Podcasts about Interleukin

A Gluten Free PodcastEpisode 176On today's episode I chat with Associate Professor Dr Bob Anderson — a world-renowned gastroenterologist, immunologist and trailblazer in coeliac disease research. From his foundational work at the Walter and Eliza Hall Institute (WEHI) to creating Nexvax2, leading Novoviah Pharmaceuticals, and becoming President of the International Society for the Study of Coeliac Disease (ISSCD), Bob has shaped the coeliac research landscape as we know it.We discuss how his career began, what he's most excited about in current research, and what's ahead for coeliac disease globally — including a look at ICDS 2026 in Melbourne.What We Cover

In this week's episode we'll learn about the role of interleukin-1 signaling in the bone marrow microenvironment in the development of myelodysplastic syndromes, the immune checkpoint regulator VISTA as a potential target for preventing graft-vs-host disease, and epcoritamab plus gemcitabine and oxaliplatin in transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma.Featured Articles:IL-1R1 and IL-18 signals regulate mesenchymal stromal cells in an aged murine model of myelodysplastic syndromesTargeting cell-surface VISTA expression on allospecific naïve T cells promotes toleranceEpcoritamab plus GemOx in transplant-ineligible relapsed/refractory DLBCL: results from the EPCORE NHL-2 trial

A Gluten Free Podcast Episode 174In today's episode I'm joined by Olivia Moscatelli, a PhD student and scientist researching coeliac disease at the Walter and Eliza Hall Institute (WEHI) in Melbourne. Olivia works alongside Associate Professor Jason Tye-Din, one of the world leading experts in coeliac disease research. Not only is she making pivotal contributions to the field, but she also brings a unique and deeply personal perspective—because she lives with coeliac disease herself.We'll dive into Olivia's diagnosis story, what led her into the world of scientific research, and the groundbreaking studies she's currently working on that could transform the way coeliac disease is diagnosed and treated in the future.What we'll cover: 

In today's episode, we are happy to hear from our clinic's Dr. Scott and one of his patients, Keith about his successful experience tackling gut health issues. Keith's case posed a very common conundrum that we've seen in many with gut health issues - are we dealing with bacterial overgrowth (SIBO), fungal overgrowth (candida) or potentially both? We'll walk through some of the key indications that Keith's initial SIBO diagnosis was actually a candida case, and we'll cover the best testing and treatments that led to Keith's recovery.  Need help navigating your digestive or other health conditions? Learn more about our virtual clinic: https://drruscio.com/virtual-clinic/

How to lower chronic inflammation naturally. Here are 17 things that either have been shown to work or don't work. Chronic inflammation, that low-grade inflammation that occurs, even though you are not sick, is implicated in diseases ranging from arthritis, diabetes, cancer and heart disease. The term “Inflamm-aging” is a reference to how inflammation is linked to the aging process.   ·      What is chronic inflammation ·      Diseases associated with chronic inflammation, including Inflammaging ·      How to test for inflammation: C-reactive protein (CRP) and Interleukin 6 (IL-6) ·      Effects of Weight loss on inflammation markers CRP, IL-6 and TNF alpha (TNF alpha) ·      Cholesterol, LDL and chronic inflammation ·      How exercise affects inflammation ·      what foods raise systemic inflammation? ·      Health conditions associated with pro-inflammatory eating. ·      Chronic inflammation telomere effects ·      Foods that reduce inflammation & Advanced glycation end products ·      Fiber and the microbiome. Short-chain fatty acids (Butyrate) ·      Skin moisturizing ·      Curcumin and turmeric ·      Ginger ·      Garlic and garlic powder &  Aged Garlic Extract ·      Vitamin B12, B6, Folic Acid & Homocysteine ·      Nattokinase ·      Homotaurine ·      Fish oil ·      Resveratrol & NF-kB (Nuclear Factor-kB) ·      Vitamin D ·      Vitamin C and Orange juice ·      What is the best way to reduce chronic inflammation (most return on investment)   Supplement Facts Coffee Mug: https://joecannon.creator-spring.com/listing/supplement-facts-mug   Consultations  https://supplementclarity.com/private-consultations/     Get My Rhabdo Book   Education is the best defense against getting rhabdomyolysis. I've been teaching about rhabdo for over 10 years. If you are in the US, you can order my book directly from me. Purchase My Rhabdo Book Order on Amazon       Connect With Me Joe-Cannon.com SupplementClarity.com YouTube    About Me   For over 30 years I've been sorting nutrition facts from fiction, busting myths and helping people understand dietary supplements using clinical research as my litmus test.    I have an MS in exercise science and a BS in biology & chemistry. I've written several books, including Rhabdo, the first book about exercise-induced rhabdomyolysis.   Disclaimer   Episodes are for information only. I'm NOT a medical doctor. NO medical advice is given or implied. ALWAYS consult your physician for the best health advice for you. I participate in the Amazon Associates program which means if you click on a link to amazon and make a purchase, I may make a small commission at no extra cost to you.    

Description: Co-hosts Ryan Piansky, a graduate student and patient advocate living with eosinophilic esophagitis (EoE) and eosinophilic asthma, and Holly Knotowicz, a speech-language pathologist living with EoE who serves on APFED's Health Sciences Advisory Council, interview Jason Ingraham, an adult living with eosinophilic fasciitis (EF), and Dr. Catherine Sims, a rheumatologist at Duke University and a Health Services Research Fellow at the Durham Veterans' Affairs Hospital. They discuss Jason's experiences living with EF and Dr. Sims's experience treating EF. They share Jason's journey to diagnosis and the importance of working with a group of specialists. They share tips on medication and physical therapy, how to communicate with your medical team, and manage your activity and mindset. Disclaimer: The information provided in this podcast is designed to support, not replace the relationship that exists between listeners and their healthcare providers. Opinions, information, and recommendations shared in this podcast are not a substitute for medical advice. Decisions related to medical care should be made with your healthcare provider. Opinions and views of guests and co-hosts are their own.   Key Takeaways: [:50] Ryan Piansky introduces the episode, brought to you thanks to the support of Education Partners Bristol Myers Squibb, GSK, Sanofi, and Regeneron, and co-host, Holly Knotowicz.   [1:14] Holly introduces today's topic, eosinophilic fasciitis, with guests, Jason Ingraham and Dr. Catherine Sims.   [1:25] Jason is an adult living with eosinophilic fasciitis (EF). Dr. Sims is a rheumatologist at Duke University and a Health Services Research Fellow at the Durham Veterans' Affairs Hospital.   [1:52] Dr. Sims explains what EF is. Patients may present with symptoms of large plaques on their skin, edema of arms and legs, Raynaud's Phenomenon, contractures of arms or legs, limited mobility, or loss of the ability to do tasks they used to do.   [2:42] EF, as with most eosinophilic disorders, doesn't follow the textbook. Some people will present with one symptom and some with multiple symptoms. There is a disconnect between how we diagnose conditions like EF and how patients present.   [3:01] There are major and minor criteria for the diagnosis. As in Jason's case, it takes time for the symptoms to present. Things develop over time. It took multiple specialists to diagnose Jason.   [3:38] Eosinophilic conditions are incredibly different from each other. When Dr. Sims sees a patient with high eosinophils, she thinks of three major buckets: infection, autoimmune diseases, and cancer.   [4:12] Patients will often see many different specialists. In Jason's case, they had done a skin biopsy that wasn't as helpful as they hoped. That led him to get a deep muscle biopsy to collect the lining of the muscle.   [4:47] Fasciitis is the inflammation of the muscle lining or fascia. A sample of the fascia can demonstrate under the microscope if there is a thickening, swelling, or inflammation of the lining of the muscle.   [5:24] Dr. Sims as a rheumatologist treats a number of rare diseases. Eosinophilic fasciitis is an ultra-rare disease.    [5:43] Jason had a local primary care doctor and a rheumatologist who both did a really good job and referred him to Dr. Sims. She had the benefit of their hard work to guide her next steps. Because EF is so rare, she has pitched Jason's case twice in rheumatology grand rounds sessions.   [6:18] During one of these sessions, Dr. Sims was advised to get the fascial biopsy that ultimately led to the diagnosis. She benefited from the intelligence and input of dozens of doctors.   [6:59] In the Fall of 2022, while hiking on vacation with his wife, Jason was extremely fatigued, and his forearms and lower legs swelled. His socks left deep impressions. It was difficult to reach his feet to put socks on. He spent a lot of time uncharacteristically resting.   [8:09] Jason's primary care doctor ran lots of blood tests. He thought it might be a tick bite. Jason started seeing specialists, having tests and hospital visits.   [8:57] Jason worked with a rheumatologist in Wilmington, an infectious disease doctor, and a hematologist/oncologist who reached out to a Duke expert. He also saw a pulmonologist and a dermatologist. He got the referral to Dr. Sims for March of 2023.   [9:57] The first diagnosis Jason received was after his first hospital stay in January of 2023, when he had bone marrow biopsies, CT scans, ultrasound, and other tests. He was deemed to have idiopathic hypereosinophilic syndrome (IHES).   [10:30] It was only a few weeks before his local rheumatologist said his panels were back and one tipped it from an IHES diagnosis to eosinophilic granulomatosis with polyangiitis (EGPA). He joined the Vasculitis Foundation and researched EGPA.   [11:03] Dr. Sims told Jason that EGPA was a working diagnosis but he didn't check all the boxes. There was the underlying thought that maybe it was something else. He had a second flare when he came off of prednisone in June of 2023.   [11:48] Dr. Sims scheduled Jason for a muscle biopsy while he was off steroids. That's how he got the diagnosis of eosinophilic fasciitis (EF). Jason says the disorder is hard for him to pronounce and he can barely spell the words.   [12:52] Jason's wife Michelle encouraged Jason to track his symptoms and medications and keep track of data. Going from specialist to specialist, the first thing he did was give the history.   [13:31] Jason found it helpful to create a spreadsheet of data with blood test results, meds, how he was feeling each day, his weight, and even notes about when he had difficulty putting his socks on. Jason is an advocate of owning your continuity of care as you see different doctors.   [14:42] Jason says the doctors at Duke talk very well between themselves.   [14:49] Jason likes to look back at that spreadsheet and see how far he's come, looking at the dosage he was on during and after flares and the dosage he's on now, or zero, on some of the medications. That's a little bit of a victory.   [15:16] Holly works at a private hospital without Epic or CareEverywhere so she gives physical notes to her patients to give to their doctors. She comments that a great PCP, like the one Jason had, can make all the difference in the world.   [16:18] Jason's PCP, Dr. Cosgrove, referred Jason to Duke for a second opinion. That was where he met Dr. Sims. He's glad to have both Dr. Sims and his PCP accessible.   [17:35] Jason says the number of questions you have with this type of thing is immense. When you look up EF, you find very little and the literature isn't easily digestible by patients. Being able to reach out to your doctors for a quick question is super helpful. [17:56] Jason has been able to do telehealth follow-ups and not always have to travel or take off work, which has been extremely helpful. He has been at Duke a good handful of times for various things but remote follow-ups are helpful.   [18:52] Dr. Sims says people just don't know about EF as it is an ultra-rare diagnosis. Even physicians don't understand what causes it. It's lumped in with all other eosinophilic conditions but these disorders don't all present the same way.   [19:19] EoE doesn't look like EF, even though they're both driven by the same immune cells. Dr. Sims says the first need is educating providers and patients on what the diagnosis is; awareness in general when a patient is having this swelling of extremities.   [19:44] Dr. Sims says at his baseline, Jason is very active with multi-mile hikes. When Dr. Sims met him, he was off from the baseline of what he was able to do. Being aware of your baseline and changes from that is very informative for doctors.   [20:07] Dr. Sims talks about the patient being a liaison between multiple specialists. Bringing data to your subspecialist always helps facilitate care and come up with a bigger picture of what's happening.   [20:23] Jason first went to Dr. Sims with the diagnosis of EGPA. She said, let's treat the EGPA and see what happens but they kept an open mind. With ultra-rare diseases, sometimes it's difficult for patients not to have a label for their condition.   [20:45] Dr. Sims explains to her patients that sometimes we live in the discomfort of not having a label. She keeps an open mind and doesn't limit herself to just one diagnosis. She seeks feedback from providers who have seen this before and know what works.   [21:07] Just as Jason described, you will go through multiple diagnoses. Is this cancer? Is it a parasitic infection? Where did you travel? You will see many subspecialists. It's extremely anxiety-provoking.   [21:31] When Dr. Sims did her grand rounds, she gave a third of the presentation, and the other two thirds were presented by an infectious disease doctor and a hematologist. In these cases, you need more than one subspecialist to complete the workup.   [22:10] Dr. Sims says there are a lot of misconceptions that the patient will get the diagnosis right away and the right therapy and get better. There are multiple therapies, not just medications. There are lifestyle and work modifications; it's a gradual process.   [22:22] One of Dr. Sims's goals for Jason and Michelle is to get back to doing the things that they enjoy, tennis and hiking. That's a measurement of the quality of life that a patient has.   [22:34] Talking to your doctors about how you're feeling and how you're functioning is huge. It may be that this is your new normal, but it may also be that we can make adjustments to maximize your quality of life.   [23:00] There are misconceptions about the journey of diagnosis and treatment. Have a close relationship with your subspecialist. PCPs have a high burden of expectations. As a rheumatologist who treats rare diseases, it's helpful to take on a part of that burden.   [22:31] If you don't have good communication with your providers and they aren't listening to you, you can always go get another opinion. The provider relationship is life-long.   [23:43] It's important for your provider to take what's important to you into consideration when they make treatment decisions.   [25:00] As a rheumatologist, steroids are a first-line therapy for Dr. Sims. Their role is the quick control of inflammation. The goal is always to get you off of the steroids as soon as possible, in the safest way possible.   [25:17] When Jason came to Dr. Sims, he was on mepolizumab for the working diagnosis of EGPA. Mepolizumab is one of the primary therapies for EGPA. They talked about not making treatment changes as they were navigating what was happening.   [25:40] They didn't want to make a change of medication and then have that be mistaken for disease activity. They didn't want too many variables moving at once.   [25:47] Typically, the first-line therapy is steroids, meant to help with the swelling, pain, and tightness that patients will get lining their muscles and give them a bit more functionality and decreased pain.   [26:00] Long-term, Dr. Sims gives immunosuppressant medication. She prescribed methotrexate for Jason. In EF, the immune system is overly activated, attacking the lining of the muscles and causing the symptoms.   [26:51] If you suppress the immune system activity, that leads to decreased inflammation and symptoms in the patient. Steroid use, over a few months, is detrimental, with low bone density, weight gain, high blood pressure, and diabetes.   [27:14] Dr. Sims starts with prednisone and folds in medications like mycophenolate or methotrexate.   [27:19] Mepolizumab is an interleukin 5 blocker. Interleukin 5 is part of the immune system and is necessary for eosinophils to grow, function, and multiply. The goal of using mepolizumab is to lower the eosinophils that are contributing to the disease symptoms.   [27:48] Methotrexate, prednisone, and mepolizumab can work synergistically or independently. Most rheumatologists start with methotrexate or mycophenolate which have fewer side effects and have been around longer. We know how to manage those.   [28:08] If there is no response, we may add something like mepolizumab. As Jason was already on mepolizumab, Dr. Sims added methotrexate.   [28:20] IVIG, an infusion of immunoglobulin, has also been used as a quick way to control inflammation. It is used in other autoimmune diseases like myositis, which is inflammation of the muscle itself.   [29:08] With untreated eosinophilic fasciitis, the lining of the muscle may continue to be inflamed and can lead to fibrosis, damage that cannot be reversed. The patient can become very disabled. Contracture is one result of this.   [30:16] Jason says when he tried a new medication, he monitored if it was a good fit and if the side effects were less impactful than the underlying disease. Dr. Sims adjusted his dosages or tried to get off certain medicines as needed.   [30:59] After his muscle biopsy from his left calf, it took about a month to get back to walking easily. He was already in physical therapy, going many times for a variety of things. He had back pain, potentially related to his EF. His physical therapist was great.   [31:56] The stretches alternated between upper and lower body. Jason bought tools to do the stretches at home. When he's not feeling as well, he goes back to some of those same stretches. When he was on steroids, he took long walks to strengthen his bones.   [32:39] Jason started making phone calls to supportive family and friends on his walks and started listening to podcasts related to his condition or medications. Getting back to tennis and hiking is important to Jason. He's happy to be out there.   [33:20] Jason was open with his employer about his condition. Some of the weekly meds can make him not feel well. His employer gives him some flexibility. He has good days that far outnumber the bad days. He doesn't have to think about EF too much now.   [34:33] It's nothing like when he was in a flare, especially when he was in a flare before being diagnosed. What gets him through a bad day is giving himself some grace and understanding while he waits for his meds to catch up. He rests more than he wants to.   [35:33] Low-impact exercises like walking help Jason. He's trying to find a support network that gets EF. That led him to APFED, to find anyone experiencing something like what he was. He saw a conference that included a session on EF.   [36:09] Jason signed up for the conference and there he met Ryan's mother who has EF. They were each the first person the other had met with EF. They decided to connect after the conference. They talked on the phone for about an hour.   [36:39] She told Jason how she got into APFED and talked a lot about her son who had eosinophilic diseases. Soon after, Jason talked to Ryan as a primer for this podcast.    [38:15] Having a community to relate to, even if it's one person, is massive. It can make you feel less isolated.   [38:42] Holly says it's hard having a chronic illness. She thanks both Jason and Dr. Sims for sharing so much information and their journey and she asks for last words.   [38:58] Dr. Sims believes finding a community is critical. She interviews a lot of patients for research and isolation is a frequent theme. Even the doctor doesn't know what it's like to live with the condition you live with daily. As Jason said, give yourself grace.   [39:33] Dr. Sims tells her patients that they're different from the general population because they have to spend so much time and energy managing their condition that they can't do x, y, or z today, and that is OK. She says to stay motivated and positive.   [40:12] Find what works for you. Walking is good for your physical and mental health. Have the goal of getting back to what makes you happy. Take initiative and find non-medication ways to recuperate. You have control over ways you can feel better.   [40:43] Connect with others and share your story, like Jason did today. It may make someone's journey a little easier and make them feel less alone. Utilize your condition for good, for a bigger purpose.   [41:04] Jason had wished he could meet someone who could tell him what EF would be like over the years. He says to stay positive and find out what you have control over. Jason believes the future is bright for being able to do many things for a long time.   [42:26] For our listeners who would like to learn more about eosinophilic fasciitis, please visit APFED.org and check out the links in the shownotes.   [42:33] If you're looking to find a specialist who treats eosinophilic disorders, like Dr. Sims, you can use APFED's Specialist Finder at APFED.org/specialist.   [42:43] If you'd like to connect with others impacted by eosinophilic diseases, please join APFED's online community on the Inspire Network at APFED.org/connections/.   [42:55] Ryan thanks Jason and Dr. Sims for joining us for this excellent conversation. Holly also thanks APFED's Education Partners Bristol Myers Squibb, GSK, Sanofi, and Regeneron for supporting this episode.   Mentioned in This Episode: Dr. Catherine Sims, rheumatologist Duke University Hospital Durham VA Medical Center   APFED on YouTube, Twitter, Facebook, Pinterest, Instagram Real Talk: Eosinophilic Diseases Podcast apfed.org/specialist apfed.org/connections   Education Partners: This episode of APFED's podcast is brought to you thanks to the support of Bristol Myers Squibb, GSK, Sanofi, and Regeneron.   Tweetables:   “EF patients may present with large plaques on their skin, edema of arms and legs, Raynaud's Phenomenon, contractures of arms or legs, limited mobility, or loss of the ability to do tasks they used to do.” — Dr. Catherine Sims   “Steroids are … first-line therapy. Their role is the quick control of inflammation. The goal is always to get you off steroids as soon as possible, in the safest way possible.” — Dr. Catherine Sims   “Methotrexate, prednisone, and mepolizumab can work synergistically or independently. Most rheumatologists start with methotrexate or mycophenolate which have fewer side effects and have been around longer.” — Dr. Catherine Sims   “Stay positive and find out what you have control over. The future is bright for being able to do many things for a long time.” — Jason Ingraham

Literature Review Week Why do some people react to mosquitoes so vigorously? There is fascinating data for me in the Nature article, as I see lots of kids that react strongly to mosquitoes while others do not at all. A hyper primed immune reaction makes a lot of sense as the immune system is extra sensitive to the insult in individuals that have chronic allergic phenotypes. They are in effect polarized to see the outside world through an irritant lens and thus react in a more robust way. The cell called GD3 releases Interleukin 3 or IL-3 which is a cytokine signaling molecule that tells skin based sensory neurons to become more sensitive to allergens like house dust mites, environmental molds, and in this case mosquito saliva. Thus, the mosquito saliva induces more of the itch scratch cycle. The effect is to increase the gain sensitivity on the skin to 10. This is likely a main reason why having an allergic child take immunotherapy against allergens that they react to lowers the rheostat for all irritants. It is like a global check on the sensory system. This is another reason to consider SLIT and or SCIT immunotherapy in allergic children... Plus a discussion on the Joe Rogan podcast with Callie and Casey Means. Enjoy, Dr. M  

Over 20 years ago biologics were introduced for psoriasis and PsA. Since then even more targeted treatments have been introduced. Listen as dermatologist Dr. Steven Feldman from Wake Forest University School of Medicine, shares his perspectives on the latest treatments, resident memory T-cells, and what's to come (such as an oral IL-23 agent) with moderator Max Blitstein. This episode is provided with support from Bristol Myers Squibb. 

