Hour 1: Union Pacific is facing so much theft of cargo trains that companies like Amazon are using other methods to deliver products. Boris Johnson and his staff held holiday parties while the rest of Britain was locked down and couldn't leave their homes by law.
Ray Cardello is here with his daily podcast for January 3, 2022. Episode 5 of Season 8 How do you get to be so privileged you are above the law? Ray is a member of the team and a contributor to The Liberty Loft. His writings can be viewed by visiting The Liberty Loft at www.thelibertyloft.com
01: Chris Rea - My baby told me (Blue Guitars 11 - 60s & 70s,2005)02: Duane Allman – Goin'down slow (anthology I, cd 1)03: Boo Boo Davis – Snake remix (remixes, 2010)04: Nick Moss – Georgia redsnake (Privileged, 2010)05: Jimmy Bowskill –rattle shake snake (Live, 2010)06: Magic Slim – Living in my Neighbourhood (Highway is my home, 1999)07: Joe Bonamasa – Nightlife (Black Rock, 2010)08: Mike Griffin – Fifth of Whiskey and a case of the blues (Gimme what I commin', 1993)09: Whitesnake ,Brian Knight-W-Lawrence Scott-Mickey Moody - Take This Hammer (VA - Blues Legends - Vol. 5 - Screamin' The Blues ,1995)10: Barbara Lynn - Lynn's Blues (VA - Blues Guitar Women - Disk1 , 2005)11: Dirty Sweet – American Spiritual (American Spritual, 2010)12: Erik Hovey –Ask the Stars (Recyceld souls, 2009)13: Luther Guitar Jr Johnson – Mother in law blues (Luthers's Blues , 1976)14: Sonny Landreth – Pine Grove Blues (blues attack , 1982)
On this Wednesday episode of THE POLITICRAT daily podcast: You just have to listen to this episode. It's the case of a man in Minnesota who in April 2021 fled police, assaulted police, and lived to tell about it. He wasn't even so much as touched. Omar Moore tells the story. December 22, 2021. Please get involved! Call President Biden on the WH comments line: 202-456-1111 and call U.S. senators at 202-224-3121 or 202-225-3121. Tell the Senate to pass the John Lewis Voting Rights Advancement Act and the For The People Act. FREE: SUBSCRIBE NOW TO THE BRAND NEW POLITICRAT DAILY PODCAST NEWSLETTER!! Extra content, audio, analysis, exclusive essays for subscribers only, plus special offers and discounts on merchandise at The Politicrat Daily Podcast online store. Something new and informative EVERY DAY!! Subscribe FREE at https://politicrat.substack.com Buy podcast merchandise (all designed by Omar Moore) and lots more at The Politicrat Daily Podcast Store: https://the/politicrat.myshopify.com The Politicrat YouTube page: bit.ly/3bfWk6V The Politicrat Facebook page: bit.ly/3bU1O7c The Politicrat blog: https://politicrat.politics.blog PLEASE SUBSCRIBE to this to this podcast! Follow/tweet Omar at: https://twitter.com/thepopcornreel
OH, JADI ITU ANAKNYA DONATUR KAMPUS? Punya orang tua dengan jabatan yang tinggi tuh rasanya gimana sih? Apakah menyenangkan atau justru malah membawa beban? Trus gimana sama mereka yang anak tunggal dan menanggung ekspektasi keluarganya? Di episode kali ini, Home Rules akan membahas tentang privilege seorang anak. Penasaran? Yuk dengerin episode terakhir Tata di Home Rules bersama (special guest) Viona, malam ini pukul 20.30 WIB, hanya di Spotify dan Anchor kesayangan kamu~
We not only have eternal life if we are born again but we can rule and reign with Christ, in which His word gives us assurance in the work He's doing in us and will complete it because He's the author and finisher, it not being up to us.
A new MP3 sermon from BibleWay Church is now available on SermonAudio with the following details: Title: Saints, Ruling and Reigning Are Privileged to have Assurance of Their Salvation Part Subtitle: Assurance, Security of believe Speaker: Elder Emerson Jackson Sr Broadcaster: BibleWay Church Event: Bible Study Date: 12/12/2021 Bible: Isaiah 32:1-20; 1 John 3:1-5 Length: 58 min.
A new MP3 sermon from BibleWay Church is now available on SermonAudio with the following details: Title: Saints, Ruling and Reigning Are Privileged to have Assurance of Their Salvation Part Subtitle: Assurance, Security of believe Speaker: Elder Emerson Jackson Sr Broadcaster: BibleWay Church Event: Bible Study Date: 12/12/2021 Bible: Isaiah 32:1-20; 1 John 3:1-5 Length: 58 min.
This message explains the many privileges the nation of Israel received from God. In spite of having these blessing that no other nation had, they did not believe in Jesus. The Apostle Paul will explain how God sovereignty planned Israel's response to these privileges to show His plan - promises did not fail.
2:1 Thus saith the LORD; For three transgressions of Moab, and for four, I will not turn away the punishment thereof; because he burned the bones of the king of Edom into lime: 2:2 But I will send a fire upon Moab, and it shall devour the palaces of Kirioth: and Moab shall die with tumult, with shouting, and with the sound of the trumpet:
Caring Sister Association are a collective of women with aim of educating young girls and women to be great leaders and role models.Caring Sisters is a 501(c)(3) NGO. All Contributions are tax deductible. Website: www.caringsisters.org Instagram: caringsisters Twitter: _CaringSisters Email: firstname.lastname@example.org Hosted by: RIFLEX ► SUBSCRIBE NOW TO SITM: https://www.youtube.com/c/SitMPodcast ________________________ Stuck in The Middle features Entrepreneurs, Innovators, Creatives of African descent. Hear stories, ideas, experiences, & advise on breaking barriers weekly.
