legs walking out of the hospital with our bags on our shoulders. I was like, “Oh my gosh, those nurses are going to watch us and think we are causing harm to our baby.” But as we were walking out, it was the coolest thing ever. All of the nurses, I think they could tell that I was a little bit insecure about my decision or just not sure, but they were giving me thumbs-ups and silent, “You've got this” clapping. I was like, Oh my gosh, okay. This wasn't a dumb call. One nurse stood up and said to me as we were about to leave the door, “Thank you so much for advocating for your own health and standing firm in the decisions that you want to make for your birth.” It was so affirming for me. Meagan: I seriously have chills and goosebumps right now just hearing you say that and her saying that to you and you being able to leave feeling that especially when you felt like it was right, but then the way the world makes us feel about going against medical advice, you had that, Oh, I don't know if I should be doing this feeling as you were walking out. To have that advocacy as you were walking out I'm sure put so much power in your pocket. Caitlin: Totally. Totally, totally. That nurse was life-changing for me and I just felt okay going into the next day waiting to see my doctor whom I thought was going to be on my team with all of this stuff that I had been sticking up for. I get to my doctor on Monday. I rested for the weekend. There was nothing crazy. We just relaxed. I got a blood pressure cuff to monitor. It wasn't good. It was elevated but it never got to that zone where it was on Friday night when I went in. I went to my doctor on Monday. My blood pressure was elevated but not very high. He said, “Let's have you just lay low. Let's check you again on Thursday morning.” I went in Thursday morning and it had gotten higher again. He was like, “I'm not comfortable playing this game with your past and how your baby was the first time around.” He was like, “Let's not do that. Let's not push it to that point again and see.” I agreed with him in that. I was like, “Yeah, no. We're now playing Russian Roulette of it's high. It's not as high. It's high. It's not as high.” I was like, “Okay, great. What are we going to do to get the VBAC going? How do you usually approach this?” He completely froze. He was like, “Wait, no. I think we're going to do a C-section.” I was like, “What?” I was shocked and so confused and still only at 1 centimeter. I was like, “What are we talking about here? This is not what I said to you at every appointment.” My husband knew. He saw it all over my face. I was like, “Where is this coming from?” My doctor said, “I'll let you guys talk about it.” He left the room for a minute. When he left, my husband was like, “Caitlin, we have to trust our doctor.” I was like, “I do trust the doctor, but I trust what I know more,” then he was like, “You're not a doctor.” I was like, “No, I know but I've heard enough where these stories come into play.” All of the stories that I heard of people who had been successful with this, that's where it all comes into play and that's why I'm so passionate about sharing this because that's what made me be like, No. I know it can work and I've heard of it working. I went on. I think my doctor came in and he thought that he was going to come into a room and us be like, “Okay, yeah. We have to do what we have to do,” and no. Instead, I was like, “I would like to give myself all chances for a vaginal birth.” Now again, I said this before. “I am not scared of a C-section. I had a great experience. I recovered really well but I want to give myself a shot at this.” A question I should have asked way previously was about the balloon Foley thing but here I am, he was still positive the whole time that I just assumed that surely, if push came to shove, we would know what we were going to do. He told me that he had ever only done one and he doesn't really know or feel comfortable doing another. He said that I might not be dilated to get one in. Meagan: Okay. Caitlin: I was like, “Okay. Well, typically that's how you approach inducing a VBAC.” Meagan: Yeah. Caitlin: I was like, “Okay.” I told my husband, “I don't know what either of you want me to say. I would like to do a balloon Foley.” My doctor was like, “I don't feel comfortable.” Meagan: Did he say why? What about it didn't make him feel comfortable? Caitlin: He said he had only ever really done one. Meagan: That's why. Caitlin: I was like, “I'll be your second.” Meagan: Yeah. Yeah. Caitlin: Then it was more so the approach of, “I don't think one would fit.” That might be true. I don't really even know. I was at a 1 so I don't know but– Meagan: Usually if you're at a 1, and even people without an open cervix like even at half a centimeter, they can get it in. It's usually a little less pleasant, but typically a Foley will go in. Sometimes the cervix is still posterior which is also a sign that our baby is not ready to come, but if so, it can go out and around. One in his whole career? He's only placed one? That seems kind of crazy to me. Caitlin: That's what he told me. That's what he told me. I'm like, “Okay. Here's what I need you to do. Phone a friend or I will.” The power of Google, I started to Google local doctors in the area who were VBAC-friendly who were at the same hospital I had already been registered at and all of those things. He looked at me like I was absolutely insane. My husband did a little bit too, but I was like, “No. Find somebody then. If you won't do it, find somebody who will.” It was very awkward because when he did find a doctor who would do it for me, that was great. I was in the room or whatever and they were– he wasn't at the hospital when I got the balloon Foley, but the doctor who would, before I left my actual doctor's office, all of those nurses were very not on board with the call that I was making so that's an awkward feeling to be like, Okay. Everybody in this room thinks that I'm doing something wrong. It felt really good to leave. It felt good to go get to the hospital with a new set of nurses and a different doctor doing it. All went well. She placed it just fine. I'm so grateful that she was willing to just pop in for a patient that wasn't even her own. We got to the hospital around 12:15 and I had a male nurse. He was awesome. I was at a 1.5 when I got there so more than a 1. The doctor who did the Foley for me was great. When she got it in, she said she might have broken my water. She wasn't sure. She couldn't tell. It was pretty tight. It wasn't comfortable but I wouldn't describe it as painful. They started low-dose Pitocin and we hung out basically. I waited on that Foley to do its job and yeah. From noon until 6:00 PM, I was dilating. Things were happening and I think I got the epidural and it fell out right about the same time. I got the epidural right before it fell out. My contractions were picking up and coming really fast which was interesting because I just didn't expect it to happen that quickly. Everybody told me, the doctor on the phone, everybody told me, “It's going to take forever. Forever. You're not going to dilate. It's going to take forever.” It really wasn't taking forever because I had been there from noon to 6:00 and things were happening. The nurse I had was wonderful, wonderful. He was super helpful. He was super team VBAC. You've got this. When it came time for my shift change, I was so bummed. He was like, “I'll get a good one for you. I'll get a good one for you.” When the nurse came into the room, she was so excited it was me. It was the nurse who stood up and told me, “Thank you for advocating for yourself and how you want to bring your baby into the world.” She was just amazing and she was so excited it was me. I was so excited it was her and that was just a huge full-circle moment. She was like, “You're doing it. You've got it.” I was like, “Girl, you have no idea.” Once the balloon fell out, we spent the night repositioning just to keep things moving along. At midnight, the doctor came in to check and see, “Okay, did your water break when I put the balloon in or did it not?” It turned out that my water was already broken, but she also said there was pooling of a lot of blood. I was losing a lot of blood. She was very confused by that. She did a rushed ultrasound in fear of placental abruption and she did prepare us that if that was the case, I would be going back for an immediate C-section. My husband thinks it's funny. He made a joke, “Well that would have made all of this worth the time.” I was like, “It's not time for that but whatever.” That would have been a bummer if that was the case but there was a lot of bleeding so I knew that if it was placental abruption that we would go back for a C-section and all would be fine. That's the biggest thing that I want to say is that it would have been okay. It wouldn't have been earth-shattering to me. But the placenta looked good. I was like, “Praise be. Let's keep trucking along.” She was going to monitor the bleeding. She wasn't sure where it was coming from. We'll just wait on my body to do its thing. I'm just so grateful that this random doctor, I'd never met her. I never had met this woman but she made me feel that I was the one making the decisions about my body and my baby because that isn't how I had felt by the other three doctors who I had talked to in the process of this up to that point. Meagan: Yeah, which is sad. Three out of four providers made you feel like that versus uplifting, being part of your birth, making choices for yourself and your baby. Caitlin: Totally. Totally. I felt like maybe everybody who was looking at me thought I was maybe a pushover or just didn't know what I was talking about so when I pushed back on things, people backed off and were like, “Oh gosh, we don't want to deal with that girl.” Nobody wants to be that girl but everything continued to go great. We did lots of new positions and dilating was happening fairly quickly. I got to 9. In the morning, that same male nurse requested me again. I loved that. My nurses changed my life. They were amazing and the nurses were my cheer squad. They were amazing. They made me feel like things were going great. Meagan: They were doulas. They were acting as doulas in here. They were requesting you which is awesome and very rare. That's very rare. Caitlin: Yes. They were phenomenal and every time one of the familiar ones came in, I was like, “We're good. I'm good. I trust you with my life.” They were amazing. That was encouraging for me because having a doula wasn't really in our budget unfortunately, but I did need somebody else because my husband is very like, “Yeah, Cait. Whatever you feel passionate about you needing to do,” and he was totally on board, but it was nice to have somebody with a medical background saying, “No, you are doing the right things. Here's how we can progress you forward. Here's what we should do next.” I had never had a vaginal birth. He came back. He requested me. He was my nurse again. Then at 10:00 AM, my contractions became so intense and so on top of each other. I think it was worse that this happened after. I wish I had either never gotten the epidural and built up to that. The taste of having the pain relief and then it going away was not fun at all. It would have been better to just never have had the pain relief at that point. I was at 9 and they called the anesthesiologist. They did a flush of medication to offer some relief. That didn't change anything. So 2 hours later, they came back and he checked. He was like, “Oh, your epidural became dislodged.” I wasn't getting any of the medication that I was getting previously. So unfortunately, at 9 centimeters, you're in full-blown labor labor and they didn't realize for 2 hours what the problem was. Finally, it took my husband saying to somebody, “I don't think she is just feeling intense feelings. I think she is feeling the actual contraction,” which also was discouraging for me because that 2-hour span of no changes was the longest span I had gone with no progression in the entire experience. I was getting nervous about that. I was like, Not only am I in immense, excruciating pain, but why am I not dilating to a 10? Why am I not a 10? What's going on here? The anesthesiologist said to me, “Hey, you're at a 9. You can wait it out and when it's time to push, just push. You don't need the epidural to be working.” I was like, “I could do that, but I also got an epidural for the pain relief.” I was like, “No. I want the relief and I also want to be able to relax and see if that gets me to a 10.” They did place a second epidural. It helped. It took a while. It was basically the whole process restarting. My doctor told me, “Hey, since you were just up for 2 hours with contractions on top of each other, how about you try to rest? I'll check on how you guys are doing in a little bit.” He popped in a few minutes later and asked to check me. I was like, “Yes.” He lifted up the covers and my baby's hair was there in 30 minutes. Meagan: What? You were crowning? Caitlin: Yes!Meagan: Oh my gosh. Caitlin: I went from 2 hours at a 9. They gave me the second epidural and then within 30 minutes, they went to check and they didn't have to check anything because the baby was there. It's funny because we had just reset the room to be dark, comfortable, rest, and it was like, “Nope. Open the blinds. Get ready to go.” It was a crazy turnaround. My husband and I didn't believe it when he said it. We were like, “Hair? Already? We just sat here for 2 hours at a 9.” I never even got measured. Do they measure at a 10?Meagan: I mean, they can go in and be like, “You're complete.” Yeah. Caitlin: Right. Right. It went very fast. I was shocked by that. I pushed for 15 minutes and baby was born. It was smooth sailing from then on out. It was 24 hours total. Everybody's biggest threat to me was, “It's going to take forever. You're going to be there forever. You're going to be doing this forever.” It was 24 hours from start to finish. Baby being born. Baby being healthy. Me getting the VBAC. Me getting the golden hour because with my first, he was straight to the NICU. I didn't get to hold him or anything and I really wanted that. It was super redemptive for me and just super special that my husband and I were in the same room after the baby was born because he went to the NICU with our first. Having the VBAC made me so proud and confident in myself and any future births that I'm blessed with. Now I know. I'm an advocate and other moms can put their foot down for themselves. You have control of what happens to you as you bring a baby into this world. I don't think I knew that before being in the thick of it that I actually did get to make the calls. Meagan: Yes. Caitlin: Yeah. All of these medical things that came up like the high blood pressure and how easy I could have been like, “Okay yeah, whatever you say,” but just because of things that come up in pregnancy, it doesn't mean that you need to get straight to a surgery room. Meagan: I mean look at that. Your blood pressure did go back up to that high range and you didn't just go in and have a C-section. You had a slowly induced VBAC. Did your original male provider ever come back to the scene? Did that provider catch baby? Caitlin: He is the one who when I was stuck at the 9, he was in at that time. Meagan: Okay. Caitlin: He was there from being at 9 centimeters and he is the one who delivered my son. The other doctor came in to check on us after which was super sweet. She was incredible. But yes, he did come back for all of that. There was a sense of me being like, “Huh. This all worked out.” Meagan: Look at that. Caitlin: It all worked out. Would you look at that? It was interesting because he was very much like, “I knew you were determined.” I was like, “Okay, yeah. I was but you were trying to make me not be.” Meagan: Yeah. Caitlin: I don't know. I do believe that he did incredible with my first birth and especially with a first-time mom with that scary of a situation happening. I just think that sometimes it's what's more comfortable. It makes me sad because if that was my first baby, I literally would have not ended up in the situation I was in. I just wonder how many moms get put in these positions and then have to make– don't get to make the call because they don't know they can make the call. They don't know they are the ones who get to make the choice. Meagan: Yeah, exactly. It goes back to the review where it says that this podcast is for people who have had a previous Cesarean but also for people who haven't had a previous Cesarean and who haven't had these experiences and who may not have that full education yet. Caitlin: Right. Meagan: I think this podcast is so great for people who want to learn what happens out there and what could happen and what your options are and how people advocate for themselves. I'm so grateful for the nursing staff. Caitlin: Oh my gosh. They were so amazing. When we got moved to the other room after the baby was born, the nurse who was there when I signed my AMAs and stuff, the one who did all that with us, she came into the room and was clapping. She was like, “You did it!” Everybody was so on our team which was truly incredible. That meant everything for us. Meagan: Absolutely. Absolutely. Oh, go ahead. Caitlin: Another thing just for new moms too who haven't gone through it, the recovery is different. C-section moms are absolute heroes. They are tough as nails but also, the doctors were telling me, “You're so young and you'll bounce back so fast from a second section. It's not that bad. You healed great the first time.” That's all true. But the recovery was different because I didn't have a major abdominal surgery. Meagan: Yeah. Yes. Oh my gosh. Well, thank you so much for sharing your stories. Thank you for advocating for yourself and being an example to others on how to advocate for themselves. We know with preeclampsia that it really can be an overnight serious thing but it doesn't always mean that you have to just go and have a C-section. There are so many times where I see births where we have preeclampsia with really high blood pressures and proteins and all of the things. We go in for an induction and then it's managed. The blood pressure is managed throughout the entire rest of the pregnancy so I don't know. There's that. I just want to say there is that. Caitlin: There is. Meagan: A lot of times, providers say, “Oh, your blood pressure is so high. Labor would be far too stressful,” but there are so many ways to help manage the blood pressure. We do know that sometimes there are medically emergent reasons to go in and have a C-section but it doesn't always mean you have to. We have a preeclampsia blog. We are going to drop it in the show notes so if you want to learn more about preeclampsia and the risk factors and how to prevent it because there are ways that we can try to prevent them– getting our omega 3's, calcium, choline, getting a good salt intake, getting really, really great rich foods, proteins, fruits, vegetables. The Brewer's Diet is another amazing thing to check out. They have a whole preeclampsia section. Definitely check these things out. If you also have had preeclampsia before like Caitlin, the risks of having it again are slightly higher just because we've had it and things like that so if you've had it before, definitely check this out even before getting pregnant. I think there is a lot of preparing to do before we get pregnant. Sometimes it happens no matter what efforts you've had. Maybe you've done all of the things. Sometimes it just happens and it's out of our control. Like Caitlin was just talking to me about this before, she doesn't struggle with high blood pressure. It just comes during pregnancy. Caitlin: Mhmm. Yeah. My hope is that in future pregnancies that I wouldn't have high blood pressure again, but if I do, I just feel more equipped and more confident in how I want to manage that. Meagan: Exactly. Caitlin: Yeah. It's hard because when you are being told things by medical providers who do know what they are saying in regard to some extent and you want to continue to be like, “I'm going to do what's safest throughout my baby,” but my favorite question throughout my whole experience was, “If my baby is okay, if my blood pressure is lowering, then why are we making the decisions that we are making?” That's the pillar that my husband and I lived on in those disagreement conversations. Meagan: I wanted to point out before we go just piggybacking off of that that it is okay to ask questions. You can say, “Okay, but why?” or “What is the evidence on that?” or “What are the medical reasons you are suggesting for this or that?” You can ask questions, Women of Strength. That is advocating for yourself. Ask the questions so that you can make the final decision. Caitlin: If they don't have an answer, it's probably because there isn't an answer. Meagan: Right? And/or if there is some gaslighting happening, that probably means there is also not an answer but they are trying to create an answer and make you feel scared or like you would be stupid to make that choice.Caitlin: Mhmm. Mhmm. I really wish all nurses were like the ones we had. We had awesome nurses. Meagan: They sound incredible, absolutely incredible. Caitlin: They were. Meagan: Shoutout to them. Happy birthday again. Congratulations. Caitlin: Thank you so much. Thank you. Meagan: We will talk to you later. Caitlin: Thank you. ClosingWould you like to be a guest on the podcast? Tell us about your experience at thevbaclink.com/share. For more information on all things VBAC including online and in-person VBAC classes, The VBAC Link blog, and Meagan's bio, head over to thevbaclink.com. Congratulations on starting your journey of learning and discovery with The VBAC Link.Support this podcast at — https://redcircle.com/the-vbac-link/donationsAdvertising Inquiries: https://redcircle.com/brands

The MYC oncogene is notorious in the cancer research world because it is implicated in many advanced or aggressive cancers such as treatment-resistant prostate cancer. In this episode, Sarki Abdulkadir, MD, PhD, shares how his team bucked the conventional notion that the MYC gene is “undruggable” and uncovered a handful of compounds that block MYC gene activity, making prostate cancer tumors sensitive to hormone therapy and opening up a potential new therapeutic target for treatment-resistant prostate cancer. 

¡Estamos de vuelta con la tercera temporada! Y qué mejor manera de hacerlo que con este capítulo en el que hemos tenido el placer de conversar con Laura Soucek y Marie-Eve Beaulieu, CEO y CSO, respectivamente, y ambas cofundadoras de Peptomyc. Peptomyc es una empresa centrada en el desarrollo de péptidos de penetración celular (CPP) innovadores dirigidos a la oncoproteína MYC para el tratamiento del cáncer. Con el desarrollo de su molécula, OMO-103, Peptomyc está revolucionando el tratamiento del cáncer, ya que es la única empresa que utiliza estas mini-proteínas terapéuticas para inhibir directamente MYC, un factor crucial en la proliferación y supervivencia de las células cancerosas. No te pierdas la historia de Laura y Marie-Eve, dos auténticas fuera de serie que, además de desarrollar sus brillantes carreras científicas, decidieron fundar en 2014 esta spin-off del VHIO e ICREA con la cual han levantado 42M€, y llevarla hasta donde están hoy, en un estudio de fase Ib. Más información sobre Merck's Advance Biotech Grant: https://informaconnect.com/bioeurope/merck-advance-biotech-grant/ O contacta con Iñigo De la Fuente en Inigo.delaFuente@merckgroup.com Merck KGaA, Darmstadt, Alemania tiene los derechos del nombre y la marca comercial "Merck" a nivel internacional, excepto en los Estados Unidos y Canadá. En EE. UU. y Canadá operamos como EMD Serono en el sector de la salud, MilliporeSigma en el sector de ciencias de la vida y EMD Electronics en el sector de materiales de alta tecnología. La música que escucharás en este podcast es: Obra: Instinto Animal Música de https://www.fiftysounds.com/es/ Obra: Planeta Líquido Música de https://www.fiftysounds.com/es/ Obra: Futuro Asombroso Música de https://www.fiftysounds.com/es/

Mycènes, capitale légendaire d'Agamemnon où fut organisée la conquête de Troie, est un site archéologique majeur de la Grèce. Des ruines plus qu'imposantes évoquent une grandeur passée. On peut y voir par exemple, la citadelle qui se trouve en haut dʹune colline dans un paysage de toute beauté. Histoire de cette cité avec Julien Beck archéologue, chargé de cours à l'Université de Genève Sujets traités : Mycènes, Agamemnon, Grèce, citadelle, Troie, Merci pour votre écoute Un Jour dans l'Histoire, c'est également en direct tous les jours de la semaine de 13h15 à 14h30 sur www.rtbf.be/lapremiere Retrouvez tous les épisodes d'Un Jour dans l'Histoire sur notre plateforme Auvio.be : https://auvio.rtbf.be/emission/5936 Et si vous avez apprécié ce podcast, n'hésitez pas à nous donner des étoiles ou des commentaires, cela nous aide à le faire connaître plus largement.

With her first birth, Amy hired a doula and planned to birth at a birth center. During labor, her baby kept having late heart decels which led to transferring to the hospital. At the hospital, Amy stalled at 9.5 centimeters. Baby was having a hard time descending and continued having decels. Amy chose to have a Cesarean and while she was at peace with the experience, she knew she wanted another chance at a vaginal birth. Amy proactively prepared for her VBAC by educating herself and working with her provider to find common ground. Her labor progressed well, Amy coped beautifully, and was able to push out her 10-pound baby! Amy talks about how recovering from birth can be difficult no matter what type of birth you have. Our VBAC Link Doula, Desiree, joins as Meagan's co-host and touches on the importance of breathwork. As a licensed therapist, Amy also talks about how she uses breathwork with her own clients. “Practice it before you are in labor because then it's easier to do while you're in labor.”Desiree's WebsiteHow to VBAC: The Ultimate Prep Course for ParentsFull Transcript under Episode Details Meagan: Welcome, Women of Strength. It is an amazing day to listen to another VBAC story. We have our friend, Amy, from Massachusetts coming your way sharing her VBAC story with you. Then we have one of our VBAC Link doulas, Desiree, with us as well. Welcome, ladies. Desiree: Hi.Amy: Thank you. Meagan: Hello. Thank you so much for being with me today. We do have that Review of the Week so I'm going to actually turn the time over to Desiree and read that. Desiree: Yeah, so the Review of the Week this week is provided by Ashley on the VBAC Doula course which I am very familiar with. I am so excited to read this one. Ashley says, “TOLAC/VBACs should be treated just like any other birthing person but there is certain preparation and information that needs to be offered to them. Your course covered that. The value is held in your careful recognition of how to best support our clients who are doing a TOLAC. I cannot praise you two enough for the fear-release activity. Honestly, it is something I can apply to even myself before and after birth and even in life in general. Thank you for that. It has already helped three of my VBAC clients.” Meagan: Oh, that's amazing. That just gave me the chills. I love that. Fear release is so important. Women of Strength, if you are listening, we have that in our course because we truly believe in it. I think fear release in anything in life. We could just be scared to go in and take a test and fear release of that. But when it comes to birth specifically, I don't know if both of you would agree, but we've got to do some fear releases and let go and also process the past, right? Desiree: Absolutely. Yes. I would say it's good for everybody going into birth, but definitely, if you're a VBAC or going for a TOLAC because you take your previous birth experiences into the room with you and if you haven't done the work, then you are just setting yourself up for roadblocks. Meagan: It's so true. I will admit that I did fear releases and I did lots of processing and I still had little bits of bouts of roadblocks in my VBA2C birth. That was really hard, but I was so grateful for the knowledge of how to do that fear release and work through it in those moments in my labor and because I had already done so much beforehand, the little roadblocks that were there even though they were roadblocks, I was able to get through them so much faster and more efficiently. Okay, Ms. Amy. Thank you so much for joining us. Amy: Sure. Meagan: Yes. We would love to turn the time over to you. Amy: Okay. So I actually gave birth to my two kids and then I gave birth in two different states. My C-section story was from when I lived in Massachusetts then I moved back to Minnesota and had my son which was my VBAC and now we are back in Massachusetts. Yeah, so with my daughter, I hired a doula. I gave birth and wanted to give birth at a birthing center that was outside of the hospital but it was connected to the hospital system but it was run by midwives and more holistic, more of what I was aiming for. Just like with your first births, you have all of the plans and I think partly that is some anxiety mitigation of if I feel like I have a plan then maybe I know what to expect. I worked with a really amazing doula. We didn't take a birthing class through the hospital. She did that education and I was feeling relatively prepared as much as you can with a first birth. I had a week's worth of prodromal labor. I always am very cautious. I always call it prodromal labor because I feel like the term false labor is so demoralizing when you're in it like this isn't real labor and I'm like, No, it is. It just isn't progressing the way I want it to. Meagan: Well, but it's still your body working. I think that's what a lot of the time we forget. It's not progressing the way we want but our body is still very much working and making progress behind the scenes whether or not a number of centimeters or a number of effacement is reflecting. We are still doing work and making progress. Amy: Yes, exactly. But my prodromal labor liked to happen only at night so I was going off of probably three or four nights of really not sleeping through the night. Again, as a first-time mom, I didn't really know. I was up with adrenaline because I didn't really know 100% what I was experiencing. I did stop going to work. I was going to work up until labor and then I just stopped going to work the last couple of days because I was like, I'm not sleeping. I'm stressed and tired.I went into labor the night before my daughter's due date and felt the contractions getting a little bit stronger around 10:30. I went to bed. I woke up around 12:30 and told my husband, “Okay, I think this is really actually happening now.” We labored through the night. At 4:00 AM, I called my doula. We met up at the birth center. I was already 6 centimeters. I was obviously so thrilled about that. I was like, “We're going to have this baby by mid-morning. It's going to be great.” Then they started checking her heartbeat. From the beginning, she was having a lot of decels and they kept monitoring it, monitoring it, and monitoring it for 20 minutes which again, wasn't really the plan that I was going to be sitting in bed monitoring her heart rate the whole time. I wanted to be up and moving around but they just couldn't get her heart rate to stabilize at that point so they moved me over to the hospital then. It's a birth center but they are across the street from the hospital so they literally put me into a wheelchair and rolled me across the road. That's when all of the interventions started. From there, I progressed I think to about 8 centimeters but she was having those decels off and on the whole time. Then I think we ended up getting an epidural. I wasn't planning to but I got an epidural about that time. I don't know what time of day this was, maybe noon just because it had been a while now. I was tired and they were like, “Maybe if you rest a little bit, we can get her into a better position or something.” Really, what ended up happening was because of her decels, they wanted me to be on continuous monitoring which made it so I couldn't move around as much because the nurse didn't know how to apply the wireless ones. That happened so it was just one thing after another and my doula was great. She was really supportive. We did try a few different positions, but it was like every time I got in a position that felt good, they were like, “Oh no, we lost her heartbeat. We have to have you move again.” I think the process was frustrating. I did get the epidural. I got all the way to 9.5 centimeters dilated and then we just sort of stalled. And then of course probably around 5:00, this had been close to 20 hours of labor and they were like, “Yeah, I don't know. We could try a few more positions but I think this is just going to keep happening and now we are worried that she's going to get distressed.” So it wasn't really an emergency C-section at all. They were like, “Here's what we think. We'll give you a few minutes to talk about it with your husband and doula and see what you guys think.” It was definitely hard. I was discouraged and frustrated by that but at that point, I just wanted her out. Now that I've read, and when I was listening to The VBAC Link and listening to so many other stories where we probably could have given it more time and all of these other things, they did a C-section and they actually found that her umbilical cord was wrapped around her neck twice. She never really descended into the birth canal fully. She never really engaged in my pelvis. Part of me wonders if it was partly that where she had that umbilical cord and that was going to be tough for her through the birth canal. I don't really know. But she was healthy and everything was good. I honestly didn't feel super traumatized by that experience but obviously I wish it had gone a different way. That was my first birth and then about two years later, well, my daughter was 2.5 when I got pregnant with my son. I was the middle of the pandemic. It was 2020. Is that when I got pregnant? Yeah. It was the fall of 2020. I definitely started looking into VBAC and found your podcast and was like, I would like to really try for a vaginal birth this time around. I think what was challenging about that and as you are talking about going in with fear is that I felt like even though it was my second baby, I felt like I was going through the process like a first birth because I never pushed. I never got to that point with my daughter so I felt like I had that anxiety almost like I was going into my first birth again. That was hard for me, I think, mentally. But we had moved to Minnesota at that point so unfortunately, I didn't get to use the same doula that I had before. I found another doula and I think she had a lot of knowledge and I think she did a good job but I think overall, we just didn't connect as well emotionally. Honestly, I realized that was almost more important to me. Obviously, knowledgeable and certified is good but not feeling like we were always connected, I struggled with that at times. Meagan: Sorry, not to interrupt you but I was just going to say that can impact the way you are feeling and walking into any experience so that connection is really, really key. Amy: Yes. Yeah. I'm a therapist. That's my job and so obviously, I say that to my clients all the time about therapy too. I never got to the point where I was like, Oh, maybe I should look for somebody else, but I think looking back, sometimes I wish I had. But during the labor and stuff, I think she was great. Yeah. It was different than my first time. So yeah, I did a lot of research about Spinning Babies. My doula helped me with some of those exercises. It was stuff I was aware of before, but I didn't look into it as much. Then one of the things I was curious around because when I had my C-section, my OB was like, “Oh, well you have a flat pelvis so it is going to be hard for you to ever have a baby vaginally” is what she said to me. My doula was like, “Well, you know. Around pelvis shapes and stuff like that, that's a very gray area. Generally speaking, we don't subscribe to that because your pelvis is moving and it isn't a shape.” But I was curious about that so I looked into that through Spinning Babies and some of those other resources and about how babies engage in your pelvis and how does baby engage to progress labor.Meagan: Yeah, different stages. The baby can be in sometimes different– I mean, we all have different shapes of pelvises so the baby has to come in different positions and sometimes that even means posterior so sometimes we do all the things to avoid posterior babies, and then our babies still go in posterior but that's actually because of the way our pelvis is shaped or the way it was that day that our babies needed to get into the pelvis in that position. Sometimes they can kind of hang up until we find those positions that can help them navigate down. Amy: Yes. I mentioned that to my doula and we both did some research on it because I think that was part of the issue with my daughter. There wasn't a consistent engagement. Even though my labor progressed for the most part, I was sort of wondering about that. I also was– I can't remember when this exactly happened but I think around 32 weeks, I started measuring big. Of course, my OB who I would say was VBAC tolerant. I wouldn't say she was VBAC-supportive. I did like her quite a bit but she was like, “Okay, your baby is measuring big and because of your history–” she goes through the whole, “here's your percentage of having a successful VBAC.” I'm 5'9”. I'm larger. I'm not a petite person so even if I had been, I don't subscribe to that because of listening to VBAC podcasts and stuff, your body can birth a large baby, but also, I wasn't as worried about it because I know that sometimes those projections are completely off and so it was part of that process of learning to respectfully disagree with a medical professional who I did have respect for and did feel like they had some expertise but to say that we don't have to agree on everything for me to work with you. That was a huge turning point for me just in my life in general working with medical professionals of, I don't have to completely throw everything you say out the window but I also don't have to agree with everything that you say and we can respectfully disagree on that issue. So I was like, “Respectfully, I'm not going to schedule a C-section at that point.” She didn't pressure me at all. She was like, “I understand. Let's move forward with the plan.” That's what we did. I think that was empowering. As we moved closer to my due date, he was big. I was not sure at the time, but I was like, I'm going to go into labor early. That was a mental block for me. Then as it gets closer and closer and closer to my due date, I'm going out of my mind just losing patience. I'm not a good, patient-waiting person as it is so I'm having prodromal labor for the whole week before my due date and at that point, I actually did schedule a C-section for the following week because I needed mentally an out-date. That was what it was in my mind of, Okay. If this goes on for another week, I have an out, even though that's not what I wanted. I think honestly mentally, it took a weight off my shoulders which is counterintuitive to what you would think when everything in me was working toward this VBAC then I was like, No. A couple of days before he was born, I needed that second date in my mind somewhere. Meagan: Well– oh, sorry. Go ahead, Desiree. Desiree: I was going to say I think it actually makes a lot of sense. You say it's counterintuitive, but you're right. We spend so much time and energy thinking about achieving our VBACs and having our babies. Sometimes having– well, even if I don't do all the things, I can still have my baby and then relaxation happens. That's when we see labor starting to take off for a lot of people. Amy: Yep. Yeah, I definitely think that was a piece of the puzzle. Yeah, and I think it was helpful.So yeah, I'm trying to think of how this went. Yeah, so we were doing some Spinning Babies things. We did some side-lying releases all throughout the pregnancy and then on June 4th which was actually my son's due date, having prodromal labor all week and then I felt like there was a little bit more intensity in the contractions I was having that morning so I sent my daughter off to her grandparents' and was like, Okay. I'm just going to focus today. I'm going to focus on getting my body in gear. It wasn't that I was in this mindset of, I'm going to make myself go into labor today, it was just this intuition around I needed to be able to focus on what was going on. We had that plan that my daughter would go stay with her grandparents while I go into labor and I thought that maybe she was just going to go earlier than I thought she would because I wasn't in any kind of active labor. Then I had my doula come over at 10:00 AM and we did more different exercises. I can't remember all of the ones we did because what would happen was that I would have contractions 15 minutes apart, 15 minutes apart and then they would just stop and that would be the end of it and then the next day, the same thing. Or they would be 10 minutes, 12 minutes, 20 minutes– nothing consistent so what we found was if I laid on my left side in the flying cowgirl position, then my contractions were more intense and more consistent. It was again this think of, in my mind I was like, While I'm in active labor, I'm going to be walking around and trying all of these different positions and all of this different stuff, and what I ended up doing is honestly just laying in bed and watching TV in that position almost all day. So again, it was this thing of that's not what I've heard is helpful or whatever but I just think that was where he needed to be to engage in my pelvis at that stage. Then every hour or so I'd get up. I'd do curb walking. I would just get out, walk around, and be active but it was way more laying down than I ever planned to do. You hear that's not how you get your body engaged in labor, but that was what worked for me so that was an interesting, Release what you think is going to work for you and do what your body is telling you is working for you. But it was actually kind of nice. It was relaxing. My daughter wasn't there. It was the summer. We had the air conditioning on in that room. My husband brings me a bubble tea or whatever and I was like, This is actually not so bad. This is okay. Contractions were probably 15, 10 minutes apart that whole day then in the evening is when it ramped up. I turned toward active labor and we called my doula again at 8:00 PM and the contractions were very intense. I was leaning on an exercise ball. My husband was trying to do some counterpressure to get me through it and then she did– and again, this is something where my doula and I were not always on the same page, but I was explaining to her my contractions. “They are about a minute and half long. They were maybe 7-8 minutes apart,” and the first thing she said was, “Oh, well that contraction isn't long enough to progress you at all,” or something like that. She said something about my labor process and it was so discouraging because I felt like I had taken so long to get to that point that when she said that, I was like, Oh, so all of this was for nothing. I know that's not what she meant but I remember just feeling very discouraged by that comment. So that was tough. Then she did the abdominal lift and tuck. I do feel like that helped get my son into my pelvis and more engaged in my pelvis because from that point, contractions were two minutes apart. They were very intense. I ended up signaling. I was like, “I'm ready to go to the hospital.” We agreed to labor at home as long as possible, but I was like, “I think this is the time.” Again, my doula was like, “I think we should wait longer.” My contractions were two minutes apart at that point and I was like, “I don't think we should. I want to go.” I'm glad we did actually because that ended up being the right time. But I remember rolling into the hospital at 12:01 AM and I remember my husband saying, “Well, I guess we're not going to be having the baby on his due date,” because my daughter was born on her due date. I was in active labor on my son's due date and then we just missed it. I remember being like, “That's true. We're not going to make it but that's okay.” So yeah, we walk into the hospital and go through triage. My water breaks while we are in triage and of course, they bring out their little testing stick and they're like, “We're going to make sure this is actually your water breaking.” I was like, “Okay, but I've never wet myself during a pregnancy. This is what it is.” Then we go back in the labor and delivery room and the doctor who is on call is not my doctor. I find out later that this is the most anxious, not-nice-to-work-with OB in that practice. So that was tough. I could tell from the beginning she was just very brusk. She didn't have a great bedside manner at all. She was like, “I see that he's measuring big so we're going to make sure that–” she was really worried about shoulder dystocia. I was very glad again that I had read up on that and that I was not concerned about that. So she was like– they had big birthing tubs there but they don't let you birth in them. They just let you labor in them. I was in there and feeling like I wanted to push for a while and I remember I went to the bathroom and she comes in the room and she's like, “Well, let's get you on the table.” I'm like, “I'm just going to the bathroom.” I don't know if she thought that I was going to try to have the baby without her or something, I don't know. Her whole vibe was very anxious. That was hard. That was definitely discouraging. I think at that point, I actually had asked for an epidural. Both times, I asked for an epidural at transition and then once I'm through transition, I'm fine. They didn't come in time and they checked me and I was already at 10 centimeters so they were like, “Okay, it's time to push. We don't have time for the epidural.” I'm like, “Okay, this is what it is.” That was okay and then I pushed for about an hour on my back which was again, not my choice but the OB was like, “No, I need to be able to see what's going on. I don't want you in any other position,” because again, she was so worried about shoulder dystocia and him being big. Halfway through pushing, she was like, “Okay, you can try on all fours.” But at that point, I was so exhausted that I couldn't even imagine myself getting on all fours. I was like, “That ship has sailed.” That was tough because I had planned the whole time to try to push at least for a little while on all fours because again, knowing about big babies and how that can be a really good position for that, but I just didn't feel like I could advocate for myself. I don't know. In both of my births, when I get in labor, I go very inward. I think having a doula was great, but both times I don't think my doula was super outwardly advocating. But again, maybe they were looking for a signal from me and I was just in my own world. It was okay though. I pushed for an hour. He came out just fine. It was that euphoric moment of, Oh my gosh. That just happened. That was crazy. Having only pushed for an hour felt great with my first vaginal birth. They took him out and they weighed him and he was 10 pounds, 4 ounces. Meagan: Yeah!Amy: Yes. It was so funny because the nurses were trying to guess. They were like, “9 pounds. He's big.” Yes. I felt great and actually, it was funny. The next morning, my OB came in. She was on then. She comes in and she goes, “Well, he was big.” I was like, “And I did get him out, so we were both right.” We were able to laugh about that. Meagan: I love that you said that. Like, “Hey, I was right too.” Amy: Yes. Yes. Yeah, and I felt like it was a good ending. I felt like she was like, “Yep, you're right. You did.” I did tear. I had two second-degree tears which again was maybe not as bad as I expected with a baby that size, but it was no fun. I think that's the other thing that I talk about often is either way, with a C-section or with that kind of a birth, I felt like it took me about two weeks to be able to feel like I could even walk normally. I think the difference with the vaginal birth is that I do feel like I made improvements every day where I gradually got better whereas with the C-section, it was really hard for two full weeks and then it was like then I felt better. It was a different recovery but I would say– and I think other people have talked about this here before but either way, it can be a tough recovery. Meagan: For sure. For sure. Amy: It's hard because my sister had two vaginal births and her second one, she was up and walking. We walked a mile when she was two weeks postpartum and I'm like, gosh. I couldn't even walk down the block at two weeks postpartum after my son. I think obviously not to compare yourself one or the other but I had a big baby and there was some trauma down there and that takes time as well. But it was a great feeling and I think that obviously, it ended up really good. Yeah. That's my story. Meagan: I love it. Thank you for sharing it and congratulations. I think that it's so hard to sometimes have providers who will meet you in the middle. It sounds like you both met in the middle along the way and I think in a perfect world, I just wish that this would happen where providers would meet us a little bit more but there are so many providers who won't even come in. We talk about it all the time with finding the right provider and if the provider is not right for you and if they are not willing to budge at all and meet you in the middle or be a part of the conversations where you were saying things and she was like, “You know what? Okay. Okay. Let's go back to the original plan then.” She said her piece. She said her suggestions. You were like, “No. I don't feel comfortable with this. This is not what I want,” and she was willing to be like, “Okay. Okay. All right. Let's go back to that original plan.” Look what would have happened if you weren't able to advocate and stand up for yourself and be like, “Actually–”, it could have been a very different outcome. Amy: Yes. Yes. For sure. Meagan: Desiree, do you have anything to share on that just as a birth worker or anything to share as far as tips go when we've got situations like that where maybe it seems like it could get really combative but it doesn't have to be? Desiree: Yeah. I mean, I just want to commend you, Amy, for being able to voice your opinion in that way because I think that's really hard for a lot of us to stand up in spaces with doctors who we think are in a position of authority. Yes, they have experience, but no one lives in your body. No one has the lived experience of your body except you. That makes you an equal expert in what's happening. I think it's great that providers bring advice and recommendations and they have a plan for what they want to see, but I think a truly great provider does meet you at least halfway. Ideally, you're right Meagan, they're coming a little bit more than halfway, but I mean, it's nice to hear that your provider was willing to listen to you and follow your plan and probably have hers in her back pocket as the fallback. But that's just great that you were able to advocate for yourself in that way. It doesn't always have to be combative, right? It can be as simple as, “Thank you for your advice. I appreciate your expertise. This is what I'd like to try and if it doesn't work, then we can try something else.” Amy: Yeah. I think that I was feeling anxious about that too and this big realization of, I do. I like her. I trust her as a doctor. I feel like we're on the same page, but that doesn't mean that I have to agree with everything she says and it also doesn't mean I have to fire her and find a new provider. Again, there is a happy medium there. You're right. I was taught that doctors have this authority. They know. They go to years of schooling. Of course, they do. But also keeping in mind that their worldview and perspective might be very different and the lens that they are looking at this through is very different than mine and how do I keep this in mind that they have this medical perspective of what they've seen. They've seen the worst of the worst medical scenarios but also to keep in mind that there's this whole other worldview around that so that ws helpful for me. Meagan: Yeah. That was definitely something that stood out to me with your form. It was, “Disagreeing with a provider doesn't mean that you can't work with them.” You said it in your story too. That is so, so true. It doesn't mean we can't work with them and if it gets to a point where it's like, “Okay, there is no working with this,” and it is actually not working, then we can make a different choice. We can change things up, find a different provider, look at our VBAC Link provider list, and see if there is someone else. But if you can work with it and everything is feeling good and there are a couple of things but we are working together, that is so great. That is so great. Amy: Yeah. Meagan: Awesome. Well, I just wanted to let Desiree share a couple of tips. I love when we have our VBAC Link doulas come on because it's so fun to get different tips and different perspectives from other doulas around the world. Desiree is in California with Be_Earth_Mama. Is that right? Desiree: Yeah. My husband gives me a hard time about this all the time because I guess nobody gets it but it's Birth Mama. Meagan: Oh, I thought it was Be Earth Mama. Desiree: That's what he says. Meagan: That makes so much sense, so much sense. She is in California. Remind us exactly where in California because California is ginormous. Desiree: California is ginormous. I am in the San Francisco Bay Area so Northern California. Meagan: And you do birth and education. Desiree: I do birth and education primarily. Meagan: You do webinars and all the things, right? Desiree: I do webinars. I do online classes. I teach in-person classes. I'm getting ready to start a prenatal belly dance class that I think is going to be in-person for now but might go to virtual if there is an interest so all things birth preparation essentially. That's my niche. Meagan: Really, really cool. Awesome. I know there were a couple different topics that you were talking about and I was like, ooh. Breathing and active relaxing. Tell us all the things. Desiree: Yeah, it's one of my favorite topics and I feel like it's one that is on the list but it's low on the list because you think about breathing. Why do you need to practice breathing? You just naturally do it but if you've been in labor, you know that when that intensity starts to pick up, breathing is the first thing that goes out the window so having a strong breathing practice is the first step to staying really calm and grounded in labor. But even beyond that, I think having a practice is about the process and I think especially for me in my VBAC journey, it sounds like Amy was sort of like this where contractions start and they stop and they start and you are in this waiting game. Is your body going to do the thing or is it not going to do the thing? What's wrong? I feel like having the practice to fall back on gives you a way to stay grounded and centered in your body as you are waiting for labor. So it's two-fold. Keeping your body nice and relaxed while you're actually working through labor but giving yourself the time to be nourishing yourself in those last precious days and weeks leading up to labor I think is almost more important. Something that I work with all of my clients on is having an established breathing practice. It's not about the breathing technique because there are so many different ones out there. There is the up breathing. Up breathing is my favorite, breathe in for 4, exhale for 8. There is box breathing where you breathe in for 4, hold for 4, exhale for 4, and hold that for 4 counts. And for some people, it's just simply breathing as slow and controlled as possible. I think it's about finding something that feels natural and intuitive to you that you can lean into but it's about finding time and practicing really dropping into your body and dropping out of everything that's going on around you and playing into your senses with that. That's something I like to talk about to my clients is hacking your body. Building muscle memory because it's so hard to relax and stay calm when you're going through surges, the contractions are really building, and telling you to stay relaxed is not really going to work. Nobody wants to hear that. But if you have this practice and if you've built in sensory cues– I like recommending people to pick a birth scent either an essential oil or a candle or a lotion, picking a song or a sound, it could be even a meditation track and setting aside just 2-3 minutes every day to run through whatever your breathing technique is with your scent or your sound, maybe you have something to hold onto and practice just actively relaxing every single part of your body through the process of breathing when you get into labor, your body is going to remember that once you launch into this breathing routine and you put on your birth scent and you have your sound or your meditation track playing, your body is naturally going to relax because you've told it that that's what this time is for. I think it's a really special thing that we can do for ourselves to give ourselves this time and this practice where we are just nourishing the deepest parts of us. It's of course helpful for labor, but I think it's also a helpful practice to take into postpartum and into parenthood. I can say I've been doing this for 5 years. My oldest daughter is 5 years old and I still do it every day. I have to run through my breathing practices. Yeah. I think it's especially important for VBAC mamas to have this type of self-care routine. Meagan: Yes. Oh my gosh. I love that so much. Like you said, it just becomes intuitive if we can practice this so much and instill this into our lives, it just becomes intuitive in that labor journey. There are going to be times where we were talking about roadblocks and stuff earlier, but those might come in and breathing in itself is something that can get us through those things. When you talked about the box breathing, I've done that before and I have this weird thing when I do box breathing. My body moves and I'm creating a square. Desiree: I do too. We don't have our cameras up, but I have to do the square. Meagan: Same. I do a square. I literally draw a square with my whole body and my torso and everything looks like a tree swaying in the wind and I can just feel it. I literally, the relaxation from head to toe just comes in. Like she said, there's not any specific way. You don't have to choose one way. You can use them all. You can use anything, just really, really, really having active relaxation practices before you go into labor is so good. And I think it can help along the way. Even when we have a provider who comes at us with, “Hey, we're going to meet you in the middle,” it still can be in our head. We can be like, Okay, she said this. I said this. This is what we're going to do. You've just got that whole conversation and it's just that you're breathing through that and you're processing that and you're going to apply it later on in labor. I don't know. I just love breathing so much. Desiree: I do too. I think it's the most important tool that we have that everybody has. It's the most powerful tool that's available to us. Meagan: We have to do it to live. Desiree: Mhmm. Meagan: We just have to. It's intuitive. We have to do it and we talk about intuition here and tuning into our intuition. If we are really, really tuning into our intuition, that breathing is part of that. Then our minds and our bodies can respond. Amy, did you ever do any breathing or anything like that? Have you ever heard about any of the things we are talking about? Amy: Yeah, yeah definitely. It's something I use in my therapy practice a lot. Meagan: I was wondering if you did. Amy: I work with college students primarily so this is a lot of time for some of them that they are facing some of this but I love what you were saying Desiree about practicing ahead of time because that's what I'll say. They'll be like, “Oh my gosh. I had a panic attack. I practiced your breathing and it didn't work.” I was like, “Did you practice that ahead of time?” When you're in crisis, it's hard to do it then. But if you've practiced it before and cued your body to that place, that's where it is so useful. Ironically, it was something that I didn't use a ton during my labor process as far as intentional breathing practices. I think I wish I had because I think that would have been useful, but my doula would coach me about some forms of taking deep breaths and sort of how you are breathing through some of the surges and stuff. But yeah, I love that. I love the practice it before you are in labor because then it's easier to do while you're in labor. Meagan: Mhmm, absolutely. Such a powerful message. Okay, one more time, Desiree, tell everyone where they can find you. Desiree: Yeah. I'm on Instagram. You can find me at b_earth_mama pronounced “birth mama”. You can find me on my website which is www.b-earth-mama.com and that's primarily where I'm at. Meagan: Awesome. Well, go give her a follow everybody especially if you are in California and looking for a doula. And Amy, thank you from the bottom of my heart for joining us today and sharing your amazing stories. Amy: Awesome, thanks for having me. It was great. ClosingWould you like to be a guest on the podcast? Tell us about your experience at thevbaclink.com/share. For more information on all things VBAC including online and in-person VBAC classes, The VBAC Link blog, and Meagan's bio, head over to thevbaclink.com. Congratulations on starting your journey of learning and discovery with The VBAC Link.Support this podcast at — https://redcircle.com/the-vbac-link/donationsAdvertising Inquiries: https://redcircle.com/brands