Immunotherapies continue to redefine treatment for many types of cancer and one of the first immunotherapies approved and used clinically as a therapeutic is Interleukin-2, or IL-2. Aulos Bioscience is an immuno-oncology company that has developed AU-007, a potential best-in-class IL-2, that improves on many of the other IL-2 products in development. In this episode, we discuss the promise of AU-007 with President and CEO, Aron Knickerbocker. Link to Interleukin-2 review article can be found here: https://www.nature.com/articles/s41587-022-01390-3

Subscribe to our channel: https://www.youtube.com/@optispan Check out paper #1 on IL-11 signaling: https://www.nature.com/articles/s41586-024-07701-9.pdf Check out paper #2 on combination trametinib/rapamycin treatment: https://www.biorxiv.org/content/biorxiv/early/2024/07/25/2024.07.25.605097.full.pdf Related episodes: An introduction to the study of RAPAMYCIN: https://www.youtube.com/watch?v=czx_-DqnnrQ&t=1s In this episode, Matt discusses two recent mouse lifespan studies: one focused on inhibiting IL-11 signaling, and one focused on combined trametinib and rapamycin treatment. IL-11, or Interleukin-11, is a protein that plays an important role in modulating inflammation and healing, while trametinib is an FDA-approved drug that targets certain cancers, particularly melanoma. You can find extensive discussion of rapamycin in our R-Files series linked above. Matt explains the "900-day rule" for evaluating mouse lifespan studies such as these two, and provides his take on whether these results are game-changers for the geroscience field as well as whether we should consider these interventions for human use at this time. Producers: Tara Mei, Nicholas Arapis Video Editor: Jacob Keliikoa DISCLAIMER: The information provided on the Optispan podcast is intended solely for general educational purposes and is not meant to be, nor should it be construed as, personalized medical advice. No doctor-patient relationship is established by your use of this channel. The information and materials presented are for informational purposes only and are not a substitute for professional medical advice, diagnosis, or treatment. We strongly advise that you consult with a licensed healthcare professional for all matters concerning your health, especially before undertaking any changes based on content provided by this channel. The hosts and guests on this channel are not liable for any direct, indirect, or other damages or adverse effects that may arise from the application of the information discussed. Medical knowledge is constantly evolving; therefore, the information provided should be verified against current medical standards and practices. More places to find us: Twitter: https://twitter.com/optispanpodcast Twitter: https://twitter.com/optispan Twitter: https://twitter.com/mkaeberlein Linkedin: https://www.linkedin.com/company/optispan https://www.optispan.life/ Hi, I'm Matt Kaeberlein. I spent the first few decades of my career doing scientific research into the biology of aging, trying to understand the finer details of how humans age in order to facilitate translational interventions that promote healthspan and improve quality of life. Now I want to take some of that knowledge out of the lab and into the hands of people who can really use it. On this podcast I talk about all things aging and healthspan, from supplements and nutrition to the latest discoveries in longevity research. My goal is to lift the veil on the geroscience and longevity world and help you apply what we know to your own personal health trajectory. I care about quality science and will always be honest about what I don't know. I hope you'll find these episodes helpful!

Darshan H. Brahmbhatt, Podcast Editor of JACC: Advances discusses a recently published original research paper on Interleukin-6 and Cardiovascular Events in Healthy Adults in the Multi-Ethnic Study of Atherosclerosis

Bei Menschen wird mit zunehmendem Alter ein bestimmtes Protein produziert, das für verschiedene Alterserkrankungen verantwortlich ist. Interleukin 11. Auch Mäuse besitzen dieses Protein. Forschende des Medical Research Council Laboratory of Medical Science und des Imperial College London konnten das Protein in Mäusen jetzt erfolgreich abschalten. Ihre Ergebnisse haben sie in der Fachzeitschrift Nature veröffentlicht. So konnten die Forschenden zeigen, dass durch das Ausschalten des Gens die Lebenserwartung der Mäuse um bis zu 25 Prozent verlängert werden kann. | Diese Podcast-Episode steht unter der Creative Commons Lizenz CC BY-NC-ND 4.0.

Bei Menschen wird mit zunehmendem Alter ein bestimmtes Protein produziert, das für verschiedene Alterserkrankungen verantwortlich ist. Interleukin 11. Auch Mäuse besitzen dieses Protein. Forschende des Medical Research Council Laboratory of Medical Science und des Imperial College London konnten das Protein in Mäusen jetzt erfolgreich abschalten. Ihre Ergebnisse haben sie in der Fachzeitschrift Nature veröffentlicht. So konnten die Forschenden zeigen, dass durch das Ausschalten des Gens die Lebenserwartung der Mäuse um bis zu 25 Prozent verlängert werden kann. | Diese Podcast-Episode steht unter der Creative Commons Lizenz CC BY-NC-ND 4.0.

Bei Menschen wird mit zunehmendem Alter ein bestimmtes Protein produziert, das für verschiedene Alterserkrankungen verantwortlich ist. Interleukin 11. Auch Mäuse besitzen dieses Protein. Forschende des Medical Research Council Laboratory of Medical Science und des Imperial College London konnten das Protein in Mäusen jetzt erfolgreich abschalten. Ihre Ergebnisse haben sie in der Fachzeitschrift Nature veröffentlicht. So konnten die Forschenden zeigen, dass durch das Ausschalten des Gens die Lebenserwartung der Mäuse um bis zu 25 Prozent verlängert werden kann. | Diese Podcast-Episode steht unter der Creative Commons Lizenz CC BY-NC-ND 4.0.

In this episode of "The Court of Public Opinion," Jeremy Cordeaux hosts from his garage, discussing a variety of topics including union corruption, historical reflections, and current events. Here's a summary of the main topics discussed: Introduction and Audience Engagement: Jeremy thanks his audience for their comments and phone calls. CFMEU Corruption: Extensive discussion on the corruption within the CFMEU, likening it to the mafia, and the need for strict action. Nick McKenzie and Senator John Quirk: Recap of recent interviews with investigative journalist Nick McKenzie and Labour Senator John Quirk about union corruption. REM Building Project: Historical anecdotes about the REM building project and its financial mismanagement. Trade Union Influence: Discussion on the power and financial influence of trade unions in Australia, particularly through industry super funds. Compulsory Trade Union Membership: Advocacy for the removal of compulsory trade union membership. Student Union Militancy: Historical account of student union militancy, including the takeover of a radio station. Government and Trade Union Relations: Commentary on the relationship between the government and trade unions, and the potential for trade union delegates on company boards. Climate Activism and Methane Emissions: Critique of climate activists' focus on coal mines emitting methane, arguing that wetlands are a larger source of methane emissions. Climate Demonstrators Jailed: Approval of British courts jailing climate demonstrators who caused significant public disruption. Australian Wine Industry: Discussion on the sale of popular Australian wine labels to American venture capitalists. Sydney's Smut Ranking: Mention of a survey ranking Sydney as the top city in Australia for interest in sexually explicit content. Economic Update: Brief update on unemployment and potential implications for interest rates. Interleukin 11 and Longevity: Introduction of a new scientific breakthrough likened to the "fountain of youth." Historical Events and Birthdays: Notable events and famous birthdays on July 24th, including Amelia Earhart and the debut of Marvin the Martian. See omnystudio.com/listener for privacy information.

In this week's episode we'll discuss new insights on the role of GM-CSF in establishing immune memory. The authors propose that the coordination of opposing immune memory programs, driven by GM-CSF, may be essential to efficient, yet controlled, innate immune responses. After that: Interleukin-1 inhibition in TTP. Researchers explore the potential of recombinant IL-1 receptor antagonist, anakinra, in a murine model of thrombotic thrombocytopenic purpura—an uncommon but potentially fatal disorder with limited therapeutic options. Finally, we'll learn about CAR T-cell therapy outcomes by race and ethnicity in large B-cell lymphoma. Non-Hispanic Black patients had lower rates of response and progression-free survival in axi-cel clinical trials and real-world data, raising awareness and giving further insights into potential inequitable access to care.Featured Articles:GM-CSF receptor expression determines opposing innate memory phenotypes at different stages of myelopoiesis Mortality, cardiac and cerebral damage reduction by IL-1 inhibition in a murine model of TTP Real-World and Clinical Trial Outcomes in Large B-cell Lymphoma with Axicabtagene Ciloleucel Across Race and Ethnicity 

Send us a Text Message.In this FRIDAY 5 episode of "The Autoimmune RESET," VJ Hamilton explores key markers of inflammation from a functional medicine perspective. VJ dives into the roles of C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR), Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin-6 (IL-6), and Homocysteine in indicating both acute and chronic inflammation. VJ explains how genetic variations in IL-6 and TNF-alpha can predispose individuals to higher inflammation levels and discusses the importance of tracking symptoms even when these markers are normal. VJ also cover how localized inflammation, such as in the gut, can be detected using calprotectin. Learn how understanding these markers can provide a comprehensive view of your health and guide effective holistic management strategies. Tune in for valuable insights into maintaining a balanced lifestyle and reducing inflammation naturally.If you would like to book a free initial consultation with VJ Hamilton, The Autoimmunity Nutritionist, to find out about allergy testing and how nutritional therapy and functional testing could improve your health, you can book an appointment here.Learn more about the functional medicine services at The Autoimmunity Nutritionist Clinic here.Thanks for listening! You can join The Autoimmune Forum on Facebook or find me on Instagram @theautoimmunitynutritionist.

Send us a Text Message.A Gluten Free Podcast Episode 127 My guest on today's episode is Associate Professor, gastroenterologist & coeliac disease researcher, Jason Tye-Din. We'll talk about his own allergy journey & personal connection to coeliac disease, developing simple diagnoses, gluten exposure testing, possible preventions for this condition & the mental health research around coeliac disease.   What we'll cover: * Jason's personal journey of living with a peanut allergy * Jason's wife's coeliac disease diagnosis * Developing simple & effective diagnoses: Interleukin 2 (possibility of avoiding gluten challenge & gastroscopy in future) * Stool & urine gluten exposure testing  * The current research into brain fog & other various mental health associations with coeliac disease * Disorder of the gut/brain axis (DGBI), gut hypnotherapy & the gut microbiome * Australia first ENDIA study (Environmental Determinants of Islet Autoimmunity) in relation to Type 1 Diabetes & coeliac disease research * How to get involved & find out more about the research & trials Links WEHI website Current coeliac disease clinical trials Buy tickets to A Gluten Free Evening

Although immunotherapies for patients with solid tumors such as melanoma can be dramatically successful, the majority of patients are resistant and require alternative treatments. While the cytokine interleukin-12 is well known for potentiating the effect of immunotherapies, such as checkpoint blockade, it couldn’t be used because of toxicity. At the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, Jun Ishihara, PhD, a lecturer at London’s Imperial College reported on a protein bioengineering approach in which IL/12 is bound to collagen from the extracellular matrix of the tumor. This targets the cytokine’s action to operate specifically on cancer while hopefully avoiding most of the off-target toxicities previously observed with unbound IL/12. After the conference, OncTimesTalk’s Peter Goodwin called to see him at his London laboratory.

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Update on Chinese IQ-related gene panels, published by Lao Mein on December 14, 2023 on LessWrong. It turns out that Chinese 23-and-me-esque gene panel already include intelligence markers! For example, 23mofang uses Interleukin 3 as a proxy for brain volume, citing this paper. It's... only significant in women. Not a good sign. But the cited study notes a Danish gene-correlation study that included brain scans, from which they obtained brain volume. Apparently, the correlation is true across races. In any case, I've been reaching out to past coworkers, and they agree with my assessment that a polygenic database for the purpose of embryo selection would be easy and mostly cheap to do. Being Chinese, we of course have no issues with including factors like eye color, height, intelligence, ect. However, I have several questions before I proceed further. What is the overall demand? How many customers would be interested? What specific traits are parents most interested in? Funding is the single biggest obstacle I face, and I will be applying for AstralCodexTen funding. If enough interest is displayed or if I get charitable funding, my gut feeling is that I can offer analysis for

In today's episode, we're exploring 3 different topics. First, we'll unravel the intriguing world of beta-glucans and their dual role in regulating the immune system. Then, we'll venture into the ancient practice of Agni Sara, a yoga exercise renowned for strengthening digestive organs. Finally, we'll unveil two unique methods to trigger the acute relaxation response, encouraging parasympathetic activity. Stay tuned for this 3-topic episode! Topics: 1. Agni Sara Exercise - Definition and Purpose - Origin and Traditional Yoga Practice - Physical and Energetic Benefits - Research Study on Agni Sara - Study Involving 12 Volunteers - Ultrasound Examination of Superior Mesenteric Artery - Increase in Blood Flow and Digestive Function Improvement - Traditional Agni Sara Exercise Instructions 2. Beta-Glucans - Definition and Classification - Interaction with the Immune System - Immune System Review - Role of Dectin-1 Receptors - Immune-Boosting Effects - Stimulation of Immune Cells, Phagocytosis, & Antibody Production - Modulation of Inflammation - Stimulation of Interleukin 10 - Balancing Immune Response - Food Sources of Beta-Glucans - Mushrooms Rich in Beta-Glucans - Mushroom Extract Supplements 3. Tibetan Singing Bowls and the Acute Stress Response - Introduction to Tibetan Singing Bowls - Composition and Original Use - Sound Characteristics - Benefits of Tibetan Singing Bowls (TSB) - Impact on Distress, Anxiety, Depression, and More - Physiological Effects on Heart Rate, Respiration, and More - Research Study on Acute Relaxation Response - Comparison of TSB and Progressive Muscle Relaxation (PMR) - Evaluation of HRV, Alpha Power Band (EEG), and Anxiety - Study Findings - Promotion of Acute Relaxation Response by TSB and PMR - TSB's Pronounced Effect on HRV Parameters and Alpha Band Activity - Acknowledgment of Individual Preferences for Relaxation Techniques - Emphasis on Research-Backed Tools for Stress Reduction Thanks for tuning in! Get Chloe's Book Today! "⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠75 Gut-Healing Strategies & Biohacks⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠" If you liked this episode, please leave a rating and review or share it to your stories over on Instagram. If you tag @synthesisofwellness, Chloe would love to personally thank you for listening! Follow Chloe on Instagram ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠@synthesisofwellness⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Follow Chloe on TikTok @chloe_c_porter Visit ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠synthesisofwellness.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ to purchase products, subscribe to our mailing list, and more! Or visit ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠linktr.ee/synthesisofwellness⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ to see all of Chloe's links, schedule a BioPhotonic Scanner consult with Chloe, or support the show! Thanks again for tuning in! --- Support this podcast: https://podcasters.spotify.com/pod/show/chloe-porter6/support

Among patients with non-small cell lung cancers driven by mutations in the epidermal growth factor receptor (EGFR), those with MET-amplification can now be selected for therapy with two tyrosine kinase inhibitor drugs, not just standard osimertinib. That’s according to conclusions from the INSIGHT 2 study reported at the AACR-NCI-EORTC international conference on Molecular Targets and Cancer Therapeutics.Presenting author Xiuning Le, MD, PhD, from the MD Anderson Cancer Center in Houston, Texas, has been talking with OncTimes Talk’s Peter Goodwin about her group’s study in which osimertinib was combined with the MET-tyrosine kinase inhibitor tepotinib in patients who tested positive for MET-amplification.

This amazing study demonstrates the influence of plant-based (high-fiber) and/or fermented food diets on our immune system. Researchers found that fermented foods like yogurt, kimchi, and kombucha caused a reduction of 19 cytokines including IL-6, IL-12b, and IL-10. This reduction may potentially lead to reduction in chronic inflammation. Let's review this study. DrBeen: Medical Education Online https://www.drbeen.com/ FLCCC | Front Line COVID-19 Critical Care Alliance https://covid19criticalcare.com/ References (August 18, 2023) Gut Microbiota-Targeted Diets Modulate Human Immune Status - PMC https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9020749/ Figure - PMC https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9020749/figure/F6/ Interleukin-6 as a Multifunctional Regulator: Inflammation, Immune Response, and Fibrosis - Ernest Choy, Stefan Rose-John, 2017 https://journals.sagepub.com/doi/10.5301/jsrd.5000265#:~:text=IL%2D6%20is%20produced%20by,cells%2C%20fibroblasts%2C%20and%20hepatocytes . Role of Interleukin 10 Transcriptional Regulation in Inflammation and Autoimmune Disease - PMC https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410706/#:~:text=In%20vivo%2C%20major%20sources%20of,granulocytes%20like%20neutrophils%20and%20eosinophils . Regulation of IL-10 and IL-12 production and function in macrophages and dendritic cells - PMC https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754024/#:~:text=Interleukin%2D12%20signaling,dendritic%20cells%20(DCs)%202 . Interleukin-10 production by effector T cells: Th1 cells show self control - PMC https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118719/ Disclaimer: This video is not intended to provide assessment, diagnosis, treatment, or medical advice; it also does not constitute provision of healthcare services. The content provided in this video is for informational and educational purposes only. Please consult with a physician or healthcare professional regarding any medical or mental health related diagnosis or treatment. No information in this video should ever be considered as a substitute for advice from a healthcare professional.