Joe Budden Yells At Chance The Rapper About His Privileged Career Is @chancetherapper really independent? @JoeBudden doesn't seem to think so. And he has a compelling argument. But, what does @joebudden know about being an independent artist? He was signed his entire career. Just like there are levels to being a signed artist, there are levels to being an independent artist. Independent artist can be someone who is doing everything in their bedroom by themselves to someone who is signed to an independent label that doesn't have any major label affiliation. Chance falls in the middle. He is signed to himself, but, through is father he had a bunch of high-profile relationships (@barackobama) that helped him tremendously. This oversimplifying of independent artistry needs to stop. THIS SHIT IS HARD AND AIN'T FOR EVERYBODY. Some of ya'll need to sign a record deal. Because if you don't want work 20 hours a day for the next 60 months, it's going to be tough for you to be a true independent artist. What do you think? Is @chancetherapper really independent? Sell My Course and I'll Pay You $1,000 Need more help developing the foundation for your brand so you can make $100,000 yourself? Click the link in and buy my “How To Market Your Music On Social Media” Course: www.group82university.com Do you want to make $5000/month from YouTube? Download this free tool Dorian uses to optimize his YouTube Channel to get the most views and revenue. It's FREE: https://www.tubebuddy.com/doriangroup82 Get Your Free Ebook: “How To Get 1 Million Streams On Spotify” by clicking the link below. It's FREE. https://www.group82music.com/linkinbio Follow Dorian on Instagram - https://instagram.com/doriangroup82?igshid=ful32lx6msk4 Subscribe to Dorian's YouTube for free daily content - https://youtube.com/c/DorianGroup82 Follow Dorian on TikTok: https://www.tiktok.com/@doriangroup82 Song: “Don't Sleep” by Dorian Spotify - https://open.spotify.com/track/0LBy5ZtXyq45yKkxyIo2cH?si=te--_7vzT1KtdEJyu186GQ Apple Music - https://open.spotify.com/track/0LBy5ZtXyq45yKkxyIo2cH?si=te--_7vzT1KtdEJyu186GQ Watch the full video on Youtube: https://youtu.be/ffG0wSheqXI --- Send in a voice message: https://anchor.fm/82pointsofview/message Support this podcast: https://anchor.fm/82pointsofview/support
SEASONED COMIC FINALLY ON STAGE & THE PRIVILEGED CHRIS CUOMO PLUMETS Humor is part of Chriss Buckley's DNA. She has lead a most colorful, challenging and spirited life and now audiences are reaping the benefits of her decision to become a pro comic and she and her guide dog are rocking NYC clubs giving audiences non-stop reasons to laugh. See Chriss in action: https://www.youtube.com/channel/UClqUcggvKtcbz8EWGxP79-Q Have Mark speak at your company, organization, conference and or retreat to increase morale, productivity, confidence and more with an in-person or virtual event. Mark also has riveting talks for students k-12 and college on: overcoming adversity, anti-bullying/anti-teasing, mental health, drugs/alcohol, celebrating differences, self-entitlement, life preparedness, senior send-off and more. All of Mark's talks are from his vast life experience. Reviews, videos, booking info and more at: www.markfarrellmotivation.com Email: email@example.com “Mark invigorated our conference! His genuine enthusiasm and professionalism, combined with an amazing topic, made for a marvelous presentation” Catharine Leahy - Speakers Chair Princeton University “Mark's willingness to use his disability to uplift others is both generous and remarkable. His message resonates with all of us who have worked hard to overcome life's adversities. If you're looking for a podium speaker, look elsewhere. Mark stays on the move and keeps the audience engaged. Thank you, Mark” Johnny Callebs KAPP Executive Director “Mark spoke to our high school students, teachers and volunteers and they are clamoring for him to return. Mark tells stories of his failures and triumphs with humor, compassion, unblinking honesty and with an energy that ignites the room leaving us connected to him and feeling a whole lot better about ourselves. Our time with Mark Farrell was unforgettable and joyful. This man is a treasure. Dennis Danziger, Venice, CA High School & POPS The Club Co-Founder
In a cloud environment, securing privileged identities and DevOps pipelines with privileged access requires special attention. In this session, Sean Deuby and Gil Kirkpatrick (Semperis Chief Architect) discuss Microsoft's current guidance for securing privileged access in Microsoft Azure with Thomas Naunheim (Cloud Architect at glueckkanja-gab AG). They cover how to design a secure foundation for privileged identities, including how to prevent privilege escalation by implementing a well-designed and delegated Azure RBAC model.
Growing up, Susan R. Madsen didn't look at her future beyond getting married and having a family, but after she started having children, Susan realized she was being called by God to get more education. She earned a masters degree and then obtained a doctorate and now works as a professor at Utah State University. Susan is also the founder and director of the Utah Women and Leadership Project and is a global thought leader on women and leadership. In this interview, Susan warmly opens up with insights from her own life, including how she learned to follow personal revelation, despite going against cultural norms. She also discusses her new book, A Future Only God Can See for You: A Guide for Teen and Young Adult Women on Preparing to Lead and how the book can help Latter-day Saint women of all ages lead out by doing what God prompts them to do. which is focused on helping young adult and teen Latter-day Saint has done extension work when she didn't feel full-time motherhood was the perfect fit her, she followed promptings to pursue her education, eventually earning a doctorate. Professor at Utah State University. Utah Women and Leadership Project director. 4 adult kids. raised in the church. Daughter of seminary teacher. A Future Only God Can See for You. Does a lot of writing mostly scholarly Does firesides but wanted to write something for women of the church. Started writing in March and it just came, even in a busy season. Wrote in 7 1/2 weeks. Felt very natural. Not sure how she did it. It wasn't just her. HF helped her. January - workbook coming out for reflection and journal. "the path that I've taken, it's absolutely from God." Education up to a doctoral work. Didn't know why but knew that it was preparation for the work God had for her to do. Upbringing - Father dominant, strict family. Loved her upbringing. Only daughter. Background has a ton to do with leadership skills. Took a lot responsibility. Distinct gender roles but also participated in sports. Adults let her lead at church and school. Taught piano lessons. Taught violin and filled in directing junior high orchestra. I didn't look at what my life would be after marriage. Did not plan on working. Stayed home and it was rough and got into depression. Started masters and loved it. Juggled. What type of personal revelation did you receive? How did you fight against the culture. Woman in Minnesota. Why are you getting education to raise children? "Because God told me to." Feels called. Privileged that education was mentioned in her patriarchal blessing. Knew because of the promptings she was doing what she was supposed to do. Head, heart and hands Intellectual, listen and feel, Your callings - you can be called to mother and other things at the same time. "And we have this culture often where women just if people tell them, " You did great on this," they're like shoving it aside. "Oh, not a big deal," or give all credit to somebody else. That's how we're socialized to do it. We do that sometimes because we're supposed to be humble, but humility is not being small. It's being teachable .And we can be confident. And we can use our voice and we can understand our strengths and we can be teachable at the same time." Have hope and courage. It's not either or. Focus of book is 15 and up. Women of any age will benefit. Used by parents, YW leaders, book club. Do exercises and activities. Sections - first on leadership. God needs you. quotes from church leaders. Why is it beneficial to have women leaders out there. prepare to lead overcome challenges Act on what you read What is the next step? Personal revelation. We all are different. Last chapter is the road less traveled. Tried to get who she was to fit in a box. Hard on self. Prayed for years and asked why she was made wrong. "And I prayed for years and asked Heavenly Father, 'Why did you make me wrong?' Until I realized that He made me right. He just made me different. He needs me with my unique, busy brain, with my passion for being the voice for people that need me to be a voice... to accept that I have His work and I need to do what He needs me to do, not what the culture [wants me to do], not what people are telling me. But what God and my relationship to God and my ability and work to hear His voice has been the thing that has guided me, especially as I've moved forward in my choices to do the advocacy work, the research work to move forward." How have you seen the Savior? So many points where you make decisions. I feel it almost every day. It feels right. I am connected. Learning to feel the Spirit and understand my strengths and myself, all of those things have helped me to trust myself. I trust that because I know He knows me and I know He needs me to do the work that only I can do. I trust that He needs me to do is more important than anything else. Amazon Cedar Fort Publishing Susan R. Madsen Google search Journal Questions Susan shared how another women once asked her why she was furthering her education while she had young children. Susan's simple response was, "Because God told me." What has God told you to do? Write about what you have personally learned by following what Heavenly Father has asked you to do, even when others' have judged your choices. During the interview, Susan pushed back on a question I asked and brought up how we sometimes have a mentality in the church that women's choices have to be "either or." How has this thinking affected your choices? What do you think you can do to change the "either or" culture around women's choices? By following the Spirit, understanding her strengths and figuring out how her brain works, Susan shared she has learned to trust herself and know God needs her and her unique strengths to do the work that only she can do. What is the Holy Ghost prompting you to do to learn to trust yourself and know that God knows you? What part of God's work is He saving just for you? Take some time to ponder and write your thoughts and feelings. Episode Links Read Susan's book: A Future Only God Can See for You Visit Susan's website susanrmadsen.com Join the Spiritually Minded Women email list: spirituallymindedwomen.com/prayerjournal/ Follow Spiritually Minded Women on Instagram: @spirituallymindedwomen Watch the podcast on YouTube: Spiritually Minded Women channel Visit the website for more resources: spirituallymindedwomen.com