Caylee joins us from Canada sharing her experience with two VBACs after a twin Cesarean birth. She also shares what it was like having cholestasis in all three pregnancies. Cholestasis is a liver condition that slows or stalls the flow of bile. Meagan and Caylee discuss in greater detail what cholestasis means during pregnancy, what symptoms can look like, and how it is diagnosed. One of Caylee's most intense symptoms was incessant itching. She talks about how it affected her not only physically but mentally as well. While all three of her pregnancies were preterm births and her two VBACs were medically necessary inductions, Caylee advocated throughout her entire labors and was able to stay the course to achieve the vaginal births she knew she was capable of. Cleveland Clinic Article: Cholestasis of PregnancyAmerican Journal of Obstetrics and Gynecology Article: Risk of Stillbirth in U.S. Patients with CholestasisHow to VBAC: The Ultimate Prep Course for ParentsFull Transcript under Episode Details Meagan: Hello, everybody. Welcome to the show. We have our friend, Caylee, with us and her little wee, tiny little newborn. Caylee: Hi everyone. Meagan: Oh my gosh. Welcome to the show. How old is your baby? Caylee: He just turned 3 months. He was born a month early though. Meagan: Okay, 3 months and a month early. We are going to talk about why he was born a month early. You guys, today we are going to be sharing some stores and talking a little bit about cholestasis. This is something that we actually don't have a lot about on the show. When you were listening, Caylee, did you? Caylee: I don't think I've heard a single episode, yeah. Meagan: Did you hear about it in general on other platforms? Was it talked about?Caylee: Not really, no. I found it online on Facebook. I'm in the ICP Care Facebook group and that's super helpful. They are amazing in there and super knowledgeable, but yeah. It's not very common. It's quite rare. I think it's 1 in 1000 women who end up getting it. Meagan: Yeah. Caylee: So yeah. It's not very well known about and even with providers, providers don't know about it very well either. Meagan: Yeah. I think that can be part of the problem, right? Because we've got providers who don't know a lot about it and then it can cause a little bit of a panic and then a lot of the times, it can cause Cesareans or lead, I should say, to Cesarean. We're going to be talking about that today and sharing her stories. Review of the WeekMeagan: But I do have a Review of the Week so I'm going to get into that and then turn the time over to cute Caylee. This is from Cori and it doesn't say where it's from. Somewhere in the universe, it is from. It says, “The VBAC Link is gold.” It says, “Of all of the things I did to prepare in pursuing for a VBAC after two C-sections, I think is one of the most important is that I was listening to this podcast. Hearing these stories and information from Meagan and Julie made the dive into learning about VBAC and birth in general so much easier. I was blessed with my VBA2C” so VBAC after two C-sections “with my sweet Brynne Lynn and I sincerely believe I wouldn't have gotten to that point without this resource and the community. Thank you guys for all that you do.” Oh, that just makes me smile so much because this community– oh my gosh. I mean, Caylee and I were kind of just talking about this. Yes, Julie and I are here, but there is this community, this absolutely incredible community and all of the people coming forth to share their stories. And Caylee, you just said it yourself when you were like,  it's like all of these people who came and shared these stories impacted you. Caylee: Yeah, totally. Meagan: Yeah, they are the reason. You are the reason right here. Caylee, you are the reason why what Cori said in this review is possible by sharing your stories, by coming in the community on Facebook and on Instagram and having these conversations and learning and also being vulnerable. There are so many times where I see posts where it's the most vulnerable, genuine post and I can't explain to you the outpouring of love that I see come in for this person from this community. The VBAC Link Community, just the VBAC community in general, oh my gosh. You are all amazing. Thank you so much and yes, if you want to join that community, check us out on Facebook at The VBAC Link Community. It is a private group. You do have to answer the questions to get in so just keep that in mind. If you are not answering questions, you might not be allowed in. And on Instagram, and of course, if you want to have a review that I could share for the Review of the Week, please do so. We would love that.  Symptoms of Cholestasis Meagan: Okay, Caylee. Are you ready? I'm so ready. Caylee: I am ready, yes. Meagan: Awesome, I would love to turn over the time. Caylee: I don't know where to start. Should we start by talking a little bit about cholestasis so that they understand the risks? Meagan: Yeah, I think that– well yeah, the risks, the symptoms, and then also how it can be missed and then how it can sometimes– well it kind of goes with the risk, but there are other things that can come in I should say from cholestasis and I actually even had a client myself, a VBAC client after two C-sections. She had cholestasis, preeclampsia, VBAC after two Cesareans, and was induced. Caylee: Wow, good for her. Meagan: Yeah, but preeclampsia, right? Okay, let's talk about the things. So what are the symptoms that you one, may be experiencing, and two, that there may be that someone might not experience? Caylee: Yeah, so for me, it was intense itching mainly on the bottom of my feet and on the palm of my hands but I had it everywhere. I have scars on my ankles, up my arms, on my belly just from scratching. Meagan: From scratching? Caylee: Yes, incessantly. It's an itch that you can't really scratch. It's in your blood that is making you so itchy so you can scratch all you want and it's temporary relief but as soon as you stop, it's like, oh. I broke down in tears so many times and had ice packs on my feet and on my hands while I was trying to sleep. Another symptom is darker urine output and some upper right quadrant pain. Meagan: Yes. Yeah. Caylee: Those are very common and some people also experience jaundice. Meagan: I was going to say yellowing, jaundice. Decreased appetite. Caylee: Yeah. You're more likely to get preeclampsia and gestational diabetes. Yeah. Meagan: Mhmm, yeah. So nausea, feeling unwell, dark urine, lack of urine output which a lot of the time, dark urine is the beginning of that. Your kidneys are warning you and then you stop. Yeah. I had a client, not the one I was telling you about, but another client. She said that her bowels like her poop smelled really weird, like abnormal. Caylee: Yeah, I've heard that before too. Meagan: Yeah. That's the first time when she was like– that was actually one of her first symptoms that she noticed. Thinking back, she was like, “Yeah, I guess I was kind of itchy, but I wasn't itchy-itchy until later.” But that was one of the things where she was like, “I just thought I ate something weird.” Caylee: Yeah. Meagan: A decreased appetite. Pain in your belly and your quadrants, jaundice, and of course, itching. Those are the main signs. Caylee: Itching. And the severity of the itching can vary greatly between cases so the first time, it was quite mild and then it progressively got worse throughout my pregnancies. That's different for everyone who experiences that so if you have any itching, you should ask for LST's and bile acid tests from your provider. Itching can also precede the bile acids rising and the elevated bile acids is what's dangerous for the baby. It increases the risks in the baby where they might pass meconium before birth and also stillbirth risk goes up a lot if the bile acids are above 40. Meagan: Too high, yeah. So when you are pregnant, if you are having symptoms, definitely go in and get checked like she said. Get these tests. Then if you have cholestasis, if you test positive and things are looking like you have it, it is something that may increase extra testing and extra visits because you do want to keep a close eye on this. Again, like she said in the beginning, it's really rare. Even right here, it shows on this link that I'm going to put in the show notes, it's from the Cleveland Clinic, but it shows 1-2 in 1000 people during pregnancy will experience this. It's pretty low, but it can be a serious thing. Also, I was going to ask you because I know my clients have in the past. They've been given some things to try and control, to minimize, to control, to lower things to try and continue pregnancy to a good, safe term stage. Were you given anything like that? Caylee: Yeah. I was put on a medication called Ursodiol. It helps lower bile acids to make it a little bit safer for the baby so you can continue. With my last pregnancy, they were very severe levels. They were over 100 so it was kind of touch and go there whether we could get him to 36 weeks or not. They were talking about inducing me at 34 weeks. We ended up opting for non-stress tests and biophysical profile ultrasounds just to keep an eye on him. Meagan: And he did well? Caylee: He was doing well. He had already passed meconium sometime before I was induced though at 36 weeks. It was time for him to come out. He was already in distress so it was good that we did end up taking him out at 36 weeks, but he did great. Really great. Meagan: Good. Good. That's another thing I would like to drop in and note that if you do have cholestasis, it may be something that brings you to something like an induction that is earlier than expected. Obviously here, we're going to share this story in just a second about VBAC and induction. It's possible and totally doable, but that is a thing. Cause of CholestasisMeagan: She's mentioning bile. It is in the liver, right? Am I correct? It's in the liver. Caylee: Yeah. Meagan: We don't really know why. I don't know why. Do we know exactly why it happens?Caylee: They don't. They think it's something to do with pregnancy hormones and the placenta, but they don't know for sure. It's some sort of genetic factor as well, but no woman in my family who I know has had it. So I think it's just something that can happen sometimes. Meagan: Yeah. I have heard the hormones like estrogen and progesterone can be too much in the body. So just to circle back around again, if you have had any of these symptoms or if you are having any of these symptoms, it's okay. Don't hesitate and go in and get checked out. Caylee: And if you go in and get a negative result and still have symptoms, ask your provider to keep testing you. Meagan: Yes. Go back and check again. Okay, so baby number one? First pregnancy: TwinsCaylee: Twins. Meagan: Twins! Caylee: Baby one and two, my first pregnancy. Meagan: So twins. You had symptoms? Caylee: I did, yes. I got it pretty early on and they tested me and it was negative. They just put me on Ursodiol before anything came back positive. They didn't do anymore testing or anything. I didn't have any itching. The medication must have made it go away somewhat. Yeah. I was only 21 when I was pregnant with the twins so I was pretty young. I didn't know much of anything. I knew I wanted a vaginal birth. I had actually switched providers in my third trimester to somebody who was comfortable with vaginal birth with twins and they ended up being breech when they decided they needed to take them out. Preterm Cesarean at 36 weeks due to breech presentation and IUGRIt wasn't due to cholestasis, but I did have them at 36 weeks because one of the twins had stopped growing so they took them out. Meagan: IUGR? Caylee: Yeah. Yeah. He was quite significantly smaller than his brother. Meagan: Okay. That can happen with twins too, I know. Caylee: Yeah, totally. Yeah. My twin A was 6 pounds, 7 ounces, and twin B was 4 pounds, 4 so it was quite a big difference. Meagan: Mhmm. Caylee: Yeah, so it was a C-section with them. We were in the NICU for two weeks. Second pregnancyCaylee: I ended up getting pregnant again when the twins were 16 or 17 months old. I knew I did not want to do that again, having a C-section so I found supportive midwives and got on with them. Unfortunately, I don't know if it's in Canada, but they don't allow home birth for your first VBAC for some reason. Maybe it was just those midwives, I don't know, but I really wanted a home birth and they were like, “No, let's do hospital. It's safer.” I was like, “Okay, as long as I can still have my VBAC. I'll just do that.” The pregnancy went well. I thought I wasn't going to get it again. No itching, then I hit 34 weeks and the dreaded itching started again. I kind of had a feeling that I had it during my first pregnancy too from my own research. I had mentioned it to my midwives beforehand so we were looking for it seeing if it would happen. They sent me for testing right away at 34 weeks. It came back negative so they ended up testing me again weekly and then at 36 weeks, they tested me and my liver function tests were very high. My liver was basically failing and they didn't even wait for the bile acids to come back. They just brought me in for an induction. Meagan: What week again? Caylee: I was 36 weeks and 2 days when they started my induction.Meagan: Okay, so technically preterm. Caylee: Yes, yes. InductionCaylee: When I went in, they started with a Foley balloon to help dilate my cervix and that was awful. It's like a torture device, I swear. But it was effective I guess. It dilated me and then it fell out and I don't know if they didn't have a nurse for me or something, but I was waiting 8 hours for them to continue my induction. The OB came in and he wanted to break my water. I said, “No. Let's start low Pitocin.” He was like, “Well, it's not really going to do anything if you're not going to break your water too.” I said, “Okay, let's see how it goes.” Meagan: Yes. Caylee: We did that. Labor was going smoothly. I loved being in the shower. It was amazing. Then they made me get out because his heart rate was dipping really high so they wanted to get me out and be able to monitor him a little bit better. That's when things got really intense and I felt like I wasn't able to cope as well after I got out of the shower. I think in the back of my mind, I was still pretty young with him too for my first VBAC. I was only 24 and I know that uterine rupture risk is very low, but for some reason, I just couldn't get that out of my mind and every contraction I'd have, I'd just feel like I was being ripped open and was so scared that I was having a uterine rupture. I ended up– it was 32 hours into my induction and I still was at 4 centimeters just because I wasn't letting my body relax and do the work. I was tensing and fighting every contractions because I was terrified. I ended up getting an epidural at 1:00 AM and 5 hours later, I woke up and was fully dilated and pushed for 15 minutes and he came out. Meagan: 15?! 1-5? Caylee: Yeah, 1-5. Meagan: Oh my goodness. Caylee: As he was coming out, I pulled him up to my chest and it was just this amazing feeling like, Oh my god, I did it. The high that comes with that is unbelievable. Meagan: Yeah. Caylee: I just kept looking at everyone saying, “I did it. I did it.” Meagan: Absolutely. Caylee: It's an amazing feeling. Meagan: It really is. Caylee: I fought with the OB who was on call a little bit, the one who wanted to break my water. He kept saying, “Does she want to do this? Let's just go for a C-section.” I'm like, “Yeah, I can do this all night long and he can stay out of my room until I'm pushing. My midwives have got this, thanks.”Unfortunately, because I had to be induced, I had to be overseen by an OB so my midwife ran the show and was able to be with me and do everything, but he had to be there in case anything went wrong I guess. Meagan: That's kind of normal. A lot of the times, when there is a hospital midwife, there are OBs who oversee them. Caylee: Yeah. Yeah. So yeah, that was my first VBAC, first induced VBAC. Second Induced VBACCaylee: I just recently had another induced VBAC. With this one, my levels went up high. I think it was 28 weeks that I tested positive so it was sooner. Meagan: Significantly sooner. Caylee: Yeah. They went from 0 to 100 within a matter of days. They put me on Ursodiol immediately as soon as it came back positive. I was being monitored weekly with NSTs, non-stress tests, and they were sending me for biophysical profiles as well weekly which is an ultrasound to check on the baby's well-being. He was doing well so they just were keeping going with that and unfortunately, the Ursodiol did not help my itching this time around. It was so severe. I was in tears pretty much daily from the severity of the itching. Yeah. It was really bad this time. The mental health aspect of having that incessant itching I don't think is talked about a lot either. It really gets to you. It's depressing. Meagan: Oh, I would not do well with that. I would find myself getting very anxious probably and out of control. Caylee: Even now, if I get an itch, I get PTSD. It's like, Oh my god. It's not going to stop. I freak myself out and work myself up. I remember that after my second pregnancy as well. It was like I'd get a bug bite and I'd just have to itch and itch and itch until it was bleeding. Oh, it was just bad. I don't know how to leave itching alone now. His levels were very severe, or my levels I guess. My liver function tests were some of the worst that my OB had ever seen. Meagan: Interesting. Caylee: So yeah, it was just really bad. Caylee: I had actually applied for midwives. We had just moved from Alberta for BC pretty much as soon as we found out we were pregnant with Henley here. I applied pretty much as soon as I found out I was pregnant for the midwives here. I ended up hearing back from the midwives in Edmonton which is an hour and a half away that they could see me up there but once I got the itching and cholestasis, I was like, “Just transfer me to an OB where I live. It's just easier for me then all of my appointments will be out here and I don't have to drive 1.5-2 hours to appointments in the middle of winter.” Yeah, so they scheduled my induction for exactly 36 weeks because of the high levels. They didn't want me going past that because with levels over 100 bile acids, the stillbirth risk goes up very high after 37 weeks. Meagan: Did they give you a percentage or anything like that? Caylee: Yeah, I think it's upwards of 15% with very severe levels. Meagan: Oh wow. Caylee: If levels stay under 40, your risk of stillbirth is around the same as anyone else's. They go up 3% over 40 and over 100, it's even more. So it was a bit touch and go there. They were talking about inducing at 34 weeks and we were able to get to 36. Still preterm, but a higher likelihood that he wouldn't need additional support. InductionCaylee: I was induced at exactly 36 weeks. I actually had influenza B when I had to be induced. Meagan: That's miserable. Caylee: As if labor isn't hard enough alone, I had to have influenza B. It was great. Meagan: Miserable. Yes. Caylee: Yeah, one perk though was that we got a private room right away. I didn't have to labor in triage until I was far enough along to get my delivery room or whatever. They put me right in there. I was able to get set up and feel like it was my space and get more comfortable. So yeah, they started with the Foley balloon again to open the cervix. They can't do Cervadil or a few of the other cervical ripening– Meagan: Cytotec. Caylee: Yeah, because it really does increase the risk of uterine rupture with induction, but the Foley balloon is a safer option and it works. Within an hour and a half this time, my cervix was 4 centimeters. Meagan: Wow. Caylee: From barely a 1. It was kind of funny. I was standing there talking to my husband and I took a step toward the bathroom and it just flopped out and there was this line of blood up and down the floor. It was like a total bloody show. Meagan: Mucus. Caylee: In a perfect line. Meagan: Oh my gosh. Caylee: Because they attach the tube to your leg. They tape it to your leg so when it falls out, it makes a long, smooth line. My husband pulled the nurse call button and she's laughing. She ended up cleaning me up. Things picked up pretty quickly from there this time. I felt it was much more manageable though. I don't know if the nurses were nicer this time and they were doing the Pitocin a bit slower because I remember with my first VBAC, the contractions just felt back to back like I wasn't getting a break at all and it was really mentally wearing me out after 32 hours. I hadn't slept. I ended up getting the epidural but this time, it felt like more of a natural progression. I don't know. I've never had natural labor, but for me, I was able to handle it a lot better. Maybe that's because I knew what to expect this time so it wasn't as scary. Meagan: It could be. Caylee: Yeah, I don't know. Or I've heard too that with cholestasis that the bile acids or something make Pitocin more effective so maybe I didn't need as much of it this time because my levels were higher. I don't know but it was much more peaceful this time and I knew what to expect even though I was sick. I labored in the shower for a little bit with the mobile monitor because with inductions, they want to be able to monitor the baby constantly which I know is talked about a lot on here as something that is not ideal. Meagan: Yeah. Even if no induction with VBAC, it's really, really common if not 100% that your hospital is going to want that monitoring. Caylee: Yeah. And having that mobile monitor though is so helpful if your hospital has one of those. Definitely ask because oh my gosh, it's so nice to be able to get up and walk around and move and shower. Unfortunately, because of the flu, we were battling a fever. I had a fever so as soon as my Tylenol would wear off, my fever would spike and then his heart rate would go up. I had an anterior placenta so it was kind of in the way of the monitoring and it was hard to get him constantly so they ended up wanting to do the electrode. Meagan: The IUPC and the FSC? Caylee: Yeah, I think so. It's the one that they put on the scalp. Meagan: Okay, that's an FSC, fetal scalp electrode. Caylee: Yeah, that unfortunately didn't work very well. I was bed-bound but I was so sick that I didn't even really care. I was just switching sides laboring through, using the gas. I loved the gas this time.Yeah. I ended up getting to an 8, 8 centimeters and the OB unfortunately was not the OB who I had through my pregnancy. She had gone on vacation for my induction, unfortunately. I was really sad about that, but the OB on call came in and he was like, “You know, this is taking pretty long. I think it's time that we start thinking about a C-section. I'm getting worried about your scar.” I'm like, “I've done this before and it took longer last time. I am not having a C-section.” Meagan: Good for you. Caylee: I don't think he really liked that though because he was like, “Well, then you're getting an epidural because at least if you have the epidural and something happens, we can rush you in and open you up faster,” and blah, blah, blah. I'm like, “It has to be at least 24 hours and it's only been maybe 12 hours of hard, active labor here. My C-section scar is strong. It's been over 7 years since my first C-section. We are both doing well. Yes, I'm sick. Yes, his heart rate keeps going up when we have a fever but when the Tylenol kicks in, his heart is going back down and his tracing is normal. Why would I have a C-section?” Meagan: The fact that you're having a fever is more likely to the fact that you are sick versus that you have an infection.Caylee: Yeah, exactly. They tested me when I got there and they knew that I had influenza B and I tested for Group B strep so I was just having to fight with another OB again which is really frustrating, but yeah. He ended up leaving the room and my doula and my nurse were both like, “Wow, you're amazing. I'm actually so impressed with you saying no to him.” I guess a lot of people just go with what the doctor says. Meagan: Well, I guess. Caylee: That is why there are so many unneeded C-sections. Meagan: Well, we've talked about it on the show where it's like, I didn't go to years and years of medical school, so okay, I guess. Same thing with me, I was like, Okay, and went down and had a C-section when I completely did not need a C-section. Caylee: You hope that doctors are saying that when it is actually medically necessary and not when it's convenient for them. I think he was getting like, It's been 24 hours. I'm almost off-shift. I don't know, but I was not having it. It was actually funny. When he texted me, he was like, Oh, you're 8 centimeters, but he's -2 position and not coming down. He was like, It's probably time to do a C-section. I was like, “No, it's not actually.” Meagan: Oh my gosh. He really wanted to do a C-section. Caylee: Yeah, so I was like, “No, I'm not having a C-section.” He ended up leaving the room and pretty much immediately, I had a super strong contraction. I jumped off the bed trying to get away from it because apparently, that can help. I kind of grabbed my nurse's shoulders, the poor thing. She is this tiny, little 20-something nurse. I grabbed her shoulders and my body was pushing. I was farting and things were moving down there. Meagan: I bet that baby was coming down quickly too. Caylee: Yeah, that quick movement. Popping up just brought him down and she was like, “Are you pushing?” My doula was like, “Well, that's a good sign.” I was like, “I don't think so.” But my body was just doing it and then I barely made it back on the bed before his head was out. Meagan: Oh my gosh. So was the provider even in there? Caylee: No. Nope, he was just leaving the room telling me that I needed a C-section because I wasn't progressing. Meagan: I know that he had left but I didn't know if she was beeping him back in like, “Come back in!”Caylee: I guess he was down the hallway at that point and his head was out. I made it back onto the bed thankfully. My nurse was down there taking the fetal electrode out of his scalp panicking a little bit being a nurse. She was like, “You need to keep pushing.” I'm like thinking in my mind, No, I need to rest for a second. His head's out. He's fine. I knew in my soul that he was okay. I took half of a second to rest and then my body was pushing again and he was out. Meagan: Oh my gosh. Caylee: He had the umbilical cord wrapped around his neck and his armpit. I thought that maybe was why he wasn't coming down. Meagan: It could be. Caylee: Maybe he was tangled up in there a little bit and couldn't come down fully but maybe that quick movement that I did to pop out of bed was just enough to let him come down. It was so quick. I was looking around. My doula ended up riding out into the hallway to call my OB back and my nurse was frantic. She was like, “This was my first baby I caught!”Meagan: Aw, and it was a VBAC. Caylee: Yeah, yeah. I'm looking around the room like, “Whoa. What just happened?” I went from 5 minutes ago being told it was time for a C-section to my baby on my chest. Meagan: Yes. Oh, that is amazing. You know, maybe that person needed to leave to also relieve some stress so baby could come down. That's another thought I had. Caylee: Yeah, I think that was it and maybe my baby was like, Yeah, we're not going for surgery, mom. Let's show this OB what's up. Meagan: Yeah, seriously. It reminds me– is it the tiger or the lion? I can't remember the thing, but when you are being chased or when you are in a hostile environment, you either tense up or you run or whatever. We've got all of these senses and you could have been like, Nope. I am not having this baby with you in this room. I've had enough of your C-section talk. So cool. So after, with all of the babies, but especially with this one because your levels were so bad, were there any complications? Caylee: I guess I did touch on this a little bit before. I forgot though during my birth story there, when they broke my water, because I did allow it earlier this time because I felt with my first VBAC that that actually helped speed things up a little bit. I did allow them to break my water and start Pitocin at the same time this time. When they broke my water, it was full of meconium. They weren't too worried about it. Thankfully, that OB seemed pretty C-section happy and he was still like, “Oh, no big deal. We'll just monitor him. It's okay. There is a risk there for aspiration, but it's not a total risk that that will happen.” So they were just monitoring that. When he came out, he was fine for being 36 weeks. He was breathing good. They wiped his face because there was the meconium on his face, but no. He was great. It was more me that I was worried. I was like, “Is he okay?” They were like, “He's fine.” Meagan: Good. That's so good to know. I was just curious because he was early, high levels, induction, fevers, all the things so that's so good to hear that he was really great. Caylee: Mhmm, yeah. Even my twins were 36 weeks, 2 days when I had my C-section. They were in the NICU for 2 weeks and that was just for feeding and growing. They didn't know how to suck and then with my now 5-year-old, he was totally healthy when he came out too. He was 36+4 at the time he was born because my induction took so long with him, but yeah. He was healthy. He did have jaundice quite badly though so he needed the bilirubin lights and then with my baby now, he also had jaundice but he was able to stay off of the lights. He was just under that level for needing phototherapy. That's pretty common with early babies anyway. I don't know if that had anything to do with cholestasis in general or if that was just them being early that it was more likely to happen.Meagan: Yeah, that makes sense. Oh, well thank you so much for sharing your story and talking more about cholestasis with us. Like you said, there is not a lot out there. It is not very common so it makes sense that it is not talked about that often. However, uterine rupture isn't very common but it is talked about all the time. Caylee: Yeah. Meagan: So you know, but it's good. It's good to be aware. It's good to understand the symptoms and what's going on and why so I'm so grateful that you shared your stories. I'm so grateful that everyone is healthy and happy and wonderful and you are smiling and have some good birth experiences and maybe some healing birth experiences. Caylee: Yeah, totally. Meagan: You showed yourself that you could stand up to pressuring doctors. Caylee: Yes. I honestly thank my doula for being there for my last birth because I don't know if I would have had the confidence to be that firm with such a pushy, “this is what's going to happen” doctor. We had talked about it previously that she can't say anything for me but that she will be there to support and give me the power to advocate for myself. I totally felt that power from her. She was amazing. I'd like to shout her out to Little Loves Doula in Red Deer. She was amazing. Stephanie, she's great. If anyone is in Red Deer, Alberta, definitely contact Stephanie from Little Loves. Meagan: Well, you know that we love doulas here and always encourage checking out a doula. We do have VBAC Link-certified doulas. She's got her doula. Yeah. Caylee: I think she was also VBAC Link certified. Meagan: Was she or is she? Caylee: Yeah. Meagan: That's so awesome. You can check out The VBAC Link doulas at vbaclink.com/findadoula. Let me tell you, it's so fun to see all of the doulas in all of the different states. We are growing within the States. And if you have a doula in mind who is not on the VBAC list, send them the link. We would love to have them and have them support our VBAC clients and our VBAC community. Thank you so much again. Caylee: Thank you. ClosingWould you like to be a guest on the podcast? Tell us about your experience at thevbaclink.com/share. For more information on all things VBAC including online and in-person VBAC classes, The VBAC Link blog, and Meagan's bio, head over to thevbaclink.com. Congratulations on starting your journey of learning and discovery with The VBAC Link.Support this podcast at — https://redcircle.com/the-vbac-link/donationsAdvertising Inquiries: https://redcircle.com/brands

Matthew Kyle Levine is a filmmaker and cinematographer based in New York City. His short films have won awards and played at numerous film festivals throughout North America, including the Williamsburg Independent Film Festival and the Canada Shorts Film Festival, most notably for his short film “Miss Freelance”.Watch 'Caleb and Sarah" and other short films on Mathew Kyle Levine's Vimeo:MKL VimeoSRTN Website

Dr. Benoit Chabot from Université de Sherbrooke in Quebec, CA, discusses a research paper he co-authored that was published by Oncotarget in Volume 15, entitled, “The anticancer potential of the CLK kinases inhibitors 1C8 and GPS167 revealed by their impact on the epithelial-mesenchymal transition and the antiviral immune response.” DOI - https://doi.org/10.18632/oncotarget.28585 Correspondence to - Benoit Chabot - benoit.chabot@usherbrooke.ca Abstract The diheteroarylamide-based compound 1C8 and the aminothiazole carboxamide-related compound GPS167 inhibit the CLK kinases, and affect the proliferation of a broad range of cancer cell lines. A chemogenomic screen previously performed with GPS167 revealed that the depletion of components associated with mitotic spindle assembly altered sensitivity to GPS167. Here, a similar screen performed with 1C8 also established the impact of components involved in mitotic spindle assembly. Accordingly, transcriptome analyses of cells treated with 1C8 and GPS167 indicated that the expression and RNA splicing of transcripts encoding mitotic spindle assembly components were affected. The functional relevance of the microtubule connection was confirmed by showing that subtoxic concentrations of drugs affecting mitotic spindle assembly increased sensitivity to GPS167. 1C8 and GPS167 impacted the expression and splicing of transcripts in pathways relevant to tumor progression, including MYC targets and the epithelial mesenchymal transition (EMT). Finally, 1C8 and GPS167 altered the expression and alternative splicing of transcripts involved in the antiviral immune response. Consistent with this observation, depleting the double-stranded RNA sensor DHX33 suppressed GPS167-mediated cytotoxicity on HCT116 cells. Our study uncovered molecular mechanisms through which 1C8 and GPS167 affect cancer cell proliferation as well as processes critical for metastasis. Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28585 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, CLK kinases inhibitors, EMT, antiviral immune response, microtubules, metastasis About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY- May 20, 2024 – A new research paper was published in Oncotarget's Volume 15 on May 16, 2024, entitled, “The anticancer potential of the CLK kinases inhibitors 1C8 and GPS167 revealed by their impact on the epithelial-mesenchymal transition and the antiviral immune response.” The diheteroarylamide-based compound 1C8 and the aminothiazole carboxamide-related compound GPS167 inhibit the CLK kinases, and affect the proliferation of a broad range of cancer cell lines. A chemogenomic screen previously performed with GPS167 revealed that the depletion of components associated with mitotic spindle assembly altered sensitivity to GPS167. In this new study, researchers Lulzim Shkreta, Johanne Toutant, Aurélie Delannoy, David Durantel, Anna Salvetti, Sophie Ehresmann, Martin Sauvageau, Julien A. Delbrouck, Alice Gravel-Trudeau, Christian Comeau, Caroline Huard, Jasmin Coulombe-Huntington, Mike Tyers, David Grierson, Pierre-Luc Boudreault, and Benoit Chabot from Université de Sherbrooke, Université de Lyon, Institut de recherches cliniques de Montréal, Université de Montréal, and University of British Columbia a similar screen performed with 1C8 also established the impact of components involved in mitotic spindle assembly. “Accordingly, transcriptome analyses of cells treated with 1C8 and GPS167 indicated that the expression and RNA splicing of transcripts encoding mitotic spindle assembly components were affected.” The functional relevance of the microtubule connection was confirmed by showing that subtoxic concentrations of drugs affecting mitotic spindle assembly increased sensitivity to GPS167. 1C8 and GPS167 impacted the expression and splicing of transcripts in pathways relevant to tumor progression, including MYC targets and the epithelial mesenchymal transition (EMT). Finally, 1C8 and GPS167 altered the expression and alternative splicing of transcripts involved in the antiviral immune response. Consistent with this observation, depleting the double-stranded RNA sensor DHX33 suppressed GPS167-mediated cytotoxicity on HCT116 cells. “Our study uncovered molecular mechanisms through which 1C8 and GPS167 affect cancer cell proliferation as well as processes critical for metastasis." DOI - https://doi.org/10.18632/oncotarget.28585 Correspondence to - Benoit Chabot - benoit.chabot@usherbrooke.ca Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28585 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, CLK kinases inhibitors, EMT, antiviral immune response, microtubules, metastasis About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

We can hardly believe that we have recorded 300 episodes! Meagan brings Julie on the podcast today to take a look back at how The VBAC Link Podcast started, the growth they have both experienced along the way and where they are now. Since 2018, we have shared laughter, tears, heartache, and joy through your stories. Thank you to all of our listeners and guests for your support. Together, we are changing the birth world for the better through all of our ripple effects!Meagan promises to continue the journey and bring you more powerful stories. It's been quite the ride and we don't plan on stopping anytime soon!Needed WebsiteHow to VBAC: The Ultimate Prep Course for ParentsFull Transcript under Episode Details 01:11 Review of the Week04:05 How the podcast started12:09 How the podcast has grown 16:40 Changes in birth22:11 Celebrating differences within the birth community28:45 Challenges bring growth35:35 Julie's photographyMeagan: Hello, you guys. Today is a very, very exciting– for me at least and I'm sure for Julie– episode because it's the 300th episode. 300 and Julie is here with me because I couldn't share this exciting episode without her. Julie: I cannot believe it. I seriously cannot believe it. So wild. Meagan: It's so crazy. 300 episodes and we've had so many other crazy things like special episodes so it might even be more than 300, but it is the 300th on my form and I'm really, really excited. We want to share more about where we are today but also recap a little bit about where The VBAC Link started. I know we have a lot of listeners who have joined us in more recent years. We started in 2018. 2018, is that right? Julie: Yeah. Meagan: So we have a lot of new listeners who maybe don't know our full story and know what we are and what we're doing and all of the things. 01:11 Review of the WeekMeagan: So we are going to be talking about that, but we do have a Review of the Week. I'm going to share that. It is from Michelle. She listed this on Google and it says, “Thank you so much for inspiring and informing me through the journeys of VBAC mamas. As I prepare for my VBAC in October after a recent traumatic Cesarean, I feel empowered, motivated, and healed knowing that there are so many women who are out there preparing in the same way that I am. I recommend this podcast to all mamas.” Now, this was about a year ago so I'm assuming Michelle has had her baby. So Michelle, if you are still with us, let us know how it went and as always, if you wouldn't mind leaving us a review, it helps all of these other Women of Strength find these amazing stories and information as well as our blog and all of the wonderful things I believe that we provide. You can do that on Google. You can do it on Apple Podcasts. You can even send us a message or on Spotify. I mean, really wherever you are listening should have a ranking– Google, Apple, or wherever you are, we would love your review. 04:05 How the podcast startedMeagan: Okay, Julie. 300. Julie: 300. I can't believe it. Do you know what is wild? It's so funny because I left. I'm using air quotes right now. I know people can't see it. I “left”. It's been 2 years. 3 years, oh my gosh. 3. I left in 2021. Meagan: It has. 2021. You did. Julie: My gosh. Isn't that wild? When is this episode airing? Meagan: May. Julie: May, so it will almost be 3 years. It's really funny because life is definitely much easier now and more manageable, but there are parts of me that still feel very strongly connected to The VBAC Link. I appreciate you for including me and having me back on the podcast and things like that but it's also sometimes so weird when I'm scrolling through Facebook and I see The VBAC Link recommended, sometimes people talk about Meagan and Julie still which is so cool, but also it's sometimes like Meagan Heaton has The VBAC Link and it's really amazing and she does a great job. I'm like, “Aww,” but also, it's weird. It's this weird little thing because I still believe that I made the right decision. My life has a much better balance and everything I needed it to be by letting go of The VBAC Link. It's right there where it needs to be, but there's also part of me that is just kind of like, “Man, that was a big part of my life for so long,” and it still feels weird not being in it. Meagan: I'm sure, absolutely. I miss you. I love you. Julie: I miss you too. Meagan: I'm so glad that you come on and join me here and there or take random phone calls when I call you to vent or something. Yeah, you guys. It's kind of crazy to think that it's 2024. It's even more crazy to me to think that I've been solo for that long. Yeah. Just thinking back in 2018, I still will never forget the moment that I saw Julie Francom pop up on my phone out of nowhere, out of absolutely nowhere. We knew each other. We knew we were VBAC passionate. We were doulas. I would say we were kind of really kicking off into the prime doula stages of our careers and it was just so crazy. My personality is sometimes where if someone is calling that I don't really know this person super, super well, I'll let it go to voicemail and see what they say. Julie: You're like, “Why is this weirdo calling me?” Meagan: You're not a weirdo, but we weren't the absolute tightest doula friends in the community. We just really knew each other and respected each other through going to ICAN meetings and things like that. I so easily could have not answered. I always wonder if I didn't answer what would have happened. Would you have texted me and said, “Hey, call me?” Julie: Probably. Meagan: Would you have called me right back? Would you have just said, “She didn't answer.” I don't know. Julie: No, it had to be you, my friend. It had to be you. Meagan: I'm so grateful that it happened. You and I personally have grown so much over the years. We also have grown a lot as a partnership. We decided to start this company and it was exciting and if I'm going to be honest, I'm going to say that Julie had more positivity or ambition behind her. I was feeling it. I could feel it inside of me. I was like, “Yes. This is amazing and I want to do this. I really want to be part of this,” but I was reluctant a little bit more. She was like, “Let's do this. Let's do this. Let's do this.” I was like, “Oh, my gosh.” Do you remember the day when you called me? You were like, “So, we're going to start a podcast and it's going to be super easy and I'm going to edit it.” Do you remember that day?Julie: Yes. I remember. I was in Target. I was walking around in Target. Meagan: I remember where I was. I was in my laundry room. Julie: I was like, “Oh my gosh. We should start a podcast.” I was super confident. In my past life, I worked a lot in the tech field. I had edited a lot of videos and audio and things like that before when I was in the military so I knew the technical side of it would be simple. I thought it would be easy. It's very simple for me. I knew that we had a lot to say. We've never not had a lot to say. I knew that the– I don't know what the right word is– whole sphere of audio was growing rapidly, like the digestible content of podcasts was a fast-growing entity or whatever. It just seemed like the right thing to do. It just seemed like the right thing to do. I remember I was like, “Oh my gosh. How am I going to convince Meagan to do this?” We were already so busy writing our course and our manual with our doula contents. I think you had 12 births coming up in October that year because you were putting your husband through law school. I was just like, “I don't know how I'm going to talk Meagan into this.” I feel like you were reluctant but you for some reason just had this hint of, “Okay, let's just see. Let's let Julie do this. I'll get on the phone and talk about it.” Then I was like, “Okay. We'll do this.” I signed up for a free Podbean account and we did a free conference call on our phones and recorded our phone calls. It didn't cost anything at first and things are very different now, but it didn't cost anything at first. I was like, “See?”Meagan: “This is great.” I remember some of the days, I was like, “Okay, sure. I'll jump on and do a podcast, but I'm driving to a prenatal right now. I literally have 35 minutes because my client is 38 minutes away.” We were recording and I remember back in the day when I was in my husband's car and his trunk sensor was bad and it was dinging, so oh my gosh. If you guys have listened back to those episodes, wow. Thank you for sticking with us. Julie: At the very beginning. Well, we used to take turns hosting like we would just do one at a time. I remember the first OB that we had on our episode. It was in the teens. I was out in my car in my garage in the middle of summer because my kids were inside. It was the middle of the day and it was the only time they could do it. I remember hiding in my closet so that the clothes would absorb the sound of the audio echoing around so it was better acoustics on our free conference call. Meagan: Oh my gosh, yeah. I remember sometimes when I was in the closet literally under the clothes and Jess, she was one of our clients from Russia and I was in the closet for that one. In the husbands' episode, I was in the closet on that one. It's just so crazy. We've come so far. Yeah. We had a whole bunch of people who were like, “I want to share my story. I want to share my story.” 12:09 How the podcast has grown Meagan: We were realizing that this is a serious need. Julie: We had to hunt people down at first. Meagan: Yeah, we did. Julie: We would message people at first. Kelsey, what's her name? Is it Likowski? Kelsey, super cute. She was Episode 8 or something. We were like, “Oh my gosh. She has 10,000 Instagram followers and she's so cute and she wants to talk to us.” Meagan: I know. That was so weird to us. We went to this little marketing conference thing and we were watching our Instagram account grow and we were watching our podcast grow. We started getting people like, “Hey, I heard,” and we were like, “Whoa, this is insane.” It was so exciting and so motivating and we really, truly realized that this was such a need. Let me tell you, our heart was there. Our hearts were there so we were so excited to dive in. So we did. We started sharing stories. We tried to get different content-type stories and different types of births. We tried to get OBs. I remember I reached out to this OB and they randomly responded. I was like, “Oh my gosh, this is insane.” We really tried to get the most we could while still doing birth and writing manuals for our VBAC course and– Julie: And wives. And being moms and wives. Meagan: And being moms and wives and friends and humans who were ourselves. Julie: Too much. Meagan: It's so crazy to look back and think about that time and where we were and all that's happened. It's kind of crazy to also think about birth and how we have seen it change and how personally, I think I've even seen it change in some good ways and in some bad ways. We talked about this a little bit before we started recording, but COVID. COVID was a really, really difficult time as moms giving birth, as doulas supporting birth, even as podcasters weirdly enough. We had this entire– we went from this really junky set up all over to having an editor and having a podcast studio and in this really amazing space which– shoutout to our favorite editor. I just have to say that he is amazing for all that he has done for us over the years. But we had all these things that were really helping us and really changed our lives for the better as far as podcasters goes and VBAC Link facilitators or whatever. It all changed. It all changed so fast. Julie: Yep. We had to go back to recording at home. We had to– oh my gosh, getting into hospitals was just nuts and wild. Meagan: A nightmare. Julie: There were so many clients of ours having to switch plans and a lot of people shifted to out-of-hospital birth because the hospital policies were so flip-floppy and so strict. They were limiting who could be in your birth space. I actually think that's a really positive shift. That's just me. Meagan: Yeah, no. I actually agree. Julie: Out-of-hospital birth is still growing. I think it's super cool. At least in Utah, it is. I'm not sure of the numbers in any other state, but I know in Utah, it used to be that 1-2% of births were out-of-hospital, but now as of 2024, so far, just under 5% of births in Utah are happening out-of-hospital which is super cool. But not enough. Meagan: It is super cool. Yeah, I would agree that through COVID, that was one of the positive shifts of helping people see the different options. Julie: Forcing people to really, seriously look hard at them. Meagan: Yes, and then also seeing that those options actually are pretty dang safe. But yeah, so COVID. We've had even so many people on the podcast sharing their stories through COVID. Man, it was rough. We were seeing induction taking off because they could control who had COVID and who didn't. 16:40 Changes in birthMeagan: Then we also went through the ARRIVE trial just before that. Julie: Oh jeez, yeah. Meagan: So there was all of that we saw making changes. You know, birth is constantly changing and evolving and growing. It's pretty cool, I feel like, to say. I've been in the birth world for 10 years now as a doula. It's pretty cool to say that I've been there. I'm here. I don't know how to say that. I just feel like it's really cool to be a part of this community and to see these changes. I've talked to some people who did birth back in the 80's and the 90s and it's kind of crazy to think about how it's changed. I want to go back and listen to some of those earlier podcasts and see, has birth changed? Are we changing and what can we do to make birth change in a positive way? I think this podcast honestly is one of those ways to help people change their birth experience in a positive way by going in and listening to what is happening. What is happening? What to expect? How to avoid those things? Right? Don't you think, Julie, that this is a really great place for all moms and all people preparing for birth to come?Julie: Well, and here's the thing. We all have a threshold for what is and is not acceptable to us. Going back to talking about COVID a little bit. COVID and the things that were happening due to COVID didn't sit right with some people and caused them to question and explore other options. Hearing The VBAC Link Podcast creates realizations for people that could cause them to question the things that they are presented within their own personal life as far as giving birth goes and what their provider is saying and the policies of their hospitals and things like that. I think that is the way that ultimately birth in the United States will change and all over the world really is when people are faced with the things that cause them to feel uncomfortable about their current situation and explore other options and seek out those other things that will resolve whatever their intuition is telling them needs to change and shift. Here's the thing. We don't know what things will make us uncomfortable until we have all of the information available to us. You don't even have to have all of the information, but any information available. That's been the goal here. It's been really cool to see things shift and I mean, there's obviously not a study or research or anything on how much The VBAC Link Podcast is causing a shift or whatever, but I do know that we do hear these stories from people and I do know that it is creating a shift and a change in our birthing culture however small that might be.I just think it's really cool to hear people say that it was this thing that gave them the confidence to stand up to their provider or talk to their husband or their partner or look into other options. Meagan: Mhmm, it really is. It's just– I don't even know. I'm almost speechless to get those reviews or to get people saying those things when we are recording a story and they're like, “It's just so crazy to me that this is coming to full circle that I'm now sharing my story when all of these other Women of Strength's stories is literally what changed my life or my path or whatever.” I think I've said this before, here we are. We started this podcast randomly as you come up with this idea in Target and you're like, “I've got to convince this girl that we've got to do this,” and here we are when really in so many ways, it's you, Women of Strength, who are changing. Julie: Yeah. Meagan: You. So it's like, okay. Yes, it's us at The VBAC Link but then also where is the stat for all of them? All of the listeners and supporters? You guys, it's been a long time and to say thank you isn't enough. I don't know what to say. I feel emotional, but I don't know how to say thank you enough. Julie is laughing at me because I'm always the crier. Julie: I'm not laughing, well I am laughing. Meagan: I don't know how to say thank you enough to this community because it's been absolutely the craziest, sometimes most stressful but most amazing journey and I'm so excited that we can still be on it with you. Like I said, I know these listeners are the people. They are the people. They are the reason. So thank you for making this happen. 22:11 Celebrating differences within the birth communityMeagan: In the midst of meeting all of these incredible people who are sharing their stories, we have also met incredible people throughout our own community who are trying to do the same thing we are trying to do– educate, support, motivate, empower. I mean, all of these words. We have made some amazing connections with people within their own community and I'm just so grateful for that as well. Julie: I agree. I am really proud of all of the people who have chosen to start their own podcasts and their own VBAC education platforms too. There is a home birth after Cesarean podcast. I actually haven't been as good at keeping up with other VBAC podcasts or whatever, but there are people– and I don't know whether it's influenced by us or not but definitely coming after us, there have been other things popping up here and there. I love that and I'm so proud of those people for choosing to pursue their passions as well for VBAC in spaces like this. I think it takes a village. It takes a whole– I don't know, what's the saying? A rising tide lifts all boats. I don't know. It's something like that where the more people talk about VBAC, the more people are talking about VBAC, so yes. Let's bring more people into this space. There is room for everybody. There is room for all of us here to grow and educate and inspire and uplift. We might not always see things the same way and that's okay, right? It's okay if we don't see things the same way as everybody else as long as we are all trying our best to create a positive influence in the birth space. We are not the same as anybody else and nobody else is the same as us and that's cool. That's okay because if you don't resonate with us, there are other people who you can resonate with and vice versa. I think it's really important to say that we welcome everybody here and we want you. We don't have to be the only thing that you follow. Go follow all of the things. Meagan: Well, I love that you talked about that because back when we were going for our VBAC, for me, it was back in 2015/2016 when I had my son and the resources were more slim. Now we have all of these incredible resources and it makes me so dang happy because that is what this VBAC community needs– more info, more support, more people backing them up, more places or people to go and like you said, I mean, we would love to always be in your circle. We love this community so stinking much, but we also know that not everything we say or not everything we do resonates. I mean, it comes down to this podcast where we share CBAC stories and uterine rupture stories. We share stories that are out of the hospital and we've even had free birth stories on this podcast. Not everyone may agree with those types of birth or people advocating for that, right? It's not even that we are gung-ho about anything specific or not gung-ho about anything specific. It's that everyone has a space in this community because if we were to completely eliminate a uterine rupture story, no. I'm sorry, that's just a no for me. Julie: Yeah. Meagan: We want to share those stories and CBAC. The CBAC community is so precious to me and near and dear to my heart. Sometimes, that can be a really hard community to be in. I say that personally. I have been in that CBAC after my two C-sections. I wanted a vaginal birth. I had a Cesarean birth after a Cesarean. It wasn't what I wanted. I had healing to do. I had a lot to overcome, but I'm so glad that people come on this podcast and are willing to share those stories because our CBAC community deserves that. Like we were saying earlier, not every desired vaginal birth ends in a vaginal birth, so we have to learn through these stories. Like Julie said, everybody has a place here at The VBAC Link and yeah. We support everybody else as well. We love this community so much. Julie: Do you know what? Maybe I'm out of line to say this. Please, you can tell Brian to edit this out if you want, but I just think it's no surprise to anybody that our world can be pretty hateful right now. Even people doing the most good things can face criticism or cancel culture or the mob or the mafia– not the mafia, the wokeness, or whatever, all of the things. There are so many things coming at you no matter how pure your intentions are or whatever. I just remember one time a few years back, somebody was talking crap. This was my gosh, 4 years ago and they called us “wholesome-looking podcasters from Utah”. Do you remember that?Meagan: I don't remember that. Julie: I will never forget that phrase. Sorry, I'm laughing now. I'm crying. They said something like, “It's easy to want to trust wholesome-looking podcasters from Utah,” or something like that because it's fine. There's going to be people who don't love us and that's totally fine. But gosh, when you were saying that, I was like, “Are we wholesome-looking?” Meagan: Are we wholesome-looking? I don't know. Julie: I don't know. Meagan: I don't remember that. Julie: It's so funny. I'm sure there's a screenshot of it somewhere, Meagan. My gosh, I can't even. 28:45 Challenges bring growthJulie: I want to circle back to you talking before about the struggle. There has been so much struggle. There have been a lot of challenges. Challenges due to our own creation, challenges due to technical difficulties– do you remember the time I changed the URL of the podcast and the whole thing went down? It was the day that the podcast was supposed to go live and we were meeting with Lynn, our first business coach. Oh my gosh, there have been so many things. Meagan: She broke the podcast, you guys. Julie: I broke the podcast. Things where we have definitely butted heads before and had to do a lot of growth in our relationship. Meagan: Yep. I was going to say you and I. Julie: There have been other VBAC groups out there who railroad us completely. There have been other birth people in our local communities and otherwise who are not big fans of The VBAC Link and I think that– I don't want to get pulling a little bit into saying, sorry. I don't know what I'm trying to say here. No, I do know what I'm trying here. I'm trying to figure out how to say it the right way. There is opposition in all things, right? I feel like, oh my gosh. I'm going off on six different tangents right now. My therapist told me one time– it always comes back to my therapy. Meagan: I love it. Julie: When you want to strengthen a muscle, if you want stronger arms, you can't just sit there and be like, “Hey arms, get strong.” You have to put it under tension and stress. It's lifting the weights. It's under the tension and strain where that muscle grows. Such is life. Such are relationships. Such it is in business. It is everywhere. Things don't grow and become stronger in comfortable times. It's the strain and the tension and the struggle that ultimately causes that strength and that growth. I feel like there have been moments of really beautiful and incredible and empowering moments along this journey for The VBAC Link over the last 7 years now, but there have also been incredible moments of tension and struggle and strain. Meagan: Hardships. Julie: Yeah. Those moments really have the most growth. They are the most identity forming and I don't know. They are the things where it really solidified what we are doing. Sometimes, in the face of people who should be doing the same things as us and sometimes, it's from people who just for whatever reason, don't want to see other people succeed. It's come from a lot of other different places, but also going back to what you said before, I'm so grateful for the people who are still here, the people who support us, the people who love us, the people who are still here and challenge and question the things that might not be 100% true. Yeah. I don't know. I love all of that and I don't know. There is this quote I heard forever ago, probably decades ago because I am old now that said, “Don't compare your backstage footage to someone else's highlight reel.” I feel like sometimes it's really easy to see all of the beautiful things that The VBAC Link puts out and all of these other birth organizations and see the highlight reel and think that everything is sunshine and butterflies, but I know that for us and for everybody else too, everybody else that has any kind of online presence anywhere, there is so much struggle that can go on behind the scenes. Yeah, I just wanted to talk about that. Meagan: It's intimidating sometimes. It's intimidating. But this community, I feel like, offers something special and it truly is the most motivating thing for me where I do wake up and I'm like, “I can't wait to record more podcasts” or “I can't wait to go and see what people are asking in our Q&A's” or whatever. I love that you talked about a little bit how sometimes you are going to make decisions or you're going to do things and some people might not agree with you. I think that applies so much int his community because let me tell you what, when I decided to VBAC after two Cesareans out of the hospital, I had some haters. I had some haters. Julie: Yep. Meagan: Those haters and doubters, some of those were even in my own family. Julie: Sometimes it's the people who are supposed to love you the most, right? Meagan: And support you the most. Sometimes, they were people in my own circle, so it can be really hard when you're getting pressure from people who you love and respect or people who you idolize or whatever, right? But it's up to us to conquer, to have faith, to move forward, to grow, to adapt, and all of those things. I think that as we grow, more people in this community get to experience it. I mean, truly, the community grows through hardships and strengths and podcast-breaking and all of the things.Julie: And wholesome-looking.Meagan: In a wholesome-looking way apparently. Julie: I don't know if that's a compliment or not. Am I wholesome-looking? I guess that's good. We look wholesome. Meagan: We look whole. Julie: I want to look up the definition of that really fast. What is wholesome? What does it actually mean? Meagan: What does wholesome mean? Yeah, and is that supposed to be not a compliment?Julie: I think the intention was that they look good. They look legitimate, but–Meagan: They might not be because they represent some birth stories that we don't support or whatever. Julie: Whatever. “Conducive or suggestive of good health and physical well-being. Conducive to or promoting moral well-being.” Wholesome-looking. Meagan: Interesting. Julie: Hmm, I don't know. I could not not say that. Oh my gosh, I'm sorry. You can have Brian edit it out if you want. Meagan: No, no. You are good. Julie: You're the boss. Meagan: No, I love that. Now I'm going to think about myself being wholesome-looking. 35:35 Julie's photographyMeagan: Okay, we talked a little bit about where we've gone, where we've started, what we've gone through, and all of the things. Now, where are we at today? I just have to gloat a little bit about Julie. She is phenomenal, you guys. If you have not been in our email or if you haven't been on our social media, I definitely suggest you check it out and go follow her because she has taken a step back from The VBAC Link. We are so grateful that you come on here and there. You have taken a step back from doula work, but you are killing it in the photography world. Julie: Aw, it's the best. I love it so much. Meagan: You're doing so good. I'm so impressed. I just love seeing her photos on her Instagram and I love being able to chat with her and even connect more to the story. Sometimes, she will tell me the story that goes with the picture. I'm like, “Oh my gosh.” It's so amazing. I'm so happy for you. Do you want to talk a little bit about what you are doing now that you are not doing The VBAC Link?Julie: Oh my gosh, I have to tell you. I sent you these pictures. I think I texted you. There was this girl. She reached out to me 2 years ago and she was like, “My C-section baby just turned 1. I'm thinking about getting pregnant again.” She wanted to connect with me for doula work. At the time, I was doing doula-tog so I was doing both doula and birth photography. So we talked and we connected. Then I sent her a couple of different local resources to connect to, then a few months later, she reached out and she was pregnant. She was going to hire me for doula-tog then she had a miscarriage, then it was a little while that passed again. She reached out to me again later and she was pregnant again, but by this time, I had phased doula work out completely, so I had referred her to a local doula here that I absolutely love working with. Anyway, super long story short, she ended up hiring this other doula and me as a birth photographer and she switched from hospital birth to a home birth and I just attended this beautiful VBAC birth at home last week. It was so neat to have somebody come full circle and follow their whole journey. She called me and we talked on the phone forever 2 years ago when she was starting on her VBAC journey because she had found The VBAC Link.It was just really neat. I know more about her journey. It's hard sometimes as a birth photographer because I don't have an initial connection with people as much as I did when I was a doula. Sometimes, the first time I see people is when I walk into their birth space with my camera which is okay. I like it when it is a little more than that beforehand, but it was really neat. Her name was Emmy and I'm sure that one day she will share her story on the podcast because I want her to. It was just a beautiful birth. I got called at midnight. The baby was born at 3:45 in the morning and it was just a really beautiful story with really powerful, empowering photos for this girl. She got to 10 centimeters with her first baby and she pushed for 6 hours. She got the epidural when she was 4 centimeters. She got to pushing. She was flat on her back the whole time, a classic story. She didn't know. Anyway, it was a really beautiful and very empowering story. I got to document it and I just think that some of the imagery, I cannot wait for her to tell me that I can share these. She wants to see. I respect everybody's wishes. Some people want me to share everything. Some people don't me to share anything and I respect all of that. Anyway, it's just really cool and really neat. I love being able to document that. I tell people, “My gosh, just hire the birth photographer. These moments are fleeting. They change so fast. One of the biggest days of your life, you're not going to remember what your baby looked like, what their cry sounded like, and the joy on your face as you met them. Just invest. Do whatever you can to be able to invest if that's what you desired. Don't let finances get in the way.” I personally now offer several financing options I can implement and things like that because I know it's not super cheap, but I love being able to capture and preserve people's stories. I also do videos. Videos are my favorite. I love being able to see the motion and hear the sounds of those babies' first little noises. Oh my gosh, there was this cute little baby making fish faces an hour after it was born the other day. I could not believe it. It was amazing. These people wouldn't have that. Sure, there are cell phones and things like that you can take pictures on. There are some cell phone cameras that are really good quality now, but you're going to miss out on so many things because who is going to be taking the picture on your cell phone? Your partner? Your doula? You're not going to be able to see how your doula supported you. You're not going to be able to see the beautiful moments your partner and you had because they are the ones holding the camera. You're not going to be able to see the look on your partner's face because it's all going to be baby or you. Plus, most partners are not really that great at taking pictures, let's be honest. It's okay. It is okay but it's such a fulfilling thing. I love being able to go and witness the power that women have in all of the stories. There is so much power in scheduled C-sections, in unplanned Cesareans, in vaginal births, in medicated births, unmedicated births, hospital, out-of-hospital, all of it. All of it takes so much power and strength, all of it. I get to witness that but not only do I get to witness that but I get to document it. I get to come home and I get to witness it again as I'm editing photos and video. I just think it's a really, really, really cool and really inspiring thing. I love it. I love it. Meagan: I agree. It's actually one of my biggest regrets not having that. We had some candid– not even candid, some photos that were snapped really quickly, but not being able to see, I really wish it was recorded. So dang it. Julie: Yeah, I feel like that's the biggest regret I hear from first-time moms too. They will be like, “I didn't have a birth photographer for my C-section. I wish I would have though. I wish I would have. I wish I would have been like, ‘Well, I'm having an induction now. I was thinking about it, but I really wish I would have had one,'” because there is just so much. Cell phone pictures just don't do it justice. Meagan: I agree. Well, I love what you are doing. I'm so grateful that you are in that space and I'm so grateful for you letting us use your images that of course are approved. I definitely highly suggest going over to Julie Francom Birth Services, right? That's your page, right? Julie: Birth Stories. Julie Francom Birth Stories. Well, it's just Julie Francom Birth on Instagram and on YouTube and on Facebook. Meagan: Go find her, you guys, so you can still follow her journey. Thank you, Julie, for joining me on the 300th episode. I really am so grateful for all that we have done, all that you have done, all the growth that we have seen, and I'm excited to keep going. Julie: Thank you so much. ClosingWould you like to be a guest on the podcast? Tell us about your experience at thevbaclink.com/share. For more information on all things VBAC including online and in-person VBAC classes, The VBAC Link blog, and Meagan's bio, head over to thevbaclink.com. Congratulations on starting your journey of learning and discovery with The VBAC Link.Our Sponsors:* Check out Dr. Mom Butt Balm: drmombuttbalm.comSupport this podcast at — https://redcircle.com/the-vbac-link/donationsAdvertising Inquiries: https://redcircle.com/brands