This weeks guest is Professor Marcel Nold, MD. Dr. Nold is a clinician scientist in the research environment of neonatal immunology and microbiomes at Monash University in the city of Monash in Melbourne, Australia. Professor Nold received his Doctor of Medicine degree at the JW Goethe-University at Frankfurt am Main, Germany, including final year rotations in Zürich (Switzerland), Montréal (Canada) and Capetown (South Africa). For his biomedical research training he spent six years at the Pharmazentrum at Frankfurt am Main and three years as a research Fellow at the laboratory of Professor Dinarello, at the University of Colorado Denver. In 2009 he was recruited to The Ritchie Centre in Melbourne and finished his specialist training at Monash Newborn. Professor Nold is a leading researcher worldwide in the field of immune cytokine signaling and was the key contributor to identifying Interleukin 37 or IL37. His research has been published in the journals Nature Immunology, Science Immunology and many others. His academic Inflammation in Neonatal Diseases Research Group and his industry programs aim to characterise underlying pathways of inflammation in early life diseases, with a focus on interventional immunology in cardiopulmonary and intestinal diseases of the preterm. For the purposes of this interview, Dr. Nold is a researcher with a view of the maternal child dyad that is prevention focused and health span conscious. His research has led to many critical discoveries in the neonatal health space that I find deeply intriguing. We get into some deep immunology at times which is critical for total understanding. Enjoy, Dr. M

Welcome to Olink Proteomics in Proximity Podcast! Below are some useful resources from this episode: Highlighted publication: Diaz-Canestro C, Chen J, Liu Y, Han H, Wang Y, Honoré E, Lee CH, Lam KSL, Tse MA, Xu A. A machine-learning algorithm integrating baseline serum proteomic signatures predicts exercise responsiveness in overweight males with prediabetes. Cell Rep Med. 2023 Feb 21;4(2):100944. doi: 10.1016/j.xcrm.2023.100944. Epub 2023 Feb 13: https://www.cell.com/cell-reports-medicine/pdf/S2666-3791(23)00036-8.pdf PMID: 36787735; PMCID: PMC9975321: https://pubmed.ncbi.nlm.nih.gov/36787735/ Highlighted platform that was used to measure proteins in this study with a next-generation sequencing (NGS) readout (Olink® Explore): https://olink.com/products-services/explore/ Here is general information from Wikipedia about IL-6, one of the protein biomarkers identified in this study: https://en.wikipedia.org/wiki/Interleukin_6 Here is general information from Wikipedia about TFF-2, one of the protein biomarkers identified in this study: https://en.wikipedia.org/wiki/Trefoil_factor_2 Would you like to subscribe to the podcast on your favorite player or app? You can do so here: Apple Podcasts: https://apple.co/3T0YbSm Spotify Podcasts: https://open.spotify.com/show/2sZ2wxO... Google Podcasts: https://podcasts.google.com/feed/aHR0... Amazon Music: https://music.amazon.com/podcasts/d97... Podcast Addict: https://podcastaddict.com/podcast/409... Deezer: https://www.deezer.com/show/5178787 Player FM: https://player.fm/series/series-3396598 In case you were wondering, Proteomics in Proximity refers to the principle underlying Olink Proteomics assay technology called the Proximity Extension Assay (PEA), and more information about the assay and how it works can be found here: https://bit.ly/3Rt7YiY For any questions regarding information Olink Proteomics, please email us at info@olink.com or visit our website: https://www.olink.com/WHAT IS PROTEOMICS IN PROXIMITY?Proteomics in Proximity discusses the intersection of proteomics with genomics for drug target discovery, the application of proteomics to reveal disease biomarkers, and current trends in using proteomics to unlock biological mechanisms. Co-hosted by Olink's Dale Yuzuki, Cindy Lawley and Sarantis Chlamydas.

What's new in treatments for spondyloarthritis? Learn more about the rationale for novel therapies and the latest data. Credit available for this activity expires: 03/09/24 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/988291?ecd=bdc_podcast_libsyn_mscpedu

The IdeaSpace Philippines Accelerator Program Cohort 10 is having its Demo Day this March 2, 2023, which is also in celebration for IdeaSpace Philippines 10th anniversary! Ano nga ba ang IdeaSpace? What will happen in the Demo Day? Let's know with Shor Macalbe, Program Manager for Startup Development at IdeaSpace Philippines! IN THIS EPISODE | 00:00  Introduction | 00:49 Ano ang IdeaSpace Philippines Accelerator Program? | 03:03 How is Cohort 10 special/different compared with the previous cohorts? | 05:52 Can we know some of the programs, trainings, mentorships, and opportunities the startups have received? | 07:06 Who are these startups in Cohort 10 and how were they chosen? | 09:46 When is the Demo Day? What will happen? | 15:59 Happy 10th year anniversary IdeaSpace! Will there be Cohort 11? | 17:30 How can listeners know more about IdeaSpace Philippines? IDEASPACE PHILIPPINES | Website: ideaspacefoundation.org | Facebook: facebook.com/ideaspaceph QBO INNOVATION HUB | Website: qbo.com.ph | Facebook: facebook.com/QBOPhilippines OFFICIAL E-LEARNING PARTNER | Ask Lex PH Academy: asklexph.com | Get 5% discount by using the code: ALPHAXSUP CHECK OUT OUR PARTNERS | TechShake: techshake.asia | OneCFO: onecfoph.co (mention Start Up Podcast PH as referral!) | Pinoy IP Works: pinoyipworks.com | Packetworx: packetworx.com | LookingFour Buy & Sell Online: lookingfour.com | NutriCoach: nutricoach.com | Benjoys Food Products: benjoysfoodproducts.com | 8CHAIN: 8chain.io | AltSwitch, Twala, Eplayment, InterLeukin, Hive Energy PH START UP PODCAST PH | YouTube: youtube.com/StartUpPodcastPH | Spotify: open.spotify.com/show/6BObuPvMfoZzdlJeb1XXVa | Apple Podcasts: podcasts.apple.com/us/podcast/start-up-podcast/id1576462394 | Facebook: facebook.com/startuppodcastph | Instagram: instagram.com/startuppodcastph | LinkedIn: linkedin.com/company/startuppodcastph SUPPORT THE PODCAST | Patreon: patreon.com/StartUpPodcastPH | Unionbank: 109426505649 | GCash: 09623871744 This episode is edited by: Krislyn Nepomuceno

Howard Brown is an author, Silicon Valley entrepreneur, interfaith peacemaker, two-time stage IV cancer survivor, and healthcare advocate. For over three decades, Howard's business innovations, leadership principles, mentoring, and resilience in beating cancer against long odds have made him a sought-after speaker and consultant for businesses, nonprofits, congregations, and community groups. His hard-earned wisdom about resilience after beating cancer twice has led him to become a nationally known patient advocate and “cancer whisperer” to many families. Howard, his wife Lisa, and his daughter Emily currently reside in Michigan. ✨A few highlights from the show: 1. Medical technologies that played a role in Howard's recovery and expanding his family: bone marrow transplant, In vitro fertilization (IVF)/Intracytoplasmic sperm injection (ICSI), Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC), scans to video, liquid biopsy, tumor burden, clinical trials, immunotherapy, and Interleukin-2 2. It is important that you, your loved ones or family, or a patient advocate ask about what medical technologies are available to treat the type of cancer that you have. As you can see from Howard's experience, there are many options that may help save your life and improve your quality of life. 3. Don't isolate yourself. Isolation brings darkness. 4. Call for help and hold on to hope. 5. Find your happy place and go there!

Please join author Subodh Verma and Guest Editor Christopher Granger as they discuss the article "Empagliflozin and Left Ventricular Remodeling in People Without Diabetes: Primary Results of the EMPA-HEART 2 CardioLink-7 Randomized Clinical Trial." Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. We're your co-host. I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr. Peder Myhre: And I'm Dr. Peder Myhre, social media editor and doctor at Akershus University Hospital at University of Oslo in Norway. Dr. Carolyn Lam: Peder, I am so excited to be discussing this issue. So many great articles and a feature discussion coming up on the SGLT2 inhibitor, empagliflozin. And do you think it's got effects on left ventricular remodeling in people without diabetes? Very interesting question. Dr. Peder Myhre: That is so interesting, Carolyn. I can't wait to hear this discussion. Dr. Carolyn Lam: Yep, I agree, but we got to wait till we discuss the other papers in today's issue. I want to go first. So we know that non-vitamin K oral anticoagulants, or NOACs, they've become the standard therapy for preventing stroke and ischemic thromboembolism in most patients with atrial fibrillation. But, what is the effectiveness and safety of NOACs in patients on dialysis? That is hemodialysis. The AXADIA-AFNET 8 study sought to test the hypothesis that apixaban would be non-inferior to vitamin K antagonists in these very patients undergoing hemodialysis. Dr. Peder Myhre: Oh wow. This is really a gap of knowledge that we've been waiting to hear more about. NOACs in patients with hemodialysis. Tell us about this trial, Carolyn. Dr. Carolyn Lam: Sure. So this is from corresponding author, Dr. Reinecke, and colleagues, from University of Munster in Germany. And it's an investigator initiated prospective randomized open-blinded outcome assessment of 97 patients with atrial fibrillation on chronic hemodialysis randomized to either apixaban 2.5 mg BID, or a vitamin K antagonist, aiming for an INR between 2 and 3. Over a median follow-up time of 429 days for apixaban, and 506 days for the vitamin K antagonist, the composite primary safety outcome of first, major bleeding, clinically relevant, non-major bleeding, or all cause death, occurred in 46% of patients on apixaban, and 51% of patients on the vitamin K antagonist. That would be a hazard ratio of 0.91, with a p for non-inferiority being 0.157. How about the primary efficacy outcome? While this was a composite of ischemic stroke, all cause death, myocardial infarction, or deep vein thrombosis, and/or pulmonary embolism, and that occurred in 21% of patients on apixaban and 31% of patients on the vitamin K antagonists. Again, no difference when there was testing. So, in summary, Peder, there were no differences in the safety or efficacy observed between apixaban and vitamin K antagonists in patients with atrial fibrillation on chronic hemodialysis. Of note, however, even receiving oral anticoagulations, these patients remain at very high risk of cardiovascular events. So these data really support the consideration of apixaban for prevention of cardiovascular complications in patients with atrial fibrillation on chronic hemodialysis, but larger studies are definitely needed. Dr. Peder Myhre: Oh wow, Carolyn, that is so clinically relevant. And the next paper is also a clinically relevant paper. And it comes to us from the SPRINT authors. And to remind you, the SPRINT study was a study of intensive systolic blood pressure lowering compared to standard blood pressure lowering. And the results demonstrated that there was a robust reduction in both heart failure endpoints and all cause mortality. And in this sub-study that comes to us from corresponding author Jarett Berry from University of Texas Tyler School of Medicine, these authors look at the mechanisms through which intensive blood pressure lowering reduces the risk of these endpoints. And given the important role of cardiac injury and neurohormonal activation in the pathways leading from hypertension to heart failure, and strong association that has been observed between hypertension and levels of cardiac troponin and NT-proBNP, the authors hypothesized that intensive systolic blood pressure lowering would decrease levels of high sensitivity cardiac troponin T and NT-proBNP. Dr. Carolyn Lam: Cool. That's interesting. So how did they do this, and what did they find? Dr. Peder Myhre: So, as expected, Carolyn, the authors found that increases in troponin and NT-proBNP from baseline to 1 year were associated with a higher risk of heart failure and death. And there were really no significant interaction by treatment assignment. But let's look at the changes in troponin. And these results showed that randomization to intensive blood pressure lowering versus standard blood pressure lowering resulted in a significant 3% increase in cardiac troponin T level over 1 year follow up, and a higher proportion of participants with more than 50% increase, and that's with an odds ratio of 1.47. And Carolyn, in contrast, NT-proBNP decreased by 10% in intensive blood pressure arm. And these patients had substantially lower probability of increasing more than 50% in NT-proBNP, with an odds ratio of 0.57 compared to the standard arm. And now, to the most interesting part of this analysis, Carolyn, the association of randomized treatment assignment on changes in troponin was completely attenuated after accounting for changes in eGFR during the follow up, whereas the association of treatment with NT-proBNP changes were completely attenuated after adjusting for changes in systolic blood pressure. So Carolyn, the authors highlight in their discussion the importance of non-cardiac factors influencing variation in cardiac biomarkers, and raise questions about the potential role of cardiac troponin T as a surrogate marker for heart failure or death in blood pressure lowering studies. Dr. Carolyn Lam: Wow, very interesting. Thanks, Peder. Can I tell you now about a preclinical study? Very interesting, because it shows that cardiac inflammation and hypertrophy are regulated by a heart-brain interaction. Dr. Peder Myhre: Wow, Carolyn, a heart-brain interaction. I'm excited to hear more about this. Please explain. Dr. Carolyn Lam: I'd love to, but first some background. Interleukin-1 beta, now that is a pro-inflammatory cytokine that causes cardiac hypertrophy and heart failure. I need to familiarize you with this, the nucleotide-binding domain leucine-rich containing family, pyrin domain-containing-3, NLRP3 for short, which is an inflammasome, which is a cytosolic multiprotein complex that mediates active interleukin-1 beta production. Okay? So you know these terms, and now I want to tell you about the study. This is an elegant series of experiments performed by co-corresponding authors, Dr. Higashikuni, from University of Tokyo, and Dr. Sata, from Tokushima University Graduate School of Medicine, and their colleagues. They first showed that genetic disruption of the NLRP3 inflammasome resulted in significant loss of interleukin-1 beta production, cardiac hypertrophy, and contractile function during pressure overload. Next, a bone marrow transplantation experiment revealed an essential role of NLRP3 inflammasome in cardiac non-immune cells in myocardial interleukin-1 beta production and the cardiac phenotype. It was extracellular ATP released from sympathetic nerve terminals that induced the hypertrophic changes of cardiac cells in an NLRP3 and interleukin-1 beta dependent manner in vitro. And finally, depletion of ATP release from sympathetic efferent nerves, or ablation of cardiac afferent nerves, or a lipophilic beta-blocker, all reduced cardiac extracellular ATP, and inhibited the NLRP3 inflammasome activation, the interleukin-1 beta production, and the adaptive cardiac hypertrophy during pressure overload. So all of this suggests that controlling the neuronal brain signals might have therapeutic potential for the treatment of hypertensive heart disease. Neat, huh? Dr. Peder Myhre: Oh, that is so interesting. The heart and brain interaction. And, Carolyn, we're going to stay in the field of preclinical science. And now we're going to talk about another field that is really interesting, and that is regeneration of cardiomyocytes. Because, Carolyn, developmental cardiac tissue holds remarkable capacity to regenerate after injury, and consists of regenerative mononuclear and deployed cardiomyocytes. Whether reprogramming metabolism promotes persistence of these regenerative mononuclear and deployed cardiomyocytes that enhance cardiac function in repair after injury is unknown. Therefore, these researcher, led by corresponding author, Mohsin Khan, from Temple University School of Medicine, investigated whether the RNA binding protein, LIN28a, which is a master regulator of cellular metabolism, plays a role in cardiac repair following injury. Dr. Carolyn Lam: Wow. That is always, always interesting, regeneration and repair following injury. So what did the authors find? Dr. Peder Myhre: Well, Carolyn, through a number of elegant experiments, the authors made the following key findings. For the first time, they documented a role for RNA binding protein LIN28A in regulating cardiomyocyte turnover in the postnatal and adult heart. And LIN28a overexpression promotes cardiomyocyte cell cycle activity during postnatal development and extends cardiac regenerative ability of the mammalian heart to postnatal day 7. And in the adult heart, the authors could demonstrate that LIN28a drives new myocyte formation, augmenting cardiac structure and function after myocardial injury. And Carolyn, I'm sure you're going to ask the clinical implications of this study. Dr. Carolyn Lam: Indeed. Dr. Peder Myhre: And that is that these results may suggest a novel translational role for LIN28a based strategy to replenish cardiomyocytes in the adult heart after injury. Dr. Carolyn Lam: Very nice, Peder. Thank you. Also in the issue is a Research Letter by Dr. Bick on interleukin-6 receptor polymorphism attenuates clonal hematopoiesis mediated coronary artery disease risk among many individuals in the UK Biobank. There's also Cardiology News by Tracy Hampton, where she highlights few really interesting things, like aging cardiomyocytes accumulate new genetic mutations that was published in Nature Aging, cytokines promote tissue repair after a heart attack in mice, and that was published in Science, and scientists identifying molecular alterations in a failing heart at a single cell resolution, which was published in Nature. Dr. Peder Myhre: And there are a couple of other papers also in this issue, Carolyn. And there's first, an exchange of letters by Drs. Halushka, Lu, and Mayr, regarding the article "Circulating MicroRNA-122-5p is Associated with a Lack of Improvement in Left Ventricular Function after TAVR and Regulates Viability of Cardiomyocytes Through Extracellular Vesicles." And finally, we have an "On My Mind" piece by doctors Monda and Limongelli entitled "An Integrated Sudden Cardiac Risk Prediction Model for Patients with Hypertrophic Cardiomyopathy." Dr. Carolyn Lam: Oh, nice. Nice full issue. Thank you, Peder. Let's go to our feature discussion now. Shall we? Dr. Peder Myhre: Let's go. Dr. Greg Hundley: Welcome listeners to this feature discussion on January 24th. And we have with us Dr. Subodh Verma, from St. Michael's University in Toronto, Canada. And a guest editor, Dr. Christopher Granger, from Duke University in Durham, North Carolina. Welcome gentlemen. Well, Subodh, we will start with you. Can you describe for us some of the background information that went into the preparation of your study, and what was the hypothesis that you wanted to address? Dr. Subodh Verma: First, my great pleasure to be here, and thank you very much for the opportunity to discuss this paper with your viewers. As you know, SGLT2 inhibitors have been truly transformative therapies. From a heart failure perspective, we know that they prevent incident heart failure in people with diabetes who have vascular disease or risk factors. They also have been shown to treat prevalent heart failure in people with heart failure and either a reduced, mildly reduced, or preserved ejection fraction independent of glycemic status. And really, these have been the basis of very strong recommendations to use these agents in the prevention of heart failure in people with diabetes, and also in the treatment of prevalent heart failure in people with and without diabetes. Now, the fact that these drugs have such broad effects in people with heart failure has led to a theory that maybe these drugs could be introduced earlier on in the natural history of heart failure in people who neither have diabetes nor have significant heart failure, the so-called sort of stage A or stage B patient. But there really have been no clinical trials evaluating this question. There've been a lot of translational randomized trials that have provided some mechanistic insights about LV remodeling in people with diabetes or in people with prevalent heart failure. And we hypothesized that maybe the first step to evaluate whether SGLT2 inhibitors may have favorable effects on cardiac remodeling in people without diabetes or without heart failure would be to conduct a randomized double-blind control trial looking at indices of left ventricular remodeling in a population that I've just described. Dr. Greg Hundley: Very nice, Subodh. So you've started us into your study design. Maybe describe that a little more fully, and then who was included in your study population? Dr. Subodh Verma: So EMPA-HEART 2 CardioLink was a multi-center double-blind placebo control randomized trial in which we studied the effects of empagliflozin, an SGLT2 inhibitor, at a dose of 10 mg per day versus placebo in people who did not have type 2 diabetes or significant heart failure. We included people who were adults between the age of 40 and 80 who met 1 of 2 entry criteria. Either they had to have one major criteria, which was an increase in left ventricular mass index by specific echo criteria or MRI criteria, or they could have increased LVH as identified by ECG or by intraventricular septal or posterior wall thickness. They could also get in if they had resistant hypertension, hypertension despite being on 3 antihypertensive agents, or the second strata was entry through 2 minor criteria, which included a history of myocardial infarction, a GFR between 30 or 60, or evidence of overweight or obesity. Dr. Greg Hundley: And how many subjects did you randomize? Dr. Subodh Verma: So we randomized, of the 318 that we screened, 169 were randomized to receive empagliflozin 10 mg or a placebo. Patients had a baseline cardiac MRI done, and then the exposure was 6 months. They had a follow-up MRI at the end of 6 months. And the primary outcome measure was a 6-month change in left ventricular mass index from baseline to 6 months between the two groups. Dr. Greg Hundley: Very nice. And so , Subodh, can you describe for us now, what did you find? What were your study results? Dr. Subodh Verma: So, first and foremost, what we found in terms of baseline characteristics was that we enrolled a population of people with a mean age of around 60 with a BMI of around 30 kg/m2, predominantly men, about 80% or so were men. These were patients who did not have significant heart failure. The NT-proBNP at baseline was around 50 pg/mL. The eGFR was around 80 mL/minute, and the vast majority of these patients actually had a history of hypertension. Of course, none of them had diabetes by definition. The hemoglobin A1C was around 5.8%. Now what we found was, despite the fact that we went after patients who we thought would be enriched for a baseline increase in LV mass indices, the baseline LV mass index was mildly elevated, was around 63 g/m2. And over the course of 6 months, we did not find any significant difference in terms of LV mass regression between the placebo and empagliflozin groups. In fact, the adjusted treatment effect was minus 0.30 g/m2, which was not statistically significant. No other differences were found in terms of other indices of a remodeling, including left ventricular and diastolic or end systolic volume indices or in terms of left ventricular ejection fraction. There was a 2% increase in ejection fraction, and the p-value for that was 0.07, but really was not statistically significant. Dr. Greg Hundley: And very nice. And realizing that women may have smaller LV masses, any stratified analysis that evaluated effects on men versus women? And then what about, perhaps in the higher quartile versus lower quartile, of age? Dr. Subodh Verma: Right. So, Greg, we actually did look at various subgroups and covariates, including gender, including age. And age or gender did not really influence the overall result that we obtained. There was really a neutral result in empagliflozin, irrespective of these 2 covariates. We also looked at baseline blood pressure, baseline NT-proBNP, LV mass indices, the presence or absence of heart failure, chronic kidney disease. So for the covariates that we have evaluated over a short term of 6 months in this relatively low risk population, we did not find any heterogeneity the result, per se. Dr. Greg Hundley: Very good. Well, Subodh, thank you so much for that beautiful presentation. And listeners, now we're going to turn to our guest editor, Dr. Chris Granger. And Chris is an expert in the field of heart failure. Also, a lot of familiarity with HFpEF, which sounds a little bit, we're looking at precursors. We don't have HFpEF yet, but maybe trying to inhibit this from happening using empagliflozin. How do you put these results in the context with other studies that have emphasized utilizing SGLT2 inhibitors in patients with sort of a preserved ejection fraction and absence of diabetes? Dr. Christopher Granger: Yeah. Well thanks, Greg. And again, congratulations, Subodh, to your study. And I think you framed some of the context here as these drugs, the SGLT2 inhibitors, as being transformative, which I think is exactly right. And it's such a fascinating story. Right? These drugs, which we thought originally, with their cause of glucose spilling in the urine, and a modest decrease in blood glucose, might have a role for modestly improving glucose control in diabetes. And low and behold, they've turned out to be one of the great stories I think in recent, across all of medicine, in terms of their consistent and substantial improving clinical outcomes for patients with heart failure, with diabetes and cardiovascular disease, and now even kidney protection, and much broader implications. And their well tolerated, and they don't have dose titration. So there's some practical appeal to this class of drugs in terms of their benefits, in terms of clinical outcomes. But we're left with having this amazing evidence-based generated without really understanding why are these drugs so effective? And what are they doing? And you've provided, I think, an important piece to the puzzle. We did have the data from patients with diabetes and heart failure, with diabetes and left ventricular hypertrophy, that there is a modest reduce in LV mass with SGLT2 inhibitors. And what you've shown is that for patients that with mild LVH, with risk for LVH, that we simply don't see a substantial reduction in LV mass with the use of these drugs. So I think that provides this evidence that that's not a major cause of benefit, at least in this earlier phase of development of heart failure. And I think it really underscores the fact that there's a lot of work to do still to understand. We know that the renal effects are obvious place that these drugs have such an important benefit. And then the linkage of renal disease and cardiac performance is one of the areas, I think, that's a very exciting aspect of a probable contribution of the mechanism of these drugs. But I think in the end, we're left with still not really understanding why these drugs are so beneficial. But understanding that, I think, will be important, both for opening new avenues of targeting pathways, as well as being able to tell the clinical community, okay, you have these important benefits, but people do want to also know why are we seeing these benefits. Dr. Greg Hundley: Very nice. Well, listeners, we're going to turn back to Dr. Verma here. Subodh, what do you see is the next study to be performed in this sphere of research? Dr. Subodh Verma: Well, first, my thanks to Professor Granger, Chris, for handling this paper and for his very thoughtful comments. And he's absolutely right. We have such wonderful clinical data, and these results, of course, should not in any way take away from the importance of using empagliflozin or other SGLT2 inhibitors in the prevention of heart failure in people with diabetes, or in the treatment of HFpEF or HFrEF. But we're struggling with trying to understand what is the dominant mechanism of action here. And, in the previous precursor to EMPA-HEART 2, we did EMPA-HEART 1 in people with diabetes, and we saw a modest effect that was statistically significant of reduction in LV mass index. And we did not see this, of course, in a lower risk population without diabetes. And that tells me that remodeling may be occurring to a modest effect, it may require a longer time to actually show its benefits, but that this is unlikely a dominant sort of mechanism through which these drugs are working. And I do share Chris's thoughts that one of the key mechanisms of benefit that needs to be further explored is looking at the renal cardiac axes. We know that these drugs are profoundly renal protective, and that the benefits may actually be secondary to improvements in renal hemodynamics, improvements in renal function. And I think that is a population that needs to be, that's a mechanism that needs to be studied further. So I think the next generation of translational mechanistic studies need to really tease out the renal cardiac axes, maybe tease out populations that are at risk but have more significant left ventricular hypertrophy, maybe evaluate patients for a longer duration of treatment, or select people who truly have significant hypertension at baseline. I think those are groups and questions that need further exploration. And, of course, the translational science needs to be also studied in the context of larger completed clinical trials, where biomarkers are currently available and they can be linked, of course, to the outcomes in those trials. So those are some of my thoughts as to where the field could move towards. Dr. Greg Hundley: Very nice. And Chris, do you have anything to add? Dr. Christopher Granger: Subodh, I think that was a great summary. And I might just make a comment on the other end of the spectrum. That is, we have these drugs and the evidence of their benefit, and yet they're grossly underused in the populations that have proven to have benefit. Now it takes some time to educate, to get people familiar with, and get them to integrate these treatments into practice, but there's an enormous opportunity, and I think there is a linkage here. I think when people understand the mechanism, and when they're thoughtful about how these drugs may be working, that that really helps to make the case that the drug should be used, and that people are on board with using them. So I think there's this linkage here, there's the need to both better understand mechanism, and there's the need to have systems of care where these treatments are integrated to provide the benefit that's been so clearly shown in the randomized trials. Dr. Greg Hundley: Very nice. Well, listeners, we want to thank Dr. Subodh Verma, from St. Michael's University in Toronto, and our guest editor, Dr. Chris Granger, from Duke University in Durham, North Carolina, for bringing this paper highlighting that among people with neither diabetes nor significant heart failure but with risk factors for adverse cardiac remodeling, that SGLT2 inhibition with empagliflozin did not, did not, result in a meaningful reduction in LV mass index after 6 months. Well, on behalf of Carolyn, Peder, and myself, we want to wish you a great week, and we will catch you next week on the run. This program is copyright of the American Heart Association 2023. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit ahajournals.org.