Join us for a free, live book-to-film event with producers Kim Williams, Edwin Stepp, and Jonathan Burkhart on Thursday, December 2, at 8pm ET / 5pm PT (introvert-friendly! We won't be able to see you). Get your FREE ticket here: https://manuscriptacademy.com/book-to-film Want to meet a Hollywood producer, director or showrunner? Consult with them about your logline and pages here: https://manuscriptacademy.com/meet-hollywood-producers We had a wonderful event with producers Eric Mofford and Keith L. Shaw, and wanted to share with you the fun of live pitching. Over the next hour, you'll hear us reading the pitches everyone shared in the text chat—and learn about how a quick loglines summary of your work, along with a great concept, can open doors for you and your book-to-film dreams. OUR PANEL: Eric Mofford is a producer, line producer and budget consultant. He has been involved in over 150 film, television and web productions as well as numerous music videos and commercials. His credits include the Emmy-winning television series 24 and the iconic indie feature, Daughters of the Dust. Recently he served as Head of Production at Lone Wolf Media overseeing documentary projects for NOVA, Nat Geo, Animal Planet, Smithsonian Channel and PBS. Previously, he served as Head of Production at Lady of the Canyon where he produced projects such as the dramatic television pilot, Finding Hope, with Chris Mulkey, James Morrison, Darby Stanchfield and Molly Quinn; and the comedy documentary, We'll Always Have Dingle, shot in Kerry County, Ireland. He also served as Head of Production at Unconventional Media, producing the Emmy-nominated award-winning documentary, Houston We Have A Problem, and the live action portions for the EA video game, Need For Speed: Undercover, with Maggie Q. Mofford, a member of the DGA, has written and directed projects for Disney Interactive, Saban Entertainment, The Discovery Channel, Image America, United Way and TBS. He co-produced Senior Year, a 13-part PBS documentary series on high school. He has sold two feature film screenplays and has various projects in development. His dramatic blues film, Travelin' Trains, won a dozen national and international film festival awards and continues to play in art museum showcases over 25 years later. He has done schedules and budgets for both large studio productions and small indies and has shared that knowledge teaching numerous media workshops, both in the United States and internationally. Keith L Shaw is currently the Director of Operations for Jaigantic Studios. With over 27 years of experience as a Director, Producer and Assistant Director in both the television and the feature world, Keith has worked on projects for HBO, ABC, CBS, NBC, PBS, Comedy Central, YouTube Red and Teen Nick, to name just a few. Keith served as Director on Season 3 of the Sport-Docu, 3 Gun Nation and Director/Producer on the highly regarded Indie feature, Suicide Dolls. In 2006, Keith produced the feature film, Privileged for Glass House Productions. After a season on Curb Your Enthusiasm, Keith was accepted to the DGA's Director's Single Camera Program, and shortly after, directed on the PBS series, Madison Heights. Keith has filmed on many other projects across the United States and internationally, including Production Supervisor on ABC's, Oprah Winfrey presents The Big Give, 1st Assistant Director on NBC's, The Kenan Show, 2nd Unit-UPM/1st AD for the soon to be released Amazon Prime series, Jack Reacher and Field Producer for 5 seasons of The Apprentice. Keith also serves as Producer/Director and Co-Partner for Last Man Out Productions. The Company was recently nominated for an Emmy award for the Short Documentary, The Prohibition Chronicles: Echos of Point Place.
Tara Duggan is in for Niall A commission on Housing will be formally established in the coming weeks and will be responsible for drafting the wording for a referendum on constitutional right to housing Karl Deeter joins Tara to discuss this. He believes the whole thing is a "charade". See omnystudio.com/listener for privacy information.
My guest today is actress, singer, and TV personality, Lucy Hale. Lucy first became known for her roles in the series Bionic Woman and Privileged, then had her breakthrough starring role in Pretty Little Liars. She's also starred in films such as Scream 4, Dude, and Fantasy Island. Lucy ventured into music releasing her album […]
Woe to China. In this century she has butchered fifty million of her own people in the name of equality. Proud and haughty, she maintains an officially atheistic stance, persecuting the church while that church, nurtured by the blood of the martyrs, has in half a century multiplied fifty times.Woe to Russia. In the second decade of this century she embarked on a massive social experiment that resulted in the deaths of more than forty million people. She subjugated nation after nation, so certain was she that the tide of history was on her side. She became excellent at producing the “revolutionary man,” but could not produce the promised “new man” of Marxist thought, and so hid behind illusions and lies until her economic incompetence brought her down.Woe to Germany. Privileged to serve as home to some of the greatest Reformers, she became extraordinarily arrogant intellectually, and in this century started two world wars that wreaked death and havoc, including the horrors of the Nazis, on countless millions. Today she builds excellent BMWs but has a materialist soul, worshiping nothing greater than the deutsche mark.Woe to Great Britain. At one time ruler of one-quarter of the world's population; inheritor of some of the greatest Christian thought and literature ever produced, she became ever more proud and condescending to the nations she colonized and the people she enslaved. Having repeatedly squandered a heritage of the knowledge of God, she thrashes around directionless and degraded.Woe to Canada. She likes to think of herself as morally superior to her nearest neighbor, while hiding under the U.S. military umbrella. Sliding toward a moral abyss, her Supreme Court issues decisions that are as morally corrosive as any in the Western world, while the English-French factionalism drives toward enmity and breakup for want of courtesy and respect from both sides.Woe to the United States. She prides herself on being the only world power left, but never reflects on how God has brought low every world power in history. Her cherished freedoms, so great a heritage, have increasingly become a facade to hide and then defend the grossest immorality and selfishness. To the nation at large, no issue, absolutely none, is more important than the state of the economy.This is the reasoning of Amos. In Amos 1, he circles around the pagan neighbors, articulating the judgment of God. Here in Amos 2, he moves to Moab, Judah (“Canada”), and finally brings it home to Israel. Israelite audiences would begin with smug contentment during the early parts: how would they end up? And understand: the sequence of my “Woes,” above, could have been rearranged to end with any country—with your country. This podcast is designed to be used alongside TGC's Read The Bible initiative (TGC.org/readthebible). The podcast features devotional commentaries from D.A. Carson's book For the Love of God (vol. 2) that follow the M'Cheyne Bible reading plan.
In this episode I got to talk to Kristina Ann Read @readkristina and when I tell you I truly enjoyed myself and we had a ball...we really had a ball! We of course talk all things Bravo and housewives. We talk about the ladies of RHOBH (we see you Erika) and our ladies over in Potomac (do you only fellow spinners get Candiace?) And we issue a challenge to the listeners that is both terrifying and also extremely exciting! Here's a hint: swiper YES to swiping! I truly love Kristina and I know you will too!As always, shout out to my FAVORITE podcast producer @cbreezzzey
The title pretty much sums up the entire raging podcast. Aaron Rogers thinks that he is above the rules followed by every fucking body else in the entire NFL without consequence so he followed the advice or renowned covid expert Joe Rogan & is choking down the ivermectin like a misinformed tool. So lets see how the NFL chooses to punish it's White money making QB unlike how they stood or knelt with Colin Kaepernick because ASSHOLES. GET VACCINATED (save the ivermectin for the animals who need it) WASH YOUR HANDS. WEAR A MASK. DON'T BE A LYING SACK OF CRAP LIKE AARON ROGERS. subscribe, write a review and tell your friends.