Suite à la tempête du 24 juillet 2023, le Club 44, l'association Des arbres pour rêver demain, Réseau Mycélium, le MUZOO et la Ville de La Chaux-de-Fonds proposent une journée pratique, artistique et réflexive pour pe(a)nser les arbres en ville. Mettre en mots, saisir les maux, pour prendre soin de la ville, de ce qui la vivifie et de notre avenir. Conférence de Caroline Mollie "Planter la ville pour demain". _ Architecte-paysagiste et membre d'honneur de la Fédération française du paysage, Caroline Mollie a été en charge, au ministère de l'Environnement, d'un programme de protection et de réhabilitation de l'arbre d'ornement. Elle est une personnalité de référence dans le domaine du paysage et de l'arbre dans la ville. En 2020, elle rédige "Des arbres dans la ville, l'urbanisme végétal" aux éditions Actes Sud. _ Enregistré le 9 mars 2024 au Club 44

Suite à la tempête du 24 juillet 2023, le Club 44, l'association Des arbres pour rêver demain, Réseau Mycélium, le MUZOO et la Ville de La Chaux-de-Fonds proposent une journée pratique, artistique et réflexive pour pe(a)nser les arbres en ville. Mettre en mots, saisir les maux, pour prendre soin de la ville, de ce qui la vivifie et de notre avenir. Table ronde avec Gilbert Dey, Roger Hofstetter, Michaël Rosselet, Silke Roth et Antoine Sauser. Modération Pauline Seiterle. - Enregistré au Club 44 le 9 mars 2024

Myc, ras, BRCA…these are all shorthand for common cancer mutations, with a new study saying that's how cancers should be identified rather than which organ or system they're found in, since not knowing the mutations may delay proper treatment. Kimmel … Should cancers be named according to which mutations they carry? Elizabeth Tracey reports Read More »

Welcome to The Underdog Podcast where we talk about how to get more customers, impact clients at the highest level, and build great products that change the world. Daniel Francis shares his journey on the best up to date strategies to build great profitable coaching businesses. Get ready to learn & be inspired. In this podcast, I chat with my client Donny who specializes in acquiring foreclosure deals. He decided to teach others how to do the same so got the help of the MYC team to learn how to grow his business. Through the power of community building, we taught Donny how to create a community around this niche and in just a couple weeks after joining our program, he was a able to enrol his first high-ticket client. Join us as we discuss his business journey and see how community building can help you achieve your business goals. Check out my webinar: How I Built an Online Coaching Business Through Community Building ⬇️ http://masteryourcoachingsecrets.com Fill out an application for a free 1-on-1 strategy session to see how we can audit your business & provide you an immediate angle to generate high quality clients ⬇️ https://calendly.com/callwithdan/myc Join our Free Facebook Community For Coaches: https://www.facebook.com/groups/mycbusiness FOLLOW ME ON SOCIAL MEDIA Instagram: https://www.instagram.com/ceodanielfrancis/ Facebook: https://www.facebook.com/TheOfficialDanielFrancis Tiktok: https://www.tiktok.com/@danielfrancishq

On analyse Les Chroniques Martiennes de Ray Bradbury, chef d'oeuvre littéraire de l'âge d'or de la science-fiction, avec Tristan Garcia en direct de la Bibliothèque de Lyon pour le festival des Mycéliades. Un classique intemporel Découvrir Les Chroniques Martiennes c'est lire une immense livre de science-fiction constitué de nouvelles humoristiques, nostalgiques, poétiques et tragiques. Ce "fix-up" de nouvelles inédites narre les relations complexes entre les colons terriens et les martiens. Les textes qui ont été écrit entre 1946 et 1950 pour des pulps ont été compilé ensuite en 1954. Difficile de ne pas être emporté par la plumme de Ray Bradbury qui n'hésite pas à dénoncer le racisme et la colonisation. "Les Chroniques martiennes", c'est quoi écrivait Ray Bradbury ? C'est Toutankhamon extrait de sa tombe quand j'avais trois ans, les Eddas islandais quand j'avais six ans et les dieux grécoromains qui me faisaient rêver quand j'avais dix ans : de la mythologie à l'état pur. Si c'était de la science-fiction bon teint, rigoureuse au plan technologique, elle serait en train de rouiller au bord de la route. " L'auteur écrivait également sur son recueil : « Je n'écris pas de science-fiction. J'ai écrit seulement un livre de science-fiction et c'est Fahrenheit 451, fondé sur la réalité. La science-fiction est une description de la réalité. Le fantastique est une description de l'irréel. Donc Les Chroniques martiennes ne sont pas de la science-fiction, c'est du fantastique. »

durée : 00:05:20 - Le festival des Mycéliades, à Epinal du 1er au 15 février

JCO PO author Dr. Amit Mahipal shares insights into his JCO PO article, “Tumor Mutational Burden in Real-world Patients with Pancreatic Cancer: Genomic Alterations and Predictive Value for Immune Checkpoint Inhibitor Effectiveness.” Host Dr. Rafeh Naqash and Dr Mahipal discuss real world evidence of immune checkpoint inhibitors in pancreatic ductal adenocarcinoma. TRANSCRIPT Dr. Rafeh Naqash: Welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCO PO articles. I'm your host, Dr. Rafeh Naqash, Social Media Editor for JCO Precision Oncology and Assistant Professor at the OU Health Stephenson Cancer Center, University of Oklahoma. Today we are joined by Dr. Amit Mahipal, Professor of Medicine and Director of GI Oncology at the Case Western Reserve University in Seidman Cancer Center. Dr. Mahipal is also the author of the JCO Precision Oncology article titled "Tumor Mutational Burden in Real World Patients with Pancreatic Cancer: Genomic Alterations and Predictive Value of Immune Checkpoint Inhibitor Effectiveness."  Our guest disclosures will be linked in the transcript. For the sake of this conversation, we will refer to each other using our first names. So Amit, welcome to our podcast and thank you for joining us today. Dr. Amit Mahipal: Thanks for having me here. Dr. Rafeh Naqash: Excellent. We came across your article in JCO Precision Oncology and it really aroused my interest because the topic and the audience that it caters to is very important in the current times. Because immunotherapy generally is considered- pancreas cancer the graveyard in immunotherapy in essence, based on what I have seen or what I have encountered. And now you're the expert here who sees people with pancreas cancer or has done a lot of work in pancreas cancer research side. So can you tell us the context of this work and why you wanted to look at immune checkpoint inhibitors in pancreas cancer? Dr. Amit Mahipal: Absolutely, Rafeh. As you mentioned, pancreatic cancer is considered a what we call "cold tumors." They don't typically respond to immunotherapy. And when we talk to our patients or patient advocates, as you know, patients are very excited about immunotherapy. Immunotherapy has transformed the treatment for a lot of different cancers and not only has increased survival, but the quality of life is so much different than with chemotherapy. This work came from based on the KEYNOTE-158 trial, which was a tumor-agnostic trial which accrued patients who had TMB high tumor. What that means is that tumor mutation had more than 10 mutations per megabase. And what happens is because of that trial, more than 200 patient trial, the FDA actually approved this immunotherapy or pembrolizumab as a single agent pembrolizumab for any patient with a solid tumor who has high TMB. Again, tumor mutation burden, more than 10 mut/Mb. This question comes in now. Does this apply to our pancreatic cancer patient groups? Especially as we know these are "cold tumors" that typically do not respond. There have been multiple trials looking at immunotherapy, single agent, dual immunotherapy agents, as well as combinations with chemotherapy, with somewhat very, very limited success. So that was kind of the basis. So we wanted to look at this retrospective kind of review of a big database to see how many patients we can find who have high TMB and see in that patient population is immunotherapy really active based on the FDA approval or is pancreatic cancer not a tumor where we should try immunotherapy unit as a selective group.    Dr. Rafeh Naqash: Thank you for that explanation. Taking a step back again, since you see these individuals with pancreatic cancer I imagine day in and day out in the space of drug development, what is the general current standard of care approach for individuals with pancreas cancer in your clinic? I'm talking about what are the most common approaches that you utilize that seem to be working or have FDA approvals in the pancreas cancer space. Dr. Amit Mahipal: As with any tumor, the first thing is obviously staging. So depending on whether we're dealing with early stage or advanced stage and what are the goals of treatment. At this point, the only thing that can cure pancreatic cancer patients that would be considered conventional therapy is surgical resection. So any patient who is a candidate for surgical resection is in a different bucket compared to advanced patients. For early stage patients, we try to do what we call neoadjuvant treatment or neoadjuvant chemotherapy. We shrink the tumor or at least maintain it, look at the biology of the disease, and then take them to surgery, which typically involves a Whipple procedure if it's a head of the pancreatic mass.   Moving on to advanced patients, that's where we know the goal of treatment is palliative to increase survival, but unfortunately, most of the times we cannot cure them. And there the standard of care options include systemic chemotherapy. We have two typical regimens that we use, one is called FOLFIRINOX, which is a three-drug regimen of 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan. And another regimen is gemcitabine plus abraxane, which is a two-drug regimen of gemcitabine plus abraxane. These are considered the standard of care. Unfortunately, the median survival even with the best standard of care chemotherapy is only about a year, 12-13 months, depending on what trials we look at.  Dr. Rafeh Naqash: I still remember some of these regimens from my fellowship, where we had to decide which to give to each individual based on their performance status and clinical status, etc. But now I can see a lot of ongoing drug development in the space of pancreas cancer. I'm guessing that's why you wanted to assess both the molecular genomic landscape of pancreas cancer in this study and also look at the immune biomarker aspect. Could you tell us a little bit about the Foundation Medicine Clinical Genomic Database? How did you identify the patients, how many patients did you identify, what you narrowed down in the criteria, and the eventual sample size of what you were looking at?  Dr. Amit Mahipal: FoundationOne has a rich database. They have two or three things. One is a genomic database only. So in our clinical practice, I think it's some sort of next-generation sequencing or mutational testing for all patients with advanced solid tumors. All of these goes into their database. All of the samples that are sent to FoundationOne that goes into their database where they know the diagnosis of the patient and the know the sequencing results of these patients. In addition, they also have a clinical database called Flatiron. Basically, they collaborated with them. Flatiron has about 280 or so cancer clinics throughout the country, so a lot of community settings and some academic sites as well. They did not only have a genomic database, but they actually have a clinical database. They have demographics, clinical features, baseline clinical features, comorbidities, what kind of treatment they received, what would be the stage of the cancer, how many months of treatment they received, and their overall survival, and so on. So from that perspective, the FoundationOne has access to this partnership with Flatiron, clinical genomic database where they have both clinical data as well as genomic database for a lot of these patients.  In our study, we only focused on patients with advanced pancreatic cancer. We excluded a lot of patients who did not have sequencing results available, they cannot be performed due to lack of tissue. So the first we talked about the genomic database and we found about about 21,932 patients, so almost 22,000 patients and there we had the sequencing and we also had the data on TMB or tumor mutational burden. So here, we classified them into two groups: high TMB and low TMB. High TMB was seen in 1.3% of the patients, and about 98.3% of the patients had low TMB. Here we looked at the genomic alterations between the two groups. So these are like our genomic group, so to speak of about 22,000 patients. And among them, as mentioned, that the clinical data was available for about 3300 patients or 3279 patients to be exact.   After excluding some of those patients, we found about 51 patients who received immunotherapy. And when we say immunotherapy, it is single agent immuno checkpoint inhibitor like pembrolizumab or nivolumab. And then we classified them into high TMB versus low TMB and then we also looked at patients with high TMB and compared them to who received immunotherapy versus other therapies. Just to recap, we had about 22,000 patients where we have the genomic database and about 3300 or so patients who we have both genomic and clinical data for this patients. One of the key findings was that high TMB was present in only 1.3% of the patients, or about 293 patients out of 21,932.  Dr. Rafeh Naqash: Definitely an interesting sample size that you had utilizing this resource, which, of course, is more or less real-world. It is important to gather real-world outcomes that you did.   So, going to the TMB story of this paper, where you looked at immune checkpoint inhibitor use in these individuals, was there a reason why some of the individuals with low TMB were also given immune checkpoint inhibitors? From my understanding, I did see some checkpoint inhibitor use there. What could be the explanation for that? Dr. Amit Mahipal: So this data is from 2014 to 2022. So from the span of about eight or so years. And as you know, immune checkpoint inhibitors were approved in the last decade. And there were a lot of not only trials, but even in the non-trial setting, people had tried immune checkpoint inhibitors in, frankly, different tumor types because of the success in some of the common tumor types, like melanomas, lung cancer, and so on. So I agree, as of today, we probably would not use immune checkpoint inhibitors in patients with low TMB or MSS. But at that time, I think that information was not available. So people with low TMB and MSI-stable tumors also received immune checkpoint inhibitors. But those numbers are again low. So it's not very high numbers. Dr. Rafeh Naqash: Understandable. That makes it a little more clear.  Now, you looked at the TMB aspect. I'm guessing you also looked at the MSI aspect of PDAC. What is your understanding, or what was your understanding before this study, and how did it enhance your understanding of the MSI aspect of PDAC? And I'm again guessing, since TMB high individuals are on the lower side percentage, so MSI high is likely to be low as well. Did you see any interaction between those MSI highs and the TMB highs on the PDAC side?  Dr. Amit Mahipal: Yeah, absolutely. So we are very excited in general about MSI-high tumors for solid tumors because of their response to immunotherapy. Although I would do a caveat because we still don't know how MSI-high pancreatic cancer responds although there have been some real-world, very, very small series as well. In this study, one of the things is, is high TMB totally driven by MSI-high? That's a question that comes up, and TMB high may not matter. It's only the MSI-high that might matter. So definitely when we look at this patient population, we found that the patients who were 35-36% of patients who were TMB high also had MSI-high patients. So we do expect MSI-high patients to have a higher TMB compared to MSS patients. But there were about 66 or two-thirds of the patients who did not have MSI-high tumors and still had high TMB, as defined by, again, ten mutations per megabase. So we did see patients with MSI-stable tumors who had high TMB. And I think that was one of our biggest questions. I think MSI-high patients, we all tend to think that we would try immunotherapy even if it's in pancreatic cancer. I think what is not clear, at least from the real-world or any of the trial data, is if we were to give MSI-stable patients who have high TMB, if we give immunotherapy, are there any responses or any disease control that we see? And that was one of the reasons for this study.  Dr. Rafeh Naqash: Now, one of the things that comes to mind, and again, I think you based it on the FDA approval for TMB high, which is ten mutations per megabase, as you defined earlier. I do a lot of biomarker research, and oftentimes you come across this aspect of binary versus a linear biomarker, in this case being TMB, where about ten, less than ten. Do you think, in general, an approach where you maybe have tertiles or quartiles or a biomarker, or perhaps a better approach in trying to stratify individuals who may or may not benefit from immunotherapy? Dr. Amit Mahipal: That's a great point. I think when we use ten mutations per megabase as a biomarker, as a binary endpoint, do we apply it to all tumor types? I don't think that's a fair comparison, frankly speaking. We do know that high TMB, even in different tumor types, do tend to respond a little bit better to or do have better outcomes for patients treated with immune checkpoint inhibitors in different tumor types. But what that cutoff is not known in most of the tumor types. And also, one of the problems is how do you measure TMB and is it standard across different platforms? Like I'm just giving some names like FoundationOne, Tempus, Caris, and some obviously like MSKCC and some other university-owned panels as well. And frankly, I think if you look at different panels and if you send the same tumor tissue, you will get different measurements. So I think standardization is a problem as well.  In one of the studies involving cholangiocarcinoma, for example, we found that a TMB of 5 was enough to have an additive effect of immunotherapy, same with chemotherapy, so to speak. But again, this needs to be validated.  So you're absolutely correct. I don't know why we use the binary endpoint, but on the same token, the binary endpoint is easy to understand as a clinician. Like, “Hey, someone has this, do this, not this.” And when we look into a continuous range, I think the benefit obviously varies between high and low, different tertiles, and becomes somewhat challenging. How do you classify patients and what treatments to give? So I think in clinical decision-making, we like the cutoffs, but I think in reality, I don't know if the cutoff is a true representation. And maybe with the more use of AI or computing, we can just input some values, and then it can tell us what the best treatment option might be for the patient. But that's way in the future. Dr. Rafeh Naqash: That would definitely be the futuristic approach of incorporating AI, machine learning perhaps, or even digital pathology slides in these individuals to ascertain which individuals benefit.  Going back to your paper, could you highlight some of the most important results that you identified as far as which individual is better, whether it was immunotherapy, and you've also looked at some of the mutation co-mutation status. Could you highlight that for our listeners? Dr. Amit Mahipal: So the first thing we looked at was the genomic database of almost 22,000 patients, and then we classified them into high TMB and low TMB, with about 300 patients in the high TMB group and the rest in the low TMB group. And what we found was, talking about again in the genomic database, that patients who have high TMB actually have low KRAS mutation. So if we think about KRAS mutation, pancreatic cancer, almost 85% or so of patients have KRAS mutation who have pancreatic adenocarcinoma. So patients in this subgroup, so in the high TMB group, only about two-thirds of the patients had KRAS mutation, compared to 92% of the patients with low TMB who had KRAS mutation. So just giving that perspective. So KRAS mutation, which is the most common mutation in pancreatic cancer and is a driver mutation, their rates vary differ from the high TMB group versus the low TMB group.   And then in addition, in the high TMB group, we found higher rates of BRCA mutation, BRAF mutation, interestingly, and then obviously from the DNA damage repair genes like PALB2 mutation, MSH2 or MSH6, MLH1, and PMS2. So all these mismatch repair protein mutations were higher. As I mentioned before, one-third of the patients with high TMB also had MSI-high. So it's not a totally unexpected finding. I think the biggest finding was that we found more KRAS wild-type pancreatic adenocarcinoma in the high TMB group, almost a third. And those tend to have different targetable mutations like BRCA2, BRAF, and PALB2 mutations. So I think one of the interesting findings is that patients in the high TMB group actually tend to have KRAS wild-type or less KRAS mutations. So they're not necessarily KRAS-driven tumors, and they have a higher chance of having other targetable mutations like BRAF and so on, for which we have therapies for. So it's always something to keep in mind. Dr. Rafeh Naqash: Would you think that from a DDR perspective, the mutations that you did  identify that were more prevalent in individuals with high TMB, do you think that this is linked to perhaps more DNA damage, more replication stress, more neoantigens leaning toward more tumor mutation burden perhaps? Or is there a different explanation?  Dr. Amit Mahipal: For sure. As we said, MSI-high tumors have mutations in the DNA damage repair pathway and they definitely tend to have higher TMB. So I don't think that is very surprising that we found PALB2, or other MMR genes like MSH2, MSH6, MLH1, and PMS2 at much higher rates. I think the interesting finding is the fact that the KRAS wild-type and having BRAF alterations at least that's not suspected to definitely increase TMB. Although if we look at colorectal cancer, BRAF mutation and MSI are somewhat correlated to patients with BRAF mutations and to have high rates of MSI-high tumors. But that's not the case in pancreatic cancer. We also found an increase in BRCA2 mutations as well. So I agree that the DNA damage pathway repair gene alteration is not unexpected because they tend to increase TMB, but I think the other mutations were interesting. Dr. Rafeh Naqash: And I think one other aspect of this, which I'm pretty sure you would've thought about is the germline implications for some of these mutations where you could very well end up screening not only the individual patient, but also their family members and have measures in place that we're trying to enhance screening opportunities there. In your current practice, you are at an academic center but I'm talking about in general with your experience, how common is it to sequence broad sequencing panels in individuals with pancreas cancer? The reason I asked that is I do a lot with lung cancer and even now despite having all those targets in lung cancer which sort of paved the pathway for targeted therapy in many tumor types, we still don't see a full uptake for NGS Phase I drug development. And I get a lot of referrals from outside and I often see that it's a limited gene panel. So what is your experience with pancreatic cancer? Dr. Amit Mahipal: We kind of changed our practice. Similar to you, I'm involved in drug developments. I've been a big proponent of NGS for almost a decade now, when didn't even have targeted therapies but these companies first came in and they're like, “Okay. We're very very low chance.” But now obviously, we transformed the treatment for a lot of different cancers. Especially lung cancer, you don't sometimes even start treatment before you get an NGS panel like you said in situ. So what we're finding, at least for pancreatic cancer, as you know, the targetable mutations are there but they are somewhat not that common, I would say, in the 10-15% range. So many people would get dissuaded and then it's like, what's the point of doing it?   But I think for those 10% to 15% of the patients, firstly we can really change their treatment course and their prognosis. Secondly, if you don't do it and they cannot go in a different clinical trials, now we have trials targeting KRAS G12C, but not only that, KRAS G12D which is the most common mutation we see in pancreatic cancer and so on. So it's becoming very very important. One thing, at least with our practice we adopted last two or three years is sending liquid biopsies or liquid based NGS or blood-based NGS testing. Otherwise, what's happening I would send a solid tumor NGS from the tissue. And pancreatic cancer as you know has sometimes a very small amount of tissue obtained from FNA. And inevitably after four weeks, we'll get the result that there's not enough tumor to do NGS testing. And then the patient comes one or two months later and then we order the test, and that just delays everything.  So now we adopted a practice where we are trying to send both blood based NGS and solid tumor NGS at the same time the first time of diagnosis when we see the oncologist for the first time. And that has really increased the rate of NGS testing results for our patient population. And it's not 100%, even in blood-based NGS, sometimes they may not be able to find enough circulating tumor cells to do this blood-based NGS testing, but at least they're having these. But you're correct. I think we still see about one third of the patients who had not had NGS testing or referred for phase I clinical trial and have gone through more than two or three line of therapies which is unfortunate for our patients.  Dr. Rafeh Naqash: That's a very interesting perspective on how important it is to sequence these individuals. As you said, it may not be that all of them may benefit, but the ones that have those important alterations, especially BRCA, PALB, and KRAS could benefit from novel precision medicine-based approaches.  A question that came to my mind, I saw that you were trying to look at MYC and turmeric low tumors as well. So what is the role of MYC in the context of these individuals? Is there any drug development that's going on? Because I see small cell lung cancer. MYC is an important target there. These are two different tumors, but it looks like there was a hint of some correlation with respect to some of the findings that you showed. Is that something that you're currently looking at or planning to look at?  Dr. Amit Mahipal: I think that if we just talk about MYC in general, it is present at somewhat lower rate. I think we found MYC amplification in about 5% or so of TMB-low patients who had that and not really seen in the TMB-high patients. So right now, I am not aware of any trials targeting MYC in pancreatic cancer. But as you said, if it's successful in lung cancer, maybe that's when we can transform into the pancreatic cancer group. Dr. Rafeh Naqash: Of course we can all learn from each other's specialties.We learned a lot from melanoma with respect to therapy. Hopefully, other fields can also benefit from each other's experiences in the space of drug development.  Thank you so much for this interesting discussion. The last few questions are more or less about you as an individual researcher. So could you tell us briefly on your career trajectory and what led you into the space of GI oncology, pancreas cancer, even for that matter, drug development? And some of the advice that you may want to give to listeners who are trainees or early career individuals? Dr. Amit Mahipal: Sure. So I have gone through some different institutions. During my fellowship, that's when I really decided that I wanted to do GI oncology. Prior to that, I actually have a Masters in Public Health, where I learned about epidemiological research and how to design clinical trials, how to design cohort studies. My focus was on, actually there was somewhat a lot, but one of my mentors was working on colorectal cancer, and they had this huge database called the Iowa Women's Health Study Database of 100,000 patients. So that's where I started by clearly getting into colorectal cancer and GI cancer in general and how to learn from this database, how to mine these databases, how to do analyses, which seems easy but is actually quite complicated.  During my fellowship, I think the key to it is finding a good mentor during the fellowship. And I worked with one of the top GI oncologists in the country who's practicing. And I worked under her and learned a lot not only from the clinic side but also from the research perspective and how sometimes you'll come up with the ideas during the clinic itself.Like, “Hey, this patient had this and why aren't we looking into this.” And she would even do some of the therapies based on phase II trials and she was a part of a lot of these trials and learning from those experiences.  And following my fellowship, I joined Moffitt Cancer Center, where I led the phase I program there. So I was heavily involved in drug development programs, all training programs I've been to, NIH in Bethesda, an observership in the CTEP program, and also did the ASCO/AACR Vail workshop, where you really learned a lot in just like one week. So those are kind of opportunities present for fellows and even the early investigators and attendings as well in the first few years can go there, have your proposal. And really they are the world experts in trial design and they'll talk about how to design trials, how to add collaborators, improve your trial, and basically learn the whole protocol in a week so to speak.   And then I was at Moffitt Cancer Center for about five, six years. My home was GI so I did both GI oncology as well as phase I. And in terms of the GI oncology, my main focus was pancreatic cancer and liver tumors. Then I was at Mayo Clinic in Rochester for about seven or so years. I kind of did the same thing and solidified my career at GI oncology, looking at liver tumors, and pancreatic cancer and then being a part of the phase I division program. And now, most recently, about a year or so ago, I joined Case Western to lead the GI program here. Dr. Rafeh Naqash: Are the winters in Cleveland better than the winters in Minnesota? Dr. Amit Mahipal: For sure. I always say, you don't know cold until you go to Minnesota. It's a different kind of cold. I'm sure people in Dakota might say the same thing, but the cold in Minnesota is very brutal and different compared to any other place I've been to.  Dr. Rafeh Naqash: Well, it was great learning about you. Thank you so much for spending this time with us and for sharing your work with our journal. We hope you'll continue to do the same in the near future.  Thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review, and be sure to subscribe so you never miss an episode. You can find all ASCO shows at ascopubs.org/podcasts. Dr. Amit Mahipal: Thank you for having me here, Rafeh. Good luck. Take care. Dr. Rafeh Naqash: Thank you so much. The purpose of this podcast is to educate and inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.   The guests on this podcast express their own opinions, experiences, and conclusions. Their statements do not necessarily express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Dr. Mahipal: Consulting or Advisory Role:QED TherapeuticsAstraZeneca/MedImmuneTaiho Oncology Speakers' Bureau:AstraZeneca Research Funding:Taiho Pharmaceutical"

BUFFALO, NY- December 27, 2023 – A new #research paper was #published in Oncotarget's Volume 14 on December 20, 2023, entitled, “The pharmacodynamic and mechanistic foundation for the antineoplastic effects of GFH009, a potent and highly selective CDK9 inhibitor for the treatment of hematologic malignancies.” To evade cell cycle controls, malignant cells rely upon rapid expression of select proteins to mitigate pro-apoptotic signals resulting from damage caused by both cancer treatments and unchecked over-proliferation. Cyclin-dependent kinase 9 (CDK9)-dependent signaling induces transcription of downstream oncogenes promoting tumor growth, especially in hyperproliferative ‘oncogene-addicted' cancers, such as human hematological malignancies (HHMs). In this new study, researchers Fusheng Zhou, Lili Tang, Siyuan Le, Mei Ge, Dragan Cicic, Fubo Xie, Jinmin Ren, Jiong Lan, and Qiang Lu from GenFleet Therapeutics Inc. and Sellas Life Sciences Group aimed to summarize current knowledge underlying the mechanism of action (MOA) of GFH009 and explain its robust anti-cancer activity. “Understanding GFH009's MOA allows for a more optimal clinical development path, given the potential for meaningful benefits in patients with hematological malignancies.” GFH009, a potent, highly selective CDK9 small molecule inhibitor, demonstrated antiproliferative activity in assorted HHM-derived cell lines, inducing apoptosis at IC50 values below 0.2 μM in 7/10 lines tested. GFH009 inhibited tumor growth at all doses compared to controls and induced apoptosis in a dose-dependent manner. Twice-weekly injections of GFH009 maleate at 10 mg/kg significantly prolonged the survival of MV-4-11 xenograft-bearing rodents, while their body weight remained stable. There was marked reduction of MCL-1 and c-MYC protein expression post-drug exposure both in vitro and in vivo. Through rapid ‘on-off' CDK9 inhibition, GFH009 exerts a proapoptotic effect on HHM preclinical models triggered by dynamic deprivation of crucial cell survival signals. “Our results mechanistically establish CDK9 as a targetable vulnerability in assorted HHMs and, along with the previously shown superior class kinome selectivity of GFH009 vs other CDK9 inhibitors, strongly support the rationale for currently ongoing clinical studies with this agent in acute myeloid leukemia and other HHMs.” DOI - https://doi.org/10.18632/oncotarget.28543 Correspondence to - Jiong Lan - jlan@genfleet.com Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28543 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, GFH009, CDK9, leukemia, cell cycle About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