Louisa Nicola is a neurophysiologist and brain coach for many professional athletes and Wall Street execs. She discusses science-based tools and strategies to boost brain health and mental performance. Support your Workout Sessions and Healthy Hydration with this Creatine Electrolyte Combo by MYOXCIENCE Save 15% with code podcast at checkout Link to the Video Interview: https://bit.ly/3R7noel Connect with Louisa: https://www.neuroathletics.com.au Show Notes: 03:10 Louisa was elite triathlete when she realized the impact the brain had on all aspects of performance. She and her fellow athletes were not taught about sleep or nutrition. 04:20 The nervous system must be optimized to optimize performance throughout the body and as a person. 05:35 We used to sleep about 12 hours a day in prehistoric times. Sleep regenerates our brains. 06:20 There are 4 stages of sleep. Stage one is as you are falling asleep. Stage 2 is light sleep. Stage 3 is deep sleep/slow wave sleep/non-REM sleep. Stage 4 is REM sleep. Stages 3 and 4 are the most important stages for our brains. 06:52 During deep sleep, hormones are secreted: testosterone, estrogen, growth hormone. The glymphatic system is your brains sewage system. It cleans toxins, including amyloid beta. A buildup of these toxins can lead to neurodegenerative diseases. 07:50 Your brain is comprised of neurons and others. Glial cells bind neurons together. During deep sleep, glial cells shrink, making way for the cerebral spinal fluid in your brain to wash out the trash. 08:55 A groggy wakeup may be an indication that you are not getting into deep sleep. 30% of your total sleep time should be deep sleep. 20% of total sleep time should be REM sleep. 09:30 REM sleep is where memory consolidation and learning take place. 10:30 The biggest disruptor of sleep is anxiety and stress. This activation of the sympathetic nervous system may prevent you from falling asleep or wake you in the night. 10:55 Alcohol is the biggest inhibitor of REM sleep. Blue light blocking glasses are helpful, but do not block out all light. 12:00 Eating less than 2 hours before bed keeps us awake through digestion and the increase in our core body temperature. Core body temperature must drop at least 2 degrees for us to go to sleep and stay asleep. 15:00 Alcohol inhibits the action of GABA, our calming neurotransmitter. Cortisol peaks with alcohol. Alcohol and marijuana sedate you. It does not elicit sleep stages. 16:15 You are preparing for sleep the minute you wake up. Consistency is key. 17:20 Try to get as much sleep as possible before you get on a plane. It is called Sleep Banking. 18:10 Your prefrontal cortex is the ruler of your brain. It is where cognition happens: attention, reaction time, processing speed. 6 hours of sleep is a sleep deprived state, in the scientific literature. 10:20 As we age, we have a lower efficacy of our frontal lobe. There is a thinning of our cerebral cortex. Thinning in the prefrontal cortex causes a lower decision rate and worsening of our processing speed, inhibition and impulse control. 21:20 We can slow brain ageing through lifestyle interventions, such as sleep, good nutrition and exercise. 21:40 There is an atrophy of our brain white matter, where our myelinated neurons live, as we get older. Our processing speed declines. This can be seen using an EEG. 25:50 Mild cognitive impairment is a predementia state. 27:30 You should be working on your brain. It is the control center of your entire body. 27:50 You can stave off predementia states and the slowing of cognition through exercise. 29:45 Head trauma can cause an accumulation of talc proteins tolC proteins and amyloid beta, which is somewhat comparable to Alzheimer's disease. 30:30 A hard hit may require a month's recovery. Within 24 hours post trauma, decreasing the temperature of the brain, eating a high fat diet, or having exogenous ketones can help heal the brain. 33:40 Ingesting exogenous ketones can help prevent trauma from happening to the brain. 36:00 EPA/DHA are anti-inflammatory. If you have a high omega 3 index of 8% or more, you can increase your life expectancy by 5 years. 37:10 A risk factor for all-cause mortality is a low omega 3 index. 37:40 Quality supplements reduce risk of oxidation and toxicity. EPA/DHA feeds your brain what it is made of. It is made of water and fat. A high omega 3 index helps with cell membrane fluidity. 39:25 A standard omega 3 blood panel does not test the red blood cell. Red blood cell cycle lasts about 120 days. You need to ingest EPA/DHA daily for cardiac, brain and overall health. 41:20 Farm raised seafood does not contain the same amount of nutrients. 41:30 Omega 3 is made of EPA, DHA and ALA. ALA is the plant form found in flax and chia seeds. To get the recommended dose of omega 3 through ALA is a lot of food. ALA gets converted into DHA. 42:20 Your eyes are the only neurologic tissue outside your brain. Vision changes may be a way to indirectly assess brain health. 45:05 Most 2019 deaths were attributable to heart disease and brain diseases. 45:40 A healthy performing brain can make sound decisions, be rational and practice impulse control. 47:00 Your brain fatigues faster if you are not eating well, sleeping well, and exercising. You need brain energy. Stress and an inflamed brain disrupts pathways in the brain. 48:50 People who have type 2 diabetes and obesity have a higher rate of neural inflammation. 49:50 When we exercise there is a release of myokines, muscle-based proteins (peptide hormones). They act on different organs in positive ways. They are water soluble, and some can pass the blood-brain barrier. Binding receptors to myokines are on heart muscle, spleen, liver and more. Once bound, they create a chemical reaction. 51:10 Interleukin 6 myokine, is secreted with the contraction of a muscle. It is pro-inflammatory cytokine… unless it is released from a muscle – where it is released as anti-inflammatory. It affects immunity and different areas of the brain. 52:00 Irisin myokine is a messenger molecule. It crosses the blood-brain barrier to the prefrontal cortex, where it affects cognition, and hippocampus, where it induces BDNF, that induces neurogenesis. 53:56 When you learn something and immediately exercise, you can have greater capacity to remember. If you sleep for 20 minutes after learning something, you will embed everything you learned. 54:30 Irisin release is increased 1 hour after exercise. 54:50 Workouts of 70 to 80% of you one rep max for a robust release of irisin. More of a release is given during resistance training, than aerobic. The more resistance, the more the release. 58:10 You can stave of neurodegenerative diseases and states by 20 years by inducing exercise protocols that impact myokine release. 58:50 50 million people worldwide are affected by Alzheimer's disease. That rate is set to triple by 2050. 59:30 EPA/DHA can clear accumulated proteins in your brain. 00:01:00 Demyelinating diseases, MS, are becoming more prevalent. Chronic stress and chronic cortisol may be the cause.  

Can you navigate the increasingly complex treatment landscape for psoriasis and psoriatic arthritis (PsA)? Earn Credit / Learning Objectives & Disclosures:  https://www.medscape.org/viewarticle/985565?ecd=bdc_podcast_libsyn_mscpedu

Cytokines control nearly all aspects of the immune system. As drugs, though, they have limited potential because of inherent drawbacks. Simcha Therapeutics is engineering versions of cytokines to activate various immune cells in the fight against cancer. Simcha's most advanced program, ST-067, is the first in a new class of interleukin-18 based immunotherapies designed to overcome a key defense mechanism that the tumor microenvironment produces to prevent Interleukin-18 from doing its work. We spoke to Sanuj Ravindran, CEO of Simcha Therapeutics, about the company's engineered cytokines, how they work, and why they may represent a powerful addition to the immunotherapy arsenal.

Our lab studies immune dysfunction within the female gynecological disease of endometriosis. My specific project is looking at the relationship between a protein called interleukin 33, or IL-33, and a type of immune cell known as group 2 innate lymphoid cells, and how their contributing to disease severity and symptomology. For upcoming interviews check out […]

*READ THE TOPICS COVERED BEFORE LISTENING*** Case study of a 92 year old with delirium Causes of delirium Geriatric toxicology Geriatric STI's and sexual health REFERENCES: Alex Yartsev. Pharmacology and toxicology in old age. June 30, 2016. Deranged Physiology. Available from https://derangedphysiology.com/main/required-reading/pharmacology-and-toxicology/Chapter%201.3.4/pharmacology-and-toxicology-old-age Frankowski AC, Clark LJ. Sexuality and Intimacy in Assisted Living: Residents' Perspectives and Experiences. Sex Res Social Policy. 2009 Dec 1;6(4):25-37. doi: 10.1525/srsp.2009.6.4.25. PMID: 25568640; PMCID: PMC4283937. Kristen Fontes MD, Alex Koyfman MD, Brit Long MD. Common ED Medication Errors: Polypharmacy. EmDocs. July 3, 2017. Available from http://www.emdocs.net/common-ed-medication-errors-polypharmacy/ Nat. Research Council (US) Cute on Chemical Toxicology and Aging. Aging in Today's Environment. Washington (DC): National Academies Press (US); 1987. 4, Principles of Toxicology in the Context of Aging. Available from: https://www.ncbi.nlm.nih.gov/books/nbk218724/ Rashid, M.H., Sparrow, N.A., Anwar, F. et al. Interleukin-6 mediates delirium-like phenotypes in a murine model of urinary tract infection. J Neuroinflammation 18, 247 (2021). https://doi.org/10.1186/s12974-021-02304-x Stanford Medicine 25. Website: Fundoscopic/Opthalomoscopic Exam. Available from https://stanfordmedicine25.stanford.edu/the25/fundoscopic.html https://www.theseniorlist.com/sti-older-americans/