The station recently had a Trunk-Or-Treat event in celebration of Halloween. And Jason used it as a moment to show off his privilege like never before! See omnystudio.com/listener for privacy information.
The station recently had a Trunk-Or-Treat event in celebration of Halloween. And Jason used it as a moment to show off his privilege like never before! See omnystudio.com/listener for privacy information.
Bishop Stephen Neill was one of the most prolific, accomplished, and fascinating Christian leaders of the global church in the twentieth century. Privileged to live in radically different cultural contexts over the course of his life, Neill was also a supremely gifted individual. He excelled by turns as a missionary, a bishop, an ecumenist, a professor, and a prolific author, all the while travelling around the world to share his tremendous knowledge of the world Christian movement with scholars, clergy and laypersons alike. This is the first complete biography of this influential figure, and builds on Daughrity's previous work Bishop Stephen Neill: From Edinburgh to South India (Peter Lang Publications, 2008). Worldly Christian: The Life and Times of Stephen Neill (Lutterworth Press, 2022) stands to become the authoritative word on a man who understood Christianity's changing contours better than most during the dramatic diversification that it underwent during his lifetime. Byung Ho Choi is a Ph.D. student in the Department of History & Ecumenics, focusing on World Christianity and history of religions at Princeton Theological Seminary. His research interest lies in Indonesia and the Muslim dominant regions of Southeast Asia, from the postcolonial approach to Christianity and the coexistence of various religions, including the study of Christianity and the Islamic faith in a Muslim dominant society that includes challenges of ethnic diversity. Learn more about your ad choices. Visit megaphone.fm/adchoices Support our show by becoming a premium member! https://newbooksnetwork.supportingcast.fm/biography
Bishop Stephen Neill was one of the most prolific, accomplished, and fascinating Christian leaders of the global church in the twentieth century. Privileged to live in radically different cultural contexts over the course of his life, Neill was also a supremely gifted individual. He excelled by turns as a missionary, a bishop, an ecumenist, a professor, and a prolific author, all the while travelling around the world to share his tremendous knowledge of the world Christian movement with scholars, clergy and laypersons alike. This is the first complete biography of this influential figure, and builds on Daughrity's previous work Bishop Stephen Neill: From Edinburgh to South India (Peter Lang Publications, 2008). Worldly Christian: The Life and Times of Stephen Neill (Lutterworth Press, 2022) stands to become the authoritative word on a man who understood Christianity's changing contours better than most during the dramatic diversification that it underwent during his lifetime. Byung Ho Choi is a Ph.D. student in the Department of History & Ecumenics, focusing on World Christianity and history of religions at Princeton Theological Seminary. His research interest lies in Indonesia and the Muslim dominant regions of Southeast Asia, from the postcolonial approach to Christianity and the coexistence of various religions, including the study of Christianity and the Islamic faith in a Muslim dominant society that includes challenges of ethnic diversity. Learn more about your ad choices. Visit megaphone.fm/adchoices Support our show by becoming a premium member! https://newbooksnetwork.supportingcast.fm/new-books-network
Bishop Stephen Neill was one of the most prolific, accomplished, and fascinating Christian leaders of the global church in the twentieth century. Privileged to live in radically different cultural contexts over the course of his life, Neill was also a supremely gifted individual. He excelled by turns as a missionary, a bishop, an ecumenist, a professor, and a prolific author, all the while travelling around the world to share his tremendous knowledge of the world Christian movement with scholars, clergy and laypersons alike. This is the first complete biography of this influential figure, and builds on Daughrity's previous work Bishop Stephen Neill: From Edinburgh to South India (Peter Lang Publications, 2008). Worldly Christian: The Life and Times of Stephen Neill (Lutterworth Press, 2022) stands to become the authoritative word on a man who understood Christianity's changing contours better than most during the dramatic diversification that it underwent during his lifetime. Byung Ho Choi is a Ph.D. student in the Department of History & Ecumenics, focusing on World Christianity and history of religions at Princeton Theological Seminary. His research interest lies in Indonesia and the Muslim dominant regions of Southeast Asia, from the postcolonial approach to Christianity and the coexistence of various religions, including the study of Christianity and the Islamic faith in a Muslim dominant society that includes challenges of ethnic diversity. Learn more about your ad choices. Visit megaphone.fm/adchoices Support our show by becoming a premium member! https://newbooksnetwork.supportingcast.fm/british-studies
Bishop Stephen Neill was one of the most prolific, accomplished, and fascinating Christian leaders of the global church in the twentieth century. Privileged to live in radically different cultural contexts over the course of his life, Neill was also a supremely gifted individual. He excelled by turns as a missionary, a bishop, an ecumenist, a professor, and a prolific author, all the while travelling around the world to share his tremendous knowledge of the world Christian movement with scholars, clergy and laypersons alike. This is the first complete biography of this influential figure, and builds on Daughrity's previous work Bishop Stephen Neill: From Edinburgh to South India (Peter Lang Publications, 2008). Worldly Christian: The Life and Times of Stephen Neill (Lutterworth Press, 2022) stands to become the authoritative word on a man who understood Christianity's changing contours better than most during the dramatic diversification that it underwent during his lifetime. Byung Ho Choi is a Ph.D. student in the Department of History & Ecumenics, focusing on World Christianity and history of religions at Princeton Theological Seminary. His research interest lies in Indonesia and the Muslim dominant regions of Southeast Asia, from the postcolonial approach to Christianity and the coexistence of various religions, including the study of Christianity and the Islamic faith in a Muslim dominant society that includes challenges of ethnic diversity. Learn more about your ad choices. Visit megaphone.fm/adchoices Support our show by becoming a premium member! https://newbooksnetwork.supportingcast.fm/history
Today on the Matt Walsh Show, the LGBT Netflix employees finally held their big walkout yesterday to protest Dave Chappelle and biological science. Only it wasn't big. Just a small assortment of people gathered for the demonstration. Many on the Right think that the pathetic turnout was a failure and an embarrassment for the Left. But I think they're missing the point completely. Also, the State Department celebrates national pronouns day, and Donald Trump launches his own social media platform. Is it on its way to wild success, or doomed to failure? Plus, the WNBA holds a parade in Chicago yesterday and you have to see the footage to really appreciate it. In our Daily Cancellation, I must cancel a Republican candidate for a political ad that you must be careful watching, as it may cause a fatal case of the cringe. You petitioned, and we heard you. Made for Sweet Babies everywhere: get the official Sweet Baby Gang t-shirt here: https://utm.io/udIX3 Subscribe to Morning Wire, Daily Wire's new morning news podcast, and get the facts first on the news you need to know: https://utm.io/udyIF Learn more about your ad choices. Visit megaphone.fm/adchoices
Not letting Covid-19 rip through our communities has left New Zealand in a privileged position compared to England and many other countries, says London-based Kiwi doctor Will Rush. Rush is an Emergency Medicine Consultant who is working at the Royal London Hospital, which has been hit hard by Covid-19. He's seen the worst of things on the front line. The father of three trained in Auckland and worked at Middlemore before shifting to the UK. He says the UK lost its grip on the pandemic right from the start and never had control, while New Zealand has remained in a far better position with Covid-19 due to a mixture of good luck and good management.