Meagan is joined today by our friend, Hannah, who has been through so much during her motherhood journey. Hannah's experiences include a blissful first birth at a birth center, multiple twin pregnancies, miscarriages, a difficult C-section, infant loss, and a redemptive VBAC. Hannah shares her unexpectedly traumatic experiences with pregnancy, birth, and grief while living in Argentina. Yet even with all that she's been through, you can feel Hannah's strength, positivity, and light. Hannah wasn't sure if she wanted another baby, but learning about the possibility of a VBAC restored hope in her heart. Hannah spent years researching providers and birthing locations in preparation for her move back to the US. When she became pregnant, Hannah was able to feel safe in the providers she chose. Her VBAC birth was everything she hoped it would be and Hannah was able to find so much joy and healing through her experience. Additional LinksThe Lactation NetworkHow to VBAC: The Ultimate Prep Course for ParentsFull Transcript under Episode Details Meagan: Hey, hey you guys! We have another episode for you today and we are sharing stories from our friend, Hannah. Welcome, Hannah. Hannah: Hi. Thanks for having me. Meagan: Thanks for being here. We are always excited to be sharing new stories. Just a little bit about cute Hannah here– we were just chatting right before we pushed record and she's had three babies. She has had three babies in three different states which is kind of cool. You kind of know how the birth world looks in a few different areas. Would you say they are very similar? Would you say they are vastly different? How would you rate having babies in three different places? Hannah: Right. Well, I would say from my experience that they were very different but more so having a baby out of the country. I've had one in South Carolina and then I've had one in Argentina, and then one in Texas. They are very different places and have different levels of care. Meagan: Yes. I think if I were to choose to do anything with my free time– I mean there are a lot of things– but one of the things in the birth world that I'd like to do is teleport to all of the different areas, just be a fly on the wall, and witness birth all around the world, truly. I would love to see the differences between them. As a doula, I've only seen birth live here in Utah. I think that would be really interesting. Well, like I said, her last baby was born in Texas so if you guys are listening from Texas, listen up because she did have her VBAC in Texas. But yes, she is a wife. They've been married for nine years, right? You and David have been married for nine years and they have three beautiful girls. We're going to talk about their births and then we're going to talk a little bit about miscarriage too, right? Hannah: Yes. Meagan: Yes. She's got some angel babies as well. I'm excited to have you share these stories with us today. I would just love to turn the time over to you. Hannah's StoriesHannah: All right. Well, thank you. I have had, I guess, a different birth story in the sense that I've given birth in different places. I'll start with our first. I'm from a large family. I'm one of eight kids. My mom had four of us at home, so I was very familiar with midwifery and all of those things. I knew that if we had a baby when my husband and I got married, that's kind of what I wanted to pursue. My husband, of course, was not familiar with that. Meagan: A little more foreign. Hannah: Right. I think he thought it was a little weird, but he was very, very supportive. About two years into our marriage, we found out we were expecting our first. We were living in South Carolina at the time. I started researching midwives. I found one there, Labors of Love, in Spartanburg, South Carolina. She was just a great midwife. My husband went to all of the appointments. We had an initial meeting with her. I remember he had some questions, but I think what really helped us as a couple and my husband to really get on board and just to be that support that I needed is we took a pretty intensive birth class together. It was about an eight-week course. It was about two hours each night. It was with a group of other couples. We learned about labor techniques and the whole pregnancy process, and then she also covered postpartum. That just really helped, of course, me because I've never had a baby before, but also my husband to understand more and then to really be supportive because he really was there for me during my birth. In the beginning, he was like, “I don't know.” It was a little weird to him. My first birth, I'll just go over pretty quickly. It was a pretty smooth pregnancy. I wasn't sick. I was very active. Of course, I was a little bit younger. It was just very smooth. I didn't hardly gain any weight and it just went by very well. But at about 37 weeks, we went in and she was breech. My midwife suggested I try a chiropractor. I had never been to a chiropractor. I remember I went and was so nervous. We had a couple of sessions with her and thank the Lord, the baby flipped. She got in position. Meagan: Yay!Hannah: I was so excited. We were able to have that natural birth with my first daughter. I really wanted a water birth and at the birthing center, they had a tub. I was laboring for quite a while in the water, but then I had a lip. Meagan: A cervical lip?Hannah: A cervical lip, yes. She had checked me and everything seemed like it was going really well. I had been in labor for about six hours and she was like, “You're a 10. Do you feel pushy or this?” I'm like, “No. I don't feel anything.” She's like, “Let's get you out of the water and see what's going on.” It was a lip, so we tried different things to try to get that moved. We ended up going outside on the porch and walking. Meagan: Oh yeah. Hannah: My husband still reminds me of this because he's like, “Whose idea was it to go walk on the porch?” because it was my husband's idea. I didn't want to go. I was in the tub. I'm like, “I don't want to move. I don't want to walk.” He's like, “Come on.” He was putting a robe on me and he was like, “Let's go outside and walk.” Within 10 minutes of walking outside, my water broke and she was crowning. Meagan: Wow. Hannah: She was there. I remember I reached down and I'm like, “I think that's her head.” My husband called the midwife and she's like, “Let's try to get her inside,” because we were still outside at this point. They got me inside to the bed and in the next contraction, I didn't really feel like I pushed that much. It was like my body just pushed. Meagan: Involuntary. Hannah: Yes. Her head came out, and then in the next push, her body came out. It was very smooth and very quick. She was 6 pounds, 11 ounces, and was perfect. We were so excited. Then the next year, we found out we were expecting again. We were very excited. They were going to be pretty close together, but we were happy. We went and did an early ultrasound because, between these two pregnancies, I had not gotten my period back. I was breastfeeding. So I was kind of like, “I have no idea how far along I am.” I was nervous about that because at the time, we were planning to move to South America, to Argentina. We were packing up and getting ready to move. I'm like, “I don't know. Should we stay stateside and have the baby at home?”Meagan: That's stressful. Hannah: Right. So we went in for an ultrasound, but that ended up ending in a miscarriage at around eight weeks. One of the things that we didn't know– we were working with the same midwife at the time but didn't do ultrasounds in her office because she was just a midwife– it was a pretty small birthing center so you would go to another office and do ultrasounds. We had done one and they didn't tell us anything, but when I miscarried, I called my midwife to tell her that I miscarried and she informed me that I was actually pregnant with twins. Meagan: Whoa. Hannah: She said, “I was going to tell you in your appointment, but that's what the ultrasound tech saw.” So I was like, “Oh my goodness.” She said, “The reason they didn't tell you is because in one of the babies, they saw a little bit of an irregular heart so maybe you just miscarried the one and you're going to keep the other baby.” Meagan: Which does happen. It actually does happen where one twin unfortunately will pass, but then the other, if they are not identical and stuff, will continue. Hannah: I had not heard of that, but that's what my midwife had told me so I was like, “Okay.” We were actually out of state, so we were driving back home. I miscarried out of state. We were driving back home and then I miscarried a few days later the second baby. It was a rollercoaster of loss then thinking maybe– Meagan: Hope. Oh, I'm so sorry. Hannah: Yeah. That was really tough. We hadn't really told anybody we were expecting. I had told my parents but we really hadn't told anybody else. Then when we lost the baby, we just didn't really feel like telling anybody because we had lost a baby. But then as a little bit of time went on, we did end up telling people and I think for me personally, everyone's different, but for me personally, it helped a little bit in the loss because I felt like my babies were acknowledged. I know some people would maybe rather just keep it private, but for me, it actually helped me a little bit in the grieving process because I felt like they were acknowledged even though I was only eight weeks along. It was a miscarriage. We did end up telling people that we lost the babies. We lost the babies. We said, “All right. Let's go ahead and move because I'm no longer expecting.” We bought the tickets. We started packing up and then we found out we were expecting again. Yeah. So I miscarried in April and I found out I was expecting in July. We said, “Well, let's go ahead and go.” I was a little ignorant on my end. I hadn't done research, but I'm just thinking, “We're moving to South America. Argentina is a pretty modern country.” We were going to a big city, Córdoba. We were like, “There had to be people there. There have to be midwives or doulas.” I knew they obviously had big hospitals, but I wanted the same experiences so I was like, “I'm sure they have people there.” I just went with the idea that I would find care there very optimistically which is my personality. I'm just like, “We'll go and figure it out. We'll get there and we'll find people there.” We got to Argentina and I'm trying to find a house, trying to buy furniture. We started from zero. We didn't know anybody in the state that we were moving to. We're trying to meet new people and all of this stuff. I started asking people that I would meet, “Do you know midwives?” They're like, “No. We've never heard of that before.” I'm like, “What?” Meagan: Whoa, really? Hannah: Yes. They all start telling me no. So then I asked doctors because then we went in– well, let me go back a little bit. We went in and got an ultrasound because I hadn't had an ultrasound yet in my pregnancy. We found out it was twins again. Meagan: Really? Hannah: Yes. I had two twin pregnancies back to back. Meagan: Back to back. Hannah: Back to back. They told me it was twins and we were shocked because I had miscarried the twins. I just never thought I was going to be pregnant with twins again. We were very, very surprised. We did an ultrasound. I started interviewing doctors. I couldn't find any midwives so then the doctors told me, “No. Midwifery is illegal.” Some doctors would tell me that midwifery was illegal in Argentina. Other people would say, “Well, we don't have any.” It was very confusing. I was pretty bummed because I really wanted that experience that I had with my first. I felt like it was just such a great experience and such a great birth. Through different people and different connections, we started to find health food stores. I really like to eat healthy and things like that. We found more of the hippies I guess you could say. They didn't live in the city. They lived further out and they would come in and sell stuff. They told me, “We know midwives,” because they had their babies with midwives. I was like, “Oh, this is great.” We actually traveled about an hour out of the city. We would meet with these midwives. I was really happy again. I started feeling optimistic. I was very excited, but it was just very different than midwifery care stateside. For example, they were very nice, but they didn't do any medical things. Really, they would just be like, “How do you feel?” Meagan: Like more of a monitrice? Well, because midwife and doula– hmm. Hannah: Yeah. They never measured me. They never listened to the heartbeat. They never weighed me. Blood pressure, nothing. Meagan: Did you know what their credentials were? I'm so curious. Hannah: That was kind of a thing too that we were worried about in the sense that some of the people that birthed with them didn't have birth certificates for their babies. Meagan: Oh. Hannah: We're like, “Well, obviously we need their birth certificates. We need to get their papers. We need to travel to the embassy.” Meagan: Right. Hannah: Then we started learning that it was more like people who almost wanted to be off-grid. I'm like, “I'm not that natural. I don't want that.” Meagan: Like underground midwives. Okay, okay. Hannah: Exactly. I was wanting a little bit more care than that because obviously I have twins and I wanted to check on the babies and everything. So they were like, “Well, go to this doctor.” They suggested I go to a doctor so we went to this doctor. In the beginning, he seemed very supportive. That's where I did all of my bloodwork and my blood pressure. He would check on the babies and all of that. The plan was that I was going to deliver with the midwives as long as everything was looking good. He said that he would sign off on it because he was a doctor and I was under his care. So that was the plan. I was very happy. I was like, “Okay. I'm going to get it.” We were going to do a home birth this time. I had my birthing kit and everything. My parents came in from Texas for the birth so we were super excited about that. Then I went in for my 37-week appointment and everything had been good. The babies were in a good position. Nobody was in distress. My blood pressure was good. Everything was good. I was very healthy in my pregnancy. I go in and he's like, “All right. Are you going to do your C-section today or tomorrow?”Meagan: You're like, “What?” Hannah: He completely flipped. It was just like he became very disassociated almost like he hadn't talked to us about other things whereas before he had told me all of these things that he was going to let me do even if I delivered in a hospital. He said, “Oh yeah. I'll let you deliver and this and that,” but there was another head doctor that was in that appointment so I don't know if it was something. Meagan: Maybe. Hannah: Maybe he wasn't supposed to let me have the baby vaginally. I'm not sure, but it just became a very weird situation. My husband and I just left that appointment like, “What just happened?” Meagan: I bet you were very confused. Hannah: Very confused. We were just like, “We'll call you,” and just left. So then after that, he started pressuring us a lot to come in and do the C-section. We had to come in and do the C-section. I talked to our midwives about it and they said, “Oh, he called us too and we're not going to deliver your baby anymore.” I was like, “Why?” They didn't want to be involved politically because they were underground. It just became– I just felt completely abandoned really by both of my providers because I thought I had a supportive OB and then I thought I had supportive midwives and then within a week they both just abandoned me. Meagan: Switched on you, yeah. I'm so sorry. Hannah: It was very like, “Oh my goodness.” I didn't know what to do. It was just one of those things. I kept asking the doctor, “Will you just let me try to labor and try to have a delivery if I go into the hospital?” “No.” They wouldn't. The policy was that they didn't let the husbands go in. In Argentina, they don't let the hospital go in. Meagan: Really? Hannah: Yes. Meagan: These are the things I wish I could find out. I wish I could know birth all around the world. That's interesting. Hannah: Yeah, so there they don't let the husband go in with you. I think typically, the women are also knocked out under general anesthesia. Meagan: Really? Still today? Hannah: Yes. I think that's one of the reasons why the husband is not in there. It's more of really like a surgery surgery in that sense. Our doctor knew that me and my husband wanted to be together so he told us, “If you come in on Sunday, I'll do the C-section and I'll let your husband in there because we don't have any other C-sections scheduled for that morning.” So me and my husband talked about it. We cried. We didn't know what to do. I just felt like, “Well, at least he's letting my husband in.” It was just one of those things.Meagan: Yeah. You take the wins where you can. That's hard. Hannah: Yeah. It's like, “We're not going to free birth. What are we going to do?” And my parents were there. That was another thing. I knew especially if I had the C-section, my mom only had a week left to stay. Especially if I have a C-section, I had a one-year-old. She was about to be two but she wasn't two yet. We were going to have two babies. I'm going to have a C-section. We might as well go ahead and do it. That way I would have my mom here to help us for the first week. We decided to go in. Like I said, I was completely ignorant. I had grown up in this circle, I guess in the sense that my mom had home births. A lot of my friends were also doing home births or birth centers. I didn't really know anybody who had a C-section. I should have researched it, especially with twins but I really just didn't. I really did not know what to expect at all. I just went in not really knowing anything. That's one thing– I wish I had done more research and looked into what it really entails and with recovery just to prepare myself because I really went in with no idea. I went in for the C-section. I felt very forced because we pretty much were forced. It wasn't like we wanted it. They hooked me up to the monitors and then they told me they were going to monitor me for two hours. They hooked me up and watched me before they did a C-section. They hooked me up and then about ten minutes into being hooked up, they were like, “You're in labor.” I was like, “What?” They checked me and I was 5 centimeters dilated. Meagan: What? You weren't even feeling anything? Contractions? Hannah: I was feeling uncomfortable, but I was expecting twins. I was 39 weeks at this point. I'm just uncomfortable all of the time. Meagan: Right, yeah. Hannah: I mean, I felt uncomfortable. My back hurt but I didn't think it was labor. I just felt like, “I'm uncomfortable. I'm tired. I'm not sleeping well.” I didn't recognize that I was in labor. I think it probably started that morning, but that day I was so stressed just getting ready for the C-section. I had it in the back of my mind, but then when they told me that, I was like, “Oh stink. I wouldn't have come in if I knew I was in labor.” Meagan: Yes. Yeah. Hannah: Anyways. Then it just became this cascade of everybody rushing in the room. Rush, rush, rush. They were trying to get the IV in me. They couldn't get the IV in me. Of course, I was freezing. They wouldn't let me drink all day. My C-section was planned for 7:00 that night. Meagan: Whoa. Hannah: They didn't want me eating or drinking since that morning. I hadn't had anything. Then they were trying to stick all of these IVs in me and it was just not working. I had tons of bruises all over my arms so they brought in a peds to do the IV. Meagan: The light? Yeah. Hannah: That worked and then they rushed me to the OR. Of course, it was freezing. They do the spinal tap and as soon as they put in the spinal tap, I got the shakes really bad. It was just uncontrollable. I almost felt like I was going to fall off the table. My husband wasn't in there yet or my doctor so there was nobody that I knew in the room. I wasn't covered and I just remember I felt so exposed. They tied my arms down and it was just very traumatic. I know some people have C-sections and they go really well and really smoothly. I'm like, “That's great,” but that was not my experience.” My experience was very traumatic. But then my husband came in. He calmed me down. My doctor came in. He was like, “Get her drapes on,” and all of that stuff. He brought a little more order. The thing that surprised me was how fast it was. I guess from having a labor before a C-section, I just felt like they started and he was like, “Here's your baby!” I felt like I wasn't ready. My brain wasn't connecting. Meagan: Yeah. It's quick. Hannah: It's so fast. But then again, no skin-to-skin. Nothing. They just showed me the baby over the curtain and rushed it off. They showed me the next baby over the curtain and rushed it off. I told my husband, “Go with the babies.” I wanted him to be with the babies. I stayed there and they stitched me up and everything. We got back to the room and it was just a rough recovery from the beginning. I won't go into everything for time, but one of the things was that my pain medicine was not administered so they thought they had an IV in me for the pain medicine. When the nurses would come in, they kept on checking on me and I kept telling them that I was in a lot of pain. They told me, “Oh, it's because you're breastfeeding. We can keep the babies. Let us take them to the nursery and we'll give them a bottle.” I'm like, “No. I've breastfed before. No. I'm in a lot of pain.” The other thing was they had me up walking pretty quickly. Within about an hour and a half, I was up because I didn't have a catheter in. They didn't put one in during the surgery. They came in after the surgery and wanted to place one. I'm like, “No.” So I'm like, “I'll get up and go to the bathroom,” but I was in a lot of pain. I tried to get up and go to the bathroom. I didn't know what was going on. That was all night. Then the next morning, a new shift of nurses came on. I told the nurses the same thing when they came in. “I'm in a lot of discomfort and a lot of pain.” They went and they checked my IV. They were like, “Oh, it was never hooked up to the bag.” I had my IV in my arm but it wasn't connected to the bag. I was taking no pain medication. Meagan: Oh dear. Hannah: Then they just reconnected it but by that time, my pain is–Meagan: Past the point. Hannah: I needed something stronger. That was tough. Just trying to nurse and change your babies' diapers and trying to swaddle the baby. Meagan: Yeah. Oh my gosh. Hannah: So that was really hard. But we got over that and then I also had an allergic reaction to something that they cleaned me with for the C-section. I had these red, itchy bumps. Meagan: Like the betadine or something? Hannah: I think that's what it was. It was just these red, itchy bumps all over my torso. That was uncomfortable as well. We ended up being able to go home finally. We were so happy to go home. There is nothing like home. Then about a week into being home, my C-section scar reopened. Meagan: Oh no. Hannah: It was again, something I had no idea that could happen. I had never– of course, I hadn't researched C-sections, but I was like, “How can this happen? I didn't know this could happen.” We battled with that for a while. Eventually, it did reclose. We didn't have to go in and do another surgery. It was just a small part that had opened. That was good. But it was one of those other hurdles I didn't think would come from a C-section. Then about a month postpartum, the babies were doing well. They were nursing. I was able to breastfeed both of them which I really wanted to do but I didn't know if I was going to be able to. Meagan: Yeah, because that's hard. That's really hard. Hannah: Yes. I did just feel like I was breastfeeding all of the time, but I loved it because it gave me a chance to bond more with the babies. Meagan: Yeah. Yeah. Hannah: So that was really good. But then our son passed away unexpectedly. He was a month and a day old. He passed away in his sleep. That was really, really hard of course. Meagan: I'm so sorry. I just got the chills watching you. I'm so sorry. Hannah: Yeah. That was really, really tough. In any circumstance, it would be, but we didn't have any family or really any friends. We had met people and we were getting to know people, but we had only been in the country for about six months so it's different. We didn't know the procedures of funerals and just all of that stuff you don't think you're ever going to navigate. Meagan: No, no. Hannah: With a funeral and things like that, you never think you're going to plan that for your child. So it was just very unexpected and very hard. It was just something that we didn't expect obviously and something that when it happened, I was kind of like, “I never want to have a baby again.” Meagan: Yeah. Yeah. Hannah: The C-section being really hard, having a really rough recovery, and then finally feeling like I'm kind of recovering. At this point, my C-section still had not closed so I still had this open wound and I was still dealing with a lot of stuff postpartum, and then to have our son pass away, I was just like, “We're never going to do this again.” It was very, very traumatic and very hard. Me and my husband are very religious and I think that really, really helped us just clinging to the Lord and reading the songs and all of those things. Of course, we had a lot of people praying for us around the country, and in the States, a lot of people who knew us were supporting us. I think that really helped us to get through that time. Meagan: Yeah. Yeah. Hannah: About a year after losing our son and after having my C-section, I still wasn't thinking about having another baby. I didn't know anything about a VBAC or the chances of having a vaginal birth after a Cesarean. I was scrolling my Facebook and I was in a home birth group on my Facebook page. I thought I had put it on mute because it was one of those things where I didn't want to see people having these beautiful home births. I thought I had put them on mute. One day, it just showed up on my feed. It was a lady and I wish I could remember who it was, but I couldn't go back and find it. She had actually had a VBAC home birth. She was on The VBAC Link Facebook page but she had posted on the home birth page as well. She was talking about this and then I was so sucked in like, “What? This is possible?” I started researching and I found the Facebook group. Then I found the podcast and I binged every episode. I still didn't feel ready to have a baby, but just the sense of that possibility gave me so much hope. I was so excited. I remember telling my husband about it. I would listen to it during lunch because, at the time, our babies were still really little so that was my time. I would eat my lunch and I would listen to The VBAC Link. It was so encouraging and so inspiring to hear all of these stories of these ladies. They had different circumstances and different backgrounds and were able to achieve that. I was so happy. I started researching and reading anything I could about VBAC and its options. So about a year after that, me and my husband were talking. We said, “Maybe we would like to try to have a baby next year.” We weren't ready still at that time, but we were talking about, “Maybe. Maybe we could do this and that.” But I was like, “If we're going to have another baby, I really, really need to have a supportive provider.” That was my biggest thing that I just really felt like they failed me. I felt like I had support and then I really didn't have any support from either side. I felt very abandoned. I was like, “I just don't want that to happen again.” I started researching providers. We were still in Argentina and we had this app where you can call the states so I just started calling doctors, OBs, midwives, and all in different states because we were scheduled the next year to go back stateside. We had been in Argentina for a few years and then we were going to be about nine months stateside. So I was like, “I can pretty much– I'm open. I can go to North Carolina, South Carolina, Georgia, Florida.” I was just calling everywhere. Of course, originally I called my provider who I had my first with. She told me for the state that they could not do VBACs. She couldn't do VBACs anymore. I was disappointed about that. She referred me to some people who might. So I was calling that area. My parents had recently moved to South Texas. That's where I am now. We are in South Texas. It's the valley area so it's all the way down in Texas. I had not heard great stuff about providers here. I had never really lived here. I started calling around here as well. I was like, “You know what?” I was just calling everywhere. It was so funny. I was like, “I know I'm not expecting but I'm just wondering.” Meagan: Do you know what though? That is one thing I actually think is really good to do before you're expecting because we're in a different timeframe. It's actually really healthy to start before because we're vulnerable but we're not expecting. I don't know. We're in a different place. Right? Hannah: Yes, for sure. We don't feel like we're on a time clock. Meagan: Exactly. “I have to find a provider. I have to make a decision now.” It's like, “No. I'm preparing and I'm going through these motions to find a supportive provider so when I get there, it's there. I'm supported from the beginning.” Hannah: Yeah. So that's what I felt like. I wanted to find somebody before. Of course, I knew maybe once I got pregnant and once I met them in person, it might not work. Meagan: It could change, yeah. Hannah: But I at least wanted a base and something to go off to feel like I had found somebody and at least had someone to talk to if we did get pregnant. Thankfully and fortunately, I did find somebody here in the valley. I talked to her on the phone about two times. We had two phone conversations. She was so nice and really just took the time to talk with me. We went through my history and looking back, I wasn't even expecting. She just really took time with me and really talked through it. She was so sweet but also very informative letting me know, “These are things that could happen with a VBAC,” and just giving me all the facts. I really appreciated that with her. She wasn't trying to sugarcoat anything, but also not fear-mongering me at the same time. I don't know if that makes sense. Meagan: Yeah, totally. Hannah: I really liked her. Anyway, time happened. I'm trying to remember. That was the second year. So the third year, we headed back stateside and we were not pregnant. This had never happened to us before. We had always gotten pregnant pretty quickly with all of our babies. With this baby, it took us about a year to get pregnant with her. You know, six months into it, it's like, “That can happen.” But then 8-9 months you start thinking, “Something's wrong with me.” I really didn't know and to this day, I don't know because I never went in. I didn't get any testing. I just thought, “Maybe it's taking longer.” I really wasn't sure. I just started trying to focus more on my health, taking some supplements, and making sure I was eating good food and all that stuff. About around the year mark, we found out that we were expecting. We were super excited. We were living in Indiana at the time so I went to an OB in Indiana and actually, we went just because we weren't going to move here to the valley until I was 27 weeks and my midwife wanted me to have some form of care before. Meagan: Right. Hannah: Obviously, and she wanted to make sure it was not twins again with my track record. Meagan: With your history, yeah. Hannah: She said, “I do not feel comfortable doing a VBAC twin birth.” That's what she had told me which is fine. So she said, “I do want you to go in. Do an ultrasound. Have a couple of checkups. See what's going on.” We found an OB, not necessarily looking for a VBAC-supportive OB, but just going in for an OB. But he ended up being great. I really recommend him. He was Dr. Labban in Bloomington, Indiana. They were so great. I was actually kind of sad when we left them because I felt like I could have maybe had a VBAC there as well. They were very supportive of me doing a VBAC and just really, really nice. But of course, he was a doctor and an OB. They weren't at a birth center or something like that but it was a great experience. We found out it was one baby. She was a baby girl and everything looked perfect. We were so excited. We moved to the valley and I was able to reconnect with that same midwife I had called almost two years ago now when we were still in Argentina. We had done a couple of Zoom calls while we were in Indiana. It was really great just feeling like we could get to know each other. Meagan: More connection, mhmm. Hannah: Right. We could build a connection. We started care with her and really, the pregnancy was wonderful. It was really great. I was really sick in the beginning. I wasn't with my other wones but that's okay. I was sick for about four months throwing up every day which I hadn't had with my other pregnancies. Everything was well. I did start seeing chiropractic care from the beginning this time. I really wanted to stay on top of everything. I was walking. I was doing my squats. I was just trying to do everything to get this VBAC. Around 34 weeks, we decided to hire a doula which I had never had. My husband and I were talking. I was like, “I just feel like maybe I could have a little more support just coming from the traumatic experience we had with our last birth.” I really felt like I wanted that support. So I talked to my midwife and she had some recommendations. She recommended a few doulas in the area. I met with them. We hired a doula and it was really great because she really helped me in the sense of calming me down, in the sense of – I didn't want to think about if my VBAC didn't work or if I ended up in another Cesarean. I just was like, “I don't want to think about that. I just want to focus on my VBAC,” which is great, but at the same time, I think we have to be realistic. She really helped me come up with a birth plan of what if's. I really felt more prepared in the end because we had a birth plan if I transferred and if it ended up being a C-section with things that I wanted because we talked through it. She was like, “You can request skin-to-skin,” and things I didn't know about. I'm like, “I didn't know you could do that.” Something I learned just by listening to The VBAC Link, you can have skin-to-skin with a C-section. You can do the clear drape and things I didn't know about so that even if it was a repeat Cesarean, I would be able to have a better experience. I think that it is possible to have a beautiful Cesarean as well. She really helped me write everything up and that way, I think I felt a lot more prepared like, “Even if this doesn't go the way I want it to go, I can still have a really beautiful birth.” That really gave me confidence either way. Time progressed. I got to 40 weeks. I kept on telling my family, “I feel huge. I think I'm to go before. I think I'm going to have this baby early.” It was wishful thinking. I got to 40 weeks and it was a Sunday and I was having labor. I started having some contractions, nothing crazy, but I started having some contractions. We went to church that morning anyway. Sitting through church, I was very uncomfortable I guess because you're just sitting too. I was like, “I'm really uncomfortable. I don't like this.” I started losing a little bit of my mucus plug so I started getting really excited because with my first, I didn't really have any of that until I was in labor. It was like I was going to have her in a few hours when I lost my mucus plug. Oh, this was happening today. I got so pumped. After church, I told my husband, “Let's go walk,” because I just wanted to get things going. But it was a rainy, really windy, nasty day. We went to this mall and we were just doing rounds walking, walking, walking, and walking. We walked for hours and we came home. I took a bath and my contractions pretty much stopped. I was so bummed. I was like, “It's okay. It's all right.” I went to bed. I woke up at 4:00 in the morning with contractions but they were just very sporadic. So I was like, “Oh, here we go again.” I got in the water and of course, as soon as I got in the water, they stopped. They fizzled out. I had a chiropractic appointment though that morning. I was like, “Maybe you'll get adjusted and it will start things up.” So now I'm 40 and 1 day. I go in. I'm adjusted. Nothing happens. Then I was talking to my mom. She was like, “Maybe I'll come and get the girls,” because I had the two girls at the house still. “I'll go ahead and pick them up,” and that way me and my husband could just have time by ourselves and see if we could get something started. So she came. She took the girls and really, nothing happened that day. I mean, I was on the ball. I was walking. I was doing squats. I was just so ready to have the baby. Looking back, I don't know why I was in such a hurry, but I was so ready. Meagan: Just ready, yeah. Hannah: I was ready. We started timing contractions at 10:00 that night because they did start getting more regular. They were about 5-7 minutes apart lasting about 45 seconds. I was like, “Well, I don't know.” They were regular for about an hour. My doula is about an hour from us, so I really wanted to labor at home with our doula and then go to the birthing center. My midwife is about 30 minutes from us so I'm kind of trying to calculate all of this. My husband was like, “I think we should call the doula. Let's go ahead and call her.” So we did. We called her and she was so sweet. She came and of course, as soon as she came, she took my phone away. She was like, “You don't need to be timing your contractions.” She was like, “I'll time your contractions.” She turned off the lights. She just really brought everything down. I actually ended up going to sleep. She put me in this exaggerated side–Meagan: Side-lying, yes. Hannah: She's like, “I think you need to rest,” which was true. I hadn't rested Sunday night. I hadn't rested Monday night and this was now Tuesday. So I did. I fell asleep and I slept for about probably 30 minutes and then I woke up and I was contracting again. They were pretty regular and we were here about an hour or so. Then we said, “Okay, let's go in. Now they were about 5 minutes apart. We went in and we got checked in. My midwife checked me and listened to the baby. Everything looked good. I got in the water because I really wanted my water birth and then within about an hour or two, it was like my contractions just stopped. I was just having prodromal labor now looking back. Meagan: Oh, yeah. Hannah: I didn't register it during the days that it was going on. I actually ended up going to sleep. I remember I got out of the water and she had these stairs. I wanted to do the curb walking. I wanted to get them started again, but they could tell that I was very tired. They said, “Why don't you just lay for a few minutes, and then you can start walking again?” I lay down and I went to sleep. I woke up and it was about 6:00 in the morning. I was so mad. Like, “What?” I had no contractions, nothing. We ended up going home. I cried the whole way home because there was no baby and all of this stuff. We went back home and slept. The next day, I was like, “I'm not timing my contractions. Whatever.” Around 1:00, I was having some contractions and my midwife sent me home with a TENS unit. I had never used it before so my husband was like, “Well, maybe just put it on and try it. We've never used it before.” So I put it on and within 15 minutes, my water broke. I was like, “Oh my goodness.” I called my husband in the bedroom. I was actually in the bedroom. He came running in. I was like, “My water just broke.” There was some meconium in the water, just a little bit. I called my midwife and she was like– we were about to eat lunch. It was about 1:00. She was like, “Well, how do you feel? How are contractions?” While I was on the phone with her, I had two big contractions that just felt very different than what I was having before. We were going to have lunch at the house and then go. I'm like, “No. Let's go. Let's go.”I labored in the car. It was very uncomfortable laboring in the car. By the time we got in the car, I was like, “Okay, this is the real thing.” It felt different. Meagan: This is labor. Hannah: I was like, “I'm in labor.” I just remember my husband doing the countdown like, “20 minutes. 15 minutes.” Meagan: Until you got to the birth center? Hannah: Until we got to the birth center. We made it and then again, of course, she had filled up the tub. I was a little nervous to get in the tub because I was like, “What if it stops?” Meagan: Sure. Hannah: But she really encouraged me. She was like, “If you want to get in the water, get in. Go ahead and get in. Relax.” So I was like, “Okay.” I got in the tub and I'm sitting there. They did slow down a little bit, but then I'm sitting there. My husband had actually stepped out to let people know, let my mom know, and my parents that we were back at the birth center. I remember hearing my midwife tell my doula, “You probably want to bring her husband back in.” I kind of thought, “Why? Why? I don't know what's going on.” Then within about 10 minutes, I hit transition. It hit so hard. I was just like, “Oh my goodness. I do not remember transition being like this.” My husband came in. He actually got in the birth pool with me. Meagan: Oh cool. Hannah: I really loved that. He was helping me through the contractions. My doula was giving me counterpressure and another thing at the birth center that I hadn't had with my first birth was that she had the nitrous oxide. Meagan: Uh-huh, yeah. Hannah: I didn't know if I wanted to use it, but I remember being in transition and I had in the back of my mind that I wanted to use it but I didn't verbalize it. I looked up and my midwife was like, “Do you want to put this on?” “Yes, I do.” She noticed that I wanted it, so I did use that during transition and if anything, I think it just really helped to steady my breath because you have to hold it up and breathe that in, then breathe that out. I think it just helped to calm me and ground me if nothing else. Meagan: Yeah. Hannah: But that was super helpful and again, two things that I didn't have with my first birth center birth. So I went through transition and then I just started feeling that pushy feel. I reached down and I could feel her head. I could just feel this head full of hair. I was like, “She's going to have a lot of hair.” I was so excited. I had envisioned leaning back onto my husband in the birth pool and catching my own baby. That was what I really wanted to do. That was my vision for this VBAC. That's really what I wanted. So I tried leaning back on my husband and it was just horrible. I couldn't do it. I was like, “I need to be on all fours.” It was a huge birthtub, obviously, because we were both in there. I was like, “I just need to be on all fours.” My husband had already told me previously that he did not want to catch the baby which is fine. He was there to support me but that's why I really wanted to catch the baby. But then I remember, I'm in this zone on the baby's traveling down. I'm pushing the baby. I have my hand on her head. I remember hearing my husband ask my midwife, “Can I catch the baby?” I was like, “Yes.” Meagan: I love that. That's awesome.Hannah: So he actually caught her. She came out. It seemed like I was pushing forever with her just because with my first, it was two pushes and she was out and with this one, I would feel her head come out and then with the end of the contractions, it would go back in, retract, and then come back in, then retract. It took forever. Once she was out, it was only about 20 minutes that I was pushing, but it felt really long. Meagan: I'm sure, yes. Hannah: But my labor was really short. It was about three hours from start to finish. Yeah. So prodromal labor did do something. It was working. Meagan: Yes, so for those listening, if you have a history of prodromal labor or are having prodromal labor, it's not always this so I don't want to tell you for sure that it's always this, but there's a very possible chance that you will have a precipitous birth once labor does begin. So anytime we have clients that are having prodromal labor, we are on extra alert because we do see those 3-5 hour births and a precipitous labor with prodromal labor happening especially if it's been happening for days and days and days like in your case. Hannah: Yes. I was happy about that because it is a very defeating feeling to have prodromal labor and to feel like nothing is going on. Just to back up, that morning when she ended up sending us home, she did ask me before sending us home, “Do you want me to check you?” I never had a cervical check. I didn't have any cervical checks during that labor so she did ask me, “Do you want me to check you?” I went back and forth, but I ended up deciding no because if I am not dilated, I am going to feel very defeated in the sense that I feel like I've been laboring on and off for two days and I just feel like it's going to make things worse. Meagan: Yeah. Yeah. Hannah: I'm going to feel like it's not doing anything. I'm sure it was, but at the same time, if I am dilated far along enough, I'm going to know so it's kind of one of those things that we wait out and we just decided that I wasn't going to be checked. So through my whole labor, I never had a cervical check which was great. I was just in the zone doing my thing and we just decided we weren't going to do any. It worked out really great with this labor. I know some people want to know and everyone's different but with me, what if she checks me and I'm a 4 and I feel like I've been laboring for two days and get really discouraged? What if I'm a 2? I didn't know what I was going to be. That worked out really well. But going back to her birth when she was born, her head came out. My husband was back there. He caught her and then her body came out later. She opened her eyes and she actually looked at my husband. It was so sweet. He was like, “I can see her!” Of course, I couldn't see her. I'm like, “What does she look like?” It was really neat. She came out and he passed her to me. We were just in the water with her and it was so magical. It was everything I wanted even from my first. Even though my first birth went so well, it felt rushed being outside and then having to be rushed to bed. This was very much more on my terms in the sense that nobody was down there with me when I was pushing. I didn't have any cervical checks. I was just very hands-on the whole time with my baby and I just really, really loved that. She was born. We were in the water. We stayed in the water for about 15 minutes just having that time with her. Then we got out of the water because I had decided that I would prefer to deliver the placenta out of the water. I know with water births it goes either way depending on your provider. We get out of the water and we just have this golden hour. I didn't really realize anything was going on. It goes by quickly when you give birth. You don't have a concept of time. My midwife came up and she was like, “You know what? It's getting close to two hours and the placenta is not–”Meagan: Detached? Hannah: Yes. The placenta was not detached and the thing that was worrying her was that I wasn't bleeding. She said, “I don't see any bleeding.” Of course, in my mind, I'm thinking worst case scenario, placenta accreta. Is that what it's called when it's attaches? Meagan: Attaches to the scar, yeah. Hannah: So I was like, “Oh no.” Again, she was just very realistic and so they gave the baby to my husband. They got off the bed and went over there. She told me, “I have this water saline that I can inject into the umbilical cord.” She said, “We'll wait ten minutes but if nothing happens, I'm going to call an ambulance and we're going to have to transfer you to get the placenta out.” Oh, my. I had this beautiful birth. It was such a great experience. That was the last thing I wanted to do was to have to be transported. My midwife took out this shot and it's huge. It was about this big, this really, really thick thing, and at first, I thought, “Where is she going to do that?” “Don't worry, it's going to go into the cord.” I remember I got the shakes. I don't know if it was the postbirth shakes. I did feel very nervous. My doula started praying. She was a believer and my husband was praying that I wouldn't have to transfer. So she injected it into the cord and then in about 10 minutes, I started bleeding and contracting. It was just the best feeling to feel like I was going to get this out. Meagan: Wow. Hannah: They stood me up and my midwife was on one side– no, her assistant was on one side, my doula was on the other just standing to give me some gravity and I was able to deliver the placenta with no transferring. Meagan: That's awesome. Really awesome. Hannah: Yes, so it was one of those really scary moments. It didn't last that long, but at the time, it felt like this could be really scary because we didn't know what was going on. My midwife later, she didn't tell me at the time of course, but later when she came and did visits, she was like, “I've never done that before, the injection.” She said, “I had just taken a class a couple of months ago about it and learned that you can do that with placentas if they're not detaching.” She said, “I've never used it before.” I was like, “Oh my goodness.”Meagan: That's really cool though. I want to research it. I've never heard of it. Hannah: I'd never heard of it either. She was kind of explaining it to me but not if it's a placenta accreta and not if it's ingrown obviously, but if it's just kind of stuck, when you inject that water in it, it almost blows it up a little bit and it helps to move it. It gets it a little heavier where it comes down almost. What my midwife explained to me afterward is my placenta did have a big blood clot that had formed on it. She said it was almost like it had formed a suction. I don't know if that makes sense. My blood clot was in the middle almost like it had a sucky. You know like those bath toys that have you stick on the bath is kind of how she explained it. She said that it wasn't really stuck-stuck like ingrown, it was just suctioned because of that blood clot. I don't really know why. Meagan: Very interesting. Hannah: Yeah, so that was something very interesting that happened after the whole beautiful birth was the whole placenta which was a whole other thing. I had never heard of that before and of course, my midwife had never used that technique, but we were very happy with the outcome. Meagan: I just Googled it really quick and it says, “Umbilical vein injection for management of retained placenta.” Hannah: Yes. Yes. Meagan: Cool! I am totally going to geek out on this. This is very, very cool and I'm so glad that you didn't have to transfer because that would be a bummer. Right? That would be a bummer but oh my gosh. Your picture– if you guys are listening, go check out their picture on Instagram or Facebook. You and your husband are in the tub holding your baby. Oh, it gives you all of the feels. Hannah: I love it. I love it. That's another thing. My doula actually just snapped that picture on my phone. She had asked me previously of course. She was like, “Do you want me to snap some pictures? Really, once you start pushing, my job is done.” Of course, unless there were other issues, but she was like, “I can just use your phone. I'll snap some pictures and videos. If you don't like them, you can delete them. They're yours.” I was like, “Sure,” because when you're in labor you just kind of feel disconnected and I love them. Even though they are just snapshots from her, and we have a video of the baby being born. I love it. I'm so glad that she did. Yes and that I have that as a memory.” So yes, we had our VBAC baby. She was my biggest baby by far. We were very surprised. I'm pretty petite and pretty small. My babies were 6 pounds, 11 ounces, 6 pounds, and 5 pounds, 13 ounces. So I've had pretty smaller babies. That's normal for my family. All my sisters have had babies like that and my mom. I did feel like she was big when I was birthing but then I thought that maybe I just forgot what that feels like. When they weighed her, she was 8 pounds, 11 ounces. Meagan: Wow!Hannah: Yes. Compared to my other babies, she was a pretty hefty baby. I had no tearing and I think that letting my body work even though it was a little frustrating to feel her crown, then to feel like she was going back up. I think that allowing your body to stretch and work with your body, our bodies are made to do that and I just feel that if we give it time, I almost wanted in some instances to grit down and push, but I kept trying to slow myself down and have my hand there. Yeah. It was really happy. I'm so thankful. I had a great VBAC. It was a little scary with the placenta, but everything was really, really great. Meagan: Well, huge congratulations. Huge, huge congratulations and we learned something new about a way to help get out a retained placenta. So if you are having that and if you are having an out-of-hospital or even an in-hospital birth, maybe that's something to ask your provider about and see. It looks like this Cochran data-based review was published in 2021 so definitely check that out especially if you have a history of that. That is such a great educational piece so thank you so much for that. Thank you for being here and sharing your beautiful stories. Hannah: Yeah. Thank you for having me and just thank you for everything you do. Like I said, that really encouraged me to have another baby but also to know that I could attempt this VBAC. I didn't know it was possible and then just finding a community of other people who have gone through this. Thank you so much for everything you do and all of the research. I know that it takes a lot of time and effort, but thank you so much. Meagan: Absolutely, thank you. ClosingWould you like to be a guest on the podcast? Tell us about your experience at thevbaclink.com/share. For more information on all things VBAC including online and in-person VBAC classes, The VBAC Link blog, and Meagan's bio, head over to thevbaclink.com. Congratulations on starting your journey of learning and discovery with The VBAC Link.Support this podcast at — https://redcircle.com/the-vbac-link/donationsAdvertising Inquiries: https://redcircle.com/brands

Have you heard of radical acceptance? Julie Francom leads our episode today alongside Meagan as they discuss what this concept is and how it is helping them process their births even now, years later. Meagan gets especially vulnerable today as she shares a part of her VBA2C birth story that has never before been shared on the podcast. Women of Strength, birth can be all of the things– empowering, euphoric, intense, and traumatic. We want you to know that we are processing and healing right along with you. We all have work to do and we are all in this together. Has radical acceptance helped you process your births? We would love to hear your experiences!Additional LinksAccepting Reality Using DBT Skills ArticleHow to Embrace Radical Acceptance ArticleNeeded WebsiteHow to VBAC: The Ultimate Prep Course for ParentsFull Transcript under Episode DetailsJulie: Heyo, it's Julie here, your co-host for the day of The VBAC Link Podcast. I am joined by Meagan Heaton, the ever-wonderful, always amazing, always uplifting and inspiring. Man, did I already say your name? I forget. I went on a tangent. Meagan: You did. Hello, everybody. It's so fun. When we were just talking about it, I was like, “Julie, you lead the episode today.”Julie: I'm out of rhythm. Meagan: It's great. You did a great job. Julie: We are here today. We were just hashing over topics that we could talk about something that I am working through always in my life and different things that we could possibly introduce today and we landed on the topic of radial acceptance. I think we're going to tell you about why we chose that topic here in just a little bit, but I'm really excited today because birth is complicated. I feel like everyone coming here in this space with us has probably had a complicated birth or witnessed a complicated birth. Hello, birth workers. Review of the WeekWe're going to talk a little bit about that and what happens when you just can't get over it or overcome it. But before we do any of that and before I ramble on my merry little way today, Meagan's going to read a review for us. Meagan: Yes. Okay, so we have this review from Apple Podcasts. This is from our friend, Tiffany. She said, “VBAC After Two Cesarean” as the subject. She said, “After two C-sections, I doubted if it was possible to VBAC for my third. I listened to your podcast my entire pregnancy and it gave me the strength and the knowledge to advocate for myself. I changed my provider three times before finding a supportive OB. My third baby came into this world on her due date with a successful VBAC after two Cesarean and I couldn't thank The VBAC Link enough.”Oh, I am so happy for you, Tiffany. Huge congrats. This podcast is literally meant for exactly that– to give you the knowledge, to give you the strength, and to just give you the connection and this community. This community is so beautiful, so vulnerable, and obviously so near and dear to both my and Julie's hearts. That is exactly what we want this podcast to do– to build you up, to strengthen you, to educate you, to go on and have the birth that you desired, and if you don't have the birth that you desired, to have a better birth outcome. We don't have to have a VBAC in order to have a better birth outcome. That's really important to talk about too. Through this podcast, we share all of it. We share CBAC stories and elective inductions and all of these things because we know that one size does not fit all. That's exactly what we are going to be talking about today during the episode. Julie: Yep. I love that. Meagan's going to get a little bit vulnerable. Meagan: I am. I'm going to talk about a thing that I don't think I've fully opened up to yet years later. Radical AcceptanceJulie: I'm getting old now. I know that everyone is like, “Oh, you're not old.” I'm 38 though and I'm feeling it. I can't even come home from a birth now without creaking my bones in the shower and into bed. I am feeling it. I know 38 is really not that old, but I feel like I look at my friends who are 28 and I'm 38. That's a 10-year difference, right? I'm starting to see some differences between myself and them just in the space on the time lived and the amount of life lived and the amount of time spent on this twirling rock in the universe. It's interesting because I know it's not a secret here that I've had a huge mental health journey over these last two years. I feel like a lot of that has helped me grow and evolve as a human. Maybe I'm a little bit older and wiser than I was when I was 28. Oh my gosh, I hope so. I don't know. Yeah. I've come a long way since then. But, we wanted to talk today about a term that I learned in therapy called radical acceptance. I'm just going to get right into it. I don't know. Do you want to say anything, Meagan, before?Meagan: Yeah, so are you going to define it? I was going to say that radical acceptance is something that can be defined as the ability to accept situations that are outside of our control without judging them which in turn reduces the suffering that is caused by them. I think, Julie, what we talked about before is that you should start right out there and talk about radical acceptance, how you learned about it, and how it came about. Julie: Yeah. Gosh, I love it. I remember when I was going through my big trauma-processing journey a few years back, that's when I really learned the term “radical acceptance, radical acceptance” and I love it because radical acceptance is where you have to stop fighting reality. You stop responding with impulsive behaviors or destructive behaviors when things aren't going the way you want them to or looking back on the way things happened. You've got to let go of the bitterness that can be keeping you trapped in this cycle of suffering and to truly accept the reality, to radically accept the reality, we have to understand the facts about the past and about the present– like what's going on now– even if they're uncomfortable or if there is something that we didn't want to happen or to be happening. We can examine the cause of this suffering that we have encountered, the events surrounding it, or all of the situations that we went through that have caused us pain or are causing us pain. But by radically accepting them, stopping fighting them, and stopping living in this cycle of suffering, we are better equipped to move forward into a life that is better and that is more promising, and more hopeful and causes us less anxiety and less pain. I feel like it's just all about embracing things as they were, embracing things as they are, and being able to live in that even though you haven't changed any of it. I was telling Meagan before we started– I am saying this. This is a perfect example. I will never, ever, ever, ever know if my Cesarean was necessary. I won't. I think I can list ways and reasons why it probably was and I can also list reasons why it probably wasn't. I'm just never, ever, ever– I can say ever so many times– I will never know–Meagan: Never, ever, ever. Julie: –for certain whether it was necessary or not. Was my induction necessary? I think so, but I mean, I don't know really. That used to really bother me because I'm a very analytical person. I liked fixed facts and data. I like to know things with certainty. I do. That is something I won't ever know. I'm okay with that. I feel like getting to the point of being okay with not knowing and with the certainty that I will never know is very freeing. It's freeing. I feel free. I am not haunted by it. It doesn't keep me up at night. Moving beyond that, I know that I am a good mom even though I didn't know everything that I wish I would have known going into my first birth. I have radically accepted the fact that there were things I didn't know and that's okay. I am okay with that fact. I have radically accepted the fact that I cannot be a human superwoman who can juggle all of the things in my life that I need to– my kids, my husband, my birth photography, doula work, The VBAC Link, and all of these other things. I had to drop these other things and I had to radically accept that I could not keep going in the life that I was doing. It doesn't mean that anything has changed. My C-section was the way that it was. There was no change there, but I have changed the way that I thought about it, the way that I continue to receive it, and the way that I respond to those circumstances. I feel like that's what radical acceptance is all about. You can't just turn on a switch and be like, “All right. Radical acceptance. Schwink”, but I feel like if you move forward with the desire of that radical acceptance, then that will impact how you respond physically and emotionally to the thing that you're trying to accept. I don't know if that makes sense or not. Meagan: No, yeah. It does. This is going to apply to all things. In all things in life, it's really hard because like you said, it's not just a “schwink” like you say. It's not a switch you can turn on and off like, “Okay. It's gone. I accept it. Moving on.” It's not like that. It takes a lot of time and it takes a lot of mind-power and will. You have to be okay to let it go and to let the attachment to the painful past or the pain that you are holding onto go because really what is happening in so many ways is that pain is overcoming you. It's taking over you. Like Julie said, she's not staying awake all night thinking about it. It's not consuming her thoughts anymore. She's let it go and it's in a healthy place. “Okay. This happened. It's not what I wanted. It's not what I would have chosen, but it happened. I don't know if it was needed. I don't know. I really don't know, but I'm going to accept that it happened and I'm moving on.” Yeah, so I think it's so important to know that you can't expect yourself to just do it. Right? But it can be done. So yeah. Keep going. Julie: Yeah, no. I feel like another simple way to say it, and it's not simple, but a simple way to say it is understanding what you have control over and what you will never have control over. I can control how I respond to things. I can control how I do my self-care. I can control whether I meditate or not. I can control what type of clients I take on and what my travel radius is. I can control what provider I choose. I cannot control what provider I chose. It's already happened. I cannot control how Meagan thinks or acts in any situation. One of the things that radical acceptance term really clicked and the first thing that I radically accepted was my sister-in-law and I butt heads a lot sometimes. It's gotten better over the last year and a half because I have radically accepted that she is the way she is. It took me a long time. It sounds easy, but it took me a long time where I just don't worry about it anymore. She does this. She says this and I don't worry about it. I interact with my children the way I want to interact with them. I teach them how to treat other people. I respond to people how I do. I know how to treat other people and try my best to treat other people well although I am not perfect at it because none of us are perfect, but just radically accepting it– I remember the day where I was just like, “Yes. She is the way she is and I'm okay with that.” It felt like a light switch at that time, but it was a lot of things building up to that moment. I feel like we should probably say that we are not medical professionals. We are not mental health professionals. We are just talking about our real-life experiences so I feel like if you have things that you need to process through, you should see a therapist or you should see a mental health professional or somebody that can really help you. Meagan, I just sent you an article. You can link it in the show notes. Meagan: Yeah, I have it. Something that I really love is what is reality acceptance. Julie: Yeah, so drop this in the show notes. I feel like this has got lots of helpful tips there, but I want to skip to the end where it says, “10 Steps for Practicing Acceptance”. I'm using DBT. DBT is just a different type of therapy, but I feel like the first one is such a big deal. I could go off on another therapy tangent, but I won't. The first one is “Observe that you're fighting against reality.” It shouldn't be like this. Every time you say, “I should” or “I shouldn't” or “He should do that. My doctor should know better. I should do this. My kids should go to bed.”Those are requirements that you have for the world and requirements are not usually healthy. They're just not. I could go off on a whole thing, but I won't. “I should do this. He should do that. I shouldn't feel like this. I shouldn't feel sad. I have a healthy baby. I shouldn't feel sad about it.” No, that's a requirement and that is fighting against reality. You're fighting against reality when you say things like that. That's a sign that you're fighting against reality. I feel like sometimes awareness is the first part of it. Or “so-and-so shouldn't post triggering things like that. Those things trigger me. They shouldn't be posting that. They should post a trigger warning with their comments.” Those are all signs that you're fighting against reality, right? Some type of reality that exists somewhere inside of you. And then the second is just reminding yourself when those things happen, instead of sitting with that, “It shouldn't be like this. She shouldn't have said that,” remind yourself that that reality, you cannot change it. You are not in control of it. Sometimes that awareness, being like, “Oh, I'm doing this. Okay no, you're right. This is fine. It's not going to change. I can't change this. I have no control over that.” That's the first step into your radical acceptance path. I'm just going to read through the rest of these really quickly and I highly recommend that you sit with these if you can. “Acknowledge that something led to this moment.” Something happened to you to lead you to have this kind of response. The next one is, “Practice acceptance with not only your mind but your body and spirit.” Be mindful of your breath and your posture. Use your self-care skills. Use half-smiling and take deep breaths. That's a big thing for me. I take deep breaths when I feel those sensations and that tightening and tensing in my body. The next one is, “List what your behavior would look like if you did accept the facts and then acted accordingly.” Imagine what it would be like if these things didn't bother you. Meagan: How would you look? How would you feel? How would you be living your everyday life?Julie: How would your environment change? How would your body feel? How would your breath feel? “Plan ahead with events that seem unacceptable and then plan how you should appropriately cope.” Oh my gosh, we go to my in-laws for Sunday dinner every other Sunday. It was like, every Sunday dinner going in, I would see my sister-in-law. We've had moments where we've been grumpy with each other and moments where we've been fine. But during those grumpy stages, I would walk in bracing for a fight, but when I became aware and was working on my radical acceptance, I would just meditate before, breathe deeply on the way in, and walk in with a posture of lightheartedness and airyness and it helped so much. “Remain mindful of your physical sensations” because your body will respond before your mind catches up to what's going on. So being more mindful of your body is so important. “Embracing feelings of disappointment, sadness, or grief.” It's okay to have those sad feelings and those hard feelings. It's okay. You should sit with them. You should sit with them and explore them and let them move through your body, but don't stay there. Don't stay there with them forever. “Acknowledge that life is worth living even when there is temporary pain.” Things are worth moving forward and moving through. And then the last one is, “If you feel yourself resisting, complete your pros and cons exercise to better understand the full impact of your choices or your experience.” I feel like all of those things, wherever you're at in the process, moving through these steps or these little feelings are going to help you grow and become better. You're going to be released from these things that are burdening you, this reality that you don't like or that you don't accept. But yeah. Meagan: Yeah. That's what I was saying. Radical acceptance doesn't have to mean that you agree with what happened. Julie: Yes. You don't have to endorse it. It doesn't mean you have to like it. Meagan: Right, but it gives you a chance to accept things and not fight against it because it is insane how much we don't realize that sometimes these things will bring us down. They're going to bring us down. There are many times– we were talking before we were recording about how sometimes it's not even to us. As birth workers, we see things and we're like, “No!” You know? Or we have friends and we're like, “No, don't do that.” But we can't control them. We have to know that we can't control them and it's okay that we can't control them. We may not agree with the choice that they are making, but it's okay. We have to accept that. That is a choice that they feel is best for them. That is what they are doing whether or not we would do that or not. So, kind of in the beginning, Julie was talking about, “I will never, ever know if my Cesarean was truly necessary,” and something when we were talking about this is that I'm never going to know blank, blank, blank. I don't know if I've ever really, deeply talked about a part of my birth story that happened and that does affect me. It's really hard. As I'm learning about this radical acceptance, it's like, “Have I done radical acceptance? Have I practiced this or is it still eating at me?” I think it probably is still eating at me. I probably fully haven't. I'm working that way and I'm waiting for my light switch to go on and off, but I'm working up to it. It's like my light switch is half on. It reminds me of Hypnobabies. My light switch is dim. It's coming down but it's still there. So yeah, I'm going to open up to you and just tell you guys. I don't think I've ever talked about this that I know of. Julie: I'm so curious. Sorry. Meagan: You're just fine. So after I had my son, Webster– he's my VBA2C baby– I was so happy. I was so happy and I will never forget that moment of, “You guys! I did it!” and just ugly crying, screaming, and looking around the room and everyone– not a dry eye in the room– looking at me just smiling from ear to ear. And then what happened after is what I may need to work on accepting. I remember sitting there holding my baby and hearing everyone talking and then all I heard was, “Riiiiing.” Yep. I heard ringing, just like that in my ears, high, high-pitched. My ears were just buzzing. I'm sitting on a horseshoe thing holding my baby. We're waiting for my placenta. I'm hearing it and it's getting louder and then everybody started going fuzzy. I woke up on the floor covered in blankets confused. My husband said, “You passed out.” I said, “Okay. I thought I was going.” I knew what was happening, but I didn't want to say anything. He said, “I looked over,” because he was right behind me. He said, “I looked over your shoulder and your arms just went limp so I hurried and grabbed the baby and said, ‘You guys, she's passing out.'” I pass out. I'm on the ground. I wake up and I'm like, “What just happened?” Everyone is still so happy. They're not acting really any differently. They're just like, “You passed out.” I'm like, “Okay, well I did just go through a long labor. 42 hours of labor, pretty intense pushing. I hadn't eaten a ton. I hadn't eaten a ton the day before either because I was not feeling very good.” Anyway, so I was like, “Okay, cool.” A phone was handed to me and they're like, “Your chiropractor is on the phone. You've got to tell her,” so I'm like, “Hi!” I'm telling her how I did it. I'm so excited and back to normal. But laying on the floor, I guess pushing out the placenta, I don't remember. Then they're like, “Okay.” I hang up the phone and they're like, “Okay, let's get you to the bedroom.” I'm at a birth center. I'm like, “Okay great.” We stand up. We walk to the bed and I'm not feeling very good. I'm feeling really funny. I can just feel my heart. It's pounding. I think I made it to the bedroom and I was in the bed. I just remember not feeling very good. They were taking my vitals. My vitals were off, but I was just so happy. I was so elated. I was nursing my baby. He latched really fast and I was so happy. Then they're like, “Okay, we've got to get you to the bathroom.” This was a couple of hours later. They fed me some food and I was hoping that maybe it was blood sugar or something. Anyway, they fed me my food and were like, “Okay, let's go to the bathroom.” I get up and before I know it, I'm waking up. I wake up and the first thing I say is, “I'm on the ground again.” They're like, “Yeah, you just passed out again.” Did you know this, Julie?Julie: Okay, so it's kind of ringing a bell a little bit, but I don't remember.Meagan: You don't remember all of it, yeah. Julie: Well, I remember other little parts, but I just don't want to get ahead of you. But go ahead, you're fine. Meagan: Yeah, you're fine. I'm like, “I'm on the ground again.” They're like, “Yeah, you just passed out again.” I was like, “That's weird.” So I sat on the ground. We're talking about random stuff, you guys. I still remember to this day. Serial podcasts, Adnan Syed, if anyone likes crime, that was my favorite podcast. I was like, “What do you guys think? Is Adnan guilty or is he innocent?” We were just talking about all of this random stuff. They were probably thinking, “What?” It was like my fight or flight was like, “I can't deal with what is happening right now. I have to talk about something else.” So we talked about that. We talked about such random stuff. I was like, “Okay. I feel better.” I had sat up and I was like, “I'm feeling really good.” So I sat up. I walked to the toilet. I sat on the toilet and I was like, “I'm going again.” I could feel it. I communicated it. My doula and my husband run over. I'm literally falling off the toilet and I wake up to an alcohol swab. My doula had an alcohol swab on my nose. I wake up and I was like, “What the heck? What is happening?” I go to the bathroom. I go back in and I'm just not doing very well. My vitals are not good. My pulse is really high and my heart rate was actually really low. My blood pressure was low. I'm actually showing signs of shock is what I'm showing, but it's not clicking in my head. “What in the heck, right?” Needless to say, I go home. I'm not doing really well. The next day, I'm really not doing well. I'm white as a ghost. I have this weird, crazy thing. I stand up. I've got ringing in my ears. I feel like garbage. I'm very dizzy. I can't get my breath. It's just really weird. Anyway, I went to the hospital because I had gone to the midwife the day before. We did a blood draw and she said, “Yeah, you've got low blood counts.” I was like, “Okay.” It was the Fourth of July. I'm really not feeling good. We go to the hospital. We do my blood tests. The doctor comes in and has a very serious face and I'm actually really mad. It's the Fourth of July. I just had this beautiful VBAC and I'm in the hospital emergency room without my baby. Without my baby. My mom stayed with my baby. I'm pissed. I'm like, “What the heck is happening?” So he comes in and he's got this very serious look on his face. He says, “Well, we're going to have to run some more tests.” I said, “Oh, okay. What's going on?” He said, “Well, half of your body's blood is missing.” Julie: This is the part that I remember. Meagan: Yeah. Yeah. He said, “Half of your body's blood is missing. You said you're not really bleeding, right?” I said, “No.” After you have a baby, you're bleeding, but it wasn't bad. I was like, “No, yeah. Pretty normal.” He was like, “Okay. Well, we're going to do some tests to see if we can find internal bleeding and if you're bleeding internally.” I said, “Okay.” So anyway, we did all of these tests. We can't find my blood. It's gone. It's missing. I have no blood– or half of my body's blood. I look like a ghost. I feel terrible. I can't function very well and he's like, “We can't find it. We don't know. You're not bleeding internally. You're not bleeding externally. We have no idea what's happened to you.” I'm like, “Okay.” So they said, “You need four bags of blood. Two blood transfusions. Two bags each.” I don't know why. It freaked me the heck out. It was a lot of someone else's blood. I know we've come a long way. I thank all of the donations. I thank all of the donations out there, but it freaked me out so I actually declined and to this day, I need to have radical acceptance. I question, “Why didn't I get blood? I would have felt better.” Julie: It took you forever to feel better. Meagan: It did. My levels were back to pretty much just above normal at six weeks. Everyone told me it wouldn't happen. Sorry, I'm weird. Yes. I ate my placenta. I did placenta encapsulation. I swear it helped. Everyone told me I was crazy. They were like, “You're not going to be able to breastfeed. You're in bad shape. You're really bad.” And I didn't do it. So I had that. Why didn't I do that? But all in all, I still have this, “What in the heck happened to me? What happened? How did that happen? Why did that happen? How does someone lose half of their body's blood?” Julie: And don't know where it goes because you didn't hemorrhage afterwards. Meagan: No. No. I had very little, normal blood loss after. Anyway, I have lots of questions. I have lots of hypotheses. I have a lot of things. Could this have happened? Could this have happened? I don't know. Maybe this happened. And some days, Julie, it does take over my mind. I get angry. I get confused and I sometimes question my team. Is there something that they know that they're not telling me? I don't know. I struggle. So I need to practice radical acceptance. Julie: Radical acceptance. Yes, you do. Meagan: Because that did happen to me and it is frustrating because I did say– so the signs of lack of acceptance is “This isn't right. It's not fair. It shouldn't be like this. I can't believe this is happening. Why is this happening to me? Why did this happen?” I have all of those feelings still. It's not fair. I had this beautiful VBAC. Now, I have this shitty– yes, I'm saying the word shitty on the podcast– postpartum experience. It was really hard and I was mad. I couldn't believe it was happening. It shouldn't be like this. I should be screaming from the rooftops, “You guys, I had my vaginal birth after two Cesareans!” But instead, I could barely walk. So I need to practice this radical acceptance. I need to recognize these signs and I need to get better because I am angry with the situation and confused. Julie: Yeah. Meagan: I feel stuck. I feel stuck. What happened? But like you don't know if your Cesarean was ever necessary, I may never know what happened to me. Julie: You will never know where all your blood went. Meagan: I will never know where all my blood went. Julie: Nope. Meagan: I will never know why I had ringing in my ears and why I passed out three times after I had him. Right? I will never know. So I have work to do. Julie: We all have work to do. Meagan: I was going to say, it's okay if you have work to do too. Women of Strength, we all have work to do just like Julie said. We have to take one step at a time moving forward and working through it and letting go of the painful past of the unknown. Julie: Oh my gosh. Okay, so I have something to say. Surprise. My therapist is obsessed with his wife. Obsessed. You wouldn't want anyone to be more obsessed with you if you are married to this guy. A few months ago, she came to him and she wanted a divorce. They are getting divorced now. Meagan: Oh my gosh. Julie: I know. It took everybody by storm. I was like, “What is happening?” Anyway, the details are not important, but he came to one of our trauma support groups the other night. He's not affiliated with the company anymore, but he just came because I told him to come and he listens to me because I'm his favorite. We were all going around the room sharing how we were doing and he wasn't going to share, but everyone got done. I came a little bit late and I was like, “Oh, did I miss his check-in?” He said, “Oh no, I wasn't going to share.” Then somebody else came in and they shared, and then he said, “You know, actually, I think I will share.” He was like– anyways, he had some concerns about sharing or not and he decided to share. What he said, I think, will always stay with me. But while he was sharing, he said, “This is the most pain I have felt in a long time, but I am sitting with it and I am letting myself feel it because I know it is the fastest way for me to get through it.” I was like, “Yes. Yes.” Sitting with that pain and that hurt and that discomfort is hard. It is so hard. So, so, so hard, but allowing yourself to sit with it and feel it and hurt and suffer is going to be the fastest way for you to get through that suffering. It's going to shorten the amount of time you have to suffer and it's going to stop it from controlling your life– maybe not right now. Probably not right now, but as you move on and as you go throughout your life, if you don't let yourself sit in that pain and struggle, then it will continue to control you and you will continue to be miserable. I just thought that was so impactful that he said that. I know that is the fastest way for me to get through this is to feel it. Meagan: Yeah, and that's scary, right? That's scary to say, “I'm going to open up and I'm going to welcome this pain.” Julie: And be vulnerable and receive it and hurt from it. Meagan: Yes. Women of Strength, as you are going through your births, you may run into this where you feel cheated or lied to or you are starting to question your own decisions or whatever. We've had an undesired birth outcome or experience and we hurt. They sting. They sting. But it's okay to one, sit with it like she said, and two, be vulnerable and be mad or angry or sad. It's okay to feel the feelings and then it's okay to have radical acceptance and move on. It's okay if it doesn't happen overnight. I love that. He sat with it or he's sitting with it. It's the fastest way for him to heal. Julie: Yeah, because he's a therapist, right? He obviously knows a thing or two. But sometimes it's hard even when we know. Meagan: Even when we know. Yeah. Yeah. So as you walk away from this episode today or drive away or wherever you are listening, we hope you know that we love you. We love you and you need to love yourself too. Offer yourself grace. Sit with it. Sit with it and find radical acceptance. Julie: We wish that for you. Meagan: Mhmm. ClosingWould you like to be a guest on the podcast? Tell us about your experience at thevbaclink.com/share. For more information on all things VBAC including online and in-person VBAC classes, The VBAC Link blog, and Meagan's bio, head over to thevbaclink.com. Congratulations on starting your journey of learning and discovery with The VBAC Link.Support this podcast at — https://redcircle.com/the-vbac-link/donationsAdvertising Inquiries: https://redcircle.com/brands