Drs Stanley Cohen and Caylib Durand discuss the treatment paradigm for psoriatic arthritis and the role of methotrexate and other conventional synthetic disease-modifying antirheumatic drugs. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/970783). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals. Resources Psoriatic Arthritis https://emedicine.medscape.com/article/2196539-overview Psoriatic Arthritis: Expert Review and Commentary From Published Literature https://themedicalxchange.com/en/2021/11/23/3021-new-grappa-treatment-recommendations-for-psoriatic-arthritis/ GRAPPA Treatment Recommendations: 2021 Update https://www.jrheum.org/content/early/2022/03/10/jrheum.211331 What Is GRADE? https://bestpractice.bmj.com/info/us/toolkit/learn-ebm/what-is-grade/ Rheumatoid Arthritis (RA) Workup https://emedicine.medscape.com/article/331715-workup#c6 leflunomide (Rx) https://reference.medscape.com/drug/arava-leflunomide-343203 sulfasalazine (Rx) https://reference.medscape.com/drug/azulfidine-sulfasalazine-343280 AB0533 Combination of Methotrexate and Leflunomide Is Safe and Has Good Drug Retention Among Patients With Psoriatic Arthritis https://ard.bmj.com/content/80/Suppl_1/1298.1 apremilast (Rx) https://reference.medscape.com/drug/otezla-apremilast-999915 Etanercept and Methotrexate as Monotherapy or in Combination for Psoriatic Arthritis: Primary Results From a Randomized, Controlled Phase III Trial https://onlinelibrary.wiley.com/doi/10.1002/art.40851 Psoriatic Arthritis Treatment & Management https://emedicine.medscape.com/article/2196539-treatment Iritis and Uveitis https://emedicine.medscape.com/article/798323-overview Paradoxical Gastrointestinal Effects of Interleukin-17 Blockers https://ard.bmj.com/content/79/9/1132

This week, please join authors Paul Ridker and Eric Van Belle, editorialist Robert Harrington, and Guest Editor Allan Jaffe as they discuss the original research articles "Effects of Randomized Treatment With Icosapent Ethyl and a Mineral Oil Comparator on Interleukin-1β, Interleukin-6, C-Reactive Protein, Oxidized Low-Density Lipoprotein Cholesterol, Homocysteine, Lipoprotein(a), and Lipoprotein Associated Phospholipase A2: A REDUCE-IT Biomarker Substudy" and “Cerebral Microbleeds During Transcatheter Aortic Valve Replacement: A Prospective Magnetic Resonance Imaging Cohort” and the editorial "Trials and Tribulations of Randomized Clinical Trials." Dr. Carolyn Lam:             Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the Journal and its editors. We're your co-hosts. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center, and Duke National University of Singapore. Dr. Greg Hundley:           And I'm Dr. Greg Hundley, Associate Editor, Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Carolyn Lam:             It's double feature time Greg. We've got two totally unique and interesting papers that we'll be discussing. The first, a biomarker substudy from the REDUCE-IT trial, that is looking at the effects of randomized treatment with icosapent ethyl, versus a mineral oil comparator, on inflammatory biomarkers. Now, don't use roll your eyes at me, because I'm telling you, this has results that you may not expect, and very, very important clinical implications, and implications for clinical trials. The second paper, very much up your alley, Greg, is a prospective MRI study of cerebral microbleeds during TAVR. But okay, enough now to whet your appetite, let's now just first grab coffees, and discuss the other papers and the issue, shall we? Dr. Greg Hundley:           You bet, Carolyn. And how about if I go first? Dr. Carolyn Lam:             Please. Dr. Greg Hundley:           So, Carolyn, my first paper comes from a group of investigators led by Dr. Araz Rawshani from the Institute of Medicine, and it included 715,143 patients with diabetes, registered in the Swedish National Diabetes Register, and compared them with over two million match controls, randomly selected from the general population, to determine the role of diabetes in the development of valvular heart disease, and particularly, the relation with risk factor control. Dr. Carolyn Lam:             Huh? Interesting, diabetes and valve disease. All right. What did they find, Greg? Dr. Greg Hundley:           Right, Carolyn. So they found, that individuals with type one and two diabetes, have greater risk for stenotic lesions. Whereas, risk for valvular regurgitation was lower in type two diabetes. Patients with well controlled cardiovascular risk factors, continued to display higher risk for valvular stenosis, without a clear stepwise decrease in risk between various degrees of risk factor control. So Carolyn, diabetes and a link with valvular heart disease. Dr. Carolyn Lam:             Wow. Really interesting, Greg. Thanks. Well, the next paper is a preclinical study with really interesting clinical implications. Now, we know the human heart has limited capacity to regenerate new cardiomyocytes, and that this capacity declines with age. Now, because loss of cardiomyocytes may contribute to heart failure, it is important to explore how stimulating endogenous cardiac regeneration, to favorably shift the balance between loss of cardiomyocytes and birth of new cardiomyocytes, occurs in the aged heart. Now, these authors, Doctors Rosenzweig, from Massachusetts General Hospital, and Dr. Lee from Harvard University and colleagues, previously showed that cardiomyogenesis can be activated by, guess what? Exercise in the young adult mouse heart. However, whether exercise also induces cardiomyogenesis in aged hearts, however, is not yet known. So in today's paper, the authors aim to investigate the effect of exercise on generation of new cardiomyocytes in the aged heart. And here, we're talking about 20 month old mice, who were subjected to an eight week voluntary running protocol, and age matched sedentary animals who served as controls. Dr. Greg Hundley:           Wow, Carolyn. Really interesting evaluation of exercise on cardiomyogenesis. So what did they find? Dr. Carolyn Lam:             Endogenous cardiomyogenesis can be stimulated by exercise in aged hearts. Comparative global transcriptional analysis further revealed, that exercise and age specific changes occurred in gene programs. The regulator of calcineurin RCAN1.4 was specifically found to be induced with exercise in aged hearts, and was accompanied by reduced calcineurin activity. So what's a take-home message? Exercise induced cardiomyogenesis may counter the increased cardiomyocyte loss and reduced cardio myogenic capacity in elderly patients. Dr. Greg Hundley:           Great, Carolyn. Well from the mail bag, there's an exchange of letters to the editor from Professor Zhou and Veith regarding a prior letter to the editor from Professor Jin and associates, pertaining to the previously published article “SPARC, A Novel Regulator of Vascular Cell Function in Pulmonary Hypertension.” And also, there's a Perspective piece, from Professor Mentz entitled, “Catastrophic Disruptions in Clinical Trials.” Dr. Carolyn Lam:             There's also a Research Letter by Dr. Kumar on [entitled] “von Willebrand Factor Is Produced Exclusively by Endothelium, Not Neointima, in Occlusive Vascular Lesions in Both Pulmonary Hypertension and Atherosclerosis.” There's also this beautiful tour of Cardiology News from the literature, from Tracy Hampton, which ranges from a study linking COVID-19 to higher long term cardiovascular risks, which was published in Nature Med, to uncovering alternative metabolic pathways involving cell fate transitions, published in Nature, to designing an autonomous biohybrid fish, from human stem cell derived cardiac muscle cells, that was published in Science. Wow. Isn't that amazing, Greg? Well, let's get on now though, to our two feature papers. Shall we? Dr. Greg Hundley:           You bet. Welcome listeners, to these two feature discussions on this particular day. And our first feature today, we have with us Dr. Paul Ridker, from Brigham and Women's Hospital in Boston, Massachusetts. Dr. Bob Harrington, from Stanford University in California. And also, Dr. Allan Jaffe, from Rochester, Minnesota. Welcome to you all. And Paul, we're going to start for you. Can you describe for us, the background information that really went into the construct of your study, and what was the hypothesis that you wanted to address? Dr. Paul Ridker: Sure, Greg. So first of all, my thanks to the AHA and the Circulation for publishing this paper, we always want to support the AHA, and we're delighted to be here today for these podcasts. The field of omega-3 fatty acids has been a complicated one for a long time. Epidemiology suggested that, fish consumption would lower cardiovascular risk, and there was a number of trials done. And my friend and colleague here at the Brigham, Deepak Bhatt, was the lead of a very big trial, called REDUCE-IT. Some 8,000 plus patients who received EPA alone, and they got a terrific result. A 25% reduction in their primary endpoint. And this was a New England Journal paper, back in 2019 or so. But another friend of mine, Steve Nicholls, ran another large trial of a combination of eicosapentaenoic acid, or EPA, plus docosahexaenoic acid that's DHA called STRENGTH. And that one showed, really, no benefit. And so, there's been some controversy out there. In any event, when Deepak and his colleagues published their original paper, they said it's interesting, because they got this big risk reduction, but it wasn't apparently due to the triglyceride lowering of the drug. And so, my interest, as many people know, has largely been in inflammation biology. And so we said, well maybe we should just do a test. Well, we said, we'll measure a number of biomarkers that we know were associated with atherosclerosis, some inflammatory, some with coagulation. And so, that was the core hypothesis, was simply to look at some other markers, and see what we might learn. And sometimes, you learn things that you didn't expect. And I think, that goes to the heart of what complicated clinical trials are all about. And I'd also say perhaps, what the roles of surrogate endpoints are, as compared to hard clinical endpoints, and things that make this whole field kind of interesting. Dr. Greg Hundley:           Right. Very nice, Paul. So you mentioned REDUCE-IT, so describe a little bit more for your study. What was the study population, and what was your study design? Dr. Paul Ridker: We were fortunate enough to work with REDUCE-IT investigators, to use their biobank. They had put together, again, it's 8,000 plus patients. I think, it was two thirds secondary prevention, one third primary prevention. And when they received the combination of EPA and DHA, as I said earlier, they had about a 25% reduction in the risk of their primary endpoint, which was cardiovascular death, nonfatal AMI, nonfatal stroke, coronary revascularization, and the like. What we did is, we basically said, "Okay, since the mechanism was uncertain, why don't we go ahead and measure a series of biomarkers?" Things that a lot of us are interested in, homocysteine, LPLa, oxidized LDL, my own interest in inflammation. We measured, IL-1β, we measured, IL-6, we measured CRP. We measured another molecule, Lp-PLA2, that people have been interested in. And the hypothesis, of course, was to see what the drug did, as compared to the comparator did. And the findings were interesting to us, in that, to simplify them, the actual icosapent ethyl arm didn't do much to most of those biomarkers, very little change. But the mineral oil comparator arm had some small to modest effects on all those biomarkers, all of which went up again. Now, some of these effects are pretty small, two to 3% for things homocystine, LPLa. Others were moderate, 10 to 20% increases in oxidized LDL, Lp-PLA2. And the inflammatory markers went up about 25%, sometimes, even a little more. So it's complicated. It's important to point out, that these changes on an absolute scale are relatively small. On a percent scale, they're different. The REDUCE-IT investigators themselves, to their credit, had earlier published that, they saw some increase in LDL cholesterol as well, about 10, 11% in those who had received the mineral oil comparator. So it's not exactly what we thought we were going to find, I guess, is the simplest way to express it. Dr. Greg Hundley:           Very nice. And so, describe for us just a little bit more, any differences in men and women, and what about age? Or for example, premenopausal, postmenopausal women. Dr. Paul Ridker: No, the effects were quite consistent across all various subgroups. It's a very large study. There were, again, 8,000 patients, lots of blood samples been drawn. And I should again, commend the REDUCE-IT investigators, for allowing us to do this work with them. And again, as I point out, sometimes you find things out that weren't what you expected. And the hard part, I was glad this got tossed over with Dr. Harrington, is sort to figure out well, what's it really mean? Because again, as a clinical trial list, I will say, my instincts are to trust the primary endpoint of the trial. That's what they did. They're going to go out and lower heart attacks and strokes. And then, here we are a couple years later, trying to figure out what the mechanism might be, and just came across some puzzling results. Dr. Greg Hundley:           Very nice. Well, next listeners, we're going to turn to the editor that actually processed this manuscript, Dr. Allan Jaffe. Allan, what drew you to this particular article? Dr. Allan Jaffe:   Well, I was asked to be a guest editor this week, by the Journal, because of some conflicts that were intrinsic to the editorial board. And since I have an interest in biomarkers, and had for a long time, it made perfect sense for me to become involved. I was particularly interested in this particular area, because I was aware that there were these two trials that had found different endpoints, and that there were some controversy as to what the mechanisms might be by which these effects could occur. And so I was pleased to get involved. And I think it's a compliment to the REDUCE-IT investigators, and to Dr. Ridker, that they were willing to put the data out there so that everybody could see it. And we could then begin to look. So it was of interest to me. I thought it was important to the field, to get really good reviewers who would be, make sure that the data that would eventually be published was clear, so that readers would understand it. And so that, at the end, we'd be able to at least, come to some conclusions that we could end up having an expert in clinical trials. And I thought about Bob Harrington, right from the beginning, might be able to comment on. Dr. Greg Hundley:           Very nice. Well, Bob he's setting you up here nicely, both Paul and Allan, to really help us put these results in perspective with other studies that have been performed in this space. What are your thoughts? Dr. Robert Harrington:   So first off, Greg, thanks for having me. And Allan, thanks for inviting me to review and comment on the paper. As both Allan and Paul have indicated, that I've spent the last 30 plus years doing clinical trials of all sizes. Very small, where we try to understand mechanisms, and very large, where what we're trying to understand is clinical outcomes. And I've been intrigued in this field, because of the inconsistency of the data across the field. Where in some trials, Paul had indicated this STRENGTH, there seemed to be no effect of omega-3 fatty acids, and in REDUCE-IT, there was quite a pronounced effect of the test agent. And so, when one sees discordance in a field, one tries to understand, well, why might that be? And so in the editorial, I took the position that, well, what are we trying to do in clinical trials? And in outcomes trials, we're trying to figure out what matters to patients. Do they live longer? Do they feel better? Do they avoid bad stuff happening to them? Like having to undergo revascularization procedure. So you're trying to do things that are really clinically meaningful, but that doesn't say that you're also not trying to understand mechanism. And as Allan said, there have been some questions raised. And so, trying to understand mechanism in the edit in trials can be quite useful, not just to understand that trial results, but to really form hypothesis for a field going forward. And so, I took the approach of, we learn things from different trials, and sometimes we learn things in the same trial. Meaning that, there's mechanistic work embedded in the large trial. One of the most famous examples of this, in the GUSTO trial 30 years ago, we learned through the mechanistic substudy, that it was rapid reprofusion TIMI-3 establishment of TIMI-3 flow, that really explained the difference between TPA and streptokinase. So I was very intrigued by how we might use these data to explore the results. And I find the findings fascinating, as Paul said. It is complicated, but it raises a really fundamental issue in clinical trials. There's an assumption in a placebo control trial, that because randomization is allowing you to balance everything, except for the randomized treatment groups, and therefore, that comparison has causal information in it. There's an underlying assumption that's really important. And that is, that the placebo is inert. That it has no biological effect of its own. Well, that assumption was violated here. The placebo is not inert in this clinical trial. Now, the investigators, I think to their credit, have said, "Well, this is small, probably doesn't matter." And that might be right, but it also may be wrong. And you can't just say, well, it doesn't matter, these are small effects. As Paul said, some of the effects are small, some are medium, some are large. So what explains it? And I made a point in the editorial, you could model all of this. If you get 5% of this, and 10% of this, and 20% of this, you could make some assumptions and say, well, the magnitude of the benefit was so great that it couldn't have been overcome by this. But that's just modeling, and there's uncertainty. So for me, as a trialist, and somebody who really believes in using evidence to guide practice and to guide public policy, I think there's uncertainty here. It's likely that the treatment effect is not as large as was observed, but how large is it? And how large is important? And how large might we want to consider to put into our practice guidelines? I think all of those open questions, particularly in a field where there is inconsistency across trials, in terms of the observation of the outcome. So my conclusion is, we need more work. We need another trial, if we really want to understand this. And we need to use an inert placebo, to really understand what the contribution was. I'd like nothing better to see that it didn't matter. But I can't say that it doesn't matter because I don't know. Dr. Greg Hundley:           Well, listeners, boy, we've got kind of some interest here in that an unexpected result. So Paul, it's nice doing an interview like this listeners, because each speaker sets up the next one. Paul, Bob is saying, well, what should we do next to clarify the results here? So maybe we'll go through each of you, and start with Paul. Just describe for us, what do you think is the next study that we need to perform? Dr. Paul Ridker: Well, Greg, it's a really interesting issue. We saw it, as authors, to write as neutral a paper as we could possibly write, and sort of do our academic job and say, here are the data. And I think we did it that way because, we don't really know what the interpretation should be. On the one hand, you have a very big beneficial result, which is great for patients. And there's a prior clinical trial called JELIS, which was open label, the same drug, and also got a large benefit. And we were trying to figure out mechanism. That being said, as Bob pointed out, I think what we stumbled into is some level of uncertainty. And the question is, how uncertain would it be, and does it matter in the big picture? Allan was interesting, because the Journal asked us to use the word comparator, rather than placebo. Now this was designed as a placebo controlled trial, but our paper uses the word comparator, because of the possibility, that as Bob Harrington points out, it may not be totally inert. So the writing of this was quite carefully done. I think, at the end of the day, my REDUCE-IT colleagues, who I have great respect for, and really worked terribly hard to do the main trial, understandably feel, that the trial would've showed, and I have a lot of sympathy for that, because it's the hard endpoints we should go with. On the other hand, I have sympathy with the idea that it never hurts to have more data. And if there could be a way to have a second trial, and I might change the population a little bit, maybe I'd do it in true primary prevention. This was one third primary prevention. My colleague, Joanne Manson had done her, she had a trial where they showed some potential benefit in the black populations. Maybe you might over sample some minority groups. But just the pragmatic issues here, make it tough to have a second trial. And so, uncertainty is just part of what we, as physicians, have to learn to live with. Dr. Greg Hundley:           Allan, turning to you. What do you think is a next study to perform in this space? Dr. Allan Jaffe:   Well, I think what Paul has said is correct. That it would be very hard to generate enthusiasm funding for a large trial. But it might not be nearly as difficult to begin to explore the effects of the mineral oil comparator, versus the active agent, versus perhaps, another potential placebo, and see over time what happens in primary prevention patients, as a way of beginning to put some context around what these results might mean. So for example, it could turn out that, the active agent actually kept the values from rising as they normally would've, and mineral oil had no effect at all. Alternatively, mineral oil may well have been a negative. It had a negative effect. And I think, those are the sorts of questions that could be explored reasonably in the short term, without doing another multimillion dollar randomized trial. Dr. Greg Hundley:           And Bob, your thoughts. Dr. Robert Harrington:   Well, and I mentioned this in the editorial, Greg. I didn't make my recommendation lightly. I know that these trials are expensive. I know these trials take a great deal of time, a great deal of energy. And I know that the REDUCE-IT investigators worked enormously hard over the years to get this done. So I don't say tritely, "Oh, just do another trial." But if you think about the magnitude of the public health issue here, there are millions of people to who this kind of therapy might apply globally. And so, shouldn't we be more certain than less certain, if we want to include it, for example, in ACC/AHA guidelines? I would say, the answer to that is yes. And so, I think of it as, okay, let's make some assumptions. Let's assume, that the effect that was observed in JELIS and REDUCE-IT, is the true effect. That's ground truth. Well, there are different study designs one might think about, from an analytic perspective, using Bayesian statistics, as opposed to frequency statistics. One might think about an intense interim analysis plan, to understand where the data are going, and be able to pull in the prior data for evaluation. I would advise getting a smart group of people together, who spend their lives thinking about trials in the atherosclerotic space, and the REDUCE-IT team is pretty darn good, and say, "How could we do this efficiently?" I do think, there's enough uncertainty that it would be ethical, from an equipoise perspective, to include high risk patients in a second evaluation, because we do have uncertainty. And if we really want to nail this down, I think we could look at high risk patients with hypertriglyceridemia, and try to use some interesting design issues, and some interesting analytical issues, to try to reduce the sample size, lot of attention in interim analyses, to try to answer the question. I'd like, as I said, nothing better to say, "Oh look, REDUCE-IT was the truth." This next trial is consistent. That'd be, to me, a terrific outcome of this. On the other hand, if you said to me, "Well, the effect's not 25%, it's more in the 15% range." Well, maybe then we think about how we apply it to our patients a little differently, maybe a little more cautiously. So I don't make the recommendation lightly, as I said, but I do think that there are some conversations that could be had, being respectful of the effort and the expense that goes into these kind of things. To try to answer the question efficiently. Dr. Greg Hundley:           Very nice. Well listeners, we want thank Dr. Paul Ridker, from Brigham and Women's Hospital, Dr. Bob Harrington from Stanford University, Dr. Allan Jaffe, from the Mayo Clinic, for bringing us the results of a substudy of the REDUCE-IT trial, that assessed a variety of serum biomarkers, pertaining to systemic inflammation, and highlighting uncertainty around the mechanism regarding the efficacy of icosapent ethyl, that's been used previously for primary or secondary prevention of cardiovascular events. And next listeners, we are going to move to our second feature discussion and review some data pertaining to microbleeds in the central nervous system, during and after TAVR procedures. Welcome listeners, to our second feature discussion on this August 2nd. And we are going to explore some of the world of TAVR and its potential complications. And we have with us today, Dr. Eric Van Belle, from Lille, France. And also, Dr. Manos Brilakis, from Minneapolis, Minnesota. Welcome gentlemen. And Eric, we'll start with you. Can you describe for us a little, the background information that you use to assemble and construct your study, and describe, or list for us, the hypothesis that you wanted to address? Dr. Eric Van Belle:           Yes. Thanks a lot for the question. So we knew for many years, that some of the complication of the TAVR procedure relate to the brain. And it has been described by many others, that there were some complication in the brain of patient undergoing TAVR. And there was no previous investigation on potential bleeding or microbleeding in this population. And on the other side, there are previous publication on, of course, initially chronic microbleeding, in patient with some of, let's say, disease in the brain, but also, a possibility of acute microbleeding. And especially, in some interesting population relating to the TAVR feed, that is patient with valve disease, patient with endocarditis, or patient with assist device. In this population, microbleedings, acute microbleeding, have been described. And what is interesting, if you look at all these populations, these are population in which the Von Willebrand factor has been impacted and modified, and could be one of the reason of the microbleeding. And one of the similar feature of the patient with aortic stenosis that undergo TAVI, or TAVR, that are patient with indeed also, this kind of Von Willebrand disease. So if we put everything together that is previously, we only looked at antibody complication in those population, and that Von Willebrand disease, which is present in patient with aortic valve stenosis, could promote a bleeding, in particular, bleeding in the brain. We decided to look at the potential appearance of microbleeding, in patient undergoing TAVR procedure. Dr. Greg Hundley:           Very nice. And Eric, can you describe for us, your study design, and who was your study population? Dr. Eric Van Belle:           Yes. So basically, the study population is a basic population of patient undergoing TAVI. Just to make sure that one of the difficulty of this study, was to conduct and perform an MRI, a brain MRI, before the procedure, and as short as possible after the procedure, within three days, which is logistically challenging. And also, to make sure that we keep most of the population to undergo the MRI, we had to exclude patient with a high risk of pacemaker, or patient with pacemaker that could not undergo the MRI. But basically, without this, it's just a regular population. And if we indeed, compare to some of the previous work I was mentioning, about describing the acute MRI, it was important for us to make sure, or to be as sure as we could get, that indeed, this microbleeding, if we observe them, could be related to the procedure. And it means that, the MRI, after the procedure, should be done as short as possible. And also, that an MRI, a baseline MRI, should be performed. Because we know, that in this population, you could have some microbleedings also observed before starting the procedure. Dr. Greg Hundley:           So a cohort study design where MRIs are performed before, and then very soon after, TAVR procedures. So Eric, what did you find? Dr. Eric Van Belle:           So what we observed, the first thing that we confirmed was indeed, that in this population of that age, that is patient around 80 years old, when we do the baseline MRI, you find in about one out of four patients already, some microbleedings. And this was expected, and it is very similar to what is expected in this kind of population. But what was indeed more striking, that when we repeated the MRI after three days, we observed another 23% of patient with a new microbleedings that were observed. This is indeed the most important observation. What was also important that, the patient with microbleedings, and the location of the microbleedings, were not related to the cerebellum brain, because indeed we could observe some cerebellum arise in this population, as it is expected. And there was no relation between the two. So it's also, an important observation, suggesting that this microbleeding are not hemorrhagic transformation of cerebellum brain, for instance. And we also observed that, the risk of microbleeding, or the chance to observe the microbleeding, was increased when the procedure was longer. And also, when the total duration of anticoagulation was longer, we also observed that, when the procedure was, when we used protamine at the end of the procedure, the risk of microbleeding was less. And also, importantly, the status of the Von Willebrand factor, and indeed, an alteration of the multimer of Von Willebrand factor, was also associated with the risk of microbleeding in this population. Dr. Greg Hundley:           Very nice. So in this cohort of 84 individuals, average age around 80, undergoing TAVR procedure, and about 50/50 men and women, you had several factors. Prior history of bleeding, amount of heparin, absence of protamine, all indicating a higher risk of these microbleeds. So very practical information. Well, Manos, you have many papers come across your desk. What attracted you to this particular paper? And then secondly, how do we put these results really, in the context of maybe other complications that can occur during or after TAVR procedures? Dr. Emmanouil Brilakis: Yes, thanks so much, Greg. And also, congratulations Eric, for a wonderful paper, and thanks for sending it to circulation. I think, with increasing the number of targets, as you know, TAVR now is becoming the dominant mode for treating severe aortic stenosis. Safety is of paramount importance. And even though there's been a lot of progress, we still have issues with the safety of the procedure. So understanding how can make it safer is very important. And I think, what was unique in this paper, again, congratulations for creating this study, is that it opens a new frontier. We worry about stroke. We're all very worried about the stroke, and having the patient have a permanent neurologic damage during the procedure. But there may be more to it than the classic embolic stroke. And I think, this study opens actually, a new frontier with the micro cerebral bleeds. Now we don't completely understand, despite the study, we don't understand the functional significance from this. And I think, that's one of the areas that will need further research. But I think, trying to understand what causes them, and preventing those microbleeds, would have a very important role in the future, for making TAVR even safer than it is. Dr. Greg Hundley:           Very nice. Well, Manos, you really lead us into the kind of the next question. So Eric, what do you see as the next study to be performed in this sphere of research? Dr. Eric Van Belle:           Again, to me, and to follow with the comment of Manos, we need to include, I would say, to solve two questions. We have to solve the question of, what could really impact these microbleedings. And what would be the impact of this microbleeding on the long term outcome of this patient? So it's means that we have to set, as part of the studies that we will design, potentially studies on aortic immolation. Or let's say for instance, we could investigate the role of protamine. It has been suggested that protamine could be something interesting, so it could be tested as part of a randomized study. But this means that, as part of such randomized study on the use of protamine, for instance, you would include a last cohort of patients with MRI after the procedure. And also, a long term follow of the neurological complication, which indeed, is the missing part of our current study. We would need to have a much larger cohort of patients, to be able to reconnect the neurological outcome to the MRI outcome, and also to include this. So let's say, for me, one of the studies we would be interested to perform, is to conduct a study on the use of protamine, which is very simple, randomized, yes or no, and includes brain MRI in this population, as a systematic investigation, which is difficult to conduct. You have to know that it's difficult to do, but it will be very important. And then, to look at the long term neurological outcome. Dr. Greg Hundley:           And I see, Eric, you mentioned the long term, because really in the short term, so within six months, you really didn't see any changes in neurological functional outcome or quality of life. So Manos, just coming back to you. What do you see is the next study that should be performed in this space? Dr. Emmanouil Brilakis: Yeah, I agree actually, with Eric. The next step is, this was an 80 patient study. Right? It's a very small preliminary data, all that opens a new system for evaluation, we're still a very small number of patients. So having a larger number of patients, I think for me, the key thing is to understand the connection. Does this actually cause neurologic symptoms? What does it mean having a microbleed? I think right now, we're still confused on the study. There was not really much impact on the neurologic status of the patient. So for me, the number one thing is, to understand how it impacts the patient's quality of life, the neurologic status. Perhaps more sensitive studies, neurocognitive studies, to understand exactly how it impacts. And then after doing that, I agree with Eric, if this is a bad, something really bad, then we can find different ways to prevent them from happening. Protamine is one of them during the procedure time, and not be a very feasible one. Or it could be interesting to see if different valves, for example, have different propensity for causing those microbleeds. Dr. Greg Hundley: Very nice. Well listeners, we want to thank Dr. Eric Van Belle, from Lille, France, and also, our own associate editor, Dr. Manos Brilakis, from Minneapolis, Minnesota for bringing this very important study, highlighting that one out of four patients undergoing TAVR has cerebral microbleeds before the procedure. And then, after the procedure, one in four patients develop new cerebral microbleeds. And then, procedural and antithrombotic management, and persistence of acquired Von Willebrand factor defects, were associated with the occurrence of these new cerebral microbleeds. Well, on behalf of Carolyn and myself, we want to wish you a great week, and we will catch you next week On the Run. Dr. Greg Hundley:           This program is copyright of the American Heart Association 2022. The opinions expressed by speakers in this podcast are their own, and not necessarily those of the editors, or of the American Heart Association. For more, please visit ahajournals.org.