Hanna Scott: ‘Disheartening' rise in King County gun violence has already surpassed 2020's record toll // The Democrats' Privileged College-Kid Problem // We Are Republicans. There's Only One Way to Save Our Party From Pro-Trump Extremists. // RBG Criticized National-Anthem Protests, and Katie Couric Covered It Up // Rantz: Seattle school cancels Halloween over ‘equity,' says Black kids don't celebrate // Professor Not Teaching After Blackface ‘Othello' Showing // Jeff Bezos' Blue Origin successfully launches crew with William Shatner to space and back - AUDIO See omnystudio.com/listener for privacy information.
Bill Handel on the United States inching closer to progress in addressing the climate crisis. Also, how much do wildfires really cost California's economy. For some young and privileged people, the pandemic was an opportunity. And millennials have teamed up to fulfill the dream of homeownership.
Have you ever smelled an EO (entity oder)? Resigning is such a privileged thing. Owning a planet may a thing. Does transwoman mean you are a woman? The ridiculousness of men clothing in the 90s. The saying "History always repeats itself". What if we already living in the mist of that repeat now and have been for while.
Will Fitzgibbon from the International Consortium of Investigative Journalists was one of over 600 journalists who combed through financial data from international rich and powerful individuals to show how they have illicitly hidden their wealth. He joined the show to discuss. See omnystudio.com/listener for privacy information.
COVID Chaos in LGBTQ Communities – Podcast Interview with Matt Goldenberg Calming the Chaos welcomes Dr. Matt Goldenberg, Psychologist, Psychotherapist and Teacher. Dr. Matt is a popular trainer, teacher and psychotherapist in Olympia, Washington who focuses on helping, treating and honoring those in marginalized communities, especially those who live within LGBTQ+ communities. In this podcast, Dr. Matt talks about the COVID-19 Pandemic and why this pandemic has affected LGBTQ+ communities so profoundly. Dr. Matt also presents some ideas to help individuals in LGBTQ communities calm the chaos in a pandemic that is still ongoing. Introduction to Dr. Matt Goldenberg Who are you, Dr. Matt? Your Involvement in the LGBTQ Community Historical Trauma – The HIV / AIDS Epidemic Unique challenges / “chaos” to LGBTQ Individuals during the pandemic (all life domains) Historical Oppression of those who have HIV – where is the vaccine? Vaccine for COVID-19, but lack for HIV Systemic neglect of marginalized people Emotions of Fear, Disappointment, Anger and Hopefulness Politicization: (Dr. Fauci, etc.) Cis-Normative Inclusivity: Normalizes non-trans and hetero persons, and blocks the LGBTQ+ communities Cis-Hetero Normativity: Normalizes those whose biological gender is consistent with their expressed gender Funding for programs to help marginalized individuals in these populations. Social challenges – Groups Financial / jobs Intersectionality: There has been an impact on other marginalized populations, including black, Latino and other populations that intersect with LGBTQ+ Poverty and the working class Employment Discrimination Unfavorable working conditions or lack of being able to telework Other life domains Underground economics Bad working conditions = less ability to protect yourself from COVID Lack of protections for the working class Privileged people can protect themselves better Emotional trends Isolation and psychological stress Suicidality increases with those who refuse to honor pronouns Feeling excluded, unwanted, hopeless, suicidal Solutions: Tools and strategies for LGBTQ individuals to access when in chaos Sharing messages Respecting preferred pronouns Training on LGBTQ+ populations Training on strategies of inclusion Be aware of physical safety for vulnerable populations Support mental health and access to healthcare Empowerment strategies for vulnerable populations Social Support Dr. Matt Goldenberg's website: https://drmattgoldenberg.com/ US Trans Survey at https://transequality.org/issues/us-trans-survey Trevor Project at https://www.thetrevorproject.org/ Fedup Collective at https://fedupcollective.org/ Translifeline.org at https://translifeline.org/ Matt's Trainings and more! Other resources Trainings: https://drmattgoldenberg.com/trainings/ Supervision: https://drmattgoldenberg.com/supervision/ Counseling: https://drmattgoldenberg.com/counseling/ October is National LGBTQ+ History Month https://nationaldaycalendar.com/lgbt-history-month-october-2/ October 11 is National Coming Out Day https://en.wikipedia.org/wiki/National_Coming_Out_Day Closing: LGBTQ+ people are marginalized…AND…they are: Resilient / Strong Brilliant Creative / Rich in Knowledge Respectful
This month on Episode 28 of Discover CircRes, host Cynthia St. Hilaire highlights four original research articles featured in the August 20th and September 3rd issues of Circulation Research. This episode also features an in-depth conversation with Dr Scott Cameron from the Cleveland Clinic and Dr Milka Koupenova from the University of Massachusetts Medical Center about their study, SARS-CoV-2 Initiates Programmed Cell Death in Platelets. Article highlights: Gupta, et al. Electronic Cigarettes and Oxidized Lipids Bartosova, et al. Glucose Derivative Induced Vasculopathy in CKD Atmanli, et al. DMD Correction Attenuates Cardiac Abnormalities Ma, et al. Length Dependent Activation in Porcine Myocardium Cindy St. Hilaire: Hi, and welcome to Discover CircRes, the podcast for 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 will be highlighting articles presented in our August 20th and September 3rd issues of Circulation Research. I also will speak with Dr Scott Cameron from the Cleveland Clinic and Dr Milka Koupenova from the University of Massachusetts Medical Center about their study, SARS-CoV-2 Initiates Programmed Cell Death in Platelets. Cindy St. Hilaire: The first article I want to share is titled Electronic and Tobacco Cigarettes Alter Polyunsaturated Fatty Acids and Oxidative Biomarkers. The first author is Rajat Gupta and the corresponding author is Jesus Araujo from UCLA. E-cigarettes have surged in popularity in the last decade and while many people switching from traditional cigarettes to smokeless ones view the latter as a safe alternative to smoking tobacco, emerging data shows that E-cigarettes cause adverse effects such as oxidative stress, inflammation and endothelial dysfunction in users. The aerosols produced during vaping contain similar levels of reactive oxygen species, also called ROS, as the vapors of tobacco smoke. However, data on the extent to which E-cigarettes, E-cigarette ROS, influences cardiovascular health is lacking. Cindy St. Hilaire: To address this, this group recruited 32 chronic users of E-cigarettes, 29 chronic tobacco smokers, and 45 individuals that used neither and they measured their plasma levels of oxidative biomarkers. The team found both similarities and differences between the E-cigarettes and the tobacco users. For example, both smoking groups had increased plasma antioxidant capacity and decreased levels of oxidized linoleic acid compared with the levels seen in non-users, while arachidonic acid levels were raised in tobacco smokers and reduced in E-cigarette users. Overall, however, the biomarker levels were deemed to be intermediate for E-cigarette users between the non-users and the tobacco users. This study suggests that while E-cigarettes carry a lower health risk than tobacco, they are by no means safe. Cindy St. Hilaire: The second article I want to share is titled Glucose Derivative Induced Vasculopathy in Children on Chronic Peritoneal Dialysis. The first author is Maria Bartosova and the corresponding author is Claus Schmitt and they're from the University of Heidelberg. Diabetes, high blood pressure and obesity are risk factors for both cardiovascular disease and chronic kidney disease. Worse still, loss of kidney function and even dialysis itself are thought to exacerbate cardiovascular issues. In the case of dialysis, it's thought that high levels of glucose degradation products, or GDPs, in the dialysis fluids can promote the addition of sugar moieties to vascular proteins and lipids causing vascular damage. To investigate this theory, Bartosova and colleagues studied vascular tissue from children with chronic kidney disease receiving dialysis fluids with either high levels or low levels of glucose degradation products and compared these to tissues from children not on dialysis at all. Cindy St. Hilaire: Proteome and transcriptome analysis of the vessel tissues revealed that compared with patients or no to low GDP fluids, patients receiving high GDP fluids had higher levels of damaging glycation, increased transcription of genes involved in cell death, and decreased transcription of genes involved in cell survival and cytoskeletal reorganization. In line with these findings, vessels