Drs. Lillian Siu and Melvin Chua discuss scientific innovations, disruptive technologies, and novel ways to practice oncology that were featured at the 2023 ASCO Breakthrough meeting in Yokohama, Japan, including CRISPR and gene editing, CAR T-cell and adoptive cell therapies, as well as emerging AI applications that are poised to revolutionize cancer care.   TRANSCRIPT Dr. Melvin Chua: Hello, I'm Dr. Melvin Chua, your guest host of the ASCO Daily News Podcast today. I'm a radiation oncologist and I currently practice in the Division of Radiation Oncology at the National Cancer Center in Singapore. I also served as the chair-elect of the ASCO Breakthrough Program Committee, and, on today's episode, we'll be discussing key takeaways from this year's Breakthrough meeting. The global meeting in Yokohama, Japan, brought together world-renowned experts, clinicians, med-tech, pioneers, and novel drug developers to discuss scientific innovations and disruptive technologies that are transforming cancer care today. I'm joined by Dr. Lillian Siu, the chair of the Breakthrough Program Committee. Dr. Siu is a senior medical oncologist at the Princess Margaret Cancer Centre and a professor of medicine at the University of Toronto.     You'll find our full disclosures in the transcript of this episode, and disclosures of all guests on the podcast are available at asco.org/DNpod.    Lillian, it's great to be speaking with you today.    Dr. Lillian Siu: Thanks, Dr. Chua. I'm happy to be here.    Dr. Melvin Chua: We were just at ASCO Breakthrough, and it showcased some incredible scientific innovations, and really showed us how technology innovations in precision oncology, biotech, and artificial intelligence are transforming cancer care. What are your thoughts?    Dr. Lillian Siu: Yeah, it was a really exciting meeting, Melvin. The theme of this year's Breakthrough meeting was “Shining a Light on Advances in Cancer Care.” And our Opening Session featured an illuminating keynote address by the renowned thought leader and tech trailblazer, Dr. Hiroshi or “Mickey” Mikitani, the founder and CEO of Rakuten and Rakuten Medical. In his address that was titled, “Innovative Technology and Oncology,” he spoke so passionately about innovation and really seeing around the corner to predict what is coming and taking risks. And I think that's what medicine is about, not just what we have in front of us, but to predict and forecast what's coming. I totally was inspired by his address, and I think a lot of the audience felt the same way. He also spoke to us a bit about his company's development in photoimmunotherapy using novel technology and light therapy in head and neck cancer. And I think that's also an area of new technology that we should watch in the next few years.    Dr. Melvin Chua: I totally agree with you, Lillian. And one of the quotes that he spoke about really spoke to my heart. He spoke about the 2 choices: whether to do or not to do and not to do is not an option. So, I think that was a very compelling message to a lot of our audience at the meeting.    So, on this same note, innovation is a driving force in oncology, and we saw countless examples of this throughout the Breakthrough meeting. Were there any sessions that really stood out for you?    Dr. Lillian Siu: There were so many exciting sessions. First of all, there is the “Drugging the Undruggable” session. This is a really important session because in the past we felt that certain cancer targets such as KRAS, MYC, etc., are not druggable. KRAS G12C is the poster child in this area. So, during this session we heard about many ways that we are now looking to target these so-called undruggable molecules in the cancer cell. And we talked about molecular glues, we talked about degraders, and really novel ways that are not yet reaching the clinic, called “cyclic peptides” were discussed by one of the speakers.     The other session that is very interesting also is CRISPR and gene editing. Obviously, we all know a little bit about gene editing, really trying to change or knock in some genes that are important perhaps to change the function. And one of the sessions talked about trail targeted induced mesenchymal stem cells, and perhaps this is a way to, again, deliver novel therapies and novel treatments to our patients. There were many examples of how CRISPR and gene editing can be ultimately going to the clinic to benefit our patients in terms of therapeutics.     I want to highlight another session, which is the CAR T-cell and Adoptive Cell Therapies. I think everybody knows about CAR T-cells, but in this session we talk about non CAR T-cells or newer things such as off the shelf NK cells, Natural Killer cells from cord blood. So, this way it is allogeneics, in other words, we don't have to rely on only a patient's donation of their samples, but actually get it from off the shelf from other donors. There are other ways to really use human induced pluripotent stem cells that we can armor them by transgenes and also CRISPR out any unwanted genes, for example, to enhance an effective function of T-cells. So many, many exciting ways to bring these cell therapies to the patients.     And last but not least, I want to highlight Dr. Chris Abbosh, who is one of our keynote speakers, talking about molecular and minimal residual disease and early cancer detection using circulating tumor DNA or liquid biopsy. He talked passionately about the TRACERx study, which he is instrumental in terms of leading together with Charlie Swanson in the UK. This is a study that really has uncovered a lot of science about cancer heterogeneity. And in that study, he also studied circulating tumor DNA and really shed a lot of light about clonal and subclonal dynamics over time that changes.     Dr. Melvin Chua: And just to touch on that point about innovation and how that translates to cancer care, I think it was great that we had those case-based applications in lung cancer, in breast cancer, and the virus-associated cancers. And I like how the speakers were able to bring in the Ying and the Yang, bring the West and the Eastern perspectives in these interactive sessions. I particularly enjoyed all of them. But the session on the lung case discussion where we know that there were this EGFR mutant lung cancers that are prevalent in this part of the world in Asia. I thought the interaction between the speakers was fantastic.     On the same note about therapies and we heard about novel therapeutics at this meeting as well. I wonder what your thoughts are about some of the sessions, and do you think some of these technologies were able to be brought into practice? And your thoughts on the novel therapeutic session that happened at Breakthrough, do you think this will actually impact clinical care?    Dr. Lillian Siu: Oh, for sure, Melvin. The 5 areas that were covered during the Novel Therapeutics session are really drugs already in the clinic. And for example, the first one was about antibody drug conjugates. We know there are now at least 12 antibody drug conjugates already approved by the FDA and many more likely to be approved in the near future. And the session really talked about what's next, how to improve upon ADC, for example, using better drug antibody ratio, talking about new payloads and really new formats that make perhaps ADCs even more potent in the future.     There was a session on oral immunotherapeutics. It was really how to target the innate immunity. And I think novel oral immunotherapeutics is very important because we all know PD-1, PD-L1 inhibitors have been the backbone, but we need another Breakthrough. And having oral immunotherapeutics will make it very attractive for patients because they don't have to come to the cancer center to receive the drugs.     Another part of that session was about T-cell engagers and bispecifics, really how to bring molecules to the T-cell, to the effective cells so that they are able to be phytotoxic to the tumor. We talked about also oncolytic viruses, how are the new ways to utilize this kind of natural agent to target the cancer cells. And lastly, we also talked about personalized cancer vaccine, which is obviously very timely. We all know a lot about vaccine now after the COVID pandemic and how do we use cancer vaccines to be a good therapeutic drug? I think especially important in the earlier disease stages as adjuvant therapy. Some exciting data, for example, in pancreatic cancer, as adjuvant really is groundbreaking for this whole topic of cancer vaccination.    Dr. Melvin Chua: That's great. And for me as a radiation oncologist who's not so deep in drug development, hearing all the talks at ASCO Breakthrough was really informative for me and I learned a lot. In particular, you spoke about the whole session there was oncolytic therapy and the results in glioblastoma multiforme, we know it's a deadly disease, was certainly very impressive. And so, it speaks to the whole notion that in fact, some of this stuff is in fact reaching the clinic and making a difference in deadly diseases. I think there's a lot to take in from there.    Dr. Lillian Siu: Melvin, you're so humble. I know you're a big expert in artificial intelligence and I think the whole session about AI applications in precision medicine really was not just in that session, but a whole theme that went throughout the entire meeting. So, I'm very interested to know what you think about some of the presentations around AI and disruptive technologies in precision medicine, such as next-generation multiomics, etc. What are your thoughts?    Dr. Melvin Chua: Absolutely, I agree with you. And there was so much material within the AI session, the multiomic session, as well as the keynote [address] by Dr. Maryellen Giger, which basically speaks about some of the pre-existing or historical work on artificial intelligence in radiology. And I'd like to first talk about the keynote by Dr. Maryellen Giger. It was very nice that she elegantly showed how AI was in fact already in practice in radiology, where it helped to fulfill or address a need for radiologists. Almost 20 years ago, they were able to show that using computer vision, you were able to basically facilitate the calling of abnormal mammograms. And it was inspiring to see how these early thoughts have now basically accelerated a lot of the advances that we see that are in practice today.     The other thing that was also was to see this global collaboration, the need for global collaboration in the artificial intelligence space and the radiologists are clearly leading the way. And I think part of the impetus for this effort came from an opportunity that arose during the COVID pandemic that clearly affected all facets of healthcare. That was a nice segue to the very sort of dense 1 hour session we had on precision oncology care with artificial intelligence. I think when we designed this session, we were very deliberate that we wanted to address all aspects of how AI could be applied. From real-world clinical data, we saw examples of how having good, well-annotated data sets could actually help to accelerate and facilitate liver cancer screening in Hong Kong. Then we also saw a very simple, practical application of AI in pathology, where apart from just having this tool to be able to extract features that could potentially predict outcomes of patients and predict drug responses, we saw a very practical example that applying AI in digital pathology could actually homogenize or harmonize the ways the pathologists review their cases. And so, I thought that was very neat and could speak to all our clinicians across both developed and developing countries.     We also saw very exciting stuff on the use of AI in terms of calling out mutations because we know that next-generation sequencing is pretty much a cornerstone of how we practice in oncology today. And yet we know that there are prohibitive costs that preclude this technology in certain parts of the world. And it was nice to see how AI could actually lower the cost of some of these sequencing technologies like being used in liquid biopsy.     And then finally, there was some fancy science as well that was showcased in the spectrum when we saw how industry as well as academics are thinking about integrating multiomic data sets to then be able to accelerate drug discovery, help define patients better, and so that we can think about how to look at precision oncology using targeted treatments for specific patient phenotypes. So I think this was a very nice transition to the Next-Generation Multiomic Technology session, where, again, some of these topics were touched on, ranging from liquid biopsies, and this was already covered in Dr. Abbosh's talk, which you spoke about, and as well as the preceding day session where we heard snippets of it. And it was again reinforced by the speakers when it showcased liquid biopsies. We have heard so much about it in the last decade and we see it made approved now for use in the clinic, but yet so much remains unknown, like the discrepancies between assays, addressing the cost of assays and, importantly, how we deal with the information. So, I think we are just at the tip of the iceberg here. A lot of the clinical evidence needs to be generated in due course to address some of these questions.     At the same time, it was also nice to see some of the new technologies being applied in discovery science. So, we know that immunotherapy is a major player in oncology today, and the Breakthrough represents a forum whereby we're able to bring translational scientists to showcase their work. And we saw examples of that at this meeting where single cell technology, digital spatial technology, being able to apply that in pathology specimens and how the two are integrated to be able to review more novel science to us, to show us how immunotherapy works or doesn't work in some patients. Both of us have touched on so much content that was showcased at the Breakthrough, and I think this speaks to the impact, the learning experience we've had from Breakthrough and I think that's the intended purpose of this meeting.    Dr. Lillian Siu: Yeah, I agree. It truly was a very exciting 3 days. And I particularly like the multiomics session where we see that the technology is so advanced just in a really short period of time. Over the last few years, we've been now able to go into single cell resolution where in the past I don't think we would ever dream of being able to do that. In fact, I recall in the single cell session, we can even see messenger RNA on the slide, which I thought was fascinating, something that I cannot imagine we can see by the naked eye. It really is an exciting time in oncology, Melvin, and the field is advancing with these new innovations and therapies, but at the same time, I think it's important that we do live globally and we need to work really also to help improve access to quality-assured cancer medicines and diagnostics in the low and middle income countries. What do you think about that part? Did we do a good job in addressing that in the meeting?    Dr. Melvin Chua: Absolutely, Lillian. We had a special session that was chaired by Dr. Peter Yu and the lecture was delivered by Dr. Gilberto Lopes from the University of Miami. And we know that he's a strong advocate for this. And the session title spoke to this topic very pointedly, “How Science, Technology, and Practice Can Be Enabled in Lower- and Middle-Resource Settings.” And I thought that the work that he highlighted, the whole ATOM coalition, was important. ATOM basically stands for Access to Oncology Medicines, and it was established last year by the UICC, the Union for International Cancer Control, along with global partners to improve access to anti-cancer drugs and to develop processes for ensuring quality delivery, as well as the optimal utilization of medicines in middle- and low-resource settings. And I think there's a lot more work to be done.     Some of the information they showed was very compelling to me from this part of the world. But we know that Asia isn't very heterogeneous in terms of the resources, in terms of the culture. And I thought that the drug pricing, for example, how that should be addressed across the different countries is an important topic to pick up. And I hope his lecture only invigorates this conversation going forward.     Dr. Lillian Siu: Yeah. Thanks, Melvin. I totally agree. That was very inspiring. Breakthrough is such a one of a kind, international gathering that we are not only able to network while we're there; we also have a session to really allow attendees to leverage international cancer networks, to learn a bit about them, all the way from, for example, some of the North American groups to Asia Pacific groups to even global groups, and how we interact between pharma and academia, really transcending boundaries. And I think it is really, really important for us to now have these networks address issues such as equity and cancer care innovation, novel approaches and so much more. And I think, I am sure you're going to do a good job in making sure that gets into the agenda in our next year's meeting in 2024. Ultimately, we hope that these collaborations in cancer research will help to improve the outcomes for our patients with cancer.    Dr. Melvin Chua: Thank you again for sharing the great highlights of ASCO Breakthrough, and I'm really appreciative of your work, and your commitment to build a really robust program for this year. So, thank you.    Dr. Lillian Siu: And thank you, Dr. Chua. And you can bet that I will not miss Breakthrough 2024 in Yokohama in August next year. I will be there.    Dr. Melvin Chua: Okay, I'll hold you to that.     And thank you to our listeners for your time today. You'll find links to all of the sessions discussed today in the transcript of this episode. And finally, if you value the insights that you hear on the podcast, please take a moment to rate, review and subscribe wherever you get your podcasts. Thank you again.    Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.    Find out more about today's speakers: Dr. Lilian Siu  @lillian_siu  Dr. Melvin Chua  @DrMLChua    Follow ASCO on social media:   @ASCO on Twitter    ASCO on Facebook    ASCO on LinkedIn      Disclosures:   Dr. Lillian Siu:  Leadership (Immediate family member): Treadwell Therapeutics  Stock and Other Ownership Interests (Immediate family member): Agios    Consulting or Advisory Role: Merck, AstraZeneca/MedImmune, Roche, Voronoi Inc., Oncorus, GSK, Seattle Genetics, Arvinas, Navire, Janpix, Relay Therapeutics, Daiichi Sankyo/UCB Japan, Janssen, Research Funding (Institution): Bristol-Myers Squibb, Genentech/Roche, GlaxoSmithKline, Merck, Novartis, Pfizer, AstraZeneca, Boehringer Ingelheim, Bayer, Amgen, Astellas Pharma, Shattuck Labs, Symphogen, Avid, Mirati Therapeutics, Karyopharm Therapeutics, Amgen    Dr. Melvin Chua:  Leadership, Stock and Other Ownership Interests: Digital Life Line  Honoraria: Janssen Oncology, Varian  Consulting or Advisory Role: Janssen Oncology, Merck Sharp & Dohme, ImmunoSCAPE, Telix Pharmaceuticals, IQVIA, BeiGene  Speakers' Bureau: AstraZeneca, Bayer, Pfizer, Janssen   Research Funding: PVmed, Decipher Biosciences, EVYD Technology, MVision, BeiGene, EVYD Technology, MVision, BeiGene  Patents, Royalties, Other Intellectual Property: High Sensitivity Lateral Flow Immunoassay for Detection of Analyte in Samples (10202107837T), Singapore. (Danny Jian Hang Tng, Chua Lee Kiang Melvin, Zhang Yong, Jenny Low, Ooi Eng Eong, Soo Khee Chee)       

A new research perspective was published in Oncotarget's Volume 14 on August 7, 2023, entitled, “CDK9 INHIBITORS: a promising combination partner in the treatment of hematological malignancies.” In their new perspective, researchers Daniel Morillo, Gala Vega and Victor Moreno from Hospital Fundación Jiménez Díaz discuss Cyclin-dependent kinases (CDK) in hematological malignancies. CDKs belong to a family of serine/threonine kinases that need to form heterodimeric complexes with cyclins to perform their functions. These kinases are involved in multiple processes within cells, including cell cycle, apoptosis, transcription and differentiation. These kinases are often overexpressed in different malignancies, making them potential targets for new drugs. Most hematological malignancies are characterized by overexpression of certain cancer promoting genes, such as MYC, MCL1 and cyclin D1. Preclinical studies in animal models have shown that CDK9 inhibitors suppress the transcription of these anti-apoptotic and pro-survival proteins, and suggest their potential synergism with other drugs. In its first in-human trial, enitociclib demonstrated clinical activity in a small cohort of patients with high grade B lymphoma with MYC and BCL2 and/or BCL6 rearrangements, inducing complete responses in 2 of 7 subjects (29%) in monotherapy. “In summary, most hematological malignancies are characterized by overexpression of certain cancer promoting genes, such as MYC and MCL1. CDK9 inhibitors are relatively new drugs that inhibit transcription of these anti-apoptotic and pro-survival proteins.” DOI - https://doi.org/10.18632/oncotarget.28473 Correspondence to - Victor Moreno - victor.moreno@startmadrid.com Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28473 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, cyclin-dependent kinases (CDK), CDK9, hematological malignancies About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

A new editorial paper was published in Oncotarget's Volume 14 on May 4, 2023, entitled, “AGO2 in T-prolymphocytic leukemia: its canonical and noncanonical deregulation and function.” In their new editorial, researchers Till Braun, Hanna Klepzig and Marco Herling from University of Cologne and University of Leipzig T-prolymphocytic leukemia (T-PLL) — a mature T-cell neoplasm with an aggressive and treatment refractory course. “In light of limited therapeutic options median overall survival times from diagnosis is hardly longer than 2 years.” There is currently no FDA- or EMA-approved drug for the treatment of T-PLL. Although 80–90% of patients experience a response to the most efficient single agent Alemtuzumab, relapses are common within the first 12–24 months following this first-line treatment. One of the defining characteristics of T-PLL is the presence of the chromosomal aberrations inv(14) or t(14;14), which lead to constitutive expression of the proto-oncogene T-cell leukemia 1A (TCL1A). This adapter molecule is centrally implicated in the enhanced T-cell receptor (TCR) signaling that is observed in the memorytype malignant T-cell. Other recurrent genomic alterations that have been identified in T-PLL affect the genes ataxia telangiectasia mutated (ATM), Janus kinase (JAK), signal transducer and activator of transcription (STAT), and MYC. In a recent study published by Braun et al., the team made significant advances in the understanding of the biology of T-PLL at the level of post-transcriptional gene regulation. “For the first time, descriptive and mechanistic data implicated the involvement of molecules of the RNA interference (RNAi) machinery in T-PLL's leukemogenesis and by that refined our current disease model by concepts beyond protein-coding genes.” DOI - https://doi.org/10.18632/oncotarget.28378 Correspondence to - Marco Herling - marco.herling@medizin.uni-leipzig.de Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28378 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, leukemia, T-PLL, AGO2, microRNA About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

This episode is a recording of our new live show hosted on AMP radio. You can download the app or listen to it on your computer - we go live every Sunday and during the middle of the week; Usually Wednesdays or Thursdays. So be sure to follow our Instagram (@rapnerds_msg) and Twitter (@rapnerdsmsg) pages, and follow us on AMP radio (@rapnerds) to keep up with our scheduled shows. During this episode, Curtis brought on his wife and let her curate the playlist for the Mother's Day Special Show. Check out Amber's set and listen to the discussion on why she chose these songs her for Women Empowerment playlist. Link to playlist — https://linktr.ee/rapnerds SoundCloud Edits: Doo Wop - Lauryn Hill (Josh Bracy edit) - https://on.soundcloud.com/LaZDJuRRA5yJauyp8 Energy (Remix) by Myc 88 - https://on.soundcloud.com/4AzjPWb9ru93hSzC9 Who's That Girl - Eve (DJ - Little Edit) - https://on.soundcloud.com/ykA1BQQBskoua54RA Cardi B / J Cole Mashup - DJ Leroy G - https://on.soundcloud.com/B2hggWRBWSNeRBiX8 Cardi B / J Cole Mashup by DJ Leroy G- https://on.soundcloud.com/AZhAFLRHhCs5n75g8

Brittany's first C-section came after a long and exhausting pushing phase with no progress. Her second C-section came after providers gave her a 50/50 chance of VBAC success due to the VBAC calculator. Brittany chose a repeat Cesarean for the comfort of a controlled environment following multiple traumatic pregnancy losses beforehand. She did not expect another horrible recovery with an elective Cesarean, but it was even worse than the first. Brittany immediately began devouring all information about VBAC after two Cesareans even before her third pregnancy. When she became pregnant, she found an extremely supportive provider 2.5 hours away which proved to be the best decision she could have made. Her VBA2C was everything she hoped it would be– raw, difficult, beautiful, redemptive, and empowering. Right after that birth, she wanted to do it all again! Additional LinksBrittany's InstagramHow to VBAC: The Ultimate Prep Course for ParentsThe VBAC Link Facebook CommunityFull Transcript under Episode Details Meagan: You are listening to The VBAC Link Podcast and this is your host, Meagan. I am always honored to be on this podcast with you. I love the listeners. I love the storytellers. I love the reviewers. We just love everything about this community and I am excited to bring a VBA2C– I'm not even going to be bringing it actually. Our friend Brittany is going to be bringing it. We are having a VBAC after two Cesareans story. Our most requested podcast topic is VBAC after multiple Cesareans, specifically two. We know how hard it is to find providers to support a VBAC after multiple Cesareans even though ACOG themselves says that VBAC after two Cesareans is totally acceptable and reasonable to go for. It's really hard and it's frustrating. I know as a VBA2C mom myself that it's so frustrating. It's so frustrating, right Brittany, to feel total defeat over and over again, being told that you cannot, you should not, and being filled with horror stories. I mean, all of the things. It's so frustrating and this is why we are here. We are sharing these stories. We are letting you know that you can. It is possible. It might not be easy along the way and you're going to hear today in Brittany's story that it's not easy but it is possible. So we have our friend Brittany like I mentioned. She is from southern Minnesota. She has been through quite the journey which she is going to share with you. If you want to know what some takeaways will be from this episode, one thing is finding that supportive provider just like we were talking about. It's so important. It's so key but we know that it can be challenging being rejected multiple times and being told no, and then not finding a supportive provider until the very end of pregnancy. You guys, this is something that I want you to know. If you are not feeling like you are being supported, if you are feeling or seeing the red flags, if something in your gut does not feel right, you are not stuck. You do not have to stay with any provider because they saw you for 34 weeks, 28 weeks, 40 weeks, 41 weeks, or even 42 weeks. You are not stuck. You can change. It's not always easy and we understand that, but you always have options to change. You can fire a provider at the very moment. We don't necessarily encourage you to fire your providers. I don't want to make it sound like, “Fire your provider!” but you can. If it's not feeling right, if it's not a good mix, you can say, “I would like to request a new provider at this time,” or you can start finding it through so many amazing resources like right here at The VBAC Link. Women of strength, if you are looking for a provider, write us. Go join our VBAC Link Community. We have a whole list of providers on there that have been known as supportive. I can't tell you. I'm just here in Utah. I've not met all of these providers. I've not talked to them. I've not interviewed them. These are providers that are being suggested by our other women of strength who have truly gone through this experience and believe them to be VBAC supportive. Their names are being compiled on this list for you all over the world not just here in the U.S. as guidance for you to help you find a supportive provider. So go to The VBAC Link Community on Facebook, answer the questions, and go check it out. And if you are listening today to this episode, please PM us on Instagram, Facebook, or info@thevbaclink.com. Tell us who your supportive providers are. If they are not on the list, we want to get them on. If you are a supportive provider listening, we want you on this list. It is so important and we as VBAC moms ourselves, and Brittany, I am sure you will attest to this. It is so important to have that provider on your side. It is so important. Review of the WeekOkay, I will jump off my soapbox and we will get to our Review of the Week so cute Brittany can share her stories. This is actually on our How to VBAC: The Ultimate Prep Course for Parents. Parents, if you didn't know, we actually have a VBAC prep course for you. It's filled with information on the history of Cesarean, the history of VBAC, the pros and cons, how to VBAC, and how to find these supportive providers. We will provide you with a lot of printables and things to take along with you on your journey to make sure that you've got the perfect team and that you feel confident in the birthing choice that you are choosing. This says, “This course was so helpful, especially with helping to educate my husband on the safety of VBACs. As he had previously been nervous about my choice, we watched all of the videos already and will also be reviewing the workbook again before birth. Highly recommended.” Thank you, Heather, for sharing that review. Yes, just like she said, this course is amazing. We have reading material and then we have a workbook that you can follow along. You can either download it or purchase a workbook to go along with it. We encourage your birthing partners to take this course with you because it is important for them to know this information. So check it out at thevbaclink.com if you haven't already and we will see you on the other side. Brittany's StoriesMeagan: Okay, Brittany. Brittany: Yes. Meagan: Thank you so much for taking the time today to share these stories. Like I said, we get emails and messages on Instagram and Facebook in our inbox saying, “Please share more VBAC after multiple Cesarean stories,” because there are times when we go in and we have an unplanned Cesarean and then sometimes we get coerced or we feel that it's best to choose another one, but then we start learning more and we want a different experience. We know how hard that is. I welcome you and let's turn the time over to you. Brittany: Absolutely. I am honored to be here. I am very excited to share my story. I know am a mama to three babies. I'm going to share a little bit about my C-sections before I move on to my vaginal birth. I found out I was pregnant with my first son in 2016. I'm sorry. I had him in 2016. I was actually newly sober. I'm a person in recovery so I was very new to a lot of things in life. I was going to be a single mom and I also was sober so a lot of big changes were going on at that time. I was very uneducated about birth, being a new mom, and everything at that time. I was going through so much at the time obviously and then I was nine days overdue which we know truly isn't overdue but that's what they say. At that point, I just wanted to have him. I was not educated about interventions or anything like that so I just went with the punches. Whatever the providers and team wanted, that's what I did. I also knew as much as possible, I didn't want as many pain meds as possible just because of my recovery from substances and I really liked narcotics so I knew that I didn't want to go down that slippery slope. I allowed them to induce me with two doses of Cytotec. It started working but then they wanted to break my water and I allowed them because I truly didn't know better or have any information on that. I got an epidural super early even though I think I panicked more than anything. I didn't want to have pain so I just got it not knowing that I was going to have a long labor and being stuck in bed wasn't going to do me any favors. After laying in bed basically for 24 hours, I pushed for two hours. He was not descending. At that point, I was truly done. I was exhausted. I had been up for two days being induced, so we decided on a C-section. He was sunny-side up so that's what made it more difficult for him to come down which made sense. So he was here. Recovery was rough. I'll talk about that a little bit more later. Fast forward to some time in 2017, I went into the ER. They couldn't really figure out what was going on with me. I really wasn't feeling well. Long story short, I actually had an ectopic pregnancy. I was on the IUD at the time so I had no idea that I was even pregnant. It was very traumatic. I went from not knowing I was pregnant then they had to take the baby out. I actually lost one of my tubes at the same time. I had to have lifesaving emergency surgery. I was in the hospital for five days and they couldn't do it laparoscopically. They did have to cut me all the way open and take everything out. So that was very traumatic and a very big loss. Then I met the man that I eventually married in 2018. We experienced an early miscarriage in 2018 as well so another loss. In 2019, we found in late 2018 going into 2019 that we were pregnant with our rainbow baby. At that point, I was very unsure of what I wanted for my birth. I knew how terrible my C-section experience was but I was also terrified of laboring for that long and then ending up with another C-section again. I trusted my doctors. I was listening to them. Of course, they did the VBAC calculator and at that time, they told me I had a 50/50 chance. Being that he never descended, they said, “It's up to you what you want to do” and I had lost two babies. I just wanted a baby here safe so I was like, “You know what? 50/50. Let's just go with the C-section.” I was hoping that not having that long labor beforehand would really help with my recovery. I just wanted my baby here safely too. With it being my rainbow baby, I just wanted my baby here. Meagan: Absolutely. Brittany: Yeah. My C-section, the surgery itself went fine with my second son but it was an even worse recovery. I had a severe reaction from the adhesive tape that was on my belly. I broke out completely all over my whole body.  Meagan: Oh man. Brittany: I had shoulder pain and I have high blood pressure so it was very scary to have shoulder pain. It was very scary because I instantly thought of heart problems. It was just shoulder pain from the C-section.Meagan: It's usually air actually crazy enough. Air gets trapped. I had that too. I was like, “What is happening? Is this my milk?” They were like, “No, it's air.” Getting up and walking can really help but it can sometimes get trapped up in that shoulder or even the rib area. Brittany: Yeah, so strange. I was so sick and throwing up for 36 hours. Meagan: Oh, and with a new incision. Brittany: And then I was dehydrated and blacking out from that. It was just an absolute, awful mess. Basically immediately after he was born, I began researching vaginal birth after two C-sections because I knew I never wanted to do that again and I knew we were not done having babies. I binged every single episode that you guys have. I couldn't listen to them fast enough because I knew I wanted all of the information before we had another baby. Even before we were trying, I was doing all of this. I read many books and watched YouTube videos. I was practicing meditation and mindfulness because the mindset is such a big part. I learned about HypnoBirthing and I was also so much healthier. I gained way less weight. I was eating healthier. I was being active and trying to be as mobile as possible to let the baby descend when that time came. Like I mentioned, I do have chronic hypertension so I really wanted to keep that in check because I knew that would be a big red flag for everyone. So then eventually, we did get pregnant with our third baby. I was still doing all of my research and things like that. At that time, I actually did hire a doula as well. I wanted to do everything I possibly could. She was very supportive of a VBAC after two C-sections. So then we started the hunt of trying to advocate for myself. I really worked on relaxing myself just to get in that positive mindset. Initially, where I gave birth to my birth son, they now do some VBACs but they will absolutely not look at people who have more than one C-section and then it's case by case for just a single. They were like, “No, you either have to go to a C-section or go to the high-risk unit.” I said, “Okay, then send me to the high-risk unit. That's what I want.”At 32 weeks, they saw me at the high-risk and complex unit. This was basically to see. They would assess me and see if they believed that I had a fighting chance. My blood pressure at the time was in a great range and I was actually off medication because I was so healthy doing what I needed to do. Meagan: That's awesome. Brittany: Yeah, it was great. I advocated for myself with them saying, “I hired a doula. I have a supportive husband. I have done all of this research. I know what research truly says,” and of course, they pull out the calculator. Meagan: Oh boy. Brittany: It kind of depended. Sometimes it put me at 20%. Sometimes it put me at 40% depending on who did it because of the blood pressure and because of the two repeat C-sections with no vaginal birth before that. They said they would work with me. That was their wording yet they said that they wanted me to have a C-section no later than 38 weeks. Meagan: No later than 38 weeks? Brittany: Yep, yep. Knowing that my first son came at 38.5 weeks, I knew that was probably not likely. I was also in the mindset that if I went to 42 weeks, I was okay with it because I knew that as long as they continued to monitor things, then it was okay. I knew that if I didn't go into spontaneous labor myself, so say that my blood pressure spiked or anything like that, they would not do anything to help induce me. No low Pitocin, nothing like that, no breaking of water, nothing. I would have to do it all on my own. I knew that was a huge barrier too. Meagan: Yeah. They're putting restrictions on you already. Listeners, if you are getting, “Yeah, okay,” but then you are getting restriction, restriction, restriction, then it's probably not the right space. Brittany: Yeah, exactly. Those were my first thoughts. If I'm already knowing that these restrictions are being put up, I'm going to hold in more tension even when I come here and just wait for some kind of failure in the process for them to say, “Okay, we need a C-section.” So I truly wasn't even getting a chance to try. I literally left the office bawling with my husband. And of course, my husband is not as educated as I am because he's not going to be giving birth. He's very supportive and educated just not to our level but they fearmongered him. They made us, not me because I knew the statistic and things, but he was more worried like, “Are you sure this is safe?” and things like that. I was feeling so discouraged. I was 32 weeks pregnant and I was like, “What am I going to do because I know this isn't going to work?”I actually have a very good friend who had her first baby by a C-section and then she had two VBACs after that. She was one of my biggest supporters. She rooted for me so hard. Meagan: She was your motivator and in your space. Brittany: She had to be induced at 37 weeks with her babies due to being high risk with medical complications and she still did it. She just really gave me hope. We began researching together. She literally lives in a different state and she was researching with me. Meagan: That's amazing. Brittany: It is so amazing. That's what's great about this community. We found a provider that actually is 2.5 hours away from where I live. I knew it was crazy, but I was like, “You know what? What does it hurt for me to even go and see this guy once?”Meagan: Listen, it's not crazy. It's not. I know it sounds crazy and the world we live in makes it feel crazy to go so far. It's not crazy. It's not crazy. It's just you advocating for yourself and finding what you need for yourself. Brittany: I came on Facebook groups with you guys and other VBAC groups specific to our area. I just read testimony after testimony about how amazing and old-school he is. I called and even at this point, I was okay if insurance didn't cover things. I just wanted this. He's a different breed. He's a lone wolf, one of those very rare people that we find. I made an appointment. I believe it was for about 34 weeks so it was still a couple of weeks away. When the appointment came, I actually had influenza so I had to cancel it. I was like, “Oh my gosh. Everything that could work against me is working against me.” I said, “Nope. At his next appointment, I'll go.” I went and he had my medical records but he barely looked at me and he was like, “Yep. We're going to do this.” He was so positive. Meagan: Wow. Wow. Brittany: Not that we were going to try, but that we were going to do this. That was great. I continued to go to appointments weekly until post baby's due date. But also he was not naive. He told me the risks of both very realistically but not in a scary way. Just like, “This is what it can look like.”Meagan: These are the facts, yeah. Brittany: The clinic has just a small-town, homey feel. It's truly about the patient. It's not like we are just another number. Truly at the end of the day, he gave me the empowerment that not only was I going to do this but he was going to allow me to try. That's all I wanted was to be able to try this and to have hope in myself. At 38 weeks, we discovered that my blood pressure had skyrocketed. The next day, it continued to be so they monitored me for a little while. I'm also 2.5 hours away so they kept me for a little longer. The next day, it continued to be. Being that I was in a safe zone, the doctor said, “Would you be okay if we did a slow induction?” At that point, I trusted him even though I truly barely knew him. He gave such good vibes. My husband loved him. I said, “Absolutely.” I was completely closed so it did not seem like any baby was coming anytime soon from looking at it. At 7:00 PM that night, they inserted the Foley bulb to help me dilate. At 8:00 PM, my body actually took over and I had some major contractions. My job for the night was to rest, let the bulb do its work and just mentally get in the mindset that we were going to be in labor the next day. In the middle of the night, my COVID swab came back positive even though I had no symptoms. Meagan: Oh no and you had just gotten over influenza. Brittany: Yes. That was very interesting. My doula, this was the one weekend that she was unavailable of course, so she had her sub-doula available but she couldn't come in because of COVID. She was only available by phone which was a bummer but we made it through. 12 hours in the next morning at 7:00 AM, the Foley bulb was removed and I was 4 centimeters. That was great because with my first son, I had already gotten the epidural and I was panicking at that time. I was already in a great mindset. I was managing the discomfort so great. He started the Pitocin super slow and low. That's what he's known for, starting it super low and slow at the smallest amount possible. The baby's heart rate had some decels so they turned the PItocin off for a while, no panicking. They were just going to go with the flow. At 10:00 AM, they broke my water. We just hung out. I was feeling good. My contractions picked up on their own without that Pitocin ever being restarted. My body began doing it with that very little bit of intervention. At about 1:30, I began struggling pretty badly with pain and pressure. I stated, “I want an epidural.” Everyone knew that I didn't want that so I said that I would wait another 15 minutes and give it a minute. I still wanted it 15 minutes later and I knew in my mind that I was holding so much tension in. I just couldn't let it go so I was like, “You know what? At this point, let's do the epidural.” We did it. As soon as the anesthesiologist came in, I knew that I made the right choice. I was already feeling that relief that I was going to feel from just letting my body relax. I knew how important the mindset was that I just needed to let my body do it. Baby's heart again had a few decels but the team worked great to reposition me after the epidural was in. I could still feel the pressure of the contractions. I could tell we were progressing but at 2:45, I progressed far enough to be able to push. I progressed very quickly from being completely closed to being here very quickly within less than 24 hours. The team was so supportive. I could feel the baby moving down still, that pressure. I was ecstatic. Once we started the pushing phase, I was very nervous because that's how far I got with Benny, my oldest. I had pushed with two hours with him and he had never moved down. I was very scared that that was going to happen. With the first push, I knew it was different. I could feel him moving. I could feel the baby moving down. We were gender-neutral beforehand and at 3:44, our sweet baby girl was delivered vaginally. Meagan: Aww. Brittany: Yes. It was quite amazing to feel baby on my chest. It's still shocking now feeling the baby on my chest and having my husband look. He was crying and was like, “It's a girl.” After having two boys, it was the icing on the cake. It was absolutely amazing. Meagan: Yeah, and a different postpartum experience?Brittany: Absolutely. My provider had known how traumatic my C-sections were and then of course with my ectopic, completely being cut open with that too, it was totally different. It was stunning. Even with the epidural, I barely had the epidural so it's not like it was running for a long time. I was never able to eat right away after birth. I pretty much ate almost all labor until the epidural and then to be able to eat as soon as I wanted to right after without throwing up, that alone was huge. I could walk practically right after. No crazy abdominal pain because of the C-section. I could help the baby right away whereas I was stuck in bed for so long after the C-section. The doctor looked at me and he was like, “How is this?” I'm like, “Indescribable.” Meagan: Do you even need to ask? Brittany: It's insane how different C-section versus pure vaginal delivery was. I was ready to do it again. My husband was like, “Okay, we're done having babies because we got our girl.” I was like, “I'm ready to do it again.” Meagan: Yes. Oh, I was the same way. I was like, “No, I want to do this again. This was amazing. I got the birth that I wanted.” There is something special. I want to also point out that sometimes vaginal births can be traumatic too but there is something about that baby being placed on your chest after you've gone through some less ideal or traumatic experiences. Yeah. It's hard because you compare it and you're like, “This is a breeze.” It's still hard. Recovery is still hard but it's just magical. Oh, I love it. I love that you at the end of pregnancy were like, “No. We're going to do something differently.” It ended up being an induction so it was like, “Hey, come. Drive and come and it's planned.” But I would love to know or I'd love for you to share if you can any of your plans for listeners assuming that it was going spontaneously. I think a lot of people get nervous. It's a daunting feeling. They get nervous about, “When do I go? What do I do? It's a long drive.” Do you have any tips or suggestions of what your plan was to travel that distance assuming spontaneous labor went into play?Brittany: Absolutely. We talked about that. That was one of my husband's biggest worries because obviously, he would be driving me. We knew first of all that obviously every labor can be different but that my son's took forever. He was also induced. We were hoping for that but then also, we knew and had great backup for the other kids for daycare at a moment's notice. We had great people to be able to drop them off at. We had talked to the provider too. Basically, if my labor got at all semi-regular if it had happened at home, if my water broke, I was going to head right in because we knew we would be having a baby. We also knew with having two C-sections that we wanted to be near medical attention just in case. We knew that even if my contractions started coming semi-regularly that we would likely head in. I was ready to labor hard in the car if that's what it had to be. Also, say all of a sudden, I got pushy and that's how fast it was progressing, we were okay going to our hospital closer just because then, I'm in the thick of it. We don't want anything to happen to anybody but we knew that it could possibly be a barrier having to drive all the way 2.5 hours to this hospital. Meagan: Yeah. That is a really good point. Preparing to labor hard in the car is no joke for sure. Obviously, that's not what happened but preparing yourself mentally is so beneficial because if that does happen, it can take out some trauma because it could be traumatic in the car if you're not prepared for that and labor is progressing, and then of course, having that plan of, “Okay, if things shift and I'm pushing that baby out, we'll go to this nearest hospital.” Also, I would suggest, you were saying, “Oh, if things were getting active then we would go,” but you could also, when you get there, you don't have to go straight in but just be in the vicinity. Grab a hotel or go to a park and walk around. Just be close by. Preparing for that financially as well if you're getting a hotel or something like that is something that's important because you don't want to have anything crazy happen but also educate yourself on the signs of something going wrong so if you know that it's happening in the car and you still have 45 minutes, you can just go to the nearest hospital at the next exit or whatever. Brittany: Yeah, absolutely. Meagan: Great tips. I seriously love that. Prepare to labor hard in that car because it can happen. Congratulations to you and I am so proud of you on all of your journeys. It's hard because we've had these Cesareans, undesired, sometimes traumatic, or desired with unidentified outcomes where you wouldn't think that it would have been like that. These are the stories that make us who we are today. It's these stories that are changing others' lives and empowering them. Whatever your takeaway is from today, maybe it is recognizing a supportive versus non-supportive provider. Maybe it is figuring out what you need to do for yourself. Maybe it's traveling or whatever it may be. Maybe it's scheduling that repeat Cesarean. Whatever it may be, know that it is your birth. It's your birth. This is your body. This is your baby. This is your future and whatever decision you make that is best for you, we here at The VBAC Link support but do have all of these resources for you to turn to and learn so you can know what your options really are. Brittany: Yes. Information is key. That's one of the biggest things I took away. I am all for people making whatever decision they want in regard to anything including birth, but I just want people to have the information, the correct information, to be able to make those informed decisions. Meagan: Absolutely. Absolutely. One other quick thing I wanted to talk about is how you went in for a VBAC after two Cesareans with no progress. There wasn't any progress being made meaning that your body was not showing signs at that moment of labor beginning or progressing. They started with a Foley bulb or a Cook catheter depending on where you are or what your hospital uses. That can be something that a lot of providers will refuse to use if you're not dilated to a 1. Now, I want to preface. You'll have to tell us actually. It can be very uncomfortable getting a Foley in with no dilation because they're putting a tiny little tube in something that is closed. Brittany: Yes. Yes. Meagan: That is definitely a little bit of a disclaimer there. It can be very uncomfortable but just like Brittany and I want to say it was Shannon? I could be totally wrong. It was a VBAC after three Cesarean birth. She ended up doing a little bit of Pit to try and get her cervix to do something and then got a Foley in. It barely opened if I remember right. It just shows that it is possible. It is possible. They may say that it's not possible. I will say that it's not common for them to do it but it is possible. You can request it. Yes, prepare yourself mentally because I don't know Brittany if you want to describe it at all but it's possible. It's possible to do that. So if you're in a situation and they're like, “You are in no state to be induced,” but you're really not feeling like you want to do a scheduled C-section, try it. Brittany: Yes, totally. It was very uncomfortable. It was truly painful. I had been induced with my first son so I knew what labor was like, but I was like, “Oh, this is pretty rough.” But hands down, I would do it again. After that initial insertion which took a little bit because I was completely closed– Meagan: And probably posterior a little bit so they had to send the tube up and forward. Brittany: It was rough. I was worried that it wasn't going very well, but it just takes time because I was fully closed. I had pretty good contractions just from that for an hour. My body totally took over which was good. I mean, but then it was such good progress. I slept all night. By morning, I was 4 centimeters. I mean, can you honestly ask for more than that? Meagan: That's amazing. Brittany: That was the perfect start to an induction. Meagan: Yeah, absolutely. Absolutely. That's one of the things that the Foley can do is it can get your body to 4 centimeters, sometimes even to 5 centimeters. It's also important to note that sometimes when it falls out, the cervix relaxes. Do you like my sound effects? It's hard because we can see each other. She can get my emotion. It can relax and go backward. It doesn't really go backward, it just relaxes. So sometimes keep in mind that if a Foley comes out at 4 centimeters, you might be closer to 3.5 or 3 but it stretches to a 4 because it just stretched to a 4. If you get checked again and they're like, “Oh, you went backward. You're a 3.” No. Don't let that get in your head. And then they started low-dose Pit and things. That's something I wanted to point out. It's not something that is super common and oftentimes, providers say no but it is possible. Brittany: It was absolutely incredible. I mean, really the biggest thing is to educate yourself. I went to the chiropractor. I did all of the things. I was in so much pain at 37 weeks pregnant, 36 pregnant. I'm a firm advocate of the chiropractor anyway. I love it for everything. Helping my kids poop as weird as that is–Meagan: Oh no, I know. I've done that too and it's amazing. It works. Brittany: Yes. So I had been going very regularly anyway because I knew how much that can help get baby in place and help with pain, help with hips. I was in so much pain and I'm like, “Oh no. This is not good. I can't be in this much pain going into birth.” My chiropractor actually got COVID of course right around that time so I was like, “I can't even see her. Who knows if I'll get to see her again before I have his baby?” I was lucky enough to find a very nearby chiropractor the day before I went in to be induced. I swear that helped a lot too. Just incredible. It turned out beautifully. Meagan: Absolutely. Yeah and if sometimes you're having prodromal labor or if labor it just carrying on, carrying on, and carrying on, going and getting an adjustment can be a game changer. Yes. Awesome. Well, thank you so much for being here with us today and sharing these beautiful stories. Brittany: Thank you. ClosingWould you like to be a guest on the podcast? Tell us about your experience at thevbaclink.com/share. For more information on all things VBAC including online and in-person VBAC classes, The VBAC Link blog, and Meagan's bio, head over to thevbaclink.com. Congratulations on starting your journey of learning and discovery with The VBAC Link.Support this podcast at — https://redcircle.com/the-vbac-link/donationsAdvertising Inquiries: https://redcircle.com/brands

Dr. Doug Green is the Peter C. Doherty Endowed Chair of Immunology at St. Jude Children's Research Hospital. His research focuses on the central mechanisms of cell death, survival, and the immune response. He talks about what happens when cell death fails, the role of Myc, and setting up collaborations in science.