Episode 36 A Gluten Free Podcast Today's episode is a ‘5 in 5' with Health Advocacy Officer, Penny Dellsperger and Marketing Specialist, Emily Monaco from Coeliac Australia. What we'll cover: * Gluten Free Expo update * Membership Renewals * Coeliac Australia Interleukin-2 research update* Alternative testing using Interleukin-2/ September issue of The Australian Coeliac * Answering a question from the listeners: latest on testing children for coeliac diseaseAbout Coeliac Australia Coeliac Australia is the national registered charity supporting Australians with coeliac disease and associated conditions requiring a gluten free diet. They provide membership and a range of support and information services to enhance the lives of people with coeliac disease, raise vital funds for research and create awareness of coeliac disease and the gluten free diet within the medical profession, food services industry and the broader community. LinksTesting for coeliac disease in children Coeliac Australia Website Get in touchYou can find me on Instagram @a.gffamily or send an email to aglutenfreefamily@gmail.com You can also find me writing a regular column for The Australian Coeliac magazine under the title 'Gluten Free Dad' released quarterly for Coeliac Australia members. Disclaimer The content on this podcast is not a substitution for professional medical advice, it is only the opinion and experience of the show host. Please seek professional medical advice from a medically qualified professional before making any decisions about your health or diet.

This month on Episode 38 of Discover CircRes, host Cynthia St. Hilaire highlights original research articles featured in the Jue 24th, July 8th and July 22nd issues of the journal. This episode also features an interview with the 2022 BCBS Outstanding Early Career Investigator Award finalists, Dr Hisayuki Hashimoto, Dr Matthew DeBerge and Dr Anja Karlstadt.   Article highlights:   Nguyen, et al. miR-223 in Atherosclerosis.   Choi, et al. Mechanism for Piezo1-Mediated Lymphatic Sprouting   Kamtchum-Tatuene, et al.  Plasma Interleukin-6 and High-Risk Carotid Plaques   Li, et al. 3-MST Modulates BCAA Catabolism in HFrEF   Cindy St. Hilaire:        Hi, and welcome to Discover CircRes, the podcast of the American Heart Association's journal, Circulation Research. I'm your host, Dr Cindy St. Hilaire, from the Vascular Medicine Institute at the University of Pittsburgh. And today I'm going to be highlighting articles from our June 24th, July 8th and July 22nd issues of Circulation Research. I'm also going to have a chat with the finalists for the 2022 BCBS Outstanding Early Career Investigator Award, Dr Hisayuki Hashimoto, Dr Matthew DeBerge and Dr Anja Karlstadt.   Cindy St. Hilaire:        The first article I want to share is from our June 24th issue and is titled, miR-223 Exerts Translational Control of Proatherogenic Genes in Macrophages. The first authors are My-Anh Nguyen and Huy-Dung Hoang, and the corresponding author is Katey Rayner and they're from the University of Ottawa. A combination of cholesterol accumulation in the blood vessels and subsequent chronic inflammation that's derived from this accumulation drive the progression of atherosclerosis. Unfortunately, current standard medications tackle just one of these factors, the cholesterol. And this might explain why many patients on such drugs still have vascular plaques. In considering treatments that work on both aspects of the disease, meaning lipid accumulation and inflammation, this group investigated the micro RNA 223 or miR-223, which is a small regulatory RNA that has been shown to suppress expression of genes involved in both cholesterol uptake and inflammatory pathways in both liver and immune cells.   Cindy St. Hilaire:        The team showed that mouse macrophages deficient in miR-223, exhibited increased expression of pro-inflammatory cytokines and reduced cholesterol efflux compared with control cells. Overexpression of miR-223 had the opposite effects. Furthermore, atherosclerosis prone mice, whose hematopoietic cells lacked miR-223, had worse atherosclerosis with larger plaques and higher levels of pro-inflammatory cytokines than to control animals with normal levels of miR-223. These findings highlight miR-223's dual prompt, antiatherogenic action, which could be leveraged for future therapies.   Cindy St. Hilaire:        The second article I want to share is from our July 8th issue of Circulation Research and is titled, Piezo1-Regulated Mechanotransduction Controls Flow-Activated Lymph Expansion. The first author is Dongwon Choi and the corresponding author is Young-Kwon Hong, and they're from UCLA.   As well as being super highways for immune cells, lymph vessels are drainage channels that help maintain fluid homeostasis in the tissues. This network of branching tubes grows as fluids begin to flow in the developing embryo. This fluid flow induces calcium influx into the lymphatic endothelial cells, which in turn promotes proliferation and migration of these cells, leading to the sprouting of lymph tubules. But how do LECs, the lymphatic endothelial cells, detect fluid flow in the first place? Piezo1 is a flow and mechanosensing protein known for its role in blood vessel development and certain mutations in Piezo1 cause abnormal lymphatic growth in humans.   Cindy St. Hilaire:        This script found that Piezo1 is expressed in the embryonic mouse LECs and that the suppression of Piezo1 inhibits both flow activated calcium entry via the channel ORAI1, as well as downstream target gene activation. Overexpression of Piezo1, by contrast, induced the target genes. The team went on to show that mice lacking either Piezo1 or ORAI1 had lymphatic sprouting defects and that pharmacological activation of Piezo1 in mice enhanced lymphogenesis and prevented edema after tail surgery. Together, the results confirmed Piezo1's role in flow dependent lymphatic growth and suggest it might be a target for treating lymphedema.   Cindy St. Hilaire:        The third article I want to share is also from our July 8th issue and is titled, Interleukin-6 Predicts Carotid Plaque Severity, Vulnerability and Progression. The first and corresponding author of this study is Joseph Kamtchum-Tatuene from University of Alberta.   Excessive plasma cholesterol and systemic inflammation are contributing factors in atherosclerosis. While traditional remedies have been aimed at lowering patient's lipid levels, drugs that tackle inflammation are now under investigation, including those that suppress Interleukin-6, which is an inflammatory cytokine implicated in the disease. Focusing on carotid artery disease, this group conducted a prospective study to determine whether IL-6 levels correlated with disease severity. 4,334 individuals were enrolled in the cardiovascular health study cohort. They had their blood drawn and ultrasounds taken at the start of the study and five years later. This group found IL-6 was robustly correlated with and predicted plaque severity independent of other cardiovascular risk factors. This study also determined that an IL-6 blood plasma level of 2.0 picograms/mls, identified individuals with the highest likelihood of plaque, vulnerability and progression. This threshold value could be used to select patients who might benefit from novel IL-6 lowering medications.   Cindy St. Hilaire:        The last article I want to share is from our July 22nd issue of Circulation Research and is titled, Mitochondrial H2S Regulates BCAA Catabolism in Heart Failure. The first author is Zhen Li, and the corresponding author is David Lefer from Louisiana State University. Hydrogen sulfide, or H2S, is a compound that exerts mitochondrial specific actions that include the preservation of oxidative phosphorylation, mitochondrial biogenesis and ATP synthesis, as well as inhibiting cell death. 3-mercaptopyruvate sulfurtransferase, or 3-MST, is a mitochondrial H2S producing enzyme, whose functions in cardiovascular disease are not fully understood.   Cindy St. Hilaire:        This group investigated the global effects of 3-MST deficiency in the setting of pressure overload induced heart failure. They found that 3-MST was significantly reduced in the myocardium of patients with heart failure, compared with non failing controls. 3-MST knockout mice exhibited increased accumulation of branch chain amino acids in the myocardium, which was associated with reduced myocardial respiration and ATP synthesis, exacerbated cardiac and vascular dysfunction, and worsened exercise performance, following transverse aortic constriction. Restoring myocardial branched-chain amino acid catabolism, or administration of a potent H2S donor, ameliorated the detrimental effects of 3-MST deficiency and heart failure with reduced injection fraction. These data suggest that 3-MST derived mitochondrial H2S, may play a regulatory role in branch chain amino acid catabolism, and mediate critical cardiovascular protection in heart failure.   Cindy St. Hilaire:        Today, I'm really excited to have our guests, who are the finalists for the BCVS Outstanding Early Career Investigator Awards. Welcome everyone.   Hisayuki Hashimoto:   Thank you.   Anja Karlstaedt:          Hi.   Hisayuki Hashimoto:   Hi.   Matthew DeBerge:      Hello. Thank you.   Cindy St. Hilaire:        So the finalists who are with me today are Dr Hisayuki Hashimoto from Keio University School of Medicine in Tokyo, Japan, Dr Matthew Deberge from Northwestern University in Chicago and Dr Anja Karlstaedt from Cedar Sinai Medical Center in LA. Thank you again. Congratulations. And I'm really excited to talk about your science.   Hisayuki Hashimoto:   Thank you. Yes. Thanks, first of all for this opportunity to join this really exciting group and to talk about myself and ourselves. I am Hisayuki Hashimoto, I'm from Tokyo, Japan. I actually learned my English... I went to an American school in a country called Zaire in Africa and also Paris, France because my father was a diplomat and I learned English there. After coming back to Japan, I went to medical school. During my first year of rotation, I was really interested in cardiology, so I decided to take a specialized course for cardiology. Then I got interested in basic science, so I took a PhD course, and that's what brought me to this cardiology cardiovascular research field.   Matthew DeBerge:      So I'm currently a research assistant professor at Northwestern University. I'm actually from the Chicagoland area, so I'm really excited to welcome you all to my hometown for the BCVS meeting.   Cindy St. Hilaire:        Oh, that's right. And AHA is also there too this year. So you'll see a lot of everybody.   Matthew DeBerge:      I guess I get the home field advantage, so to speak. So, I grew up here, I did my undergrad here, and then went out in the east coast, Dartmouth College in New Hampshire for my PhD training. And actually, I was a viral immunologist by training, so I did T cells. When I was looking for a postdoctoral position, I was looking for a little bit of something different and came across Dr Edward Thorpe's lab at Northwestern university, where the interest and the focus is macrophages in tissue repair after MI. So, got into the macrophages in the heart and have really enjoyed the studies here and have arisen as a research assistant professor now within the Thorpe lab. Now we're looking to transition my own independent trajectory. Kind of now looking beyond just the heart and focusing how cardiovascular disease affects other organs, including the brain. That's kind of where I'm starting to go now. Next is looking at the cardiovascular crosstalk with brain and how this influences neuroinflammation.   Anja Karlstaedt:          I am like Hisayuki, I'm also a medical doctor. I did my medical training and my PhD in Berlin at the Charité University Medicine in Berlin, which is a medical faculty from Humboldt University and Freie University. II got really interested in mathematical modeling of complex biological systems. And so I started doing my PhD around cardiac metabolism and that was a purely core and computationally based PhD. And while I was doing this, I got really hooked into metabolism. I wanted to do my own experiments to further advance the model, but also to study more in crosstalk cardiac metabolism. I joined Dr Heinrich Taegteyer lab at the University of Texas in the Texas Medical Center, and stayed there for a couple of years. And while I was discovering some of the very first interactions between leukemia cells and the heart, I decided I cannot stop. I cannot go back just after a year. I need to continue this project and need to get funding. And so after an AHA fellowship and NIHK99, I am now here at Cedars Sinai, an assistant professor in cardiology and also with a cross appointment at the cancer center and basically living the dream of doing translational research and working in cardio-oncology.   Cindy St. Hilaire:        Great. So, Dr Hashimoto, the title of your submission is, Cardiac Reprogramming Inducer ZNF281 is Indispensable for Heart Development by Interacting with Key Cardiac Transcriptional Factors. This is obviously focused on reprogramming, but why do we care about cardiac reprogramming and what exactly did you find about this inducer ZNF281?   Hisayuki Hashimoto:   Thank you for the question. So, I mean, as I said, I'm a cardiologist and I was always interested in working heart regeneration. At first, I was working with pluripotent stem cells derived cardiomyocyte, but then I changed my field during my postdoc into directly programming by making cardiomyocyte-like cells from fiberblast. But after working in that field, I kind of found that it was a very interesting field that we do artificially make a cardiomyocyte-like cell. But when I dissected the enhanced landscape, epigenetic analysis showed that there are very strong commonalities between cardiac reprogramming and heart development. So I thought that, hey, maybe we can use this as a tool to discover new networks of heart development. And the strength is that cardiac reprogramming in vitro assay hardly opens in vivo assay, so it's really time consuming. But using dark programming, we can save a lot of time and money to study the cardiac transitional networks. And we found this DNF281 from an unbiased screen, out of 1000 human open reading frames. And we found that this gene was a very strong cardiac reprogramming inducer, but there was no study reporting about any functioning heart development. We decided to study this gene in heart development, and we found out that it is an essential gene in heart development and we were kind of able to discover a new network in heart development.   Cindy St. Hilaire:        And you actually used, I think it was three different CRE drivers? Was that correct to study?   Hisayuki Hashimoto:   Ah, yes. Yeah.   Cindy St. Hilaire:        How did you pick those different drivers and what, I guess, cell population or progenitor cell population did those drivers target?   Hisayuki Hashimoto:   So I decided to use a mesodermal Cre-driver, which is a Mesp1Cre and a cardiac precursor Cre-driver, which is the Nkx2-5 Cre and the cardiomyocyte Cre, which is the Myh6-Cre. So three differentiation stages during heart development, and we found out that actually, DNF281 is an essential factor during mesodermal to cardiac precursor differentiation state. We're still trying to dig into the molecular mechanism, but at that stage, if the DNF281 is not there, we are not able to make up the heart.   Cindy St. Hilaire:        That is so interesting. Did you look at any of the strains that survived anyway? Did you look at any phenotypes that might present in adulthood? Is there anything where the various strains might have survived, but then there's a kind of longer-term disease implicating phenotype that's observed.   Hisayuki Hashimoto:   Well, thank you for the question. Actually, the mesodermal Cre-driver knocking out the DNF281 in that stage is embryonic lethal, and it does make different congenital heart disease. And they cannot survive until after embryonic day 14.5. The later stage Nkx2-5 Cre and Myh6-Cre, interestingly, they do survive after birth. And then in adult stage, I did also look into the tissues, but the heart is functioning normally. I haven't stressed them, but they develop and they're alive after one year. It looks like there's really no like phenotype at like the homeostatic status.   Cindy St. Hilaire:        Interesting. So it's kind of like, once they get over that developmental hump, they're okay.   Hisayuki Hashimoto:   Exactly. That might also give us an answer. What kind of network is important for cardiac reprogramming?   Cindy St. Hilaire:        So what are you going to do next?   Hisayuki Hashimoto:   Thank you. I'm actually trying to dig into the transitional network of what kind of cardiac transitional network the ZNF281 is interacting with, so that maybe I can find a new answer to any etiology of congenital heart disease, because even from a single gene, different mutation, different variants arise different phenotypes in congenital heart disease. Maybe if I find a new interaction with any key cardiac transitional factors, maybe I could find a new etiology of congenital heart disease phenotype.   Cindy St. Hilaire:        That would be wonderful. Well, best of luck with that. Congratulations on an excellent study. Hisayuki Hashimoto:   Thank you.   Cindy St. Hilaire:        Dr DeBerge, your study was titled, Unbiased Discovery of Allograft Inflammatory Factor-1 as a New and Critical Immuno Metabolic Regulatory Node During Cardiac Injury. Congrats on this very cool study. You were really kind of focused on macrophages in myocardial infarction. And macrophages, they're a Jeckel Hyde kind of cell, right? They're good. They're bad. They can be both, almost at the same time, sometimes it seems like. So why were you interested in macrophages particularly in myocardial infarction, and what did you discover about this allograft inflammatory factor-1, or AIF1 protein?   Matthew DeBerge:      Thank you. That's the great question. You really kind of alluded to why we're interested in macrophages in the heart after tissue repair. I mean, they really are the central mediators at both pro-inflammatory and anti-inflammatory responses after myocardial infarction. Decades of research before this have shown that inflammation has increased acutely after MI and has also increased in heart failure patients, which really has led to the development of clinical efforts to target inflammatory mediators after MI. Now, unfortunately, the results to target inflammation after MI, thus far, have been modest or disappointing, I guess, at worst, in the respect that broadly targeting macrophage function, again, hasn't achieved results. Again, because these cells have both pro and anti-inflammatory functions and targeting specific mediators has been somewhat effective, but really hasn't achieved the results we want to see.   