from high GDP patients displayed considerable evidence of damage, such as markers of apoptosis, skeletal disintegration and thickened intimas. The results confirmed GDPs can cause vasculopathy and suggest low GDP fluids should be used for dialysis patients. Cindy St. Hilaire: The next article I want to share is titled Cardiac Myoediting Attenuates Cardiac Abnormalities in Human and Mouse Models of Duchenne Muscular Dystrophy. The first author is Ayhan Atmanli and the corresponding author is Eric Olson from UT Southwestern. Duchenne Muscular Dystrophy, or DMD, affects one in 5,000 baby boys and is caused by mutations in gene for dystrophin, an architectural protein essential for muscle cell integrity. Patients display profound muscle degeneration and weakness, with respiratory and heart muscle dysfunction being a major cause for death. With the recent improvements in respiratory medicine that extend the lives of patients, this group now focused on heart dysfunction and specifically, whether gene editing could mitigate it. The team created induced pluripotent stem cells, or iPSCs, from Duchenne Muscular Dystrophy patient and his healthy brother and showed that gene editing from the DMD cells enabled their development into normal-looking cardiomyocytes with normal contractile function and calcium handling, equivalent to that seen in healthy control cells. The unedited DMD cells, by contrast, did not develop normally. For great clinical relevance, the team edited DMD cells after cardiomyocyte differentiation showing that this reduced their propensity for arrhythmia, compared with that of unedited cells. Cindy St. Hilaire: Lastly, the team provided evidence to suggest gene editing may improve heart abnormalities in mice with the same mutation. All together the results are proof of principle and support of the development of gene editing therapy as treatment for DMD. Cindy St. Hilaire: The last article I want to share is titled The Super-Relaxed State and Length Dependent Activation in Porcine Myocardium. The first authors are Weikang Ma and Marcus Henze and the corresponding author is Thomas Irving and they're from the Illinois Institute of Technology. Myofilament length-dependent activation or LDA is the fundamental mechanism coupling the force of the heart's contraction to it's proceeding diastolic volume. In other words, LDA ensures that the more the heart fills, the stronger it contracts. Studies of rodent hearts have given insights into LDA mechanics. However, how it operates in large mammalian hearts is unknown. Using structural and biochemical analysis of pig myocardial fibers, this group found that compared with small stretches of the fibers which were equivalent to small diastolic volumes, long stretches induced greater ATP turnover and greater numbers of cross bridges between myosin and actin filaments which are critical contractile machinery proteins. Cindy St. Hilaire: Myosin motors can be found in three stages, engaged with actin, unengaged in a disordered, relaxed state but ready to engage, or super-relaxed state where they are essentially switched off. The team showed that as muscle stretch increased, the amount of super-relaxed myosin motors diminished with more myosin motors becoming engaged to enable a stronger contraction. When the fibers were treated with a myosin motor inhibitor, these stretch effects were impaired. In revealing the mechanisms of myofilament length-dependent activation, this study provides a platform for studying cardiomyopathies in which this system goes awry. Cindy St. Hilaire: So today, Dr Scott Cameron from the Cleveland Clinic and corresponding author of the paper, Dr Milka Koupenova from the University of Massachusetts Medical Center, are both with me to discuss their study, SARS-CoV-2 Initiates Programmed Cell Death in Platelets. And this article is in our September 3rd issue of Circ Research and for full disclosure, the editor of Circ Res, Dr Jane Freedman is also an author on this manuscript. And for full double disclosure, I know Dr Koupenova quite well as we were both graduate students together back in the Ravid Lab at Boston University. However, the full Editorial Board selects these articles, not just me alone and this one is timely, novel, and an amazing story. So thank you both for joining me today. Milka Koupenova: Thank you for having us. Scott Cameron: Privileged to be here. Cindy St. Hilaire: So before we jump into the story that is your paper, can you give us a little bit of background about platelets? I know for years, I guess certainly before Katya's lab, I just thought of platelets as little nucleus-free particles that clot. But we know they are so much more than that. So why are they so important? And how do they function to do more than just stop a bleed? Milka Koupenova: So this is a great question, Cindy, and I am happy that you alluded exactly to the anucleated nature of platelets. So platelets are cell fragments. They're precursors in the bone marrow, the megakaryocyte. They are the second most abundant blood component after the red blood cells. And traditionally, platelets have been known, as what you pointed out, as these little units that change their conformation once there is some form of a problem with either the vascular, which we have a cut, they come together, they form this clot, and bleeding is prevented. But as we have learned perhaps in the past 20 years that platelets have a profound immune role during various immune processes and infections for different kind of microbes. And particularly relevant to this paper is that we understand that platelets have clearly a role responding to the viruses and activating the immune system. Cindy St. Hilaire: Yeah, and that was actually my next question. You and Jane are the world-leading experts on platelets and viral responses. So what was known about that interaction, I guess before we started looking at SARS-CoV-2, what was known about that platelet virus or even type of virus interaction? Milka Koupenova: So SARS-CoV-2 is a RNA virus--respiratory virus that we actually thought similarly to influenza that it mostly stays in the lower respiratory tract where it becomes problematic. However, from our work with influenza, when we saw that in certain patients you actually can detect the virus in platelet. In the beginning of the pandemic, we hypothesized that perhaps, in some people, the virus crosses over into the circulation. And based on our previous studies with influenza, we wanted to see if that indeed is the case. Hence we initiated a study here at UMass with the department head who is also on the paper, Dr Finberg, who is a leading expert in influenza and novel virus and we collected platelets from people to see if we can detect it. And so in the beginning, we were not able to detect SARS-CoV-2 in platelets. So we collected platelets from 17 patients and by qPCR with the primers that the CDC has, for whatever reason I couldn't detect anything. And I was really frustrated because previous reports have shown that about 25%, in some people even 35% of the study population, SARS can be detected. So very interesting observations. Milka Koupenova: I could see it by immunofluorescence but I couldn't detect the RNA. And the story goes, that I attended a seminar on SARS-CoV-2 and the person was actually referencing a company that started from University of Pitt where you are. Cindy St. Hilaire: Oh, very nice. Milka Koupenova: And they do specific, it's called amplicon ARTIC v3 sequencing so they enrich for the SARS-CoV-2 RNA and screen by sequencing. And when we did that, we were able to detect it in all patients. So I freaked out and I said, "Oh my gosh, something is wrong." Milka Koupenova: And so I sent plasma, and I sent controls, and actually RNA from the virus and you can see beautifully that it's only in platelets. Four of the 17 people actually had RNA in the plasma, but what you can observe in all these people is that the virus is fragmented, meaning it's not infectious. And in a way what this tells us, it suggests that platelets are super important in the removing it from the circulation and they probably serve as a dead-end for the virus because you cannot find virus coming out of platelets and the RNA is chopped off. So what I would say, is that platelets are these amazing little units that serve as removal of the viral RNA for these particular viruses, respiratory viruses that are RNA viruses. Cindy St. Hilaire: I think that is so interesting. So essentially, they're almost like little composters that are chewing it up and preventing it from spreading in the organism. Milka Koupenova: Yes, and as a result there is a response. Cindy St. Hilaire: Scott, probably the most common thing that people know with SARS is that loss of smell, or taste, and things like that, but really that doesn't send anybody to the hospital. So really what are the symptoms of COVID-19 patients that tie in with platelets specifically? I feel like that's