We are so excited to have Kaitlin McGreyes from Be Her Village here with us today! Kaitlin began Be Her Village as an avenue for women to register for birth services instead of typical baby shower gifts to help support their transition to motherhood. Kaitlin shares how through her Cesarean and VBAC stories, she learned how to become an empowered and active participant during birth. Kaitlin and Meagan also answer a burning question. What is the real formula for how to have a successful birth outcome? Research, research, research, then trust yourself to make choices that are best for YOU!Additional LinksKaitlin's WebsiteHow to VBAC: The Ultimate Prep Course for ParentsThe VBAC Link Facebook CommunityFull Transcript under Episode DetailsMeagan: Hello, hello you guys. It is Wednesday or maybe Friday or Thursday or Tuesday, whatever day it is that you are listening, today is Wednesday when we are recording The VBAC Link Podcast. I've been a little giddy for this episode because we have our friend Kaitlin. She and I connected. She is with Be Her Village and we actually connected two weeks ago. Maybe a week ago, a little bit ago. We got off the phone and we both felt the same feeling, this energy. Can we just be best friends? That's what you were saying. We're best friends. It's just so fun. We definitely have very similar passions and drives for the birth community and VBAC and all the things. She has a story of her own today that truly led her to where she is right now which I think is one of the biggest things that relates the two of us because my journeys led me to where I am right now at my desk recording this podcast and serving this VBAC community. So I'm going to introduce her a little bit more in just a moment, but we do have a Review of the Week. Review of the WeekThis was actually sent via email as well. We got two emails back to back about reviews. Just a reminder, if you have not had a moment to leave a review, please do so. We love them. They mean the world. Our team loves reading them. You can leave them on podcast apps like Apple or Google. You can send us a social media message on Facebook or Instagram or you can be like Daria did and she sent it to us via email. That is so wonderful as well. She says, “I just wanted to leave a review of my favorite podcast. It's almost an obsession at this point. I had a C-section with my twins almost two years ago and am currently pregnant with baby number three. I'm writing in March as I listen to your podcast on my walks and get ready for VBAC as much as I possibly can. I can't describe how much valuable information and most importantly inspiration it gives me. Maybe it's just pregnancy hormones but I swear I cry every time I listen to moms describing the emotional moments of their birth stories. Nothing feels more precious to me at that moment. I am dead set on having a VBAC in August and all of the episodes of the podcast give me extra encouragement and strength to advocate for myself. I religiously listen to every new episode and maybe I'll get to hear this review soon.”Yes, you will. It is coming up soon, just before your VBAC actually, Daria. It says, “Look out for my next email in August with hopefully a successful VBAC story. Thank you so much again for everything you do for women all over the world.” Oh my gosh. Then she says, “P.S. English is not my first language. I'm from Ukraine but I hope my English is fluent enough to reflect my feelings.” Oh my gosh. Kaitlin, is that not just an amazing review?Kaitlin: I really just feel it. I'm sitting here getting ready to tell my story and I'm getting teared up about the fact that the people listening are in my position right before I had my VBAC. It's such a place of unknown. It's such a place where you need support. It's such a place where there are so many forces working against us unfortunately and the fact that this podcast and my story might help someone in their preparation. It might impact them. It might be what they need to hear to stay and get furiously determined. Oh my god. I love it. I want to give her a hug.” Meagan: I know, right? I just want to squeeze her and say, “I love you. I love you. Yes, you can. Yes, you can advocate for yourself. Yes, you can do the things that so many people in this world believe are unachievable.” It makes my heart so sad to know that there are so many people out there that want a different experience and are told they can't or are told it's not possible. Yeah. I love that you're here. I love that you're in this space. I cannot wait for your email in August myself. Kaitlin's StoriesKaitlin: Oh my goodness. I am so excited. Let's get her her VBAC. Meagan: Yes! Let's do this. Yes. You get so invested Kaitlin. It's so amazing. You get so invested in this community. These people are writing and are like, “Hey, I have a question.” By the way, if you didn't know, you can always email us at info@thevbaclink.com and write us your questions. We love speaking with you. We love doing consults. We love doing all of these amazing things to connect with you and to build you up whether that be through a consult or the blog or just an email or this podcast or our VBAC course. Whatever it may be, we want to help you through your journey.Kaitlin: It's amazing. What you guys are doing, I'm so excited to even be here. This is the work. I've been a doula. I've helped so many people achieve their VBACs and witness them. I've literally been in the room with them, but this platform and everything you've created with it is helping so many people. It's so powerful to have this narrative change. It's so powerful for us to tell our stories and counter what the doctors are telling us, counter what maybe other people in our families are telling us. This fear and this risk and this, “How could you be so irresponsible to think about a vaginal birth? How selfish?”I don't know if we're allowed to curse here, but that is what drives me and that is so powerful to be like, “Nope. I did it. I trusted myself. I trusted my body. My body is not broken. I can do this with the right support, the right advocacy, and a little bit of luck.” Not going to lie, there is a little bit of luck in there. We can do this. That's such an incredible message that we need to keep spreading again and again and again. How awesome is this? Meagan: Oh my gosh. I couldn't agree more. Okay, you guys. We have Kaitlin and if you can't already tell, we just are so passionate about birth and options and birth workers and all of the things. I'm so excited and honored to have you, Kaitlin, on this podcast. You guys, she is the founder of Be Her Village. Be Her Village. Definitely go check it out. She started doula work in 2014 which, you guys guess what? So did I. I didn't know that until actually just barely. We started around the same time. She is so passionate about creating access to maternal care for all. She has a gift registry on this Be Her Village. You guys, it's a platform. It is literally– actually, I'm going to let you talk about it because it is literally amazing and genius. Genius. Kaitlin: Thank you. Meagan: It is such a great tool for people because I'm sorry. I love all baby clothes. I love my baby clothes so much. Kaitlin: I love baby clothes too. I don't tell anybody that, but I also love baby clothes. Meagan: I do, but after my two Cesareans specifically, actually even after my VBAC, luckily my husband was in a situation where he could be with me. He was home all of the time so we had the support but he could have even used some support. I loved all of those cute little baby gifts, but to have some resources or to have that doula that I wanted to hire with my second but my husband was like, “We can't afford it. I don't like the idea.” Right? Tell us about what you are doing with Be Her Village. Kaitlin: Awesome. Absolutely. First of all, thank you for having me. Meagan, I just love you. I love what you are doing. Everyone who is listening, thank you for this space to tell my story. Be Her Village is just my answer to having a baby and having this perfect nursery surrounded by all of the gifts, all of the wonderful, generous things that my friends and family showered me with, and actually having nothing I needed. Just feeling completely alone, being post-C-section because I didn't have a doula. I couldn't afford a doula. I didn't know that I needed a doula. That wasn't the norm. I was just surrounded by all of these gifts and had none of the support. Breastfeeding was hard. The C-section recovery was hard. Life with a newborn was hard. It's just difficult. What I've realized is that our community has so much love to give. They've sort of been tricked into this idea that all I need is stuff. We need stuff.Meagan: Wipe warmers. Kaitlin: Yeah, wipe warmers and seventeen different bouncers.Meagan: You don't really wipe warmers. Yeah. Kaitlin: It's a little extra. I feel like we can get all of the stuff in the baby nursery. You can get a whole baby's store worth of stuff and you're still going to need some support for yourself as a mother. So I thought of Be Her Village. I was like, “Why don't we connect parents with doulas and why don't we give doulas, lactation care, postpartum care, and pelvic floor visits as baby shower gifts?” What an incredible gift to be like, “I'm going to help you get your VBAC. Here's a doula to help you advocate for yourself. Here's a pelvic floor provider so you can get back to running, Cross Fit, or exercise,” which for many of us is a mental health tool. What about impactful gifts that actually care for the mother so she can take care of herself and her baby?Meagan: Yes. Yes. This is something Julie and I did when we were together hundreds of episodes ago saying that you can afford a doula because we are huge advocates here for our doulas. Clearly, we've seen the impact and we just know this impact, but we talk about asking for money towards something else. You don't have to. But this is an actual tool and resource where it is easy to do that. It is easy to do. It is easy to register for that. It's incredible. I'm obsessed with it.Kaitlin: Thank you. Meagan: I'm obsessed with you and I just can't wait to one day actually finally meet you in person. Kaitlin: Oh for sure. Meagan: Yes. Just yeah and just to see you grow because this is so amazing. Women of strength, we understand. We understand that finances are not always in a place to have a birth doula, a photographer, a lactation consultant, a postpartum doula, and a PT pelvic floor or to give birth out of a hospital and all of these things. We know that these things cost. We know that they do but I'm telling you right now there is serious value in this and it is honestly so amazing to have a doula or support versus a baby wipe warmer or one extra pair of newborn onesies. Kaitlin: Yeah. I want to provide insight into that. It's not just that it feels good to moms because that's something that we're not always comfortable with. “I'd rather get something for my baby. I don't need to feel good. I can do hard things.” And we can. We can do more than we know. But using a doula reduces your chance of a C-section. Using a doula reduces your chances of an episiotomy which is where they cut your perineum. It reduces the chance of forceps use or vacuum use. It reduces–Meagan: Time in labor. Kaitlin: Time in labor which I'm like, “Just sign me up right there. Are you kidding? Forget about it.” Meagan: Labor can be shortened by at least 41 minutes. Kaitlin: And you know what? It's more than just the shortness of the labor, it shortens pushing time and it increases the APGAR score of the baby which is literally the baby's health upon being born. There are just so many things that a doula does. It's not a promise that one doula will do that for you but collectively when people line up doula support, their outcomes, and their baby's outcomes are better. If you're thinking about a VBAC which I'm guessing you are if you're listening to this, you need to get a doula. You need to think about a doula. It has always been this thing that I personally even as a doula felt uncomfortable saying and recommending because how can you say, “Hey, doulas are vital. Sorry, you don't have $1000.” Meagan: Or more. Kaitlin: Or way more. It's such an uncomfortable conversation. That's why I created Be Her Village because 12 billion dollars are spent on baby gifts every year for baby showers. It's like, “Well maybe the generosity exists. Maybe the love exists and maybe the money exists. We just need to create a platform where people can line up their doulas and ask for them for their baby shower gifts.” That's exactly what we did and we've had over $135,000 gifted on Be Her Village directly to parents. They're getting the gifts. They're getting the support and it's literally the coolest thing in the world. Meagan: It's so amazing. Kaitlin: It's just so cool to see it come to life and to have people find out about it, then literally get better gifts that are taking care of them and improving their entire experience. Unfortunately, it's because I needed it. I wish I could go back in time and do it again which is something we really often hear is, “Oh my god. Where was this when I was having my baby?” Meagan: Right? That's why I'm here right now. I needed more. I felt alone in so many ways preparing for my VBAC. Everyone looked at me and was like, “What? You're doing what?” I'm like, “Yeah. I want to push a baby out of my vagina. Why does that seem so weird?” Because I had that Cesarean, everyone was like, “No, you can't do that.” I'll tell you what, when I came around to that second C-section and was wanting to have a vaginal birth, it was even more mindblowing to people. It felt very lonely and cold. I was like, “No. No.” There wasn't a lot of inspiration. Facebook was going on and there were stories being shared but there wasn't inspiration like what we have today. There wasn't a lot of knowledge in one spot so that's why we're here today. Kaitlin: I have to say that one of the things too, and there is so much to talk about, but this is actually part of my birth story too so it's such an interesting place to begin. I think people legitimately think that vaginal birth and Cesarean birth are equally risky or quite honestly even the opposite. They think that vaginal birth is more dangerous than Cesarean. It's like, of course. If that's the underlying held belief, the subconscious belief is that vaginal birth is risk and Cesarean is not, then of course, Meagan, why would you do that? Why would you risk your life and your baby's life just to have a vaginal birth? You don't get an award for that. I'm just imagining what these people are thinking. Meagan: They would say that. Kaitlin: You don't get an award and it's like, “Well, hold on a second. What if we actually find out where the risk lies?” That was something. I was not set on a VBAC. Not at all. I was totally disappointed. I was probably the least impactful word I could use but there was just a defeated feeling about my C-section. I just felt like, “Oh, that wasn't really what I wanted.” I also went into my VBAC birth, my second pregnancy sort of like, “I'm not going to take unnecessary risks for my baby or for myself just to get the VBAC badge or the vaginal birth experience.” You have to balance your desires with what's risky and what's safe. So I didn't research. I remember one of the things that stood out for me was that I had this vision of– and I'm sorry. Get your earmuffs ready. This might trigger somebody. But I had this vision of vaginal birth ending in hemorrhage and being very, very, very scary and very dangerous. I don't know. This is what you see in the movies. So I didn't research this. I don't know if you know this Meagan. I'm so excited if I can share this with you for the first time but vaginal birth hemorrhage is 500 ccs of blood loss. Cesarean normal blood loss in a totally run-of-the-mill, we-did-a-great-job, there-was no-extra-bleeding Cesarean, is 1000 ccs. It's double. Meagan: Yes. Kaitlin: As soon as I realized that, I was like, “Oh. We're not talking about the same thing. Everyone talks about vaginal birth and C-section on this leveled playing field and we are not in the same ballpark.” That is incredibly risky when it goes normally. It is twice as risky as when a vaginal birth goes horribly wrong. To me, it's like, “Oh, we're not even in the same stratosphere.” It's a completely different thing. I think once we start talking in facts and figures and we start really sharing that, it takes so much of the fear away. The fear can be such a big monster to deal with when we're talking about VBAC because it's scary. There are unknowns. Every pregnancy is a little scary because fear is what drives us but if you walk away with one fact from this podcast, just know that it is not the same thing. It's not even close to the same thing. Meagan: It's not. It is not. It isn't. Even with vaginal birth after a Cesarean, yes. There are risks to having a vaginal birth after a Cesarean, but it's also not the same thing. There are also risks for a second Cesarean, a third Cesarean, and a fourth Cesarean, and the risks are pretty substantial. It's important and I encourage you if you are preparing to actually look at the pros and cons of both sides. I also want to point out that sometimes the cons of a vaginal birth might make you be like, “Yeah, I don't want to do that. That's actually not what I feel comfortable with. That's not what my heart says.” And that is okay. Also, know the risks and the cons of the other side. So know the pros and the cons of both vaginal birth, vaginal birth after Cesarean, and vaginal birth after multiple Cesareans. Know those risks. Dial in and decide what risk is applicable, safe enough, and comfortable enough for you. My risk, I live a little bit more on the edge. I have jumped out of a plane multiple times and I have a friend who thinks that is the scariest thing and she won't do it because she has children. She fears the risk of dying. I totally understand. Kaitlin: I'm like, “I would VBAC every day of my life and I will never jump out of a plane. They are not the same risks.”Meagan: Right? So not the same risks to you and to me. So I'm like, “Yeah, my risk is nothing. It's not enough for me to not jump out,” and you're like, “Yeah, no. I'm not doing that.” So it depends. There are benefits and risks to both sides. You have to decide what is best for you. What risk is impactful enough for you to make that decision? Know that it's okay if you are not making the decision that Sally is making. It's okay. It doesn't make you any less of a woman of strength. It doesn't make you any less of a mother. Nothing. You're not failing your body. You're not failing your baby if you make one choice or another. Kaitlin: Absolutely. The big thing is that you have to get that information so that you know the right information so that when you have to go talk to a doctor and they write you off and say, “Nope. We do repeat C-sections because it's risky,” that you actually know what they're talking about and you actually know whether you are at risk or not because there is a much bigger picture than what you might get at a standard OB's office. Meagan: Yes. Absolutely, so this information is so important. Cesarean Awareness Month is April and one of the biggest things that a lot of say are, “So are we promoting Cesareans?” It's not that we are promoting Cesareans, it's that we are promoting information about Cesareans, VBAC, and your options. Even though Cesarean Awareness Month is in April, every month is Cesarean Awareness Month in my mind. Every single month and every single day is information that we need to be sharing, that we need to be getting out there because women of strength, you need to know these stats and these facts so that you can make the choice that is best for you. Kaitlin: Yes. Oh, I love that. Meagan: I don't know exactly all of the choices and the things that led up to your Cesarean but for me, I didn't know. I walked in. I was uneducated, you guys. I was young. I was 22. I just knew I was going to have a baby. I went to the same doc that my mom did who delivered me via Cesarean coincidentally and all of these things. I just didn't know. It takes knowledge. It takes time. It takes time. If you are willing to put in that time, you will likely, even if it ends in a Cesarean, feel better about your outcome and carry on with your life. Kaitlin: Yeah, and that VBAC prep, I don't think anyone here is anti-Cesarean. It's such an interesting thing to point out because there's nobody out there that is saying– April is not an anti-Cesarean month. Meagan: No. It's awareness. Kaitlin: It's awareness so that you can go in with intention, with a conscious choice, and with the information you need. You know what? I went through a whole research phase. I was not sure that VBAC was for me. I wasn't because I wasn't sold one way or the other, but the ability to have a choice is everything. That is where your power comes from. It's not from being the loudest, the strongest, the fastest, or even having a VBAC. It's about getting there on your terms. I know people who have had surprise VBACs believe it or not. I should send her to you. A surprise VBAC was not planned and she was kind of traumatized by it because she was planning a repeat C-section. She didn't go through that prenatal that a lot of people listening are going through of, “Okay, so what are my options and how do I step into my path here?” Whatever that path might be, there's a lot of power and a lot of healing in whatever birth you have, but unless you do that work of identifying your choices and not just your risk assessment but also your practitioners and lining yourself up with support, then you're going to be sort of that passive participant. I think, not all of us, some of our C-sections come after being active, but with a lot of us, myself included, there was this passivity where as soon as I hit the hospital, I was stripped of my power, stripped of my clothes, stripped of my humanness, and told to lay back flat. Keep the baby on the monitor. Here's your medication and boom. That's a C-section. It all happened to me and I wasn't actively there. That was a big part of what changed for me. I felt like I benefited from my VBAC whether I had a C-section or vaginal birth. For the record, I absolutely asked for a C-section as soon as I hit transition. I said to my doula, “Okay. I'm done. I'm done with this. Can we just get a C-section?” I'm really glad I asked my doula and not my OB. Meagan: Right? Right? Your doula and your team were probably like, “Wait, wait, wait, wait, wait. Let's give her ten minutes.” That is a very normal thing too to say. We need to hear your stories. Let's hear them. We could chat forever. But let's hear these.Kaitlin: Oh cool, okay. I know. We're already halfway through. I can give you a quick synopsis of the C-section because I feel like it's always relevant when we're talking about VBAC. My C-section was a 41-week induction, the oldest story in the book. Mine was a little bit interesting because I actually planned an out-of-hospital birth and I planned a midwife-supportive birth. I got a little bit of the bait-and-switch. It's a little spicy because in New York where I was giving birth at the time, midwives could not own a birth center. Now they can, there has been a huge push in legislation on that but at the time, I was told that midwives were in charge of my care and they were not. They were on the phone with an invisible OB I had never met. I did not know he was calling all of the shots. I always start off by saying that I planned an out-of-hospital birth with midwives. I thought I was doing all of the right things. That is part of what makes me feel a little extra angry about my treatment because I thought I was doing the right thing and I wasn't. Meagan: They never told you that you were actually under an OB umbrella?Kaitlin: Nope. Everything was midwife-facing. It was really disingenuous the way that they did that and then basically at the 41-week appointment, literally, an OB was on the phone with them in their ear telling them it was time to induce and I was sent to the hospital for an induction. I didn't know that was the bad part. It's only sort of upon reflecting and becoming a doula and realizing that, “Wait. They were never really in charge.” Meagan: You never actually had the midwife you thought you had. Kaitlin: No. I was not in midwifery care. I had a midwife mouthpiece for an OB. Meagan: Oh my gosh. Kaitlin: That wasn't great. It's also awful because that's the only birth center in New York. New York state is so far behind the rest of the country in a lot of ways and birth centers are definitely one of them. I want as a doula, in my heart of hearts, I want to recommend birth centers but I can't recommend that one because of the way that they behaved and their ownership. So I went to the hospital and it was alarming to me how fast the power was stripped away. My voice– my midwife dumped me there and left me there. This is crazy to say because I'm such an advocate and I've doula'd people through so many things that to say I allowed this for myself is kind of amazing. I was given Cytotec, a double dose of Cytotec in the C-section recovery room. That's where they sent me because I was in this busy Brooklyn hospital and I was set up with Wendy, the nurse, who I hate. I still remember Wendy. These people become bigger characters in your story. Meagan: They do. Kaitlin: Because they stay with you. But anyway, long story short, I went from nothing eating a sandwich with my family to absolutely full-blown, every three-minute transition level contractions. I couldn't move. She wouldn't let me move off of my back. I felt like a trapped animal. I ended up getting the epidural because my whole birth plan was out the window. Meagan: Oh, I'm sure. Kaitlin: I was like, “Why am I torturing myself?” and the baby didn't respond well to the epidural. His heart rate went down and I just looked at my team. They all looked very nervous and I said, “What are we doing here?” She said, “The OB is going to come to talk to you in about 45 minutes.” I'm like, “This baby is actively in distress.”Meagan: But your baby is not doing well.Kaitlin: Actively in distress. The OB was going to come in 45 minutes. I looked at her and I say this, the only reason this is okay is because I said it. I would never say this to another person but I looked at her and I said, “I want a healthy baby. I want a healthy baby at the end of this.” I say that because it's really toxic to be like, “At least you had a healthy baby.” It's like, “Okay. I get to say.” What I was trying to say to her in the fog of the labor was, “After all of this misery and all of this horrible treatment, at the very least I would like a baby that's alive and handed to me.”So I did. I got a C-section. It was scary. It was cold literally and otherwise. It was not what I wanted. It was not the ending that I wanted. I ended up in my house. My husband was back at work. He didn't have literally any time off and he was back at work the day that I was released from the hospital two days later. It was just underwhelming. It was not how I wanted to enter motherhood. Meagan: No. Kaitlin: In the least. I felt like besides the physical– the physical recovery was horrible and I recovered really well but it was just so intense. It's major surgery. I also just felt disempowered. I felt highly anxious. I didn't realize it until later that it was postpartum anxiety but I was just so set off-kilter by the whole experience. It just took my power and my voice and my strength away from me and then handed me a baby and a C-section scar. I was like, “Oh. That's not how I thought motherhood was going to go.” Meagan: Oh my gosh, yeah. That's hard and being alone. Oh, man. Kaitlin: Yeah, being alone. Meagan: It started your journey off really intensely. Kaitlin: It was really hard. Then when I had my second, I just knew it needed to be different. I knew I needed to do more research. I actually, this is funny. I did everything the opposite. I planned hospital birth. I planned an OB birth. I hired a doula. Everything I didn't do, I did the opposite. But the thing I did along the way was that I was really intentional about all of my choices. I found the doctor that does VBACs where I live. There's a handful of them and I found Jessica Jacob at North Shore. She does a lot of Orthodox Jewish women who see her. That's her practice. A lot of those women have 6, 7, 8, and 9 babies so when they have a C-section if the thing is “once a C-section, always a C-section,” that can result as we talked about earlier, that can result in really dangerous situations. So she specializes in VBAC, vaginal births, and preventing those primary C-sections.So I went to her. I had done my own research and then I went to her and said, “Knowing my story and looking at my chart, am I a candidate?” She said, “Absolutely.” I was like, “Okay, sold. I'm in.” Meagan: That's awesome. Kaitlin: Yeah, it was really good. This one was so much less traumatic and not even less traumatic. I had a full-blown spiritual experience with my VBAC. It was completely on my own terms. It was private. The day that I went into labor was my due date believe it or not. What a magical little baby. Awesome and obedient and wonderful. Now he's not. He's not obedient at all. He's 8 now. He's not obedient. But it was actually Father's Day in 2014. That was my due date. I woke up with these little Braxton Hicks turned into these contractions that would– you know the Braxton Hicks where they just tighten and release and you have them forever? It was like that except at the very height of it, it was this little squeeze that just took my attention. I was like, “Oh, what? What is this?”Meagan: You're like, “Oh, something's happening.” Kaitlin: Because I had never been in my own labor. This is part of it. I had never been. I had this suspicion, you know that intuition, I just knew that if I could get into labor, I could do this. I went to an acupuncturist, one that my doula recommended. They put these beads on my ears. I don't know if you've ever had this Meagan.Meagan: No. Kaitlin: Okay, so they put beads on my ears in these pressure points and they taped them. Then he told me as much as I could, and I am touching on the actual points because that's where they were. I'll never forget where they were. And to just pinch them and just keep doing that as much as you can to activate. Meagan: Really?Kaitlin: I did it. That was Friday. Friday night was when I went. I pinched and squeezed those until Saturday. I literally ripped the tape and the beads off. I was totally overstimulated and couldn't touch them anymore but I did as much as I could. I remember knowing that I had an instinct that I was going to go into labor because I could not stop eating the day before. It's so interesting how our bodies know. Meagan: It's fueling. They're fueling. Our bodies fuel. I did the same thing with my VBAC. It was so weird. I had all of this energy and was eating all of the stuff. Kaitlin: Everything. Meagan: Everyone was like, “How are you eating that much? You're 9 months pregnant.” I'm like, “I don't know. I'm so hungry.” Kaitlin: My husband, we went out for lunch and he got food for me, him, and my two-year-old at the time. I remember looking at him and I was like, “What are you guys going to eat?” I was insatiable which had been different from any other day. So anyways, I wake up on Father's Day, the day of my birth and it was this incredible, gentle, slow labor which was such a wonderful way to learn how to work with my body. The whole morning was this questioning time of, “Am I in labor?” In between, I was literally like this talking in between. I would convince myself, “No, not in labor.” There was this whole discussion of, “Should we go to Father's Day brunch?” Then I would have a wave come and I was like, “No, no, no. We're not going to sit at a restaurant right now.” Meagan: Yeah, no. Kaitlin: So I labored like that all day with just me and my husband. We watched World Cup soccer. We got lunch. We were eating. I was learning how to move. I was learning how to breathe. Every single contraction was just this opportunity to figure out how to work with my body. Then the nighttime came. It's what you learn in your childbirth classes. At night, the night falls and it signals this privacy and safety. Again, it was still just me and my husband. Things just picked up. Oh my goodness. I remember my doula called me. I had been texting her all day. I didn't want anyone to come. It was so private. She called me and we spoke. I just gave her an update then we hung up the phone and it's amazing the switch. Everything about labor is so mental and emotional. I just kicked into high gear. The waves that I was able to get on top of earlier, it was taking the full essence of my being to work through these contractions. It was so incredibly wild how fast that happened. We labored at home until maybe midnight. Yeah, about midnight. We called our doula. We had called the doctor and said, “Hey, I think we're going to come in.” The doctor said, “Well, she might get turned away. She's not ready.” Because this is what VBAC-supportive looks like. It looks like saying, “You might not be allowed to be here because that's how I keep you safe in this hospital.” I remember that really stood out to me. It was like, “Oh, this is interesting what she is saying. Maybe I shouldn't come.” So we waited as long as we possibly could. We called the doula around midnight. The doula came here to my house. I was on my knees next to my bed. I could not be in my bed for hours and hours. I looked at her as soon as she got there and I said, “Let's go. It's time to go.” She was like, “Oh, okay. I just got here.” Between my bedroom and my car, I had probably five contractions. It was just one after the other after the other. At this point, I'm thinking that I'm going to go to the hospital and spend the day there. My mom will come for the birth. I'm not really getting–Meagan: Where you're at. Kaitlin: Where I am in labor because it's part of labor. You just kind of can't tell. Meagan: It's true. There's no sense of time. There's no sense of understanding sometimes. You're like, “I know I'm feeling this, but it's probably going to be a while.” Kaitlin: Yeah, that's actually literally a part of it. You're not supposed to know. Your brain shuts down. The prefrontal cortex of language analysis shuts down and you're living in this beautiful other existence where you're in a wave. You're out of a wave. You're in a wave. You're out of a wave. So we went to the hospital. I walked all the way up. They offered me a wheelchair and I was like, “I literally cannot sit down. There's not a chance of that.” So I waddled my way and had contractions every few minutes. When I got to the floor, they were like, “Okay, just skip triage. Go right to the room.” They took one look at me. I think they obviously knew that I was much closer than I knew. I went to go pee in the bathroom in the room right before I went to go lay in the bed and get checked or whatever. When I sat on the toilet, I had a contraction and I now know it was spontaneous pushing. But I had this contraction where it was like, “Oooohh.” Meagan: Yeah. Uh-huh, uh-huh. Kaitlin: At the top, the peak, when you're moaning, it just caught. It was like, “Oh my god. I think I'm pushing.” It was this weird thing. It was weird because I hadn't experienced it before. So I got in bed and everything was really a blur because the doctor came. She checked me and she said I was 6 centimeters and +2 station, -2 station. I wasn't ready. When I was pushing and I was working, the best thing she did was she just said, “Okay. Just do your thing. I'm going to be right outside.” The nurses were skirting around asking me so many questions and I just ignored all of them. Where I was, was in the stars. I was just so far away from the hospital room. It doesn't make sense but I just imagined this tunnel from the top of my head to the outer regions of the universe. That's where I went. I went to this place that was just completely apart from the realities and the things that the nurses were worried about. I just could not care less. I was so deeply in tune with what I was feeling and where I was going in my brain and my body. I remember feeling so primal in a good way. The first time, I felt like a trapped animal and this time, I felt like this primal goddess being just feeling deeply connected to every sense of myself and every sense of my body. It was just wild. It's hard to put into words but it was one of the most powerful experiences I've ever had laboring my baby down and pushing him out. There was no other anything at that moment. It was just me, my body, and this baby. It was the coolest thing I've ever done. There were funny moments in it too. This is the reality side of it. At one point, I was curled up on my side against the side of the hospital bed. In the middle of a contraction, the bed starts going up and down, up and down. Meagan: Was your head pushing it?Kaitlin: I snapped at my husband, “Why are you moving the bed?” He was like, “It's you.” Meagan: It's you! Kaitlin: So it was quite the sight. But yeah, and he just flew out. My body just apparently, so I didn't realize this until a lot longer later, but I experienced fetal ejection reflex with my next baby who was a home birth, but I experienced it with him too. He went from inside of me to in the doctor's hands in one big push. It was just wild. It was really wild and it was really, really the coolest thing ever. It's hard to explain how intense the moment is and how good it feels to have that relief.Then the oxytocin was just pulsing. Everything is good. I remember he was put on my chest and he was so alert. He was so awake. He was not drugged. I was not drugged which was not necessarily part of the plan. I just want to throw that out there. I was wanting to go without an epidural but it wasn't–Meagan: Set in stone. Kaitlin: I wasn't deadset on it, yeah. I was open to whatever happened. Meagan: Which is healthy. That's a healthy way. Kaitlin: Because who knows? But it was so cool to have him go through those initial stages and be aware of his surroundings. I remember feeling even in that moment of joy, I remember feeling a little bit like I was experiencing what was stolen from me the first time around. It felt like a little bit of grief associated with that. I'm getting a little teary-eyed thinking about it right now. I honestly think it's why I had a third baby. I should have had this. I should have had this the first time. He looked just like his big brother. It was just this feeling of, “I was really robbed.” I knew I was robbed the first time but I didn't know what necessarily. Meagan: Right, because you hadn't been there yet.Kaitlin: I just knew there was something I was missing. There was this incredible feeling of triumph. That was absolutely the overwhelming feeling but there was this little linger of grief too, of just, “Oof. Now I know what I missed out on.” It was beautiful. I screamed from the top of my lungs, “I just had a baby out of my vagina!” Literally, the entire floor of the hospital could hear. My doula sent me a video of that later on. Meagan: Oh my gosh, I love that. I love that you have that. Kaitlin: Yeah, I'd have to find it but it was just this pure, pure triumph. I was forever changed by that. I was forever changed by the whole experience and that vaginal birth was the culmination of all of the work I put in. It was the culmination of doing the research, lining up my support team, and doing this work to be an active participant in my care. It was the best thing in the whole world and I am forever changed by that moment. Meagan: Yeah. I love that you said being an active participant in your care. It's so important, listeners, for you to be that person in your birth and not have birth happen to you. We know it happens. We know. It happens way too often. I hope in time that we stop seeing it happen so often and it's more of a rarity but right now, a lot of the time– I don't want to make it sound like we are painting a bad picture on providers or the system or anything like that. I mean, look. You were going out of the hospital–Kaitlin: And I still got burned.  Meagan: It depends, right? But it's so important and it all stems back to what we were talking about in the beginning is having the education, having the support, and being prepared to be that active participant and to be that person and finding those supportive providers that will say, “Hey, why don't you stay? You're probably going to get sent home for a little longer.” It's just so important and it can be vital to the outcome of our birth. Kaitlin: Yes. That's such an important thing, Meagan, if people are listening and trying to take things away. I think something that we can do often is, “I'm going to listen to this. I'm going to listen to as many birth stories as I can so I can learn exactly the formula. What did she do? What did she do? What is the thing that I have to do?” The thing you have to do is get the information and then trust your gut. Part of being an active participant is research, research, research, then trust your gut. That's what I always tell people. Do all of that research, but at the end of the day, you're the only person that can make each of these hundreds and thousands of tiny decisions for yourself. That's the real formula. Meagan: Yes. Kaitlin: Trusting our instincts, trusting ourselves, trusting our own wisdom in these moments to steer us and guide us forward. Meagan: Yeah and just like each of our bodies is made out of different things and chromosomes and hormones and all of the things, we are made to be the person we are, we have to trust all of those things. Like she said, and create our own formula because her formula is going to be different than mine. She's not jumping out of a plane. I jumped out of a plane twice because I loved it so much. I had to do it again. Kaitlin: I'm definitely not jumping out of a plane. Meagan: Right, I'm just saying that the formula is going to be different. You have to tune into your own formula and it does start with that intuition, education, and gathering support. Kaitlin: Meagan, you said it earlier too. I know we're running out of time. Meagan: No, you're fine. Kaitlin: You can see all of those stats and also do the opposite. You can see that it's safer to have a C-section and choose a vaginal birth. You can see that vaginal birth is riskier for you and choose that anyway. The evidence is there. The “evidence” is there as part of the decision making but you get to do what feels right for you and your family and your baby and your body and your birth. That is the thing. Evidence is not everything. It's one of the tools that we have. Meagan: Yes. Mic drop right there. Oh my gosh. Thank you so much for being with us today. I mean, I know that we could talk for hours and hours and hours about all of the things. We probably need to do this again because of that. Kaitlin: I would love that. I love you and everything you're doing here. Thank you so much for having me. Meagan: Thank you. Can you tell everybody where they can find Be Her Village?Kaitlin: Absolutely. Behervillage.com is a great place to start. You can just hit the “Get Started” button. You can create a registry or if you're a birth worker and you want to get involved with what we're doing, you can add your services. We have training courses. We have so many great things. You can find us on Instagram and Facebook. Both are @behervillage. I'm in the stories. I'm answering the messages on Instagram so if you want to be in touch, that's the best way. Meagan: Absolutely. We'll make sure to drop all of those links in the show notes. So while you're leaving a review, also go check all of these amazing links out because Be Her Village is incredible, doing amazing things, and is seriously so important. So, so important. Thank you again so much. Kaitlin: Thank you so much, Meagan. Bye, everybody!ClosingWould you like to be a guest on the podcast? Tell us about your experience at thevbaclink.com/share. For more information on all things VBAC including online and in-person VBAC classes, The VBAC Link blog, and Meagan's bio, head over to thevbaclink.com. Congratulations on starting your journey of learning and discovery with The VBAC Link.Support this podcast at — https://redcircle.com/the-vbac-link/donationsAdvertising Inquiries: https://redcircle.com/brands

Durant l'Antiquité, certains peuples ont dominé de vastes régions pendant des siècles, avant de connaître un brusque déclin. C'est notamment le cas des Hittites. Entre 1.650 et 1.200 avant notre ère, ils ont formé un Empire qui s'étendait sur une partie de l'Anatolie, dans la Turquie actuelle, et une part de la Syrie. Puis d'une manière assez soudaine, vers 1.200 avant J.-C., cette civilisation hittite, qui pouvait rivaliser avec l'Égypte de Ramsès II, s'est effondrée. La capitale, Hattusa, aujourd'hui classée au patrimoine mondial de l'Unesco, a été abandonnée par ses habitants et livrée aux flammes. Durant ce qu'il est convenu d'appeler l'"effondrement de l'âge du bronze", d'autres Empires, comme celui des Mycéniens par exemple, ont également périclité. Les historiens n'on pas manqué de s'interroger sur les raisons d'un pareil déclin. On a évoqué des invasions, perpétrées notamment par ceux que les Égyptiens appelaient les "peuples de la mer". On a aussi parlé d'épidémies meurtrières. Mais, même si ces faits ont dû avoir leur part dans la chute de l'Empire hittite, la vraie raison serait à rechercher dans un profond changement climatique. En effet, des chercheurs ont examiné des genévriers utilisés dans la construction de monuments funéraires. L'étude attentive des cernes de ces arbres et la présence de carbone, dans le bois, en apprennent beaucoup sur les conditions climatiques de l'époque. Cet examen a ainsi révélé le passage progressif, aux XIIIe et XIIe siècle avant J.-C., à un climat beaucoup plus sec. Les chercheurs ont même pu identifier trois années consécutives particulièrement arides, 1198, 1197 et 1196 avant notre ère. Tout laisse à penser que, durant ces trois années successives, les récoltes furent très mauvaises. Si, grâce aux réserves de blé amassées dans les greniers, il était possible de résister à une ou même deux années de pénurie, la troisième année de sécheresse a pu entraîner de véritables catastrophes. Des disettes, accompagnées de maladies, on pu se manifester dans l'Empire hittite, suscitant des émeutes et des troubles qui, d'après cette explication, ont fini par avoir raison de la puissance hittite. Learn more about your ad choices. Visit megaphone.fm/adchoices

Durant l'Antiquité, certains peuples ont dominé de vastes régions pendant des siècles, avant de connaître un brusque déclin. C'est notamment le cas des Hittites. Entre 1.650 et 1.200 avant notre ère, ils ont formé un Empire qui s'étendait sur une partie de l'Anatolie, dans la Turquie actuelle, et une part de la Syrie.Puis d'une manière assez soudaine, vers 1.200 avant J.-C., cette civilisation hittite, qui pouvait rivaliser avec l'Égypte de Ramsès II, s'est effondrée. La capitale, Hattusa, aujourd'hui classée au patrimoine mondial de l'Unesco, a été abandonnée par ses habitants et livrée aux flammes.Durant ce qu'il est convenu d'appeler l'"effondrement de l'âge du bronze", d'autres Empires, comme celui des Mycéniens par exemple, ont également périclité.Les historiens n'on pas manqué de s'interroger sur les raisons d'un pareil déclin. On a évoqué des invasions, perpétrées notamment par ceux que les Égyptiens appelaient les "peuples de la mer". On a aussi parlé d'épidémies meurtrières.Mais, même si ces faits ont dû avoir leur part dans la chute de l'Empire hittite, la vraie raison serait à rechercher dans un profond changement climatique.En effet, des chercheurs ont examiné des genévriers utilisés dans la construction de monuments funéraires. L'étude attentive des cernes de ces arbres et la présence de carbone, dans le bois, en apprennent beaucoup sur les conditions climatiques de l'époque.Cet examen a ainsi révélé le passage progressif, aux XIIIe et XIIe siècle avant J.-C., à un climat beaucoup plus sec. Les chercheurs ont même pu identifier trois années consécutives particulièrement arides, 1198, 1197 et 1196 avant notre ère.Tout laisse à penser que, durant ces trois années successives, les récoltes furent très mauvaises. Si, grâce aux réserves de blé amassées dans les greniers, il était possible de résister à une ou même deux années de pénurie, la troisième année de sécheresse a pu entraîner de véritables catastrophes.Des disettes, accompagnées de maladies, on pu se manifester dans l'Empire hittite, suscitant des émeutes et des troubles qui, d'après cette explication, ont fini par avoir raison de la puissance hittite. Hébergé par Acast. Visitez acast.com/privacy pour plus d'informations.

Crossref is a non-profit organization that logs and updates citations for scientific publications. Each month, Crossref identifies a list of the most popular Oncotarget papers based on the number of times a DOI is successfully resolved. Below are Crossref's Top 10 Oncotarget DOIs in 2022. 10: Cell fusion as a link between the SARS-CoV-2 spike protein, COVID-19 complications, and vaccine side effects DOI: https://doi.org/10.18632/oncotarget.28088 Author: Yuri Lazebnik 9: A Jurkat 76 based triple parameter reporter system to evaluate TCR functions and adoptive T cell strategies DOI: https://doi.org/10.18632/oncotarget.24807 Authors: Sandra Rosskopf, Judith Leitner, Wolfgang Paster, Laura T. Morton, Renate S. Hagedoorn, Peter Steinberger, and Mirjam H.M. Heemskerk 8: IL-37 suppresses hepatocellular carcinoma growth by converting pSmad3 signaling from JNK/pSmad3L/c-Myc oncogenic signaling to pSmad3C/P21 tumor-suppressive signaling DOI: https://doi.org/10.18632/oncotarget.13196 Authors: Rui Liu, Chengyong Tang, Ai Shen, Huating Luo, Xufu Wei, Daofeng Zheng, Chao Sun, Zhongtang Li, Di Zhu, Tingting Li, and Zhongjun Wu 7: Apatinib-based targeted therapy against pulmonary sarcomatoid carcinoma: a case report and literature review DOI: https://doi.org/10.18632/oncotarget.25989 Authors: Xiaofeng Li, Yueming He, Jinfeng Zhu, Hongxia Pang, Yongwei Lin, and Jinyang Zheng 6: Treasures from trash in cancer research DOI: https://doi.org/10.18632/oncotarget.28308 Authors: Fabiano Cordeiro Moreira, Dionison Pereira Sarquis, Jorge Estefano Santana de Souza, Daniel de Souza Avelar, Taíssa Maria Thomaz Araújo, André Salim Khayat, Sidney Emanuel Batista dos Santos, and Paulo Pimentel de Assumpção 5: Real-world survival analysis by tumor mutational burden in non-small cell lung cancer: a multisite U.S. study DOI: https://doi.org/10.18632/oncotarget.28178 Authors: Connor Willis, Hillevi Bauer, Trang H. Au, Jyothi Menon, Sudhir Unni, Dao Tran, Zachary Rivers, Wallace Akerley, Matthew B. Schabath, Firas Badin, Ashley Sekhon, Malini Patel, Bing Xia, Beth Gustafson, John L. Villano, John-Michael Thomas, Solomon J. Lubinga, Michael A. Cantrell, Diana Brixner, and David Stenehjem 4: Continuous treatment with abemaciclib leads to sustained and efficient inhibition of breast cancer cell proliferation DOI: https://doi.org/10.18632/oncotarget.28249 Authors: Raquel Torres-Guzmán, Maria Patricia Ganado, Cecilia Mur, Carlos Marugan, Carmen Baquero, Yanzhu Yang, Yi Zeng, Huimin Bian, Jian Du, Alfonso de Dios, Oscar Puig, and María José Lallena 3: Increased gut permeability in cancer cachexia: mechanisms and clinical relevance DOI: https://doi.org/10.18632/oncotarget.24804 Authors: Laure B. Bindels, Audrey M. Neyrinck, Audrey Loumaye, Emilie Catry, Hannah Walgrave, Claire Cherbuy, Sophie Leclercq, Matthias Van Hul, Hubert Plovier, Barbara Pachikian, Luis G. Bermúdez-Humarán, Philippe Langella, Patrice D. Cani, Jean-Paul Thissen, and Nathalie M. Delzenne 2: Inflammatory responses and inflammation-associated diseases in organs DOI: https://doi.org/10.18632/oncotarget.23208 Authors: Linlin Chen, Huidan Deng, Hengmin Cui, Jing Fang, Zhicai Zuo, Junliang Deng, Yinglun Li, Xun Wang, and Ling Zhao 1: Proteomic profiling of skeletal and cardiac muscle in cancer cachexia: alterations in sarcomeric and mitochondrial protein expression DOI: https://doi.org/10.18632/oncotarget.25146 Authors: Angie M. Y. Shum, Anne Poljak, Nicholas L. Bentley, Nigel Turner, Timothy C. Tan, and Patsie Polly _______________________________ About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com

Videos: Brought to you by… Pfizer! FORMER PFIZER VP, DR. MIKE YEADON – EVERYTHING WE HAVE BEEN TOLD ABOUT COVID-19 WAS A LIE Fauci didn't want autopsies done on Covid victims. I wonder why? Dr. Peter McCullough SLAMS Pfizer board member over censorship and propaganda | Redacted News Study explores effects of dietary choline deficiency on neurologic and system-wide health Arizona State University, January 16, 2023 Choline, an essential nutrient produced in small amounts in the liver and found in foods including eggs, broccoli, beans, meat and poultry, is a vital ingredient for human health. A new study explores how a deficiency of dietary choline adversely affects the body and may be a missing piece in the puzzle of Alzheimer's disease. It's estimated that more than 90% of Americans are not meeting the recommended daily intake of choline. The current research, conducted in mice, suggests that dietary choline deficiency can have profound negative effects on the heart, liver and other organs. Lack of adequate choline is also linked with profound changes in the brain associated with Alzheimer's disease. These include pathologies implicated in the development of two classic hallmarks of the illness: amyloid plaques, which aggregate in the intercellular spaces between neurons; and tau tangles, which condense within the bodies of neurons. The new research, led by scientists at Arizona State University and published in Aging Cell, describes pathologies in normal mice deprived of dietary choline and in choline-deficient transgenic mice, the latter of which already exhibit symptoms associated with the disease. In both cases, dietary choline deficiency results in liver damage, enlargement of the heart and neurologic alterations in the AD mice, typically accompanying Alzheimer's disease and including increased levels of plaque-forming amyloid-beta protein and disease-linked alterations in tau protein. Further, the study illustrates that choline deficiency in mice causes significant weight gain, alterations in glucose metabolism (which are tied to conditions such as diabetes), and deficits in motor skills. In the case of humans, “it's a twofold problem,” according to Ramon Velazquez, senior author of the study and assistant professor with the ASU-Banner Neurodegenerative Disease Research Center. “First, people don't reach the adequate daily intake of choline established by the Institute of Medicine in 1998. And secondly, there is vast literature showing that the recommended daily intake amounts are not optimal for brain-related functions.” The research highlights a constellation of physical and neurological changes linked to choline deficiency. Sufficient choline in the diet reduces levels of the amino acid homocysteine, which has been recognized as a neurotoxin contributing to neurodegeneration, and is important for mediating functions such as learning and memory through the production of acetylcholine. The growing awareness of choline's importance should encourage all adults to ensure proper choline intake. This is particularly true for those on plant-based diets, which may be low in naturally occurring choline, given that many foods high in choline are eggs, meats, and poultry. Plant-based, choline-rich foods, including soybeans, Brussels sprouts and certain nuts can help boost choline in these cases. Moreover, inexpensive, over-the-counter choline supplements are encouraged to promote overall health and guard the brain from the effects of neurodegeneration. The new study examines mice at 3-12 months, or early to late adulthood (roughly equivalent to 20-60 years of age for humans). In the case of both normal and transgenic mice displaying symptoms of Alzheimer's, those exposed to a choline-deficient diet exhibited weight gain and adverse effects to their metabolism. Damage to the liver was observed through tissue analysis, as was enlargement of the heart. Elevated soluble, oligomeric and insoluble amyloid-beta protein were detected, as well as modifications to tau protein characteristic of those leading to neurofibrillary tangles in the brain. Further, choline-deficient mice performed poorly in a test of motor skills, when compared with mice receiving adequate choline in their diet. These adverse effects were heightened in the transgenic mice. Translating these findings to humans, this implies that people who are predisposed to Alzheimer's disease or in the throes of the illness should ensure they are getting enough choline.”Our work provides further support that dietary choline should be consumed on a daily basis given the need throughout the body,” Velazquez says. (NEXT) Melanoma: Vitamin D supplements linked to reduced skin cancer risk University of Eastern Finland & Kuopio University, January 15, 2023 A new study finds that the regular use of vitamin D is associated with lower rates of melanoma skin cancer. The cross-sectional study was a collaboration between the University of Eastern Finland and Kuopio University Hospital. The research involved 498 Finnish adults determined by dermatologists to be at high risk of skin cancer, such as melanoma, as well as squamous cell carcinoma and basal cell carcinoma. According to researchers, people who took vitamin D regularly were less likely to have had melanoma in the past or currently and were deemed by dermatologists to be less likely to develop melanoma in the future. Study participants ranged in age from 21 to 79 years old, including 253 males and 245 females. Participants were divided into three groups based on their intake of vitamin D supplements: non-use, occasional use, or regular use. The researchers were also interested in finding out whether regular use of vitamin D supplements corresponded to higher blood levels of vitamin D, known as serum calcidiol or 25-hydroxy-vitamin D3. This is the “storage form” of vitamin D in the body. Some research has linked low serum calcidiol with increased cancer risk, while other research has suggested otherwise. Nonetheless, it is a measure often used to determine a person's vitamin D levels. After testing serum calcidiol levels in 260 participants, researchers found that regular vitamin D supplementation corresponded with the highest levels of serum calcidiol and non-supplementation with the lowest levels. “Human skin itself expresses [the enzyme] CYP27A1 that produces calcidiol from vitamin D, and CYP27B1 that produces biologically very active calcitriol from calcidiol,” Dr. Harvima explained, noting that enzyme expression determines the level of vitamin D and its metabolites in the body. (NEXT) New research furthers case for exercise promoting youthfulness University of Arkansas, January 17, 2023 A recent paper published in the Journal of Physiology deepened the case for the youthfulness-promoting effects of exercise on aging organisms, building on previous work done with lab mice nearing the end of their natural lifespan that had access to a weighted exercise wheel. For this paper, the researchers compared aging mice that had access to a weighted exercise wheel with mice that had undergone epigenetic reprogramming via the expression of Yamanaka factors. The Yamanaka factors are four protein transcription factors (identified as Oct3/4, Sox2, Klf4 and c-Myc, often abbreviated to OKSM) that can revert highly specified cells (such as a skin cell) back to a stem cell, which is a younger and more adaptable state. The Nobel Prize in Physiology or Medicine was awarded to Dr. Shinya Yamanaka for this discovery in 2012. In the correct dosages, inducing the Yamanaka factors throughout the body in rodents can ameliorate the hallmarks of aging by mimicking the adaptability that is common to more youthful cells. Of the four factors, Myc is induced by exercising skeletal muscle. Myc may serve as a naturally induced reprogramming stimulus in muscle, making it a useful point of comparison between cells that have been reprogrammed via over expression of the Yamanaka factors and cells that have been reprogrammed through exercise—”reprogramming” in the latter case reflecting how an environmental stimulus can alter the accessibility and expression of genes. Ultimately, the team determined that exercise promotes a molecular profile consistent with epigenetic partial programming. That is to say, exercise can mimic aspects of the molecular profile of muscles that have been exposed to Yamanaka factors (thus displaying molecular characteristics of more youthful cells). This beneficial effect of exercise may in part be attributed to the specific actions of Myc in muscle. Murach sees their research as further validation of exercise as a polypill. “Exercise is the most powerful drug we have,” he says, and should be considered a health-enhancing—and potentially life-extending—treatment along with medications and a healthy diet. (NEXT) Exploiting the synergy of nutraceuticals for cancer prevention and treatment Research suggests that free radicals (ROS) generated upon mixing two nutraceuticals—resveratrol and copper—can help ameliorate various diseases by inactivating cell-free chromatin particles Tata Memorial Centre (India), January 16, 2023 Chromatin comprises a complex mixture of DNA and proteins that forms the structural basis of chromosomes in the cellular nuclei. When cells die, they release cell-free chromatin particles or “cfChPs” into the circulatory system. In 1996, evidence for tumour-derived DNA circulating in the blood of cancer patients was first reported. This evidence caught the interest Dr. Indraneel Mittra, who is now Professor Emeritus and the Dr. Ernest Borges Chair in Translational Research at Tata Memorial Centre in Mumbai, India. His tryst with research on genetic material in cancer metastases began, and after 15 years of research he has presented various papers, developing a body of evidence that indicates the critical role of cfChPs in orchestrating development of not only cancer, but various other diseases. Emerging evidence indicates that cfChPs play an essential role in ageing, sepsis, cancer development, and chemotherapy-related toxicity. With respect to the latter, Prof. Mittra explains, “Chemo-toxicity is not primarily caused by chemotherapeutic drugs, but rather by cfChPs that are released from the first cells that die after chemotherapy. The released cfChPs set in motion a cascading effect, increasingly damaging the DNA of healthy host cells, and triggering inflammatory processes in a vicious cycle that perpetuates and prolongs the toxicity of chemotherapy.” Recently, a team from Tata Memorial Centre have demonstrated the therapeutic benefits of a pro-oxidant mixture of resveratrol and copper, R-Cu, in patients undergoing chemotherapy for advanced gastric cancer. Combining R with Cu (R-Cu) leads to the generation of free oxygen radicals which can inactivate the offending cfChPs. In this context, the research team launched a single-arm phase II clinical trial to study the synergistic effects of R-Cu administration on cfChPs inactivation in patients with advanced gastric cancer. The primary objective was to determine whether R-Cu, via cfChPs' inactivation, was successful in reducing the grade ≥ 3 toxicity seen with docetaxel-based chemotherapies. To this end, the researchers monitored the likely changes in the toxicities of chemotherapeutic treatments using a grading system that provides a framework for the assessment of unwanted physiological effects. The results were promising—although R-Cu did not reduce haematological toxicities, it significantly reduced the incidence of non-haematological toxicities comprising hand-foot syndrome, diarrhoea, and vomiting. Moreover, R-Cu reduced docetaxel exposure compared to the control arm without affecting efficacy in terms of overall survival. (NEXT) Deep meditation may alter gut microbes for better health Shanghai Jiao Tong University School of Medicine (China), January 16, 2023 Regular deep meditation, practiced for several years, may help to regulate the gut microbiome and potentially lower the risks of physical and mental ill health, finds a small comparative study published in the open access journal General Psychiatry. The gut microbes found in a group of Tibetan Buddhist monks differed substantially from those of their secular neighbors, and have been linked to a lower risk of anxiety, depression, and cardiovascular disease. Research shows that the gut microbiome can affect mood and behavior through the gut–brain axis. This includes the body's immune response, hormonal signaling, stress response and the vagus nerve—the main component of the parasympathetic nervous system, which oversees an array of crucial bodily functions. The significance of the group and specimen design is that these deep-thinking Tibetan monks can serve as representatives of some deeper meditations. Although the number of samples is small, they are rare because of their geographical location. The researchers analyzed the stool and blood samples of 37 Tibetan Buddhist monks from three temples and 19 secular residents in the neighboring areas. None of the participants had used agents that can alter the volume and diversity of gut microbes: antibiotics; probiotics; prebiotics; or antifungal drugs in the preceding 3 months. Sample analysis revealed significant differences in the diversity and volume of microbes between the monks and their neighbors.”Collectively, several bacteria enriched in the meditation group [have been] associated with the alleviation of mental illness, suggesting that meditation can influence certain bacteria that may have a role in mental health,” write the researchers. These include Prevotella, Bacteroidetes, Megamonas and Faecalibacterium species, the previously published research suggests. Finally, blood sample analysis showed that levels of agents associated with a heightened risk of cardiovascular disease, including total cholesterol and apolipoprotein B, were significantly lower in the monks than in their secular neighbors by their functional analysis with the gut microbes. (NEXT) Curcumin/Boswellia shows promise in chronic kidney disease Baylor University, January 14, 2023. The Journal of Complementary and Integrative Medicine reports the finding of researchers at Baylor University of a reduction in a marker of inflammation among chronic kidney disease patients given a combination of Curcuma longa (curcumin) and Boswellia serrata. The study included sixteen individuals receiving standard care for chronic kidney disease who were not undergoing dialysis. Participants were randomized to receive capsules containing curcumin from turmeric extract plus Boswellia serrata, or a placebo for eight weeks. Blood samples collected before and after treatment were analyzed for plasma interleukin-6 (IL-6), tumor necrosis factor alpha (markers of inflammation), and the endogenous antioxidant enzyme glutathione peroxidase, as well as serum C-reactive protein (CRP, another marker of inflammation.) Blood test results from the beginning of the study revealed increased inflammation and reduced glutathione peroxide levels. At the study's conclusion, participants who received curcumin and Boswellia serrata experienced a reduction in interleukin-6 in comparison with pretreatment values, indicating decreased inflammation, while IL-6 values rose among those who received a placebo. In their discussion of the findings, the authors remark that curcumin and Boswellia serrata have been separately shown to lower interleukin-6 via inhibition of the nuclear factor kappa beta and mitogen activated protein kinase (MAPK) signaling pathways.