Matthew DeBerge:      I think what we've learned is that the key, I guess, the targeting macrophage after MI, is really to target their specific function. And this led us to sort of pursue novel proteins that are mediating macrophage factor function after MI. To accomplish this, we similarly performed an unbiased screen collecting peri-infarct tissue from a patient that was undergoing heart transplantation for end stage heart failure and had suffered an MI years previously. And this led to the discovery of allograft inflammatory factor-1, or AIF1, specifically within cardiac macrophages compared to other cardiac cell clusters from our specimen. And following up with this with post-mortem specimens after acute MI to show that AIF1 was specifically increased in macrophages after MI and then subsequently then testing causality with both murine model of permanent inclusion MI, as well as in vitro studies using bone marrow drive macrophages to dig deeper mechanistically, we found that AIF1 was crucial in regulating inflammatory programing macrophages, which ultimately culminated in worse in cardiac repair after MI.   Cindy St. Hilaire:        That's really interesting. And I love how you start with the human and then figure out what the heck it's doing in the human. And one of the things you ended up doing in the mouse was knocking out this protein AIF1, specifically in macrophage cells or cells that make the macrophage lineage. But is this factor in other cells? I was reading, it can be intracellular, it can be secreted. Are there perhaps other things that are also going on outside of the macrophage?   Matthew DeBerge:      It's a great question. First, I guess in terms of specificity, within the hematopoietic compartment, previous studies, as well as publicly available databases, have shown that AIF1 is really predominantly expressed within macrophages. We were able to leverage bone marrow chimera mice to isolate this defect to the deficiency to macrophages. But you do bring up a great point that other studies have shown that AIF1 may be expressed in other radio-resistant cell populations. I mean, such as cardiomyocytes or other treatable cells within the heart. We can't completely rule out a role for AIF1 and other cell populations. I can tell you that we did do the whole body knockout complementary to our bone marrow hematopoetic deficient knockouts, and saw that deficiency of AIF1 within the whole animal, recapitulate the effects we saw within the AIF1 deficiency within hematopoietic department.   Matthew DeBerge:      It was encouraging to us that, again, the overall role of AIF1 is pro-inflammatory after MI.   Cindy St. Hilaire:        I mean, I know it's early days, but is there a hint of any translational potential of these findings or of this protein?   Matthew DeBerge:      Yeah, I think so. To answer your question, we were fortunate enough to be able to partner with Ionis that develops these anti-sensible nucleotides so that we could specifically target AIF1 after the acute phase during MI. We saw that utilizing these anti-sensible nucleotides to deplete AIF1, again, within the whole mouse, that we were able to reduce inflammation, reduce in heart size and preserve stock function. I think there really is, hopefully a therapeutic opportunity here. And again, with it being, perhaps macrophage specific is, even much more important as we think about targeting the specific function of these cells within the heart.   Cindy St. Hilaire:        Very cool stuff. Dr Karlstaedt, the title of your submission is, ATP Dependent Citrate Lyase Drives Metabolic Remodeling in the Heart During Cancer. So this I found was really interesting because you were talking about, the two major killers in the world, right? Cardiovascular disease and cancer, and you're just going to tackle both of them, which I love. So obviously this is built on a lot of prior observations about the effects of cancer on cardiac metabolic remodeling. Can you maybe just tell us a little bit about what is that link that was there and what was known before you started?   Anja Karlstaedt:          Yeah. Happy to take that question. I think it's a very important one and I'm not sure if I will have a comprehensive answer to this, because like I mentioned at the beginning, cardio-oncology is a very new field. And the reason why we are starting to be more aware of cancer patients and their specific cardiovascular problems is because the cancer field has done such a great job of developing all these new therapeutics. And we have far more options of treating patients with various different types of cancers in particular, also leukemias, but also solid tumors. And what has that led to is an understanding that patients survive the tumors, but then 10, 20 years later, are dying of cardiovascular diseases. Those are particular cardiomyopathies and congestive heart failure patients. What we are trying, or what my lab is trying to do, is understanding what is driving this remodeling. And is there a way that we can develop therapies that can basically, at the beginning of the therapy, protect the heart so that this remodeling does not happen, or it is not as severe.   Anja Karlstaedt:          Also, identifying patients that are at risk, because not every tumor is created equally and tumors are very heterogeneous, even within the same group. To get to your question, what we found is, in collaboration actually with a group at Baylor College of Medicine, Peggy Goodell's group, who is primarily working on myeloid malignancies, is that certain types of leukemias are associated with cardiomyopathies. And so when they were focusing on the understanding drivers of leukemia, they noticed that the hearts of these animals in their murine models are enlarged on and actually developing cardiomyopathies. And I joined this project just very early on during my postdoc, which was very fortunate and I feel very lucky of having met them. What my lab is now studying here at Cedars is how basically those physiological stress and mutations coming from the tumors are leading to metabolic dysregulation in the heart and then eventually disease.   Anja Karlstaedt:          And we really think that metabolism is at the center of those disease progressions and also, because it's at the center, it should be part of the solution. We can use it as a way to identify patients that are at risk, but also potentially develop new therapies. And what was really striking for us is that when we knock down ACLY that in a willdtype heart where the mouse doesn't have any tumor disease, ACLY actually is critically important for energy substrate metabolism, which seems counterintuitive, because it's far away from the mitochondria, it's not part of directly ADP provision. It's not part of the Kreb cycle. But what we found is that when we knock it out using a CRISPR-Cas9 model, it leads to cardiomyopathy and critically disrupts energy substrate metabolism. And that is not necessarily the case when the mouse has leukemia or has a colorectal cancer, which upregulated in the beginning, this enzyme expression. And so we have now developed models that show us that this could be potentially also therapeutic target to disrupt the adverse remodeling by the tumor.   Cindy St. Hilaire:        That is so interesting. So one of the things I was thinking about too is we know that, I mean, your study is showing that, the tumor itself is causing cardiac remodeling, but we also know therapies, right? Radiation, chemotherapy, probably some immune modulatory compounds. Those probably do similar, maybe not exactly similar, but they also cause, adverse cardiac remodeling. Do you have any insights as to what is same and what is different between tumor driven and therapy driven adverse remodeling?   Anja Karlstaedt:          So we do not know a lot yet. It's still an open question about all the different types of chemotherapeutics, how they are leading to cardio toxicities. But what we know, at least from the classic anti-cyclic treatments, is right now at the core, the knowledge is that this is primarily disrupting cardiac mitochondrial function. And through that again, impairing energy provision and the interaction, again, with the immune system is fairly unknown, but we know through studies from Kathryn Moore and some very interesting work by Rimson is that myocardial infarction itself can lead to an increase in risk for tumor progression. And what they have shown as independent of each other, is that the activation of the immune system in itself can lead to an acceleration of both diseases, both the cardiac remodeling, and then also the tumor disease. We don't fully understand which drivers are involved, but we do know that a lot of the cardiomyopathies on cardiotoxicities that are chemotherapeutically driven, all have also metabolic component.   Cindy St. Hilaire:        Nice. Thank you. When I prepare for these interviews, I obviously read the abstracts for the papers, but I found myself also Googling other things after I read each of your abstracts. It was a rabbit hole of science, which was really exciting.                               I now want to transition to kind of a career angle. You all are obviously quite successful, scientifically, at the bench, right? But now you are pivoting to a kind of completely opposite slash new job, right? That of, independent researcher. I would love to hear from each of you, if there was any interesting challenge that you kind of overcame that you grew from, or if there was any bit of advice that you wish you knew ahead of time or anything like that, that some of our trainee listeners and actually frankly, faculty who can pass that information onto their trainees, can benefit from.   Anja Karlstaedt:          I think the biggest challenge for me in transitioning was actually the pandemic. Because I don't know how it was for Hisa and Matt, but trying to establish a lab, but also applying for faculty position during a major global pandemic, is challenging is not quite something that I expected that would happen. And so I think saying that and looking more conceptually and philosophically at this as, you can prepare as much as you want, but then when life just kicks in and things happen, they do happen. And I think the best is to prepare as much as you can. And then simply go with the flow. Sometimes one of my mentors, Dave Nikon, mentioned that to me when I was applying for faculty positions, it's sometimes good to just go with the flow. And as a metabolism person, I absolutely agree. And there are some things that you can do as a junior investigator.   Anja Karlstaedt:          We need to have a good network. So just very important to have good mentors. I was blessed with have those mentors, Peggy Goodell's one of them, Heinrich Taegtmeyer was another. And now with this study that we are publishing, Jim Martin and Dave Nikon were incredible. Without them, this study wouldn't have been possible and I would not be here at Cedars.   Anja Karlstaedt:          You need to reach out to other people because those mentors have the experience. They have been through some of this before. Even if they have never had a major event, like COVID-19 in their life before, because none of us had before, they had other experiences and you can rely on them and they set you then up for overcoming these challenges. And the other thing I would say, is put yourself out there, go and talk to as many people as possible or set conferences, present a poster, not only talks. Don't be disappointed if you don't get a talk, posters are really great to build this network and find other people that you probably wouldn't have encountered and apply for funding. Just again, put yourself out there and try to get the funding for your research. Even if it's small foundations, it builds up over time and it is a good practice to then write those more competitive grants.     Cindy St. Hilaire:        Dr Hashimoto, would you like to go next?   Hisayuki Hashimoto:   Just my advice is that, could be like a culture of difference, but in east Asia, like in Japan, we were taught to, do not disturb people, don't interrupt people and help people. But I realized that I wasn't really good at asking for help. After I am still not like fully independent, but I do have my own group and I have to do grant writing. I still work at the bench and then have to teach grad students, doing everything myself. I just realized it's just impossible. I didn't have time. I need like 48 hours a day. Otherwise, you won't finish it. I just realized that I wasn't really good at asking for help. So my advice would be, don't hesitate to ask for help. It's not a shame. You can't do everything by just yourself. I think, even from the postdoc, even from grad school, I think, ask for help and then get used to that. And then of course, help others. And that is the way I think to probably not get overwhelmed and not stress yourself. Science should be something fun. And if you don't ask for help and if you don't help someone, I think you are losing the chance of getting some fun part from the science.   Cindy St. Hilaire:        That's great advice. I really like that, especially because I find at least, I started my lab seven years ago now. And I remember the first couple months/year, it was extremely hard to let go, right? Like I taught my new people how to do the primary cell culture we needed, but I was terrified of them doing it wrong or wasting money or making too many mistakes. But you realize, you got to learn to trust people. Like you said, you got to learn to ask for help. And sometimes that help is letting them do it. And you doing, you're being paid now to write grants and papers. That's a big brain, you're not paid to do the smaller things. That's really great advice. I like that. Thank you. Dr DeBerge, how about you?   Matthew DeBerge:      So I guess towards a bit of life advice, I think two obvious things is one, be kind, science is hard enough as it is. So I think we should try to lift each other up and not knock each other down. And along those lines as the others have alluded to as well, one of the mantras we sort of adapted on the lab, is a rising tide raises all ships, this idea that we can work together to elevate each other's science and really, again, collaborate.   Towards the career side of things I'll just touch on, because I guess one thing I'll add, there's more than one path, I guess, to achieving your goals. I've been fortunate enough to have an NIH post-doctoral fellowship and had an AHA career development award, but I'm not a K99 recipient. Oftentimes, I think this is the golden ticket to getting the faculty job, so I'm trying to, I guess, buck trend, I just submitted an RO1. So fingers crossed that leads to some opportunity.   Even beyond academia, I'm not certain how much everyone here is involved in science Twitter, it's really become a thing over the last couple years, but I think, kind of the elephant in the room is that academia, it's really hard on the trainees nowadays to have a living wage, to go through this. I mean, I'm really excited to see my, fellow finalists here are starting their own groups and stuff, but for many, that's not the reality for many, it's just not financially feasible. So I think, kind of keeping in mind that there's many, many alternative careers, whether it's industry, whether it's consulting, science writing, etcetera, going back to what Dr Hash says, find what you love and really pursue that with passion.   Cindy St. Hilaire:        I think it's something only, I don't know, five to 10% of people go into or rather stay in academia. And that means, 90 to 95% of our trainees, we need to prepare them for other opportunities, which I think is exciting, because it means it can expand our network for those of us in academia.   Anja Karlstaedt:          I think right now it's even worse because it's about 2% of old postdocs that are actually staying and becoming independent researchers, independent or tenure track or research track. And I think I second, as what Matt said, because I play cello. I do music as a hobby and people always ask me if I'm a musician. And at the beginning I felt like, no, of course not. I'm not like Yoyo Ma. I'm just playing, it's a hobby. And then I, that got me thinking. I was like, no, of course you are because there's so many different types. And what we need to understand is that scientists, like you are always a scientist. It doesn't matter if you are working at Pfizer or if you are working at a small undergrad institution and you're teaching those next generation scientists, you are still scientist and we all need those different types of scientists because otherwise, if everybody is just a soloist, you are never going to listen to symphony. You need those different people and what we need to normalize beyond having those different career paths, is also that people are staying in academia and becoming those really incredible resources for the institutions and labs, quite frankly, of being able to retain those technologies and techniques within an institution. And I think that's something to also look forward to, that even if you're not the PI necessarily, you're the one who is driving those projects. And I hope to pass this on at some point also to my trainees that they can be a scientist, even if they're not running a lab and they become an Institute director and that's also critically important.   Cindy St. Hilaire:        There's lots of ways to do science. Thank you all so much for joining me today. Either waking up at 5:00 AM or staying up past midnight, I think it is now in Japan or close to it. So Matt and I kind of made it out okay. It's like 8:00 or 9:00 AM.   Matthew DeBerge:      Thank you.   Hisayuki Hashimoto:   My apologies for this time zone difference.   Cindy St. Hilaire:        I'm very glad to make it work. Congratulations to all of you, your presentations. I forget which day of the week they are on at BCVS, but we are looking forward to the oral presentations of these and congratulations to all of you. You are amazing scientists and I know I'm really looking forward to seeing your future work so best of luck.   Matthew DeBerge:      Thank you.   Hisayuki Hashimoto:   Thank you.   Anja Karlstaedt:          Thank you so much.   Cindy St. Hilaire:        That's it for the highlights from the June 24th, July 8th and July 22nd issues of Circulation Research. Thank you for listening. Please check out the CircRes Facebook page and follow us on Twitter and Instagram with the handle at CircRes and hashtag Discover CircRes. Thank you to our guests. The BCVS Outstanding Early Career Investigator Award Finalists, Dr Hisayuki Hashimoto, Dr Matthew DeBerge and Dr Anja Karlstaedt. This podcast is produced by Ashara Ratnayaka, edited by Melissa Stoner and supported by the editorial team of Circulation Research. Some of the copy text for the highlighted articles is provided by Ruth Williams. I'm your host, Dr Cindy St. Hilaire. And this is Discover CircRes, you're on the go source for the most exciting discoveries in basic cardiovascular research. This program is copyright of the American Heart Association, 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more information visit ahajournals.org.  