a lot of things that we maybe in the public, or on Twitter, and things didn't hear as much about. So really what are those big symptoms linking COVID and platelets and what are the implications of platelet death in the pathogenesis of COVID? Scott Cameron: So certainly I think several investigators are in the world of now showing that platelets are hyperactivated, Robbie Campbell and Matt Rondina put a really nice paper in Blood last year showing that platelets are hyperactive and there are other investigators who found something similar. And so the question is, what are the symptoms of hyperactive platelets in the SARS-CoV-2 patient? So what most of them would find is shortness of breath or dyspnea, and when they present to the emergency department, and certainly we saw this, the oxygen saturation which should be in the mid to high 90s on room air on an average person, was quite often low. It was in the 80s or 70s, sometimes even the 60s. Scott Cameron: And the real surprising thing was those are patients that would normally immediately be on a ventilator, but yet they could still be talking to you. And so if you have a platelet that's activated in a hyperthrombotic condition, like SARS-CoV-2, COVID-19, and then that forms a blood clot, you have a situation where the amount of oxygen the patients taking in and the amount of oxygen you're measuring in the artery is quite discrepant and we call that the alveolar arterial or oxygen gradient. So if you've got lots of platelet plugs through the microvasculature, it's going to take up some space the oxygen should be using for diffusing in. And so that would be manifested as shortness of breath and that's certainly one of the biggest tip-offs that a patient might have a blood clot, particularly in the lung. Cindy St. Hilaire: Some of these symptoms of COVID-19 are really worse in patients with comorbidities, diabetes, obesity and heart failure. Are platelets central to kind of the pathogenesis of those disease or the symptoms of those diseases? I guess the root of my question is, why do the comorbidities of diabetes, obesity, and heart failure make COVID worse? Is it something about those disease states themselves or is there a role for platelet? Scott Cameron: That's a brilliant question, no one's ever asked that before. And as Dr Koupenova said, I'm a little bit biased too because I firmly believe that in different disease states, the disease educates the platelets so you've got a different platelets phenotype. So focusing on diabetes, we know the platelet phenotype is different in diabetic patients. We know that platelet reactivity seems to be higher through the P2Y12 receptor. In terms of obesity, it is true, we know that, and this has been published also, and we know that the platelet phenotype is hyperactive in a patient with obesity and so that tells me that, that's a comorbidity that might affect platelet function and also vice versa for that case. And then in terms of why is it affecting males more prominently and more severely than females, well one of the beefs, I guess, that I had is that we treat diseases in women the same as we do in men assuming that the platelet phenotype in disease must be the same, but that's absolutely not true. And that's actually a theme that we have in our lab right now, we know that the behavior of platelets, and how platelets are educated in diseases is not all the same in women as in men and I think it's a huge disservice that we really had to have a pandemic that would make that quite clear to us. Cindy St. Hilaire: You kind of hit onto something that's really, I think it's now becoming more recognized certainly in the cardiovascular field and that is so many studies are really only on male mice, or only younger or older men, and we are missing not only a huge patient population, but probably some really interesting biology that is distinct. Milka Koupenova: So expanding on that, we know that in platelets, the toll-like receptors, and we've looked at the expression of all 10 in a study that we published in ATVB in 2015, actually, significantly if you look at Farmingham Heart Study data and the expression of these toll-like receptors they are increased in women versus men. And also, an interesting observation that never got published, once upon a time when I was doing studies with TLR7 mice is that if you inject TLR7 agonists, male mice would have a higher level of reduced platelet count than female mice at the same time points, right? And at that time it wasn't published. Definitely there are differences, but I also want to extrapolate a little bit on what was said at the beginning. We have to understand that when it comes to these comorbidities, everything affects a unit that doesn't have a nucleus, right? And diabetes and obesity have the so called profound, chronic inflammation of cytokines, such as IL6, that keep circulating. These things have effect on platelets. So we have two responses, we have the environment that affects platelets and we have the direct response of the virus that affects platelets. And that cumulative response truly can exhaust them and once they become exhausted, once they release their contents, as we show in this paper, then you're compromising their function and you will be compromising taking out the virus from one side and from the other side you're going to be compromising the environment because all of the content that comes out from a unit that already has free form proteins, it exhibits a true insult on what's being surrounded. So these clots that form in the lung or the platelets that circulate they no longer can be resolved properly. Cindy St. Hilaire: Yeah. Milka Koupenova: It's a balance. Cindy St. Hilaire: Yeah, so really it's like destroying the platelet not only are you destroying the vacuum that has to suck up those particles, you're then just dumping a whole bunch of pro-inflammatory things on all of the endothelial cell vasculature that those platelets are nearby. Cindy St. Hilaire: Actually that was one thing that I thought you spent a decent portion of the discussion on, and that is the method by which the blood is collected really impacts the outputs you observe in quote unquote platelets. Can you talk about the importance of that because I think that's one thing, certainly as a PhD who's just like, "Oh, yeah. I'm just going to collect blood from my mice and do this thing," how critical is that point in the experiment, in the blood collection? Milka Koupenova: So I am very adamant when it comes to platelets for the blood to be drawn in citrate. And I have to say that a lot of the studies that you would see in the literature are done using EDTA blood or serum. They all have their importance. I'm not going to dismiss it, but if you want to truly measure what's inside in plasma, versus what's inside in platelets, or what's inside in any cell for that matter, you got to go for citrate. You have to be very careful not to shake the blood. You have to be very careful not to cool down the blood. So the nurses probably hated me because often I would be like, "You can't do this. You can't put it on ice. You can't warm it up to above certain degrees. Everything has to be controlled and done correctly." Milka Koupenova: And so I had done in the past studies in which I would take plasma from the same patient in EDTA, in citrate and then isolate the RNA, have my tech isolate the RNA, and we send it to a fragment analyzer, and you can see how much more RNA you will get in the EDTA plasma. I'm not even talking about serum. Milka Koupenova: Serum is a very different thing, then you're definitely going to get platelet content in it, in the serum, right? So it's important to distinguish that perhaps when you're getting EDTA plasma you are looking at a content that could have been inside in platelet and I can't stress enough that when it comes to these particular studies, citrate, dextrose, phosphate is your place to go and be. Cindy St. Hilaire: So in terms of translational potential, what do your findings suggest about future therapies or targets to investigate as therapy? And is modulating platelets a potential for combating viral infections or mitigating their severity? Milka Koupenova: Well, Scott and I actually talk a lot about that. Scott Cameron: That's right. Milka Koupenova: I personally would say, control the inflammation, never let it go to platelet. Let me back up a little bit, if you have to, you have to, right? But your go to method should be inflammation, if you don't get to the point that you need to control platelets then you're in a better place because it becomes very fickle. From everything that you hear me say, you push it to one side and the balance is destroyed. You deactivate platelets or inhibit platelets well, are they now not able to pick up the virus and then you're now having the virus circulating somewhere. Now, if you don't treat platelets that's also not good. So you're in the very fickle situation