A new research paper was published in Oncotarget's Volume 13 on December 6, 2022, entitled, “Expression of p-STAT3 and c-Myc correlates with P2-HNF4α expression in nonalcoholic fatty liver disease (NAFLD).” Nonalcoholic fatty liver disease (NAFLD) is associated with the metabolic syndrome and is rapidly becoming one of the major causes of hepatic cirrhosis and hepatocellular carcinoma (HCC), although some cases of HCC have developed in non-cirrhotic livers [1–8]. Although the percentage of patients with NAFLD who ultimately progress to fibrosis and later to HCC is relatively small, the number is significant because of the sheer number of patients who have NAFLD. Because there are no reliable biomarkers to predict the risk of HCC in patients with NAFLD, designing effective and cost-effective surveillance programs aimed at prevention and early detection of HCC is difficult, if not impossible. Therefore, there is an urgent need to identify such biomarkers and especially those that may appear at different stages of progression toward HCC. In the current study, researchers Mamoun Younes, Lin Zhang, Baharan Fekry, and Kristin Eckel-Mahan from George Washington University School of Medicine and Health Sciences and McGovern Medical School at the University of Texas Health Science Center (UTHealth) studied the expression of two hepatocyte nuclear factor 4 alpha (HNF4α) isoforms, p-STAT3. and c-Myc in 49 consecutive liver biopsies with nonalcoholic fatty liver disease (NAFLD) using immunohistochemistry. “The aim of this study was to determine the relationships between p-STAT3, c-Myc and P2-HNF4α expression in biopsies from livers with NAFLD as potential biomarkers of HCC risk.” All 49 biopsies (100%) were positive for nuclear expression of P1-HNF4α. Twenty-eight (57%) cases were positive for P2-HNF4α, 6 (12%) were positive for p-STAT3 and 5 (10%) were positive for c-Myc. All 6 (100%) p-STAT3-positive cases were also positive for P2-HNF4α (p = 0.03). p-STAT3-positive cases were more likely to be positive for c-Myc (67% vs. 2%, p = 0.0003). Four cases were positive for P2-HNF4α, p-STAT3 and c-Myc. p-STAT3 expression was associated with hypertension (p = 0.037). All c-Myc positive biopsies were from patients with obesity, diabetes and hypertension. Only c-Myc expression was associated with advanced fibrosis; three (60%) of the c-Myc positive cases were associated with advanced fibrosis in contrast to 7 (10%) of the 44 c-Myc negative cases (p = 0.011). “Based on these results, we hypothesize with the following sequence of events with progression of NAFLD: P2-HNF4α expression is followed by expression of p-STAT3 which in turn is followed by the expression of c-Myc. Additional larger studies are needed to confirm these findings.” DOI: https://doi.org/10.18632/oncotarget.28324 Correspondence to: Mamoun Younes - myounes@mfa.gwu.edu Video: https://www.youtube.com/watch?v=LVR29K6P5I4 Keywords: hepatocyte nuclear factor four alpha, steatohepatitis, immunohistochemistry, hepatocellular carcinoma, isoform To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter - https://twitter.com/Oncotarget Facebook - https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram - https://www.instagram.com/oncotargetjrnl/ LinkedIn - https://www.linkedin.com/company/oncotarget/ Pinterest - https://www.pinterest.com/oncotarget/ LabTube - https://www.labtube.tv/channel/MTY5OA SoundCloud - https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com

On this episode of the Dr. Tyna Show, I am going solo and I am going to be talking with you today all about Naturopathic prospectives on sauna and hydrotherapy and why I think protocols are bullish*t.Topics Covered In This Episode:Benefits of sauna therapyWhen to use a saunaWho can benefit from sauna therapyBy blanket sauna protocols are not appropriateMy personal sauna protocolWhen I use a saunaWhen I don't use a saunaSeasonal effective disorderSauna and depressionThis episode is sponsored by Sunlighten Saunas. You can save up to $600 when you purchase through THIS LINK and let them know Dr. Tyna sent you!Affiliate Link for Savings (can also be found on my website at drtyna.com): https://sunlighten.com/?utm_source=DrTyna&utm_medium=Partner&leadsource=DrTyna&utm_campaign=DrTynaFurther Listening:EP 19: My C-19 Experience - Solo EpisodeEP 24: 10 Reasons I Love My Sauna - Solo EpisodeEP 68: Hot and Healthy with Connie Zack of Sunlighten Saunas Get full access to Dr. Tyna Show Podcast & Censorship-Free Blog at drtyna.substack.com/subscribe

In this JCO Precision Oncology Conversations podcast, JCO PO author Dr. Thanh Dellinger of City of Hope National Medical Center shares insights into the research published in her article, “Hyperthermic Intraperitoneal Chemotherapy–Induced Molecular Changes in Humans Validate Preclinical Data in Ovarian Cancer.” Podcast host Dr. Abdul Rafeh Naqash talks with Dr. Dellinger about hyperthermic intraperitoneal chemotherapy (HIPEC) and the various challenges of the treatment of epithelial ovarian cancer (EOC). The study described in this JCO PO article discusses protein expression, RNAseq alterations and signature, and whole-transcriptome sequencing and signatures. Read here  https://ascopubs.org/doi/full/10.1200/PO.21.00239   TRANSCRIPT Dr. Abdul Rafeh Naqash: Welcome to ASCO's Precision Oncology Conversations where we bring you the highlights and overview of precision oncology. This podcast is here to provide interactive dialogue focusing on the excellent research published in the JCO Precision Oncology. Our episodes will feature engaging conversations regarding precision oncology with the authors of a clinically relevant and highly significant JCO Precision Oncology article. You can find all our shows including this one at asco.org/podcasts, or wherever you get your podcasts. Hello, I am Dr. Abdul Rafeh Naqash. I'm a medical oncologist and a phase one clinical trialist at the OU Stephenson Cancer Center. You're listening to JCO Precision Oncology Conversations. I have no conflicts of interest related to this podcast. A complete list of disclosures is available at the end of each episode. Today, I will be talking with Dr. Thanh Dellinger from the City of Hope Comprehensive Cancer Center, who's a gynecological oncologist, and we'll be talking about her JCO Precision Oncology article, ‘Hyperthermic Intraperitoneal Chemotherapy-Induced Molecular Changes in Humans Validate Preclinical Data in Ovarian Cancer.' Dr. Dellinger does not have any conflicts of interest. Hi, Dr. Dellinger, welcome to our podcast! Dr. Thanh Dellinger: Hi, Dr. Naqash! It's such a pleasure to be on with you. Dr. Abdul Rafeh Naqash: We recently saw your paper published. It's one of those interesting, clinical translational papers that we felt needed to be highlighted in our Precision Oncology Podcast series. So, we're really excited to have you here today to take a deeper dive into the findings and some of the novel approaches that you used in your recent publication. So, for starters, could you give our listeners a brief idea of what HIPEC is, where it's used, and when it's used in ovarian cancer? Dr. Thanh Dellinger: Right! Thank you very much for this great introduction. So, HIPEC or Hyperthermic Intraperitoneal Chemotherapy has been used in ovarian cancer for quite some time. The most relevant data giving us an indication for ovarian cancer was published by Dr. van Driel in the OVHIPEC-1 randomized trial several years ago in the New England Journal of Medicine, which demonstrated that in stage 3 ovarian cancer patients who undergo an interval tumor debulking with HIPEC, that those patients appear to enjoy both progression-free and overall survival benefit. In fact, the overall survival benefit is nearly 12 months for those patients. So, with this in mind and a number of other data, the HIPEC treatment for those patients that interval debulking has been incorporated into the NCCN guidelines. Nonetheless, there have been some criticisms of HIPEC and it still remains to be seen who those patients are, the ovarian cancer patients who really best benefit from HIPEC, given the morbidity of HIPEC. We now know also that HIPEC is probably equivalent to just cytoreductive surgery alone in terms of morbidity. Dr. Abdul Rafeh Naqash: Thank you for that explanation. And especially for people like myself, who are not surgeons or gynecological oncologists, that was very helpful. So, my next question, and you probably partly answered it, but I'm going to still ask the question is: what is the reason you think that intraperitoneal chemotherapy overall, has not been as widely adopted? Dr. Thanh Dellinger: You touch on a very good point there. As many of the listeners may understand, IP chemotherapy has demonstrated a lot of efficacies in multiple clinical trials over the last decade or two decades even. And part of why, despite its benefit, it has not been taken up in the overall community may really be the difficulty and the complexity of doing IP chemotherapy in the community, especially the side effects are difficult sometimes to take care of. There's increased abdominal pain and there are catheter issues. And so, especially with more recent data, that with the presence of Avastin, IP chemotherapy may not necessarily be as beneficial. Unfortunately, IP chemotherapy hasn't been really taken up in daily oncologic care with ovarian cancer. Nonetheless, we know that there are a lot of theoretical benefits because of the peritoneal metastasis not being as best treated with intravenous chemotherapy as with regional therapy. Dr. Abdul Rafeh Naqash: Thank you! So, now going to the data that you published. I was very intrigued with some of the findings. And from what I understood, your main aim was to understand predictive biomarkers to identify patients or basically identify molecular characteristics for patients' selection for HIPEC. So, could you tell us more about why you initiated this study? And I understand this is one of the, I believe the first study in humans to evaluate some of these interesting biomarkers, both pre- and post-. So, what was the background of doing this trial? And what led to this interesting study? Dr. Thanh Dellinger: Thank you for pointing out this aim. There's a lot of criticism of HIPEC and part of it is that we may not exactly understand the mechanisms of HIPEC, why is it that it works so well in some patients? There's a lot of preclinical data supporting hyperthermia, especially with cisplatin. There's synergy between cisplatin and hyperthermia, and improving the DNA adduct formation. There's increased cytotoxicity seen when the temperature increases up to 43 degrees. And there's also a T-cell activation and immune response that occurs during hyperthermia. So, a lot of this, however, has been done in preclinical studies, in vitro data as well as preclinical mouse models. There hasn't been much or really anything published that, as far as I know, has been done in humans. And so, this particular study looked at both pre-treatments, pre-HIPEC specimens, peritoneal biopsies, as well as immediate post-operative peritoneal biopsies, tumors, and normal samples, and we wanted to look both at the whole transcriptomic sequencing profile, but also at the tumor microenvironment. Dr. Abdul Rafeh Naqash: From a logistic standpoint, from a trial design standpoint, was this a phase 1 study? I know you use the term pilot in the publication. So, were you trying to look at safety also, or was this primarily I would say, a biomarker, pharmacodynamic biomarker-driven study that you were trying to evaluate? Dr. Thanh Dellinger: You're correct. This was essentially a feasibility study. But we additionally looked at safety and feasibility with HIPEC at our institution. And in some respects, we also looked at the feasibility of giving intraperitoneal chemotherapy normothermically early after HIPEC, and so it was also an endpoint to look at safety. Dr. Abdul Rafeh Naqash: Understand! I believe there was some difference in the dose for the cisplatin, I believe, is the chemotherapy that you use. What was the rationale for the difference in the dose for 75 milligrams per meter square that you use in your study? Dr. Thanh Dellinger: The study was initiated at a time before the OVHIPEC-1 trial was published. And so, at that time, the HIPEC dose for cisplatin was still not established. 75 milligrams per meter square for cisplatin was actually used in other trials, and has been noted to be effective in other clinical trials. Dr. Abdul Rafeh Naqash: Thank you! Now going to the patient population for this trial. What type of patients were you enrolling? Was it just epithelial ovarian cancer patients, did these patients need to have peritoneal metastases when you were doing this cytoreductive surgery? What was the patient population that you were targeting in this trial? Dr. Thanh Dellinger: The majority of the patients did have epithelial ovarian cancer. We did enroll a few, actually 5, uterine cancer patients as well, which were not included in this specific publication. But the majority of them were epithelial ovarian cancer patients. Dr. Abdul Rafeh Naqash: Going to the interesting translational analysis. So, you had three subsets of patients based on the biopsy collection. What were your hypotheses, and what drove some of those translational studies to understand the biomarkers? Dr. Thanh Dellinger: The first translational analysis we conducted was the whole transcriptomic sequencing, and specifically, we wanted to look, one, for any potential transcriptomic signatures that may correlate with survival or improved response to HIPEC. The second one was to look at whole exome sequencing. Thirdly, we looked at whole transcriptomic sequencing differences before and after HIPEC treatment. And lastly, we looked at the tumor microenvironment through multiplexing of certain markers associated with T-cell response. Dr. Abdul Rafeh Naqash: From a clinical outcome standpoint - and we'll discuss the biomarkers in more detail - from a clinical standpoint, when I briefly looked over the PFS curves, were the results, as far as expected outcomes, were they similar to what you see with the current standard? Or were there any unusual safety signals? Or would you attribute any of the adverse events that you saw to intraperitoneal chemotherapy specifically? Because I believe some patients did have some chemotherapy pre-surgery, neoadjuvant if I'm correct. So, how would you attribute some of those AEs, and if at all, did you see any interesting safety signals of concern and outcomes as far as PFS is concerned? Dr. Thanh Dellinger: So, one of the major toxicities that we saw in the first half of our trial were actually renal toxicities. In fact, there were actually two patients who could not go on to adjuvant chemotherapy because they suffered chronic renal failure. And because of that, halfway through the trial, we did actually add a nephro protectant called sodium thiosulfate. And this actually dramatically improved those renal toxicities. And for the second half of our study, no patients suffered grade three or grade four renal adverse events. And so, that did change significantly. Dr. Abdul Rafeh Naqash: From a genomic standpoint, it's very interesting that you were able to do all these very cool and interesting translational biomarker studies, including multiplex immunofluorescence. From a genomic standpoint, though, would you say it's fair to say that there was no significant correlation based on the baseline genomics for some of the patients and their outcomes? Is that a fair assessment? Dr. Thanh Dellinger: Yes, that is a very fair assessment. I think that our cohort was really too small to make those kinds of assessments. I don't know whether you saw there recently was a paper published by the OVHIPEC-1 group looking at their cohort of over 200 patients that underwent the interval cytoreductive surgery in HIPEC and they did actually demonstrate benefit in patients who are HIV-positive but BRCA wild-type, but not necessarily in BRCA mutated patients. So, I think that I would point to that study to look for genomic effects with HIPEC patients. Dr. Abdul Rafeh Naqash: Understand. Now, again, going to the biomarkers that your team evaluated, it seems from among good responders especially, you saw an increase in tumor necrosis factor, alpha signaling, NF-kappa B signaling, KRAS signaling, and then you also saw some pathways that were downregulated, especially the G2-M checkpoint, and Myc targets. What would you say the correlation of these is in terms of future drug development in this specific setting? Dr. Thanh Dellinger: I think that we did see some increase in immune pathways in patients who did better in the end. And also, our multiplex results did demonstrate that E1 expression was increased in patients who had better responses after HIPEC. So, our hypothesis is that potentially, there's an activation of T-cell response with HIPEC and that potentially PD-1 inhibitor could be added in the future. This is a hypothesis that certainly would need to have more work, but it's something that is interesting enough to really look at in ways of how to improve HIPEC. Dr. Abdul Rafeh Naqash: Going to your point on the PD-1, I found really intriguing that you were able to see an increase in PD-1 expression on CD8+ T cells but no actual increase in the number of CD8+ T cells suggesting there's some sort of activation of this marker and this may not necessarily be a marker for T-cell exhaustion. So, would you interpret it in a way that in a different setting, perhaps a new adjuvant approach with immunotherapy, would perhaps somehow augment this and then you could see more upregulation? Is there any work being done in that field? How would you put this in the context of your findings? Dr. Thanh Dellinger: You bring up a really great point because to date HIPEC has been demonstrated to have benefit in the interval setting. But there was a more recent study done by, well not recent, a more recently published study by a Korean group that demonstrated no benefit in the adjuvant setting for HIPEC and still some benefit in the interval setting. And the question is, are these really two different types of cohorts who respond differently because of potential differences in immune response and tumor microenvironment? I think that that would be a great way of delving further into this. What are really the differences in tumor microenvironment changes in those two different settings? Dr. Abdul Rafeh Naqash: Definitely! It's very exciting. You've also shown upregulation of, as you mentioned earlier, immune pathways, as well as upregulation of genes related to heat shock proteins. Does that play into future drug development as far as HSP Inhibitors are concerned? Dr. Thanh Dellinger: That is a really great question. Certainly, in preclinical models, heat shock proteins are known to be elevated and they do activate dendritic cells and result in T-cell activation. Now, whether that can be spelled out into actually some future drug therapy definitely remains to be seen. To date, there hasn't been any success in using heat shock types of agents or inhibitors, unfortunately. So, I think while this is of great interest, I'm not entirely sure that this will translate into any drug therapy in the future. Dr. Abdul Rafeh Naqash: And I totally connect with you there as a phase 1 trialist. I completely agree that we see a lot of translational data, more often than not, going into the phase 1 site because many of these targets are not actionable. Now, from a DNA repair standpoint, you did see that there was interference with DNA repair, as far as some of the analyses that you did, but I did not specifically see any markers for DNA damage that were assessed on the biopsies such as Gamma-H2AX, RAD 51, or Phospho-NBS. Was there a reason why that was not looked at? Dr. Thanh Dellinger: I think that we did look at that and there weren't really any significant results. We did put some of the data into the supplementary data. I think that in the end, our cohort was really too small to really make any meaningful data. But I absolutely agree with you looking at HSP and DNA repair is really important. And as I mentioned that most recently published paper does address that. Dr. Abdul Rafeh Naqash: Excellent! Do you think that there could be any confounders in this analysis that could have led to the upregulation of some of these pathways and may not necessarily have been the intraperitoneal chemotherapy? Could you think of some other reasons that this could have been a confounding factor? Or would it primarily be attributed to the intraperitoneal chemotherapy that you guys have looked at in this interesting paper? Dr. Thanh Dellinger: Yeah, it is a rather small cohort. So, I think that more data is required to potentially repeat this in the larger cohort. But what is interesting is that we did have paired analysis. So, we had matched peritoneal samples from the same patients looking before the HIPEC and after the HIPEC, which is very unique and hasn't really been done in the setting before. And while you couldn't necessarily repeat the same exact peritoneal tumor it was very close. And so, in the best setting, I think that we did have a good paired analysis. Dr. Abdul Rafeh Naqash: That was one of the very interesting aspects of this study that I very much appreciated, that you were able to get some of those paired biopsies and do the analyses on samples and look at all these markers. So, this was all excellent work and definitely intrigues the mind into what other ways one could use some of these findings to develop future combination-based approaches, whether it's the neoadjuvant or the adjuvant setting for patients with ovarian cancer. Are there any next steps as part of this project that you are excited about that you can share? Dr. Thanh Dellinger: Right! I'm definitely very excited about trying to build on this and essentially developing a much larger predictive study using hundreds of ovarian cancer HIPEC-treated tumors in collaboration with others. We have definitely developed a great community of HIPEC investigators who are very interested in developing somewhat of a predictive signature for ovarian cancer undergoing HIPEC. So, I'm very excited to hopefully be able to develop this consortium of HIPEC transcriptomic research. And so, I'm looking forward to collaborating with my co-investigators on that. Dr. Abdul Rafeh Naqash: It was definitely exciting to talk to you about your work. Now, I want to ask you about you as an investigator or as a researcher. How did you end up in this field? What was your background while you were pursuing science and medicine? How did you end up in this field and how are you mentoring the next generation? Dr. Thanh Dellinger: When I was a fellow at UCI, my mentor Robert Bristow introduced me to HIPEC and that has really stuck. As a GYN oncologist, it is hard to really do both chemo and be a good surgeon. And in many ways, I have really specialized in surgical oncology more than in medical oncology. And HIPEC is really a very nice blend of the two. It allows you to do clinical trials while still doing surgery and giving some chemotherapy. Really, it was for the introduction of my more recent mentor, Elena Rodriguez, who really introduced me to genomics and applying this to HIPEC samples that this all came about. And so, I think that there are a lot of opportunities for surgical oncologists who do not give chemo and may think that clinical research is not for them, but there are a lot of translational opportunities and clinical trial opportunities for those who don't give chemotherapy, but are surgical oncologists. Dr. Abdul Rafeh Naqash: Thank you so much. We are really excited for all the work that you're doing and will continue to do and hopefully, we'll see more of this evolve as time progresses. Dr. Thanh Dellinger: Thank you so much, Dr. Naqash. It was such a pleasure meeting you and talking to you. Dr. Abdul Rafeh Naqash: Same here. Thank you for listening to JCO Precision Oncology Conversations. To listen to more, visit asco.org/podcasts, or find them on Google Play Spotify and Apple podcasts. To stay up to date, be sure to follow and share JCO Precision Oncology content on Twitter. The Twitter handle is @JCOPO_ASCO. All JCO PO articles and series can be found at ascopubs.org/journals/PO. The purpose of this podcast is to educate and inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.  Guest Bio Dr. Thanh Dellinger, MD, is a gynecologic oncologist and physician-scientist who specializes in ovarian and uterine cancer. She is an expert in hyperthermic (HIPEC) and pressurized aerosolized intraperitoneal chemotherapy (PIPAC), and is the primary investigator of clinical and translational studies focusing on these therapies. She received her medical degree at University of California Irvine, where she also completed a gynecologic oncology fellowship. She is leading the first U.S. clinical trial in PIPAC (pressurized intraperitoneal aerosolized chemotherapy), a novel therapy using pressurized aerosolized chemotherapy for ovarian cancer. Her current research focuses on innovative therapies for ovarian cancer using intraoperative chemotherapy, and novel antibody and nanoparticle therapies.

C'est la fin de la guerre de Troie. Les rois grecs vainqueurs se séparent et chacun rentre chez soi, avec son armée. Avant de monter dans son navire, Agamemnon sacrifie aux Dieux. Ainsi, il fera bon voyage jusqu'à Mycènes, la cité dont il est le roi... Hébergé par Acast. Visitez acast.com/privacy pour plus d'informations.

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses. In the Research Round Up series, ASCO experts and members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today's episode, our guests will discuss new research in lung cancer, lymphoma, and childhood cancer that was presented at the 2022 ASCO Annual Meeting, held June 3-7 in Chicago, Illinois. First, Dr. Charu Aggarwal will discuss 3 studies looking at treatment options for people with non-small cell lung cancer. Dr. Aggarwal is the Leslye Heisler Associate Professor of Medicine in the Hematology-Oncology Division at the University of Pennsylvania's Perelman School of Medicine in Philadelphia, Pennsylvania. She is also the Cancer.Net Associate Editor for Lung Cancer. You can view Dr. Aggarwal's disclosures at Cancer.Net. Dr. Aggarwal: Hello and welcome to this Cancer.Net podcast. I'm bringing you updates from the Annual Meeting of the American Society of Clinical Oncology, held in Chicago in 2022. I'm Dr. Charu Aggarwal. I'm the Leslye Heisler Associate Professor for Lung Cancer Excellence at the University of Pennsylvania's Abramson Cancer Center. I will be discussing updates on 3 studies today that offer insights and new advances in the management of patients with non-small cell lung cancer. I don't have any direct relationship with any of these companies or studies, and you can view a list of my disclosures on the Cancer.Net website. First off, I would like to talk a little bit about advances in the management of patients with EGFR exon 20 mutations. We know that a lot of advances have been made in the management of patients with non-small cell lung cancer, and much of that has been attributed to the fact that we are now able to deliver targeted therapy for a subset of patients. EGFR mutations form one such subset where we have a lot of oral drugs that are available, and we can offer these that improve survival, and patients can avoid chemotherapy, immunotherapy, and other IV infusional therapies. Within the subset of EGFR mutations lies this unique subset of EGFR exon 20 insertion mutations, which have been historically harder to target with currently available EGFR inhibitors. And over the last 5 years, we have seen tremendous growth of opportunities, targets, and new drugs for this subset of patients. The mutations in this subset forms about 2% to 5% of all non-small cell lung cancers. But now we have 2 FDA-approved drugs in this space, one being intravenously administered, amivantamab, and another that is orally available, mobocertinib. We covered this in a podcast as well as a blog, so please check those out on our Cancer.Net website. But building upon that progress, there is now another drug that was reported at ASCO. This drug is called CLN-081. And we saw preliminary activity in a phase 1 and 2 study of this molecule or this drug in patients with EGFR exon 20 insertion mutations. It's an orally available drug. The top line data is that it is safe, it is effective, it was tested in different doses. It was tested at less than 65 milligrams, 100 milligrams, and 150 milligrams, again, as I mentioned, administered orally, and we saw responses and patients that had previously received other therapies and may have progressed on other therapies. And what we found was that this drug also tends to have activity against brain metastases, which I think is this huge unmet need in the management of such patients. So I think more to come, but again, I think offers us an insight into what may be in the future, an attractive drug for our patients with EGFR exon 20 insertion mutations. So stay tuned, more on that in the future. Shifting gears, I would like to now talk about one of the common mutations. So we talked about EGFR exon 20, which is about only 2% to 5%, but the largest subset of mutations in non-small cell lung cancer really revolves around KRAS mutations, and these form about 30% to 35% of all mutations in non-squamous, non-small cell lung cancer. And amongst this group there is another subset which is KRAS G12C non-small cell lung cancer, that forms about 13% of all lung cancers. We have 1 approved drug already in this space by the name of sotorasib that is FDA approved for the management of patients with this particular mutation after having received 1 prior therapy, be it chemo-immunotherapy or immunotherapy. At this year's ASCO meeting, we heard data from a study called KRYSTAL-1, which looked at the activity and safety of another molecule called adagrasib, which is an orally available drug targeting KRAS G12C, again, in a similar population of patients with advanced and metastatic non-small cell lung cancer harboring a mutation. We found that this drug is again effective, the overall response rate was about 43%, the majority of the patients had stabilization of disease, about 80%, and many patients were able to remain on treatment with stabilization of disease. We found that this drug does have side effects and adverse events and most commonly of this were diarrhea, nausea, vomiting, and fatigue. Many patients did require dose reductions, but the activity of the drug remained despite dose reductions. Now, what would be the advantage of this drug against the currently available sotorasib? In another smaller study reported at ASCO, there seemed to be activity in the brain, including intracranial penetration with the use of this molecule, adagrasib, which has not been demonstrated before with other KRAS G12C inhibitors, so I think that makes it a potentially attractive option. Again, I will say that the report of this intracranial activity was in a very small subgroup of patients, so I think needs to be further corroborated in a larger study. Shifting gears again and talking about our last study, so I would like to highlight what do we do if, in case, patients don't have a targetable mutation. I want to highlight that we do have a lot of available options, and we are continuing to improve upon available options. The way we treat such patients is by using immunotherapy, either alone or in combination with chemotherapy. But what do we do after this treatment stops working? Researchers from the Southwestern Oncology Group, or SWOG, launched a massive national effort called Lung-MAP, which is basically a clinical trial that evaluates several different strategies all at once, either for patients with targetable mutations or for patients without a targetable alteration. And they reported results from a study that evaluated the combination of pembrolizumab with ramucirumab in patients that may have progressed after frontline immunotherapy. Now, pembrolizumab is immunotherapy, so the concept was, can we continue immunotherapy beyond progression and perhaps get some synergistic activity by using ramucirumab, which is a drug that prevents blood vessels from forming in the tumor itself. It's an anti-angiogenic agent, meaning that it is a targeted molecule that prevents blood vessel formation and promotes tumor death. What they found was that patients that received pembrolizumab and ramucirumab were more likely to live longer, so overall survival was longer for patients with this combination compared to a physician investigator discretion choice, such as chemotherapy in combination with ramucirumab or other chemotherapies that are otherwise used in the second line setting. And interestingly, we did not find a significant improvement in shrinkage with this combination of pembrolizumab and ramucirumab or a significant reduction in the time of progression-- or, sorry, prolongation of the time of progression of disease. But the overall survival findings are interesting, and I think that's why we are including them in this podcast because that's one of the approaches that is leading to an improvement in survival and improvement in outcomes. I will point out that this is a phase 2 study. These results would need to be validated in a large prospective phase 3 trial so that we can account for certain confounding factors that may have led to these results. Having said that, I think there's a tremendous excitement, there's tremendous excitement in this field. I gave you examples of, or highlighted, 3 studies: one in patients with EGFR exon 20 insertion mutations, another in KRAS G12C mutations, and the third in patients who may have already received either immunotherapy or chemoimmunotherapy. We will continue to update our Cancer.Net website with updates as they come through, new advances, new studies, so thanks for following, thanks for listening, and more to come. Stay tuned. Thank you. ASCO: Thank you, Dr. Aggarwal. Next, Dr. Christopher Flowers will discuss new research in treating people with different subtypes of lymphoma, including mantle cell lymphoma and diffuse large B-cell lymphoma. Dr. Flowers is the Chair of the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center and was appointed Division Head ad interim of Cancer Medicine in August 2020. He is also the 2022 Cancer.Net Associate Editor for Lymphoma.   You can view Dr. Flowers' disclosures at Cancer.Net. Dr. Flowers: Hello and welcome to this podcast that is a review of late breaking abstracts from the ASCO Meeting and recent updates in lymphoma. I'm Dr. Christopher Flowers, professor and chair of the Department of Lymphoma and Myeloma and Interim Division Head for Cancer Medicine at The University of Texas MD Anderson. And it's my great pleasure to discuss with you some of these late breaking abstracts. I do have some disclosures that are related to the content that I will present from this year's ASCO Meeting and recent studies in lymphomas. Those are available at Cancer.Net. Those relate to my role as a consultant for the development of clinical trials in lymphomas and research funding that MD Anderson has received from companies related to my role in clinical trials in lymphoma and clinical trials across cancers. So, the ASCO Meeting had a host of new information that was presented. Some of that information centers around key clinical trials. One that was a pivotal clinical trial, the SHINE clinical trial, looked at patients with mantle cell lymphoma, a rarer lymphoma subtype, that looked at the combination of bendamustine and rituximab, a standard chemoimmunotherapy combination, compared to that same chemoimmunotherapy combination, bendamustine, rituximab, plus the Bruton's tyrosine kinase inhibitor ibrutinib. Ibrutinib, as some of you may know, is a kind of therapy that is typically used in the relapse setting for patients with mantle cell lymphoma when they have their disease come back. And the SHINE clinical trial was looking at adding it to frontline therapy. What this randomized, controlled trial in the phase 3 setting found was that patients who received the combination of bendamustine, rituximab, plus ibrutinib had improvement in their progression-free survival, meaning that the time that it took for their disease to come back or them to have deaths related to the lymphoma was longer for patients who received this combination. About 2.3 years longer than the group that received bendamustine, rituximab, plus placebo. And in total, that led to a median progression-free survival of 6.7 years. That study has now been published in the New England Journal of Medicine and was led by my colleague Dr. Michael Wong from MD Anderson. Dr. Wong also led another study that was presented at the ASCO Meeting looking at CAR T-cell therapy for patients with mantle cell lymphoma. That study has now been published in the Journal of Clinical Oncology, and it looks at brexucabtagene autoleucel, a kind of CAR T-cell therapy, where that-- the CAR T-cell therapy was successfully manufactured for 71 of the 74 patients in the trial. 68 of those patients received an infusion and the median progression-free survival, so the average amount of time that it took for patients to have progression of their disease, was about 25 months. And so a marked benefit for those patients who were receiving CAR T-cell therapy when their mantle cell lymphoma came back. There also were major breaking abstracts at the ASCO Meeting in the area of diffuse large B-cell lymphoma. As many of you may know, diffuse large B-cell lymphoma is the most common type of lymphoma that occurs in the United States. And there was a breaking trial that was presented in December at the American Society of Hematology Meeting describing polatuzumab, a CD79b antibody drug conjugate, as a new drug in the substitution of frontline therapy for patients with diffuse large B-cell lymphoma in combinations with rituximab, cyclophosphamide, adriamycin, and prednisone, or the pola-R-CHP arm, that compared favorably to rituximab and CHOP chemotherapy, which has been the standard of care for patients with diffuse large B-cell lymphoma. And that trial showed an improvement in progression-free survival. At this year's ASCO Meeting, Franck Morschhauser presented results from looking at subsets of that patient population. Those patients who had BCL2 by immunohistochemistry that was positive or MYC expression by immunohistochemistry that was positive, or both of those, what we call double-expressor lymphomas, those who have poorer risk than standard groups. And those double-expressor lymphomas, treated with pola-R-CHP, had improvement in progression-free survival compared to R-CHOP with a hazard ratio of 0.64 in that group. We also saw in a multitude of analysis that that supported the benefit of pola-R-CHP in patients with both BCL2-positive and MYC-positive diffuse large B-cell lymphoma. Another area that has been very hot in diffuse large B-cell lymphoma clinical trials is the role of bispecific antibodies. Bispecific antibodies are antibodies that bind both to CD20, a marker on the diffuse large B-cell or the lymphoma cells, and to the marker CD3, which is a marker on T-cells which brings the normal T-cells of the immune system in close proximity to the lymphoma cells and then leads to immune-directed killing of lymphoma cells. The agent glofitamab is an agent that was presented by Michael Dickinson at this year's ASCO Meeting in an abstract. And in this study, 107 patients who received more than 1 dose of steady treatment went on to have complete responses in about 35% of patients. And this showed that glofitamab induced durable complete responses and had a very favorable safety profile in patients with relapsed and refractory diffuse large B-cell lymphoma. And in this trial, they compared that also for patients who had prior exposure to CAR T-cells and showed that responses were also good in those patients. Another set of studies has also looked at bispecific antibodies and a whole host of other areas with multitude of other agents. Another study that was presented at this year's ASCO Meeting explored the use of bispecific antibodies in the frontline setting in combination with the R-CHOP regimen that I just discussed. In that study, Lorenzo Falchi presented results of the subcutaneous bispecific antibody epcoritamab in combination with R-CHOP. This was a relatively small study of 33 patients that showed that the combination of epcoritamab plus R-CHOP was something that was safe and tolerable. There were no new treatment emergent adverse events that led to discontinuation of epcoritamab in the study. And there are some adverse events that are of special interest that we see with the bispecific antibodies, and those include the kind of immune-mediated adverse events that we can also see with CAR T-cells, like cytokine release syndrome, or CRS, or neurologic toxicities that we can see there that are also called ICANS. What we've seen in this trial, that about 42% of patients had some form of cytokine release syndrome, but that most severe form of cytokine release syndrome, those that were greater than grade 3 in severity, was only in 3% of patients. And likewise, the neurologic toxicities, or ICANS, that were grade 2 was in only 3% of patients. Relatively few patients completed all therapy by the time that this was presented. Only 10 patients had completed 6 cycles of therapy, but that showed an overall response rate that was quite high in that patient population. There were a whole host of other trials that were presented at this year's ASCO Meeting, and those portend improved kinds of outcomes on the horizon for patients with lymphomas across the spectrum. And I think it's an exciting time moving forward for clinical trials in lymphoma and hopefully, to see new therapies that emerge for the management of this disease. One of those new therapies that happened outside of the ASCO Meeting was the recent FDA approval of CAR T-cell therapy in the relapse setting for follicular lymphoma. And this was based on the ELARA clinical trial. And I think the future is quite bright for therapies and for patients with lymphomas broadly. ASCO: Thank you, Dr. Flowers. Finally, Dr. Daniel Mulrooney will discuss new research in childhood cancers, including a study comparing treatment options for Ewing sarcoma, and several studies on neuroblastoma. Dr. Mulrooney is an Associate Member in the Division of Cancer Survivorship at St. Jude Children's Research Hospital. He is also the Cancer.Net Associate Editor for Pediatric Cancers. You can view Dr. Mulrooney's disclosures at Cancer.Net. Dr. Mulrooney: My name is Dr. Dan Mulrooney from St. Jude Children's Research Hospital. I'm the Deputy Director of the After Completion of Therapy Clinic at St. Jude and primary care for survivors of pediatric solid tumors. The annual ASCO Meeting is typically quite busy and full of research presentations sharing knowledge and advances in cancer treatment and care. Today, I'd like to highlight some of the exciting presentations in pediatric cancer. Please note, I do not have any relationships to disclose related to any of these studies. At this year's meeting, one of the highlights was a European study in patients with relapsed or refractory Ewing sarcoma. Ewing sarcoma is a rare bone cancer that typically occurs in adolescents or young adults. While challenging to treat, it is difficult to cure in patients who have relapsed, and studies are needed to improve the care of these patients. Investigators from 13 European countries and Australia and New Zealand studied the most common relapsed therapies, which include irinotecan and temozolomide, gemcitabine and docetaxel, topotecan and cyclophosphamide, or high-dose ifosfamide. The study enrolled 451 patients between 2014 and 2021 and randomly assigned them to one of these four treatments. Based on response rates, the first 2 arms were dropped and the study was largely a comparison between topotecan cyclophosphamide and high-dose ifosfamide. The main outcome was event-free survival. Event-free survival is a common way in a clinical trial to see how well a treatment works. It measures the time from treatment that the patient remains free of complications, such as return or progression of the cancer. But investigators also looked at overall survival, toxicity, and quality of life. The 6-month event-free survival was better for high-dose ifosfamide at 47% compared to 37% for topotecan cyclophosphamide. The median overall survival was also better for high-dose ifosfamide compared to topotecan cyclophosphamide. The results were best for children younger than 14 years old versus those 14 or greater. Toxicities included fever and neutropenia, nausea, vomiting, and diarrhea. Patients receiving high-dose ifosfamide had more neurologic and kidney toxicities, which might be expected since ifosfamide is known to affect these organ systems, while only descriptive measurements of quality of life appeared higher for those children treated with high-dose ifosfamide compared to topotecan and cyclophosphamide. The strength of this trial is its large size, particularly for a rare cancer, and the fact that it randomized patients to the most commonly used treatment regimens for relapsed Ewing sarcoma. Importantly, data did not previously exist comparing these different treatments. While the results of this study are promising, clearly more needs to be done, and there was a lot of discussion at the ASCO Meeting about how to further improve survival in these patients. This study provides some information for doctors and patients, but importantly, provides data to advance future trials, which will concentrate on incorporating new targeted drugs with high-dose ifosfamide. This study is ongoing and is adding additional arms to continue to improve the outcomes for patients with relapsed or refractory Ewing sarcoma. In addition to this study in Ewing sarcoma, several studies investigating neuroblastoma were presented. Neuroblastoma is the most common extracranial solid tumor in children and for children with high-risk disease requires intensive and prolonged treatment, including chemotherapy, surgery, radiation therapy, and stem cell transplantation. Treatment for these patients has improved since the introduction of immunotherapy, particularly an antibody directed at a particular antigen named GD2 on the neuroblastoma cells. One study showed improvement in outcomes using this antibody for children with relapsed or refractory neuroblastoma, and another study demonstrated feasibility of using this antibody earlier in treatment, which was not previously known to be safe and tolerable. In what is called the BEACON study, investigators tested whether the antibody, called dinutuximab, would be effective when combined with chemotherapy for relapsed or refractory neuroblastoma. They enrolled 65 patients from 2019 to 2021 and randomized these patients to either chemotherapy alone or chemotherapy plus dinutuximab. The median age of these children was 4 years. The overall response rate, which means either a complete or partial response, was 18% for the chemotherapy-only arm but improved to nearly 35% for those treated with chemotherapy and dinutuximab. The progression-free survival was 27% for chemotherapy only and improved to 57% for those treated with chemotherapy and the antibody. There was no change in overall survival, though investigators think this may have been due to some patients who had progressive disease and crossed over to the antibody arm of the study. This presentation was followed by a study from the Children's Oncology Group, which investigated the feasibility of adding antibody treatment earlier in the treatment regimen for neuroblastoma. Prior studies had used antibody later in treatment when the tumor burden is thought to be lower. The endpoint of this study was tolerability measured by toxic deaths or unacceptable toxicities, such as adverse reactions to the medication. For example, sustained low blood pressure requiring a ventilator or breathing machine, or severe neuropathy. 42 high-risk neuroblastoma patients were enrolled from 8 different children's hospitals between 2019 and 2021. 41 of the 42 were able to complete the induction chemotherapy plus the antibody. There were no toxic deaths or unacceptable toxicities. Importantly, 85% were able to complete the next phase of treatment, called the consolidation phase, and 79% were able to complete the following phase after consolidation, called post-consolidation. One-year event-free survival was 83%, and 1-year overall survival was 95%. Now, it's important to know these are still early results, and the trial recently closed, and some of the patients have only completed therapy within the last year. Both of these studies add to the knowledge of chemoimmunotherapy for children with high-risk neuroblastoma. These studies provide a foundation for larger randomized trials that will further advance the care of these children. And finally, another study looked at race, ethnic, and socioeconomic disparities among children treated for high-risk neuroblastoma on Children's Oncology Group studies. There were no differences in event-free survival, but there were differences in overall survival based on ethnicity. The 5-year survival was lowest for Hispanic patients at 47%, 50% for non-Hispanic other ethnicities, which included Asian, Native American, Native Hawaiian, or Pacific Islanders, and 62% for non-Hispanic Black and non-Hispanic White children. Importantly, these investigators also studied household and neighborhood poverty. Overall, survival was lower for children living in poverty, though some of these differences went away when accounting for other factors, such as stage of disease or high-risk features. This study is important because it highlights the increasing need to collect data on clinical trials that may contribute to inequities in outcomes. While most studies collect data on the race and ethnicity of participants, other factors known as social determinants of health, such as income, neighborhood, education, access to health care, and insurance coverage, may also contribute to outcomes in pediatric cancer patients. Overall, the studies highlighted here and presented at this year's ASCO Annual Meeting focused on difficult-to-treat cancers, such as relapse or refractory disease, and they have laid the groundwork for future investigations to continue to improve survival rates for all children diagnosed with a malignancy through improved therapies and by addressing potential social barriers. Thank you for listening to this brief summary of the new research in pediatric oncology presented at the 2022 ASCO Annual Meeting. ASCO: Thank you, Dr. Mulrooney. You can find more research from recent scientific meetings at www.cancer.net. Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care. And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

Back in May 2019, MTPConnect launched the Biomedical Translation Bridge (BTB) program, a $22.3 million initiative of the Medical Research Future Fund, supporting the translation of new therapies, technologies and medical devices through to the proof-of-concept stage. In a first for Australia, it did that by pairing funded projects with industry mentors and commercialisation experts.Three years on and a COVID-19 pandemic later and the program is now moving to completion. To celebrate this milestone, we brought together the 21 funded projects and our venture and education partners, Biocurate, UniQuest, Medical Device Partnering Program and the Bridge and BridgeTech programs, for the BTB Finale event at Luna Park in Sydney. In part two of this episode, hosts Caroline Duell and Dr Duncan Macinnis walk the floor catching up with awardees and partners. We hear from Dr Alison Thistlethwaite from Melbourne-based biotech MycRx - developing first-in-class small molecule inhibitors of the Myc oncoprotein as safe and effective treatments for cancer. Dr Jeremy Paull from Melbourne biotech Starpharma talks about how the funding supported the development of their anti-viral nasal spray, Viraleze™  within 12 months which is now registered for sale in more than 30 countries. And venture partners Dr Mark Ashton from Uniquest, the Biocurate team of Linda Peterson, Dr Tifelle Reisinge and Dr Eric Hayes, and BridgeTech's Professor Lyn Griffiths explains how they bring their expertise in commercialisation to assist BTB projects reach commercialisation stage. 