On this week's podcast, John Mandrola, MD discusses fish oil, America's heart health, pharmacists and prescribing and statins This podcast is intended for healthcare professionals only. To read a partial transcript or to comment, visit: https://www.medscape.com/twic I - Fish Oil - New Biomarker Data Add to Concerns Over REDUCE-IT Trial https://www.medscape.com/viewarticle/976490 - Effects of Randomized Treatment With Icosapent Ethyl and a Mineral Oil Comparator on Interleukin-1β, Interleukin-6, C-Reactive Protein, Oxidized Low-Density Lipoprotein Cholesterol, Homocysteine, Lipoprotein(a), and Lipoprotein-Associated Phospholipase A2: A REDUCE-IT Biomarker Substudy https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.122.059410 - Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia https://www.nejm.org/doi/full/10.1056/nejmoa1812792 - Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular RiskThe STRENGTH Randomized Clinical Trial https://jamanetwork.com/journals/jama/fullarticle/2773120 - Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: final results of the EVAPORATE trial https://academic.oup.com/eurheartj/article/41/40/3925/5898836 II - US Heart Health - New AHA Checklist: Only 1 in 5 Adults Have Optimal Heart Health https://www.medscape.com/viewarticle/976519 - Life's Essential 8: Updating and Enhancing the American Heart Association's Construct of Cardiovascular Health: A Presidential Advisory From the American Heart Association https://www.ahajournals.org/doi/10.1161/CIR.0000000000001078 - Status of Cardiovascular Health in US Adults and Children Using the American Heart Association's New "Life's Essential 8" Metrics: Prevalence Estimates from the National Health and Nutrition Examination Survey (NHANES), 2013-2018 https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.122.060911 III - Pharmacist Prescribing - Paxlovid Is Here: A Pharmacist's Prescribing Pearls https://www.medscape.com/viewarticle/973260 - Coronavirus (COVID-19) Update: FDA Authorizes Pharmacists to Prescribe Paxlovid with Certain Limitations https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-pharmacists-prescribe-paxlovid-certain-limitations IV - Statin Eligibility - New European Guidelines ‘Drastically' Reduce Statin Eligibility https://www.medscape.com/viewarticle/976715 - Statin Eligibility for Primary Prevention of Cardiovascular Disease According to 2021 European Prevention Guidelines Compared With Other International Guidelines https://jamanetwork.com/journals/jamacardiology/article-abstract/2793729 - Time to Revisit Using 10-Year Risk to Guide Statin Therapy https://jamanetwork.com/journals/jamacardiology/article-abstract/2793732 - Mendelian randomization studies: using naturally randomized genetic data to fill evidence gaps https://doi.org/10.1097/mol.0000000000000247 You May Also Like: Medscape editor-in-chief Eric Topol, MD, and master storyteller and clinician Abraham Verghese, MD, on Medicine and the Machine https://www.medscape.com/features/public/machine The Bob Harrington Show with Stanford University Chair of Medicine, Robert A. Harrington, MD. https://www.medscape.com/author/bob-harrington Questions or feedback, please contact news@medscape.net

Howie and Harlan discuss a concerning new COVID-19 variant, the discovery casting doubt on a major fish-oil study, and the need for new models of funding research. Links: “New Omicron subvariant Centaurus could be the most immune-evasive yet, expert warns” “Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia” “Effects of Randomized Treatment With Icosapent Ethyl and a Mineral Oil Comparator on Interleukin-1β, Interleukin-6, C-Reactive Protein, Oxidized Low-Density Lipoprotein Cholesterol, Homocysteine, Lipoprotein(a), and Lipoprotein-Associated Phospholipase A2: A REDUCE-IT Biomarker Substudy” Learn more about the MBA for Executives program at Yale SOM. Email Howie and Harlan comments or questions. 

Laila Marquez of Interleukin joins us in this episode to share how they are making medical procurement easier for hospitals in the Philippines. Laila will share how she hustled early in the medical sciences field that exposed her to a wide network in the medical industry. She will also share how she shifted careers in medical sales that led her to create Interleukin. Laila also shares the challenges she needed to overcome to get Interleukin off the ground all the way to how she was able to get funding for Interleukin.This episode is brought to you by PDAX. Join PDAX here: podlink.co/hustlesharepdaxFor show notes, go to hustleshare.comHustleshare is powered by Podmachine See acast.com/privacy for privacy and opt-out information.

How to Stimulate Your Vagus Nerve with a TENS DeviceUPDATED Vagus Nerve Stimulation Video with new Ear ClipsResearch Studies on Vagus Nerve and Brain (video)Vagus Nerve Stimulation "has been life-changing!" (video)BUY a TENS and EAR CLIPS: www.autoimmunedocpodcast.comThe Vagus Nerve is the primary nerve of the parasympathetic nervous system, and it has gained wild popularity lately in the scientific and biohacking, alternative wellness, and autoimmune disease communities. As the primary nerve of the PNS, the vagus is largely responsible for "pushing the brakes" on the stress response, the sympathetic nervous system. The vagus innervates the heart, lungs, liver, spleen, gallbladder, diaphragm, entire digestive tract, and more. It's two way nerve 'superhighway system' acts as the modulator of the "gut-brain connection", sending sensory signals upward from all of your organs and sending signals downward regulating stomach acid, enzyme, and bile release, digestive motility, and more, and back up to your brain. Decreased vagal tone is associated with both inflammatory digestive diseases as well as psychiatric diseases like depression and PTSD. The vagus also sends nerves to the spleen, and its activation blocks the release of Tumor Necrosis Factor Alpha (TNFa), and in the liver blocks Interleukin 6 release from Kuppfer cells, all through something called the Cholinergic Anti-Inflammatory pathway. The only place on the outside of the body that the vagus nerve travels is part of the ear, oddly enough, but the vagus nerve can be stimulated by acupressure or my preferred method which I talk about in the podcast - using an inexpensive TENS Device with an ear clip. The vagus nerve can also be stimulated by yoga, mediation, acupuncture, chiropractic, deep breathing, contrast showers, humming, gargling, and gagging, and I speak on all of these things in this episode!

Sauna questions answered with expert Dr. Rhonda Patrick: Infrared vs traditional saunas? Can sauna bathing lower the risk of dementia, heart disease, stroke, depression, and all-cause mortality? How exactly should we use saunas for optimal benefit (duration, frequency, temperature, etc.)? Dr. Rhonda Patrick is a cell biologist with a Ph.D. in biomedical science from the University of Tennessee Health Science Center and St. Jude Children's Research Hospital. Dr. Patrick is the Co-Founder of FoundMyFitness.com. View Dr. Rhonda Patrick's recent review article on saunas in Experimental Gerontology here: https://www.sciencedirect.com/science/article/pii/S0531556521002916   Subscribe to Dr. Patrick's YouTube channel here: https://www.youtube.com/user/FoundMyFitness?sub_confirmation=1   Interviewer: Kyle Allred, Physician Assistant, Producer, and Co-Founder of MedCram.com Topics covered: 00:00:00 - Intro to Saunas and Rhonda Patrick 00:01:04 - Summary of sauna health benefits (lowers dementia, cardiovascular, depression risk, etc.) 00:07:09 - A review article vs primary research and Dr. Jari Laukkanen 00:07:58 - More on cardiovascular benefits of sauna 00:10:48 - Does sauna use lower hypertension risk? 00:11:56 - Sauna use may improve fitness and endurance 00:14:48 - Can sauna use lower Alzheimers and dementia risk? 00:16:43 - What are heat shock proteins? 00:19:18 - Dr. Patrick's research on amyloid-beta 42 / heat shock proteins 00:20:30 - How Rhonda Patrick became interested in Saunas 00:22:20 - Endorphins, opiate receptors, depression, and sauna use 00:26:36 - Sauna associated with lower inflammatory markers 00:27:14 - Interleukin 6 (IL-6) and sauna use 00:29:20 - Brain-derived neurotrophic factor (BDNF) and neuroplasticity 00:32:01 - More cellular repair mechanisms (NRF2) and hormesis 00:34:00 - Eustress and intermittent fasting 00:37:38 - Sauna and muscle atrophy 00:39:54 - Excretion of heavy metals and toxins through sweat 00:41:58 - Heart rate variability and sauna use 00:43:30 - Sauna mimics moderate-intensity exercise 00:47:32 - What Rhonda Patrick does in the sauna 00:49:22 - Countries / cultures utilizing hyperthermia 00:51:34 - Infrared sauna benefits vs. traditional Finnish sauna (and waon therapy) 00:55:39 - Details about Rhonda Patrick's sauna routine (temp., duration, dry vs. humid etc.) 01:01:43 - Utilizing sauna to extend a workout 01:02:33 - Can a long hot shower or bath mimic sauna benefits? 01:03:27 - Hydration before and after sauna bathing 01:04:36 - Cold exposure after sauna use? 01:06:24 - How to tell if in the sauna for too long? 01:08:10 - Contraindications/people who shouldn't use sauna 01:12:28 - Continuous glucose monitors and sauna 01:14:25 - Limitations of current sauna research 01:18:06 - More on Finland and saunas 01:18:50 - More on heat shock proteins 01:19:46 - Closing thoughts FOLLOW DR. RHONDA PATRICK YouTube: https://www.youtube.com/user/FoundMyFitness?sub_confirmation=1 Twitter: https://twitter.com/foundmyfitness Podcast: https://open.spotify.com/show/5QjpaU0o1Q2MkVZwwG3y7d   MEDCRAM + MEDICAL PROGRAMS AND HOSPITALS: MedCram offers group discounts for students and medical programs, hospitals, and other institutions. Contact us at customers@medcram.com if you are interested. MEDIA CONTACT: Media Contact: customers@medcram.com Interview Produced and Edited by Kyle Allred with Daphne Sprinkle FOLLOW US ON SOCIAL MEDIA: https://www.facebook.com/MedCram https://twitter.com/MedCramVideos https://www.instagram.com/medcram   DISCLAIMER: MedCram medical videos are for medical education and exam preparation, and NOT intended to replace recommendations from your doctor. #Sauna #optimalheatlh #hottub

Cochrane is producing a growing series of reviews on the care of patients with COVID-19. In January 2022, we published a new review of a group of treatments called interleukin-1 blocking agents and we asked lead author, Mauricia Davidson from Cochrane France, to tell us about the findings.

Cochrane is producing a growing series of reviews on the care of patients with COVID-19. In January 2022, we published a new review of a group of treatments called interleukin-1 blocking agents and we asked lead author, Mauricia Davidson from Cochrane France, to tell us about the findings.

Laila Marquez is the CEO and Co-Founder at Interleukin.Interleukin is the leading healthcare platform provider for facilitating simplified procurement and customer management solutions. Interleukin is one of QBO's top 100 providing an e-commerce marketplace for the healthcare sector. Know more about bakit Interleukin?, their virtual marketplace for healthcare sector buyers and sellers, Taal volcanic eruption and the story behind Interleukin (nagkaubusan ng facemasks), and especially what they do during this time of COVID-19 pandemic.In this episode:00:45  Ano ang Interleukin?01:46  Why is the name Interleukin? :D04:15  Interleukin is building a virtual marketplace for healthcare sector buyers and sellers. Can you share more about this?06:03  "Medical purchasing made simple." How does Interleukin do this?09:45  Interleukin's inception was the Taal volcanic eruption last January 2020. What is the story behind Interleukin's birth?14:14  During this time of COVID-19 pandemic, how does Interleukin solve the problems of the medical industry?15:49  Congrats on the beta app launch last September 2021! Can you share more about the app?19:10  Interleukin also organized "Improving Healthcare through eCommerce" during PHSW2021. What are the main takeaways?22:20  What is the vision of Interleukin?23:35  If people want to know more about Interleukin, how can they get more information?INTERLEUKINWebsite: interleukin.coFacebook: www.facebook.com/interleukincoTHIS EPISODE IS SUPERPOWERED BYNutriCoach: www.nutricoach.comSTART UP PODCASTYouTube: www.youtube.com/c/StartUpPodcastPHSpotify: open.spotify.com/show/6BObuPvMfoZzdlJeb1XXVaApple Podcasts: podcasts.apple.com/us/podcast/start-up-podcast/id1576462394Facebook: www.facebook.com/startuppodcastphPatreon: www.patreon.com/StartUpPodcastPHBuy Me a Coffee: www.buymeacoffee.com/startuppodcastCREDITSIntro and outro thanks to Terence Boydon: wyrmpres.wordpress.comThis episode is edited by the team at: tasharivera.com

WHO在12月7日更新對於Omicron的了解 https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19—7-december-2021 流行病學 在南非從11月第二週開始確診就有上升，11月29日到12月5日通報了62021例，比前一週增加了111%。檢測陽性率也從1.2%增加到22.4%。 從11月中開始主要在豪登省開始的群聚主要是在大學學生之間。 而鄰近的非洲國家也有疫情上升的情形：包括史瓦帝尼 (1990%); 辛巴威 (1361%); 莫三比克 (1207%), 納米比亞 (681%)和賴索托 (219%). 這些國家的疫苗完整覆蓋率皆很低，從納米比亞的12.1%到賴索托的26.7%。南非自己則是25.2%。 目前不確定疫情上升的原因，這可能和變種病毒的散布，增加檢測量，放鬆公衛措施還有疫苗覆蓋率低都有關。非洲外，在某些其他國家也有報告到上百例的Omicron案例。目前已經在57個國家都有確認案例，但多半地域主要流行的還是Delta，目前還很難對於Omicron會不會影響全球的新冠流行病學做出確切結論。 傳染力 雖然似乎有證據表明Omicron可能比其他變種具有生長優勢，但尚不清楚這是否會轉化為傳染力增加。歐洲疾病預防控制中心以模型預測，如果目前1%的感染是由Omicron引起的，若他有Delta 2.2倍的傳染力，可能到2022年1月1日他會佔新增感染的50%以上。若有Delta 1.3倍的傳染力，則需要到2022年3月1日。 目前有許多正在或計劃進行的流行病學研究，包括詳細的群突發調查、接觸者追踪和家庭傳播研究，將有助於增加我們對其傳染力的理解。 疾病嚴重程度 目前僅有極有限的資料，這使得評估疾病嚴重程度的是否有變化非常有挑戰性。截至12月6日，在 18 個歐盟國家確認且有嚴重程度的所有212例確診病例皆是無症狀或輕症。而南非本週因新冠住院的人數增加了82%（從 502 人增加到 912 人），但目前不確定Omicron的比例。即使疾病嚴重程度相同或低於Delta，如果更多人被感染，預計住院人數會增加。並且在病例發生率增加和死亡人數增加之間是存在存在時間差的。 對於Omicron的臨床狀況還需要更多資訊，WHO鼓勵各國為住院患者數據的收集和共享做出貢獻。 再感染的風險 南非當地已經自然感染者大概佔60~80%，成人完整疫苗注射則僅有35%。初步發現自然感染針對Omicorn保護力降低可以再感染，因此在南非還是可以造成流行。接下來應該繼續研究打疫苗者突破感染的機率，還有雖然再次感染是否會比較不容易重症。 對疫苗的影響 需要更多資料。進行中的研究包括對先前接種過疫苗或感染過的人的中和抗體研究，以及疫苗有效性研究，將有助於增加我們對免疫逃逸的理解。 對診斷工具的影響 針對PCR，S-gene target failure (SGTF)可以做為疑似Omicron的指標。但還是需要定序確認，因為Alpha還有一部份的Gamma還有Delta也有可能有此現象。 針對抗原快篩，因為多半是偵測N蛋白的構造，初步評估不會受影響。 對治療的影響 Interleukin-6 Receptor Blockers 和類固醇應該是會有效的。其他還需要更多資料。 結論 對於Omicron很多還是未知的，接下來幾週應該更多資訊會出來。 Omicron變異或是好事？專家：像感冒可加速終結疫情 https://news.ltn.com.tw/news/world/breakingnews/3754307 Omicron變種病毒走向 李秉穎：一個症狀可以看出感冒化 https://udn.com/news/story/120940/5942736 南非當地於12月4日發布的臨床狀況初步觀察 Tshwane District Omicron Variant Patient Profile - Early Features https://www.samrc.ac.za/news/tshwane-district-omicron-variant-patient-profile-early-features Early data from South Africa hints Omicron variant may cause less severe Covid, but more research is needed https://www.statnews.com/2021/12/04/omicron-covid19-south-africa-data/ Omicron變種病毒懶人包 傳染力 重症 疫苗有效性 要打加強針嗎？ https://linshibi.com/?p=39815 小額贊助支持本節目： https://pay.firstory.me/user/linshibi Powered by Firstory Hosting

In Episode #42, Dr. Jill interviews Bob Miller on IL-6: Everything you need to know about this cytokine: The Good, The Bad, and the Ugly.