if you get to the point that you need to control the activation of platelets and there are trials currently that are trying to look at those things. Scott, I'm going to refer this a little bit more to you because you have done some interesting things with that particular point. Scott Cameron: No, it's a great question, Milka, and I think that as platelet biologists, nobody more than I wanted it to be true that platelets would be the ultimate target. I mean, clearly patients with SARS-CoV-2 have thrombosis, clearly platelets are activated, so should we inactivate them? That was the whole point of the RECOVERY trial and one of the benefits I'll tell you before I sort of go into that is, working in a large organization like the Cleveland Clinic and we have access to data and lots of it extremely quickly, and so because of that I of course could see how many patients were coming into our hospital with thrombotic events. And I could see what the independent predictors of thrombotic events was and it wasn't the platelet count, sometimes platelet count was low, sometimes it's high in the SARS-CoV-2 patient. And if you took those individuals that were on aspirin, comparing them to those that are not in a propensity match study, one of the things that we find is that aspirin doesn't seem to affect or improve mortality or the number of blood clots in the patient with SARS-CoV-2. Scott Cameron: We compared that to all non-steroidal anti-inflammatory medications that patients may have been taking also in a propensity match study just in case it was the mechanism action of the drug, rather than the drug itself, and we found that NSAIDs not only did not protect patients, but they were not necessarily harmful either, which was one of the things that came out at the start of the pandemic. Among, I'll add, the absence of evidence based medicine and a lot of cases where naturally people, including clinicians, were scared and so they were going off label and they were trying a lot of different medications with really not a shred of randomized controlled data. Scott Cameron: But now that we're 18 months into it, the first and biggest study that came back was the RECOVERY trial, which we were all waiting on, where patients were given aspirin and short term mortality was examined over an observational period of one month. And just like we found in a propensity match study, which is as close as you'll get to a clinical trial in a retrospective manner, the prospect of RECOVERY trial actually showed the curves were almost super imposeable, those that got aspirin versus those that didn't. So I think low dose aspirin clearly is not going to be enough for those patients, but I'll also add that over the observational period of one month they also didn't see a higher incidence of death in those patients. And I think Milka's point is really well taken that you have to remember that as well being an entity of thrombosis, platelets are immunological entities and so you've got to really consider should we be inhibiting them and if you are inhibiting them, I think the time point at which you should inhibit them is what we should examine, not just an all or nothing, inhibited or not. Milka Koupenova: It's just in our linear brains we prefer to think of it as one straight, linear pathway, but it isn't, and I think platelets are actually a great example of how many pathways are feeding into one tiny fragment and that particular blood cell is inducing this profound response during these infections. Cindy St. Hilaire: I think most people have heard that angiotensin-converting enzyme 2, also called ACE2 is the receptor of SARS-CoV-2. The virus itself uses it to bind and become internalized into the cell, but there's been some discussion or even some discrepancy of data as to whether platelets truly express ACE2 and if that is the means for the virus to enter the platelets. So can you share with us what is the current state of knowledge about that? Scott Cameron: Yeah, just as a segue of some of the things that Milka said, I think the preparation of your sample is part of the answer. If you draw in the incorrect tube, if you the tube is not completely filled, and the ratio of citrates to whole blood isn't correct you're going to have discrepant results. If you biomechanically activate the platelets by drawing through a short needle, in a small-bore needle for example, that's going to activate the platelets. If you cool them, it's going to activate them. But then also, depending on how you decide to separate them, we always washed platelets in my lab, we wash them two or sometimes three times, and I can tell you if you use flow cytometer we get one white blood cell for every 12,000 platelets. Scott Cameron: And some investigators might go one step further and they'll a CD45 depletion set, which is certainly important if you're studying RNA. But one of the issues, as you well know, a CD45 is also on the surface of platelets, so if you start with a low expressing protein and you CD45 deplete them, you are actually going to get a decrease in your platelet yields. I've seen it, I think Milka's seen it, various other investigators have, and you might find yourself at the threshold of what your antibody can detect. It's also variably expressed. If you look at even healthy individuals, some of them have almost none. So if you look at 10 individuals, you might actually find none, but then if you look at another 10, the amount of expression that we see is kind of all over the place. It's not like other receptors where one tends to express a certain amount and that's the way it is in health. ACE2 doesn't seem to be that way for whatever reason. Milka Koupenova: We were able to detect in some of the people by qPCR, but what was interesting is that from the three primers that I used there was never the same person who we were able to detect all three primers with for that receptor. That tells you that maybe they are changes of one base that is not enough for the primer to detect it, right? That becomes another possibility of not being able to detect. Milka Koupenova: And so I go to confocal microscopy where I use 100 lens and tons of hours in the microscope room, and Scott is completely right, it's really hard to see it particularly in healthy people. And it starts to pick a little bit more in people with cardiovascular disease or people with COVID that are old. So it's a bit complicated, but the important thing here is, besides the fact that we are detecting ACE2 and we're detecting proteins and I use controls, biological controls to prove that this is the case and it's not just an antibody problem, is that the virus will get picked up by platelets even if you don't have ACE2. That is the take home message from this paper is that the platelet has evolved various mechanisms by which is utilizes getting it inside. It is that important for this virus. This type of virus is not recirculating. In this case, what we observed is that the virus is attached to microparticles that are of platelet origin for that matter. Cindy St. Hilaire: So really what you're saying, what I'm hearing is the platelet is the superhero of the body. Milka Koupenova: Definitely. Absolutely. No bias, absolutely. Cindy St. Hilaire: Unbiasedly, it is a superhero. Well, Dr Cameron and Dr Koupenova, thank you so much not only for this amazing discussion, but for really an elegant, elegant paper that is really bringing to light the complex interaction between SARS-CoV-2 and platelets. So thank you so much for joining me and keep publishing amazing stories like this. Milka Koupenova: Thank you for having us. Scott Cameron: Thank you, an honor to be here. Thanks again. Cindy St. Hilaire: That's it for the highlights from August 20th and September 3rd 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 @CircRes and #DiscoverCircRes. Thank you to our guests, Dr Scott Cameron and Dr Milka Koupenova. 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 Cynthia St. Hilaire, and this is Discover CircRes, your on-the-go source for the most exciting discoveries in basic cardiovascular research. This program is copyright of the American Heart Association, 2021. 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, please visit ahajournals.org.
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Ariel Britt and host Livia Davis discuss ways to have tough conversations, increase internal awareness, and examine privilege as strategies for embedding racial equity in recovery services. This episode was originally released on January 25, 2021. Visit c4innovates.com, subscribe to receive newsletter and training updates, and follow us on Twitter, Facebook, LinkedIn, and YouTube for more resources to grow your impact. Learn More Safe Project Beauty in the Grit House of Pod Ken Hardy's Tasks of the Privileged and the Subjugated: read, watch and listen Iris Young's 5 Faces of Oppression Access a transcript of Embedding Racial Equity in Recovery Services