Meagan welcomes Julie back today to celebrate 200 episodes of The VBAC Link podcast! They celebrate this milestone with a special live Q&A podcast recording session joined by followers of The VBAC Link Facebook community. Topics include: how to talk to your provider, all about Spinning Babies, adhesions, managing sciatica pain, induction, nipple stimulation to induce labor, VBAMC, C-section consent forms, and much, much more.We can't wait to continue sharing new episodes with you as we stay committed to our mission of making birth after Cesarean better!Additional linksSpinning Babies websiteThe VBAC Link Blog: Pumping to Induce LaborFear Release YouTube VideoEpisode 18 Leslie's HBAC + Special ScarsJulie's InstagramThe VBAC Link Community on FacebookHow to VBAC: The Ultimate Prep Course for ParentsFull transcriptNote: All transcripts are edited to correct grammar, false starts, and filler words. Julie: Welcome to The VBAC Link podcast. This is our 200th episode and yes, you are listening to Julie. I'm back just for this episode and probably some more in the future at some point, but we are so excited, Meagan and I, because this is the 200th episode. We are now live in our Facebook group. Not now when you are listening to it, but right now in this moment in our timeline. It took us way too long to get in here live, but we are doing a Facebook Live podcast episode. We have never done that before and we probably will never do it again because this was kind of traumatic.Meagan: Yeah, this was a little rough, but that's okay. Now that we know, now that we know, we are good. We're good. Julie: Now we know.Meagan: It just took 34 minutes to figure it out. Review of the WeekJulie: Oh my gosh. Cool. So, let's get started first. There is a Review of the Week. Meagan, are you ready? Do you have one?Meagan: Yep, I do. This is from blpinto and it's from Apple Podcasts. It says, “Wonderful resources for ALL moms, not just VBACs.” It says, “I didn't have a C-section for my first birth, but I had a traumatic experience with a forceps delivery and an induction that was not at all what I was looking for. I started listening to the podcast before I even got pregnant a second time to prepare for a better experience. Julie and Meagan were a huge part of my process and journey. I ultimately had a beautiful home birth and a 10-pound, 6-ounce baby. I felt this podcast helped me overcome my fear that I couldn't push my baby out without help because many VBAC moms had the same feeling.”I love that. I don't know many first-time or second-time moms who haven't had previous C-sections that have listened and left a review. So that was awesome. We truly believe that this is also a podcast for everybody. Just like wonderful Brian says at the beginning of this podcast, it's for all expectant parents who want to avoid a Cesarean and want to learn their options and learn what's happening out there. So that is so exciting that we had someone who hadn't even had a C-section before. If you know someone who is expecting and has fear or maybe a first-time mom who has some doubts and problems and traumatic experiences in birth, definitely share the podcast. These stories are amazing for all to listen to. I would 100% agree with her.Julie: I love that. Do you remember years ago when we first started and we were trying to figure out how we could make something, maybe not separate, for first-time parents? We were like, “How do we get first-time parents to understand that these are things they need to know?” Because you didn't. I didn't. As a first-time mom, I didn't even think about a C-section until the doctor said, “We need to do a C-section,” and we never really got very far with that because the focus of The VBAC Link is a vaginal birth after Cesarean. Yeah, so we love that. We, I say “we”. I will always say “we” talking about The VBAC Link. Meagan: Literally, just earlier today, I was recording a podcast and I was like, “we”. I mean, “I”, but Julie is just over here. Julie: My spirit and presence exist in the VBAC realm.Meagan: Yes. But it's so much fun. It's so fun to be here and I'm excited. If you guys haven't had a chance or if you are watching live right now, we would love your reviews. Love, love, love your reviews. You can send us an email. You can write right here and I will copy it over and put it in the reviews. We are excited to dive in today on episode 200!Q&AJulie: Yeah. All right, all eight people who are watching. I guess one of those is me and maybe you, so six. Six people. Drop your questions. Nothing is off-limits. We are going to talk about everything you want to know. Everything you want to hear. We are going to get down and dirty with everything VBAC, wives, and kids. If you want to know what Meagan's kid is doing right now in the background, we will talk about it. Meagan: Yeah, drop your questions. I'm posting here letting people know that we actually are live now. Julie: Oh heavens. VBAC: Where do I start?Meagan: Yes. It's so funny. I keep looking on the wrong forum. Okay, who do we have in here? Who do we have? Kathryn, Jen, and AJ thank you so much for being here. Let us know your questions. I want to maybe start off just on VBAC options. We had someone write in yesterday and was like, “One, I didn't know VBAC was an option. I didn't even know what it was.” So that's wonderful that they're starting to find out that VBAC is an option, but let's talk about how we can have a conversation about VBAC being an option with a provider. That's just random, I know. But what would you think, Julie, if you're starting to discover VBAC, learning what it is, feeling like you want to feel it out, maybe you want to learn more about it and do it, how would you suggest approaching your provider?Julie: Oh man, that's a great question. First of all, we've got some good questions coming in too so I'm excited to answer these. Provider, honestly, I would just ask where their thought process is. I would approach them and say, “Hey. this is what I'm considering. What are your thoughts about it?” And I will tell you what. No matter what their response is and no matter what ultimately your birth plan is, you're going to get a really good feeling for how your provider feels about body autonomy, informed consent, and birth in general because if they answer and say, “Oh, well I don't think you are a great candidate. I don't do VBAC. I don't support them,” or anything that's very sounds set in stone, so, “I don't do this. We won't let you do that. We would have to look at this and make sure your percentage is high,” or whatever. Anything that is set in stone shows you that your provider is not as supportive of other options or your provider has a very set way of doing things and may not be a good choice for you. But if they answer and say, “Yeah. We can consider VBAC as an option. Let's talk about some things about what your goals are. I do VBACs a lot. I love VBACs” or anything like that with a more open or a more fluid answer is going to let you know that your provider is going to not only be good with whatever outcomes that you choose but is also very open to having the parent or the mother be part of the birth process and be involved in the decisions regarding their care. That's really what you want to have on your side no matter what type of birth you're having or where you are giving birth. You want to have a provider that is going to be open to your input, be a little flexible, a lot flexible based on what your needs are and the type of birth you want, and is able to accommodate that. Meagan: Yeah, and just that's willing to have that conversation because a lot of providers don't honestly come out and say, “Hey, do you want to have a TOLAC?” which is a trial of labor after a Cesarean. That may be something that you have to take charge of and say, “Hey. I'm learning about this. What are your thoughts? How do you feel about it? Tell me about some experiences.” We always talk about open-ended questions but really, truly if you can ask an open-ended question, you're going to be able to get more information than a “yes” or a “no” or an, “Oh yeah. Sure,” versus, “Yeah. I feel really comfortable with that. We do that all of the time. This is why.” So I love that. I know it was a random question, but a lot of people are asking, “How do I even approach this topic with my provider?”Okay, are you ready? I'm going to read some questions. We'll bounce back and forth. Julie: Yes, let's do it.What is Spinning Babies?Meagan: So Ms. Kathryn says, “I just found your podcast last night.” Yay! And now you're here on the first live one. It says, “Bingeing ever since. What is Spinning Babies? I've heard it talked about a lot on the podcast.” Spinning Babies is a wonderful resource. They have all sorts of circuits and tips and tricks on ways to navigate babies through the pelvis. Breech positions, so if you have a breech baby, they have positions and exercises to do that. We've got posterior. We talk and they also do baby mapping to help figure out where your baby is. Julie: Belly mapping. Meagan: What did I say? Julie: You said “baby mapping.”Meagan: Baby mapping. I meant belly mapping. Julie: They're the same thing.Meagan: That's what I meant. Baby mapping. I almost said it again. Belly mapping to help you figure out where your baby is. They can educate on if a baby is posterior, what types of things to do and what to do if a baby is asynclitic or comes over the pelvis, and what tips and tricks you can do. A lot of doulas are really educated in Spinning Babies. It is so awesome. So awesome when the client, don't you think, is educated in this and they are familiar with it. Julie: Yeah. Meagan: So obviously, we talk about it a lot in the podcast, but we really encourage people to check out their website. They have updated their website and it's really quite great now. It's really friendly to navigate, so check it out. It can be a game changer. I have had positions in labor where things were just hanging out, stalling, not really going anywhere, and then we have done a Spinning Babies technique and boom, that baby rotates and labor is speeding along. Julie: Yeah, I love that. I think one thing that I really like about Spinning Babies too is that it puts less emphasis on babies being in this specific position and it creates more emphasis on creating room and space in the pelvis.Meagan: Balance. Julie: And with the connective tissues and yes, balance and all of those things because sometimes, babies need to enter into the pelvis in a little bit what you would call “less than optimal.”Meagan: “Less than ideal”, yeah. Julie: But as long as baby has enough space and room to wiggle and progress through the pelvis in the way it needs to, then you're going to have a great, not a great, that's a bad promise. You're not going to have a great labor necessarily, but you're going to be able to encounter less problems that are created by a poorly positioned baby or tissues that might be more difficult to move and things like that. So yes, balance, space, and flexibility. Do adhesions impact fertility?Meagan: Yeah, absolutely. Okay, let's see. AJ Hastings. “Do adhesions really impact fertility? Currently trying to conceive for seven months and was told by acupuncture that I need 12 months of weekly treatments. I definitely want another opinion.” So the short answer is yes it can. It can affect things. In fact, we have an episode and I will go find it here. I'm going to go find it. I'm going to drop it. It's so weird because we are on Zoom, but we are on Facebook over here. I'm going to drop it in the Facebook group right here because it definitely impacted her. It impacted her and adhesions, depending on how dense and how thick and everything, it can impact fertility. 12 months of treatment? I don't know. I mean, I'm not a specialist in how intense that needs to be. I have adhesions as well, but I don't know how dense they are. I was fortunate enough to become pregnant, but it can impact it and it's something to look into. I don't think it's bad to get a second opinion for a whole year of treatments, but I also wonder if scar massage, starting with scar massage by yourself, or going to a pelvic floor specialist and starting there might be beneficial. Julie, what would you think?Julie: Yeah, right along with what you said, it can. That's the thing. It doesn't always, but it might. Adhesions, especially ones that are denser or thicker can tug and pull things in the wrong way. They can make it harder for eggs to implant and can cause a whole slew of problems for your overall health depending on the relation to different organs that they might be adhered to. All sorts of things, but it doesn't always, right? One thing that I would ask my provider that's recommending that is what other options are available, what other things might be impacting my fertility? Have you seen any other types of providers? Have you seen an OB/GYN or maybe a fertility specialist in that regard or gotten a second opinion from them? Sorry, I think she said. Yep. I'm trying to see that it was told by acupuncture. Yeah, so I would maybe consult another type of provider. But trying to conceive for seven months is kind of a long time, but it also could take up to a year without there being any problems at all for just any random average to get pregnant too. That is just what was going through my mind. Is that the only thing that you are treating and addressing or is it part of an overall care plan? Are you seeing anybody else? That type of thing. Meagan: Mhmm, yeah. And like she was saying, maybe a different provider, maybe a pelvic floor specialist to even just dig into what those adhesions look like or a care provider, but yeah. It can. I'm going to go find it. I was just scrolling, but I'm going to go find it. Do you remember, Julie, do you remember her name? Julie: You're asking me if I remember anybody's name?Meagan: I'm the name person. I keep thinking it starts with a J. I'm going to find it though and I'm going to drop it in for you, AJ. Okay, “I just had a VBAC a few months ago and,” awww. “I'm so thankful for both of you.” Thank you, Allison. That's so sweet. So, so sweet. Julie: Thank you. How to manage sciatica painMeagan: Congratulations! Okay, Jenn. “I'm 39 weeks. My sciatica only allows me to walk for about 20 minutes without cramping. I see a chiropractor twice a week, but other than that, what can I do to help keep my baby in a good position and get labor going?” I would suggest the Miles Circuit right off the bat. Miles Circuit is wonderful. You can do it multiple times a day. There are three circuits and you want to try to do it for a minimum of 30 minutes but sometimes you have to lead up to that. That would be something that I would suggest. Maybe giving it a try. Also, Spinning Babies is very much a balance factor in creating balance.It sounds like your sciatica is not loving you right now and that is hard. That is hard, so being mindful also of being symmetrical and getting out of the car. I know that sounds really weird, but not stepping out with your left. Stepping out with your right. Trying to move out together because that separation with relaxin and things like that can cause the pelvic to shift, which then causes sciatica issues and all of those things. But I would suggest Miles Circuit. I would also suggest a massage. Getting things relaxed and soft because sometimes when things are tense, we've got that sciatica issue. Julie, what else would you suggest on that?Julie: Yeah. First of all, I would say that if you are in pain, then don't do anything. It's okay to stop. You don't want to hurt yourself and cause pain, tension, and stress in your body because that could interfere with your natural labor hormones. But honestly, I would think going to a chiropractor twice a week and walking 20 minutes a day is great. I think that's great to do. If that's all you can do, then I don't think you need to do anything else. 39 weeks could still be early based on when your baby wants to come, so don't feel like you urgently have to do anything. If your provider is pushing you a little bit, then it might be time to have a conversation about what your boundaries are and where you are willing to go as far as how far along gestationally before you interfere. But yeah, what Meagan says for sure. The Miles Circuit, absolutely. Two positions in the Miles Circuit are that you are resting pretty much and just creating more space in the pelvis. I would say maybe if you want to try changing it up from walking, one of my favorite things is going up and down the stairs sideways two at a time. It's kind of like walking, but you are really opening up that pelvis. So you go up with the right foot first, down with the right foot first, then switch to the left foot first, up and down. That's creating a nice, flexible, open space and lots of equal balance like Meagan said. Meagan: And listening to your body on that. Listening to your body. If it's too much, stop or just do three sets of stairs, three stairs. Just don't push your body. Yeah. But I like that one. I actually did that with a client at a birth center where there were some stairs. We did that to get labor going and it totally helped. It was amazing. Julie: Yeah, I love that. That's my favorite or curb walking. You just walk right foot on the curb and left foot off the curb and then switch with the other foot to keep that balance and stretch both sides of the pelvis. But yeah, change it up a little bit. I think you are doing great, personally.Meagan: Mhmm, yeah. Going to the chiropractor that often is amazing. Realigning. But yeah, 20 minutes, maybe cut it down to 15 minutes. Just a little less before you are in too much agony. Yeah, yeah. Julie: It's okay to take a rest. It's okay to not do it one day too, or a few days, or every other day or twice a week. Meagan: Yeah. I would also say shaking the apples which is a Spinning Babies thing, but that actually really relaxes and softens down there and can help with sciatica pain. That's just where you put the rebozo around your bottom and have someone sift, so you're kind of doing this.Julie: It's so fun. Meagan: This is so hard to be on a Live because I talk a lot with my hands. If you can see this in this video, Julie is very much here and I'm dancing.Julie: I even brushed my hair today. Meagan: You kind of get sifted and it really is nice for that sciatica. Okay, oh let's see. Just listened to all,” oh my gosh, “all 198 episodes of you guys.” Oh yes, yes. I just can't believe that we are at 200 episodes. I was telling my husband today and he was like, “Whoa. That's a lot.” Yeah, that's awesome. So awesome. Okay, do you guys have any other questions coming in on here? What else would you like to talk about, Julie, while we are waiting on any other questions? It's been a minute. It's been a minute since you've been on here. Julie: I know. It was 15 minutes before it was about to start. I was editing photos all day, so I was like, “Oh shoot, I should brush my hair and change my shirt,” because I had this frumpy little shirt on. I'm like, “We're going to be on video today. We never usually do that.” Meagan: Yeah. You don't have to be induced at 39 or 40 weeks!Julie: So it's just interesting. Let me think. I was just trying to think what has been bugging me from The VBAC Link Community lately. Not bugging me, but you know when you just want to grab ahold of people's shoulders sometimes and say, “This doesn't have to be this way. You don't have to do this!” Or just like, “It's okay to stand up for yourself.”I think a lot of the things I have been seeing lately a little bit is when people talk about induction or their doctor not letting them go past a certain amount of weeks. Meagan: Yeah. Julie: That's really kind of heartbreaking because, in America, we have a really frustrating maternal health care system. It's really easy to get trapped in that if you're not comfortable standing up for yourself if you don't know that it's okay to stand up to you're provider, and if you don't have an opinion about everything that you possibly can in birth. It's hard when I see people going in and getting induced. We'll see posts all of the time where people will be like, “Oh my gosh, I'm 6 centimeters. I've been soft for 8 hours. I was induced at 39 weeks. My provider said this and that and the other.” I just want you to know, everybody. You do not have to be induced at 39 or 40 weeks in order to get a VBAC.Meagan: You don't. You don't. I also wanted to talk about the opposite. On the flip side of that, I want to say that you can have a VBAC if you are induced. Julie: Yes. Nipple stimulation to induce laborMeagan: So there are both sides where it's like you have to be induced or you can't go for a VBAC or it's, “I will not induce you.” And so anyway, it's so hard. I was just looking. We have a group member that posted a couple of hours ago and she said, “I have a question about nipple stimulation to induce labor. I've been trying since yesterday and I do get contractions although they might just be Braxton Hicks because they are not really painful. But as soon as I stop, the contractions also stop. Any advice?”I just want to talk about this. In fact, I think Julie wrote a blog about this. I think, didn't you write a blog about nipple stimulation and pumping to induce labor? I'm pretty sure you did. Julie: I'm pretty sure that was you.Meagan: It might have been. I don't remember. Julie: That doesn't sound like anything I would write. Meagan: Well, yes. So this is something that I actually did when I was in early labor. I wanted to talk about that, but my midwife kept saying, “Hook up to the pump. Hook up to the pump.” I hated that thing. That thing was not my friend, but it worked. It helped, I should say. But sometimes it doesn't. And so kind of similar to what this group member is saying is that it sounds like it is releasing oxytocin in your body and it's stimulating something. Something enough to cause your body to contract or have some sort of spasms in your uterus, right? Which is a contraction whether or not it is strong.But when you stop, it stops and so that is– this is what I tell my clients too. That is a sign that your body is not quite ready or it's not going to respond to this type of method right now. Pumping is a really great option, but if it's not going, I would say to pause. Maybe just give it a break and see what happens. You can try again later or follow the advice of your provider. I would say that it's not bad that your body is not responding and it doesn't mean anything like it's not going to work ever, but it just sounds like your body may not be ready. So my advice is to maybe give it a break, try it a little bit more, try it a little bit longer and see, or maybe go have sex instead and try to release oxytocin in a different way in your body. So anyway, I just saw that. Are there other questions that have come in? Do you see any?Julie: Yes, there is. Meagan: Okay.Julie: Hi Paige, by the way! Hi Paige. Paige commented on the pumping to induce labor blog. Meagan: Oh yeah. Julie: Okay, so Tiffany, nope. Not Tiffany. It's before that one. Tiffany, I'm going to get there. Angel said that if we want to read her post in the group that she would love some thoughts. So I found Angel's post and I will read it. I love this. I have lots of thoughts, so Angel, if you are still watching, could you drop your location in the comments so I know? Oh, you're in New Zealand. You already said that. VBA3CJulie: She said, “I would love your opinions. I have contacted 15 midwives in New Zealand and all have said ‘no' to a VBAC after 3 C-sections. The main reason why I don't want a fourth Cesarean is because fentanyl is in a spinal block.” P.S. a lot of people don't know that. When you have an epidural or when you have a spinal block, the epidural is not the medicine. It is the method of giving it into your body. An epidural has lots of different medications in it. Fentanyl is one of them. Tramadol is another one. Sometimes there are antibiotics in there with them. But a lot of people don't know that fentanyl is in an epidural and a spinal block. Okay, so she says, “Tramadol is the pain relief afterward.” Tramadol is a form of morphine. That will be present in the milk which is one of the reasons why she doesn't want it. Antibiotics afterward, milk again, and all of her children have had severe colic and reflux to the point of sleeping four scattered hours overnight until they are 16 months old. All day naps are held upright. This is physically and mentally shattering. Could there be a link between colic, reflux, and antibiotics? It may be a possibility. “I live a 100% organic, tox-free lifestyle. I don't even take pain relief for headaches. Cesareans go against my holistic lifestyle.”“That being said, the first two Cesareans, I believe, were medically necessary.” Cord wrapped very tightly around necks, very thin and short. Babies were wrapped up by their necks tightly and couldn't move down, couldn't descend. Fetal distress straightaway for the first baby, second repeat Cesarean for the same issue. The third, the cord was fine, loosely on my tummy, but the amniotic fluid was a 4. It should have been a 7. She was pressured into a repeat Cesarean in case there was the same issue as the first two. She said, “I just need tough love, realistic answers.” Should she just have a fourth Cesarean and do everything else holistically? Meagan: That's tough. Julie: Yes. Meagan: We had a message come in earlier. I'm wondering if it's the same person because it sounds strangely familiar. New Zealand. I can't speak. But wow, that's tough. That's tough because you have good, solid reasons, beliefs, and feelings. Yeah. You know, it sounds like you are getting a lot of pushback in your area. A lot. That's a lot. There may be somewhere underground there that would allow it, but yeah. I don't know. It seems like you have enough reason to not do certain things. I don't know. I would maybe. I would maybe, actually. What would you do, Julie?Julie: Well, she says she wants tough love and I love tough love. So when I get permission for it, I will fork it out. Meagan: Yeah. Julie: So here's the thing. First of all, vaginal birth after three Cesareans, I love, love, love that we are seeing more stories come out about VBAC after 3 C-sections. Meagan: Me too. Julie: There's not a lot of data to support its safety or not. We have a few studies if you want to google VBAMC. We have a whole blog about the information that is available, but there's just not a lot out there. The way we get a lot of information out there is for more people to do it, right? That might not be a risk that a lot of people are willing to take. Personally, I would probably try it because I kind of know all of the information and everything, but I don't know because I haven't been there.So here's my tough love, okay? It sounds like you have talked to a lot of providers. This sounds like the providers you have talked to do not want to support you in your choice. And so when that happens, and this is for anybody who can't find a supportive provider not necessarily just directed at you, Angel, you have a few options. First is to go into labor and wait as long as you can and go to the hospital and fight and fight and fight. Out-of-hospital probably wouldn't take you on as a patient. But depending on, I don't know how the healthcare system is set up exactly out there. So go to the hospital, show up pushing, which I would never recommend that ideally if you could, but that's an option for you, okay? Go into labor. Go into the hospital. Maybe get a doula. Have your partner on board or somebody there who can really heavily advocate for you and be fighting the whole time. Or you can birth unassisted at home, which I also don't necessarily recommend, but there are a lot of people that can do it and do it smartly. Meagan: They have a lot of solid resources.Julie: A lot of resources, have a really solid backup plan, know everything that you need to look for as far as warning signs in labor, maybe labor close to the hospital or in the hospital parking lot or something like that. Neither of those might be good options for you, but it sounds like there's not really a good option anyway. I think also, sometimes I appreciate and envy, to some degree, the holistic lifestyle that you have. Sometimes, if you don't feel comfortable fighting in the hospital or having a baby unassisted, your third option is to have a repeat Cesarean. Meagan: Make it really special. Julie: Maybe you won't have a holistic lifestyle at that moment. ** You're going to have to get some medications that you don't love, right? You're going to risk having those things *** began with the colic and maybe the upset digestive tract from the antibiotics and things like that, but that also might not be the worst thing to have ***. The only thing that you are going to be able to know is what the best choice is even though there is not a good choice. I don't know if that makes sense or not, but yeah. I mean, you can create a nice, beautiful space like Meagan just said. You can ask for the spinal block and see if there are any alternatives to the fentanyl or other kinds of medication that they can put in there. You can ask for a shorter hospital stay. You can look into ways to heal your baby's gut after the C-section. You can look into vaginal seeding which can get the baby's gut populated with your flora from the vaginal canal which is really helpful for the baby's microbiome and things like that. I feel really angry for you a little bit. Meagan: I know. Julie: –that the system is set up to work against you in such ways. But I feel like this is something that you are really going to have to sit with and tune into your intuition hardcore and figure out what risks you want to accept, right? Because it sounds like you are going to have to accept some whether it's birthing with a C-section and not having the birth you want and introducing those different things to your baby, birthing unassisted without a provider present, or fighting as hard as you can in the hospital for your VBAC. Meagan: It infuriates me that people even have to be in this space at all.Julie: Yeah. Meagan: The providers are so worried about supporting people doing vaginal birth after multiple Cesareans, yet they're pushing people and making people feel like they have no choice other than to birth with no provider. I am not saying that someone who births without a provider– I'm not shaming anybody for sure, but I think it's nice to have that supportive provider behind you, that trained, skilled provider. A lot of people that do go unassisted, I'm not kidding you guys, they dive in deep. They are prepared and that's awesome. Good for them. Absolutely good for them. But it just makes me so mad that someone even feels like they are stuck in making that option. Julie: Yeah, I agree. Angel also asked a follow-up question if she could decline antibiotics. Here's the thing. You can decline anything you want to decline. It's just going to depend on what's going to make your providers nervous and if they're willing to provide care or not. I don't know. I don't know if your provider will be comfortable doing a C-section without having antibiotics available during and after the C-section or not, but that's something that you can talk with your provider about ahead of time and see what that looks like. Or have a minimum dose or only one round or something like that. Meagan: Mhmm, yeah. I love that. Sorry, my little boy, this was also part of our technical difficulties. Look at his head. Show everybody your head. Julie: He got konked. Meagan: And your arms, huh. Yeah, he fell today at recess. Julie: All right, let's move on to the next question. Angel, I give you all of my love and support. Meagan: I wish you luck. Julie: Yeah, I do. Please keep us updated. Us, again. You guys, this is killing me. Meagan, you have to let me know when Angel updates you because I'm invested now. Gentle induction plansJulie: Okay, what's next? We have– oh, yes. Let's get to Tiffany. Hi Tiffany. Tiffany M. Okay, so she said that her doctors told her that they will not allow her to go past 39-40 weeks. She was able to control her blood pressure thus far and she had hypertension in her last two pregnancies. Her doctor doesn't want to induce because it allegedly increases the risk of rupture. Meagan: Your voice. Julie: Sorry. “They've been insanely supportive of VBAC but this contradicts what I've been seeing.” Yes. This is what we were talking about before, right? Induction. You can have a VBAC after being induced, but also you don't want to have to be induced at some arbitrary deadline to have a VBAC. Induction does increase the risk of rupture slightly, but when it's managed appropriately, the risk is very minimal. So definitely look into that. Poke your provider. I say “poke your provider”. Don't poke the bear, right? Don't poke the bear. Ask your provider. Talk with them and see because that might not be a provider that is that supportive. It is sad that when you have a provider that you absolutely love and there's this one thing. There's one thing and it sounds like this is the one thing.Meagan: But that's a big deal. Julie: It is a big deal, yeah. Meagan: A big deal, yeah. Julie: And people won't allow you to go past 39-40 weeks. I would bust out the ACOG bulletins on VBAC and the late-term management of pregnancies or something. Meagan: Yeah, and induction. Yes. I was just going to say. Bring them, even if it sounds over the top because I'm going to tell you, print it all off and take it to them. Julie: Do it. Meagan: And say, “But this is what this says. This is who you are under and this is what they are saying, so why can't we discuss a gentle induction plan?” Or, “Let's observe and do more monitoring with all of these things and take it day by day. Take it every other day. I'll do an NST. Let's break it down so you're comfortable. I'm comfortable. We're all doing what is safe for me and baby of course.” Sometimes it sounds extreme, but it might take bringing it in and saying, “Hey. This is what I have found. Let's talk about it. Let's break it down.”Are you going and getting that for her? Is that what you're doing?Julie: I'm responding to whatever comments. Meagan: Oh okay.Julie: Obviously now, I'll just do it verbally. So she said, “Managed how? Through a slow administration of induction medicine?” Yes, absolutely. Yes, so this is the thing. Sometimes you'll hear the phrase “Pit to distress” where nurses will, this is a real thing. It's sad but it is, where nurses will up the Pitocin so aggressively that it literally forces the baby to go into distress so they just do a C-section. It's a very aggressive way to administer Pitocin. You don't want that. You want to do a nice, slow dose. Increase it by 1 or 2 every 45 minutes to an hour. Give your body a chance to respond before upping it even more. I've seen VBAC inductions where they konk out the Pitocin by 4 every 30 minutes and before two hours happens, you're up at the max dose of Pitocin and then the baby gets so stressed out and you have a C-section.Meagan: And the body isn't responding fast enough. Julie: The body's not responding at all because it doesn't know what the crap is going on. It's being slammed with Pitocin, this artificial hormone. That is not an induction that is managed well. A managed well induction is nice and slow. Start with a Foley bulb. Start with a nice, slow dose of Pitocin. Rest during the beginning of it. Give your body time to catch up. While being monitored, that's a nice compromise and making sure everything is being tolerated well. If your body is responding, stop turning the Pitocin up at all or even turn it off after your body kicks into labor. Meagan: Yes. I was also going to say there is something called a “Pit holiday” where sometimes our uterine receptors get too full and overstimulated with Pitocin. It's okay to do a “Pit holiday” and cut it in half. So say you're at 20, let's cut it down to 10 and see how our body responds because sometimes we can be overstimulated and our body is like, “This is too much too fast. I don't know what's happening.” It's not responding and then we cut it in half, our uterine receptors empty, our body kicks into that natural labor, and then boom. We're in labor and we don't even need 20 mL of Pitocin, right? Or like Julie said, we get into this active phase and we feel like we have to keep upping the Pitocin, but if we're getting into the active phase and we're making progress, we don't need to keep pushing Pitocin. And yeah, slow dose. Sometimes, some people, we recorded a story just now and talked about this. It's coming out in October, so let's talk about it right now. Sometimes we get in a space where induction is what's needed this time, but we're not cervically progressed enough to just put in a Foley or a Cook, right? So sometimes, we have to start a low dose Pit, maybe 2, 4, 6 mL max and just let it be for hours. It could take hours, you guys. I'm not kidding. Not three hours, not four, but ten plus hours it can take sitting at that slow, low dose to get the uterus stimulated enough to open just enough to get a Foley or a Cook catheter in comfortably. And then, we start from there. We work with the Foley and the Cook. Maybe you leave Pit right there or maybe they start increasing it or they just do the Pit at 6 or 8 or 10, and then just let the Foley do its thing until it falls out and then we start from there. There are so many ways that we can manage and take things slowly. Walking in, breaking someone's bag of waters is not necessarily slow, managed, and controlled but that's what a lot of providers will do also. They say, “Oh, I'll just bring you in. We'll just bring you in and break your water.” Sometimes, the body doesn't respond to that and it takes hours, and then we've got Pitocin coming into play anyway. But then sometimes, that's the perfect way, right? So we have to take it slowly. We have to decide what's best for us and where we are at cervically can make a big difference of where we start. Julie: Where we are at cervically, I love that. Meagan: Yeah, where we are at cervically. Julie: Cervically, cool. All right. Thank you, thank you. All right, let's move on. Christine, Christina. She says, oh I think it's maybe more of a review. Thank you. Okay, so she says, “Listening in from South Africa.” We have lots of people from South Africa lately by the way. Meagan: Yay. Julie: I say “we” like I'm, anyways. “Been listening to the podcast, binge listening all the time and so amazed at how much I'm learning in each story and from you both. I also love how listening to everyone's stories, especially the C-section stories have helped me process mine and helped me feel much more peace going into my VBAC at the end of this year. Thank you so much for the podcast and everything you guys are doing. I keep sharing relevant episodes with friends that are currently pregnant with their first. Things I wish I had known despite having done a lot to prepare for my first birth.”Meagan: I love that. Thank you. Julie: Aww. I love that. Thank you. Yes, Meagan. Grab this and drop it into the review spreadsheet. Meagan: I know, will you copy and paste it for me? I'm going to read this. I pulled into the group and found a question that just was posted. We actually got a lot of recent questions here in the group and so I figured I'd throw this one in. Julie: Wait, but there are more in these comments, though. Meagan: Oh, keep going. Julie: Do you want me to do the comments first?Meagan: Yes, sorry. I didn't see it. What happens if you don't sign a C-section consent form?Julie: No, you're totally fine. There's AJ, Juleea, and maybe more. Okay so AJ said, “Hypothetically, what happens if you don't sign a C-section consent form? I know they can't just make you take you back, but how would you handle this if they were being forceful?”Meagan: Now that one's super hard because you have to be strong. You have to be really strong. But how I would handle it, I would break it down. I would ask them to break it down and talk about why. “Why are you asking me to sign this form? Am I in danger? Is my baby in danger? Are we facing death?” Julie: Facing death. “Will I die?” Meagan: Yeah, complications by dying. “Are you telling me that my baby and I are going to die right now? Because if we are having this conversation then that probably means that it's not the case.” But yeah, break it down and say, “No. I don't consent to this. I don't feel comfortable with this. If this is not life threatening right now, and this is not emergent, then I want to continue on the path that I'm going.” This sounds really bad and it's so hard because everyone can be– we've got people all over the world, right?Sometimes it's saying, “Okay. I'm going to leave. I'm going to go somewhere else.” We've had that. Julie and I personally have had clients say, “Okay, I'm leaving then. If we're not going to do this, if this is not what's going to happen, then I'm going somewhere else.” And sometimes they change their tune right there because they don't want you to leave. They usually don't want you to leave, so they change their tune and say, “Okay, hold on.” But sometimes, it takes leaving and going to somewhere else that is supportive. But that's not what you really want to do in labor. Julie: Yeah, this is why you want to figure it out before labor starts. Meagan: Yeah, it's not the space that you deserve to be in during this labor journey, but sometimes it's fighting. It's fighting and it's hard. It goes back to what we were talking about with Angel. It makes me so mad that there's not the support that everyone really deserves. We deserve the support, you guys. We're just going in to have babies. That's all. We're just going in to have a baby just like everybody else, but sometimes we're not viewed as that. So yeah. Any other tips, Julie? I mean, yeah. I would say breaking it down and having that conversation, but what would you say?Julie: I mean, I would kind of say the same thing. A lot of the times, I feel like, they just have you sign all of the forms that you might possibly ever need while you are in labor at the beginning of labor because it saves on admin time and it saves on things you have to do later on and things like that. But what I would ask about the C-section form, when they're going through that whole process is, “Do you make first-time moms sign this form?” Because I bet you, I know their answer because they don't make every laboring person sign a C-section form, but they will if they are getting you ready for a C-section or they think that you are at an increased risk for one.And so, we all know what the numbers are surrounding VBAC and what your chance of success is and how, if given the option to try, you are very likely to succeed. So I would just ask that. And if they say, “No,” or whatever their answer is, I would change my next question or next statement. My next statement after they answered would be that, “I will sign it if it is looking like that is going to be an option, but for now, I am planning on a vaginal delivery. Until a C-section becomes imminent, I will refrain from signing the form.” And then if they raise a big fuss after that, I might go to more extremes like what Meagan talked about. But I mean, this is the thing. If it's a life or death situation and you're not looking great or baby is not looking great and I'm not talking about, “Oh, we have some concerns.” I'm talking about, “We need to do something now.” They're not going to care whether the consent form is signed or not, they're going to wheel you to the operating room and save your life or save your baby's life. And so I think that waiting and asking to wait until it looks like a C-section is needed or necessary is a perfectly reasonable option. Meagan: Yeah, I agree. Okay, so I realized that I didn't see because I only saw one last comment from Tiffany saying that she is anti-Pitocin over there.Releasing fear around childbirthJulie: Yeah. Julie has one. And this is a great one for you, Meagan, too. It's how do you release fear around childbirth? I'm 40 weeks today and I'm anxious for labor. My first arrived via C-section at 37 weeks due to high blood pressure and being breech. I never experienced any part of labor and I'm just fearing the unknown. Fearing uterine rupture, not progressing, tearing, all of it. Meagan: Yeah. You know, fear release is so important. So important and I think I've talked about this maybe on my story or maybe in other things, talking about how I thought I released everything, and then I was in labor and there were still stuff that I was processing and working through and having to go through. But a few tips that I have are actually Julie's fear release that she did a long time ago on our YouTube and it's a smokeless or flameless. Julie: Smokeless fear release except that's used very loosely because we did create smoke at a fear release once. Meagan: We did. We did. We did. Julie: There were a lot of people releasing their fears, but yes. Meagan: Yes, I actually remember. That was really crazy. We did that in a VBAC class actually. Julie: Yeah, at my house. Meagan: Yeah, so I actually really, really, really love that activity and suggest it all of the time. I've actually done it with my own clients in labor. We've done it in living rooms on the floor. Obviously, it's hard to do if you're in a hospital at this place, you can't just break that out. Julie: Light a fire, yeah. Meagan: But doing it, and even if it's every night because for me, when I was preparing, I had different thoughts and being on social media didn't help me quite honestly in that very end. And so some of the tips would be the fear release activity, going through, writing them down, burning them, and truly burning them. Burning your fears. Letting them go. Letting them go and accepting whatever is coming your way. Know that you have done all that you can to prepare for whatever does come your way. So that and I also suggest doing that with partners because sometimes partners' fears will trickle in and create fear. Not that they're meaning to do it, but they have fears and then they say things and our minds are like, “Oh, I didn't think about that.” And we have to process that. Another thing would be a social media break. Sometimes social media in the end is wonderful and motivating and positive and keeps us in a great place, and sometimes, it just starts creating more fear. So sometimes we think that taking a total social media break is really healthy and helps process because you can just be with your own thoughts and not with all of the other hundreds and thousands of people on social media's thoughts because everyone is going to have an opinion. Everyone is going to have an experience. You love hearing those just like we love hearing this podcast and these stories, right? But sometimes, those feelings and those experiences can rub off on us, sometimes in a negative way. So if you're noticing that some of your fears and things you've seen and heard on Facebook or social media, any social media platform, maybe take a break from that. I would say journaling is one of the best things I did for myself in processing fear. I was told by my OB that I was for sure going to rupture. He told me that. As I was on the table, he was so glad I didn't have a VBAC because I for sure would have ruptured. For sure. When I heard the words “for sure”, that was very dominant in my mind and it hung with me. So when I'm laboring with my third, I was feeling that in my head. “What if I rupture? What am I doing? Am I doing the right thing?”I knew in my heart that I was doing the right thing but I had self doubt. And so if that starts creeping in, voice it. I would say that my suggestion would be to get it out. Get it out. I'm sure that Julie has seen it, but as a doula, sometimes we can see our clients are thinking really hard in here and they're maybe having self-doubt and things like that. It's just so good to get it out. Get it out. Processing. Getting it out, talking, saying it out loud, hearing yourself say it is the first step to processing it as well. So if you're doing a fear release, don't just write it down. Write it down. Say it out loud and then burn it. That would be some of my suggestions. And then keep educating yourself. Keep educating yourself. You said tearing, rupture, and these are all valid feelings and fears. I want you to know that. These are all valid and you're not alone. But yeah. Fearing not progressing, that's a big fear. I know that. But again, setting yourself up with a great supportive provider who's going to give you time, trust, and giving you the things you need to progress. That will help. Anything you'd like to add? Julie: No, I love that. I want to get a little bit sciency and nerdy on here. I don't know. It's not a secret or anything but I've been doing a butt load of therapy over the last year and a half and part of the things that, at some point, I learned this in therapy, but your brain, I think we all know that your emotional brain and your logical brain are in separate parts. They do not touch each other. They do not talk to each other. They do not know what each other has going on, right? Your emotional brain is very reactive and responsive. It's where a lot of this anxiety comes from. It's where your fear comes from. It's where all of your negative feelings live, well, all of your emotions live. All of your big things. Your logical brain doesn't know what's going on in your emotional brain. They do not communicate with each other or else we would probably all be a lot more reasonable about our entire lives. In order to process your emotions and reconcile them and get rid of your fears, the best thing you can do like Meagan just said, in lots of different ways, is to get them out there. Get them out. Verbally talking about them, writing them down, talking to a therapist, talking to whoever is a nice, safe space for you. Any safe way that you can get them out of your emotional brain, then your logical brain can say, “Oh. That's what's going on over here.” It gives your logical mind a chance to take over and reconcile a lot of these things that are going on and put this emotional brain at ease so they're not fighting and conflicting. They're able to reconcile with each other. I don't know if that makes sense. That's a big thing for me which is like, “Oh yes. I need to get these things out.” Don't stuff your emotions down or stuff your feelings down. Get them out and it helps your brain process and work through them together so that you're not so isolated and your feelings are not so isolated from the other parts of your body that are a lot more logical. Meagan: Yes. Oh my gosh. I love that. Thank you, Julie. Julie: You're welcome. Meagan: Okay, let's see. She has been thinking about taking a social media break, actually. It's really refreshing. Worried about tearing more than uterine rupture. And yeah, tearing is scary. It is scary to think about. Lots of people do tear and it is repairable, but I would say my tip for that would be to really follow your body when it comes time to push whether it be unmedicated or medicated, really listen to your body and when that baby is crowning, just little, little nudges, assuming all is going well and that will help. And then really, baby position, right? We want to work on baby's position because the more the baby is in an ideal position, the better it is for baby to come out. But sometimes we have these little things where we have babies doing this and sometimes we have babies doing this. Julie: Or doing this. Meagan: Or doing this or they come out like this and they do funny things. Tears happen, but try your hardest and let gravity help. Squatting on your side, positions that may reduce tearing and may focus on centered gravity versus a perfect spot, I don't know the word that I'm looking for. A specific spot of gravity. Does that make sense? On your back, the bottom of your perineum has more direct pressure than when you're squatting. It's more central. So working on positions and even if you have an epidural, you can push on your side. You can push squatting assisted. It's totally possible. But yeah, anyway. Tearing is scary. Julie: Tearing happens. I love that you said that. Meagan: Tearing happens. It does. I mean, I'm going to be honest. Julie: Most of the time, it's not that bad. Most of the time. Meagan: No. Julie: I had a first degree with my first VBAC. I didn't tear with my other two. I heard somebody say once, maybe it was on social media or something recently, but the biggest impact on whether you tear or not and how bad is your provider. Meagan: Yeah. We've got providers that just are a little rough. Julie: They force you to push on your back or stretch your perineum out so much. A lot of people think that helps, but it can actually increase your chance of tearing too. I don't know. But yeah, give that a chance too, and talk to your provider seriously about not pushing on your back. Even with an epidural, you can push on your side. Meagan: Yeah. Totally. Totally. Love it, love it, love it. Okay, any other questions that you are seeing coming in? I love that she was like, “Yeah. People say this and then we just nod and assume they're scheduling a C-section.” They just nod like, uh-huh. We have a ton of questions coming in on social media, so are you okay if we do a couple more?Julie: Yeah, I just have to grab my kids in 25 minutes, so I've got some time. And then I want to wrap up and do a little short catch-up on how I've been doing since The VBAC Link. That would be fun, right? Do you think? Meagan: Yeah. Yes. Julie: Okay. Labor expectations Meagan: Okay, so this is from an Instagram follower and she says, “VBAC after a scheduled C-section. Should I expect labor as long as a first-time mom?” Julie: Can you say that again? You broke up just a little bit. Did she say what should I expect as a first-time mom? Meagan: “After a scheduled C-section, should I expect,” assuming she's going to VBAC, “Should I expect just as long of labor as a first-time mom?” So meaning that she's scheduled the C-section, never went into labor, never dilated, things like that. In short, yes possibly. Julie: Yes. Meagan: Yes, right? So my VBAC was my third baby, my first real labor. It was kind of freaking long. It was long. But then, we sometimes have moms that had a breech baby and it was a scheduled C-section. They go in, right? Yes. Julie: Pick me, pick me. I've got some stories. Meagan: Don't share her story. Julie: Did she talk to you?Meagan: No, but I'm going to talk to her. Julie: Okay, good. Meagan: So anyway, but sometimes it just goes really fast and we don't know. So just like a first-time mom, not everyone goes long. Some people are precipitous. Some people can go really long. That can happen too and so yes, maybe is my answer. Okay, let's see. Julie: Wait, wait, wait, wait, wait, wait, wait. Before you go on. Meagan: Oh, you really wanted me to pick you. I pick you, Julie. Julie: Pick me. Pick me. Pick me. Okay, so I just want to let you know that yeah like Meagan said, you are more likely to labor for longer identical to a first-time mom, but man, sometimes this baby is going to fly out and it's going to catch you off guard. And I have two stories, I'm not going to tell them, but I have two stories where the labors were super short. Moms got their VBACs at home on their bathroom floors because the labor just catches you off guard so much. Meagan: It can happen. Julie: Plan on going to 42 weeks. Plan on a 24-hour labor because it's probably not going to be that long, but the more you can, if you expect that, then anything shorter is just going to be encouraging rather than planning on a shorter amount of time and having a longer thing being discouraging. That's my advice. Double-layer suture versus single-layerMeagan: Yeah, for sure. For sure. Okay, this next question is, “Does the type of suture matter much? I had a single-layer but read that double was better.” Julie: Oh, pick me again. Meagan: Yeah. Julie: Sorry, you're looking at me. Meagan: I'm looking at you. Julie: All right, so here's the thing. There used to be a belief that a double-layer suture is, because there are several layers of the uterus, right? The single-layer versus double-layer. A single-layer closure means they sew all of the layers up with one stitch, one suture. Double-layer is where they close it in two separate layers, right? So there used to be a belief that a double-layer suture was safer and would decrease your risk of uterine rupture if you go through vaginal birth, or I guess, overall because you don't have to go for a vaginal birth to have a rupture. But since then, there have been several studies come out that show that there's no significant difference in rupture rates between single-layer versus double-layer closures. So, no. It doesn't make that big of an impact. Now, there has been one recent study that shows that a double-layer closure is optimal, but that one study isn't very big. It's not very credible. It's not as big and not as inclusive as a Cochrane review and things that show that there are not really big differences. So sometimes, people will say, “There's this one study in 2021 that shows this.” See, probably not in that voice, but anyways. But the majority of information that we have shows that it does not matter. However, ten years ago, people used to think that it would make a big impact. Things have shifted since then. Meagan: Yeah, we still have many providers that say it actually determines eligibility based on that. Like, tons. We get emails all of the time. It's like, “Hey, I really want a VBAC but I found out that I only have a single-layer suture, so I can't. Is this true?” So yeah. Okay, ready for the next one? Julie: Yeah. Special scarsMeagan: Low, transverse uterine incision that extends one side vaginally. Vaginally? Can I VBAC? Vaginally? Julie: Vaginally? I wonder if it's a J? Meagan: That's what I'm wondering. Julie: Except she said, “Vaginally.”Meagan: I've actually never heard of a uterine incision extending all the way. Julie: I don't think it can. It can go down into the cervix. Meagan: Yeah, the uterus is up and then it has the cervix. It goes like this. Julie: Yeah. Meagan: Yeah, and then that comes down into the vagina, but they're separate.Julie: I wonder if there's some word confusion there. Meagan: Maybe. I will ask her, but I'm wondering if this is meaning a special scar. Julie: Well, yeah. Meagan: I'm wondering if maybe there is some confusion about a special scar and yeah. People still VBAC with special scars. They do. We have special scars on the podcast. Julie: Leslie's is my favorite birth story. She goes into such detail about the data and everything about that. Meagan: Yes, Leslie did a home birth, right? Julie: Yeah, I think it's episode 18 or something in the teens I think.Meagan: She was really early on. So yes you can. It's still possible. You still want to educate yourself. Just because you can doesn't mean you are going to choose to or that you're going to want to. Julie: Or that you're going to find a provider that's going to support you. Meagan: Or that you're going to find a provider that's going to support you, and so we encourage everybody to do the research, look at the education. We have some blogs. We talk about special scars in our parent's course. We have some episodes, so there is information out there for you guys. Julie: Yeah, the risk of rupture is a little bit higher with special scars, so that's something to consider too, but what an acceptable risk is to you is going to be different for everybody. So I think it goes from about half a percent to maybe 1.2% or something in that range. It's less than 2% overall, and so is a less than 2% risk of rupture acceptable for you? You're going to be the only one to answer that. Meagan: Yeah. Yeah. Julie: Does that make sense? I feel like I didn't understand the words coming out of my mouth. Meagan: Yeah, no. No, it made sense. Julie: Okay, do you ever do that? Anyways. Warning signs and symptoms for uterine ruptureMeagan: Yes. Okay, next question was, “Warning signs and symptoms for uterine rupture?” This is a really great question because we were talking about that, the fear of uterine rupture, and there are signs. There are, I should say, symptoms. Some of the signs and symptoms may be one, pain. Pain down there and if there's an epidural in place, it might radiate up. The uterine rupture that I attended a long time ago, she had an epidural and they kept calling it a hot spot, but it was way, can you guys see me? Way up here in her ribs where it was hurting which is kind of an interesting spot, but it was just radiating where she wasn't numb, where she could feel. So yeah, pain. And also pain that doesn't go away. Pain and discomfort during a contraction or surge comes and is there, and then it goes away, that may be different than the pain that is there, increases with contractions, doesn't go away, and is still very intense. Bleeding, lots of bleeding, lots of bleeding. Stall of labor, where your labor is just not progressing. Baby going up, so moving stations, but dramatically. Like your baby was +2 and now your baby is -2. Stations can be subjective, they say their baby is a 0 but now it's a -1, and they're saying that maybe it's a 0 to +1. It's kind of subjective. Julie: Yeah, they're just centimeters that we're talking about with baby's station. It can vary from provider to provider. Meagan: If you think about my hand to Julie's hand, right? Our hands are very different. They look different. I have long skinny bony dumb fingers that I can't stand. Julie: Not dumb. Meagan: Really wide palms, so my long, skinny fingers versus someone with shorter fingers may be different. One of the number one things that providers look for, although I will say that this isn't always the number one first symptom is fetal heart tones. Fetal heart tones that are just tanking and not recovering, that is a concern. That is a concern and that is a sign. Let's see, what else am I missing? Julie: I'm trying to think. I think that's it. Meagan: I think that might be all. Julie: Yeah, and that's the biggest reason why they're really particular about continuous fetal monitoring for a VBAC. But yes, if you can feel the head on top of your pubic bone, it's kind of weird to really describe that, but I'm not going to show you. Meagan: You can usually see it. There's a bulge. Baby's not in the right spot.Julie: Yeah. Meagan: We also have a blog on that. So, okay. Are there any other questions in the Facebook group that I'm missing, Julie? Because I'm on Instagram right now. Julie: Let me check. Meagan: This one is, “My C-section was because of failure to descend. Do I still have a chance to VBAC?” Absolutely. Failure to descend means that baby just didn't come down. A lot of the time, that's due to positioning, that's due to more failure to wait and let the baby have time to come down. Just because you've reached 10 centimeters doesn't mean it's time to have a baby necessarily. Sometimes baby needs to have time to rest and descend and come down, but yes. Absolutely. You guys, on Instagram, if you're not there, we did pull over. So if you're over here, yay. If not, then I'm going to try and get these answered on Instagram as well. Do we have any other questions?Julie: I didn't see any. Yep, nope. Still no. Meagan: Okay, any other final questions for the eight of you that are left? We'd love to finish up, but yeah. While we are waiting for any other final questions, Julie, did you want to update everybody on how the last couple of months have been for you? Julie's updateJulie: Yeah, I think it was a little bit of a hard transition for both of us. Meagan is doing amazing trucking along, keeping everything going and I'm super excited to see all of the changes and stuff that are going on over on social media and the website and everything like that. I'm really proud of you. You're doing amazing. Meagan: Thank you. Julie: And welcome the new admin, Katie, helping. She's doing an amazing job too, it seems like so that is really great. Yeah, I mean, I've been trucking along with the birth photography thing. I think we talked about that on the podcast episode where I made the announcement that I was leaving, but it's been going really good. I've been to several, many births since the

Myc Tyson is on a mission to spread the word about fungi to every person on the planet! Myc has demonstrated this by starting the hugely successful subreddit r/Mushroomgrowers back in 2015, starting an online mushroom culture business, and orchestrating various mycophilanthropy projects - giving back to the world via the power of Mushrooms. Click the links below to learn more about the work Myc has done in Kenya. This was such an awesome conversation and Myc is doing some really important work in the field of mushrooms. As always, let us know what you loved, what we missed, and who you want us to bring on the show next time. Thanks for watching! Chapters:0:00 Framing the Conversation0:59 Introducing Mr. Myc Tyson! (Appreciating the Beards)4:00 Myc's Mushroom Background7:45 The Creation r/MushroomGrowers and Quitting an IT Career15:00 The Power of Lion's Mane22:58 Mycophilanthropy33:03 Growing Mushrooms at Home40:40 Mushrooms Find a Way44:47 The Pros and Cons of Myco-preneurship50:57 The Secret Sauce for Agaricus Farming55:20 The Doorway to Mycology & Mike Tyson Himself1:01:50 How to Connect with MycListen on Spotify: https://tinyurl.com/2p8aks8cLinks:Myc's Website: https://myctyson.com/Hericium Labs: https://www.hericiumlabs.com/Eco Agric Uganda: https://www.ecoagricuganda.org/

This episode is sponsored by BTG Speciality Pharmaceuticals. BTG provides rescue medicines typically used in emergency rooms and intensive care units to treat patients for whom there are limited treatment options. They are dedicated to delivering quality medicines that make a real difference to patients and their families through the development, manufacture, and commercialization of pharmaceutical products. Their current portfolio of antidotes counteracts certain snake venoms and the toxicity associated with some heart and cancer medications. Their drug, Voraxaze, is for high-dose methotrexate toxicity. This talk will focus on research elucidating MYC amplification as the first genomic prognostic biomarker in osteosarcoma, which may be used for risk stratification in future clinical trials and to inform conversations with patients and families. Dr. Marinoff will discuss the tools used to detect MYC amplification, what we have learned about its association with outcome in children/ young adults with osteosarcoma, and what we still don't know but are trying hard to find out: the biological roles of MYC amplification in driving osteosarcoma and how it may serve as a potential therapeutic target in the future. Dr. Marinoff graduated from Harvard Medical School and completed her pediatric residency at Boston Combined Residency Program, during which time she worked with Dr. Katie Janeway on elucidating the genomic landscape of and novel genomic biomarkers in osteosarcoma. She is currently completing her fellowship training in Pediatric Hematology/Oncology at UCSF, where she is focused on developing novel genome-informed therapeutics for osteosarcoma under the mentorship of Dr. Alejandro Sweet-Cordero. She plans to develop an active clinical and translational research program focused on conducting early phase precision medicine-oriented trials for patients with advanced sarcomas. She is grateful to have the best job in the world.

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