Podcasts about Mediated

At Google I/O 2026, Phillip sits down with Suresh Ganapathy, Senior Director of Product Management for Consumer Shopping at Google, to unpack the day's announcements: Universal Commerce Protocol's expansion into new verticals, agentic payments arriving in Gemini Spark, and the debut of Universal Cart. We trace what these foundational pieces mean for how a billion daily shoppers, and the merchants serving them, will operate in an agent-mediated economy. Enter the Delegation Era Key Takeaways: Universal Cart maintains shopper state across Search, Gemini, YouTube, and Gmail. The cart works on your behalf: tracking prices, flagging restocks, and catching product incompatibilities. Agent Payments Protocol's (AP2) tamper-proof contracts make agent purchases verifiable and accountable to shopper intent. Merchants remain seller of record, preserving customer relationships inside agentic flows. Gemini Spark becomes Google's first consumer agent with purchasing authority this fall. Key Quotes: "We're laying the foundational building blocks of agentic commerce." — Suresh Ganapathi "People come to shop at Google over a billion times a day, and we want to make sure that we're delivering the best experience to them when they do." — Suresh Ganapathi "We want to make it really simple for shoppers to enjoy the fun parts of shopping and then delegate some of these more tedious aspects to agents." — Suresh Ganapathi "Spark is the agent. AP2 is the payments protocol. Universal Cart is the ability for consumers to have less friction." — Phillip Further Reading: More on Google's AI play: Insiders: Google Solidifies Its Place in the AI Race More on agent-mediated commerce: Member Brief: Agentic Commerce and the eCommerce Site's New Existential Crisis Our 2026 Predictions: The Age of Autonomy Learn more about Google I/O Google's Universal Cart Announcement Our Links: Check out Future Commerce on YouTube Check out Future Commerce Plus for exclusive content and save on merch and print Subscribe to Insiders and The Senses to read more about what we are witnessing in the commerce world Listen to our other episodes of Future Commerce Have any questions or comments about the show? Let us know on futurecommerce.com, or reach out to us on Twitter, Facebook, Instagram, or LinkedIn. We love hearing from our listeners! Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

Christopher Miller, Chief Correspondent at the Financial Times in Kyiv, reports on the short ceasefire between Russia and Ukraine.

5. GUEST: Cliff May. Cliff May discusses historic Lebanon-Israel peace talks mediated by the US. He cautions that progress is limited as long as Hezbollah remains an armed Iranian proxy effectively turning Lebanon into an imperial colony. 52016

John 17:6-13,“I have manifested your name to the people whom you gave me out of the world. Yours they were, and you gave them to me, and they have kept your word. 7 Now they know that everything that you have given me is from you. 8 For I have given them the words that you gave me, and they have received them and have come to know in truth that I came from you; and they have believed that you sent me. 9 I am praying for them. I am not praying for the world but for those whom you have given me, for they are yours. 10 All mine are yours, and yours are mine, and I am glorified in them. 11 And I am no longer in the world, but they are in the world, and I am coming to you. Holy Father, keep them in your name, which you have given me, that they may be one, even as we are one. 12 While I was with them, I kept them in your name, which you have given me. I have guarded them, and not one of them has been lost except the son of destruction, that the Scripture might be fulfilled. 13 But now I am coming to you, and these things I speak in the world, that they may have my joy fulfilled in themselves.”John 17 is one of the most amazing chapters in the Bible because the entire chapter is a prayer of Jesus — and it's a prayer he prays for us. We know this because of what Jesus says in verse 20. He says to his Father:“I do not ask for these only [that's the eleven disciples], but also for those who will believe in me through their word [that's us, his church].”By the grace of God, we believe in Jesus through the gospel that has been passed down to us in the apostolic word (that's the New Testament!). So when Jesus prayed in John 17 — yes, the eleven disciples were right by his side and he prayed for them — but he also had us in mind.Which means: what Jesus prayed in John 17 he prays for us — and notice I'm saying “prays for us” in the present tense.For this to make sense, I think we need to understand something important about prayer itself. In Revelation 5, when the four living creatures and twenty-four elders bow down in worship to Jesus, John makes a curious statement about prayer. He says that each of these worshipers are holding “golden bowls full of incense, which are the prayers of the saints.”It's a minor detail on one hand, but it's also a clue that the prayers of God's people are collected. I think it tells us something about prayer that we can know by experience: it's that our prayers don't ever expire, but they accumulate.The more we pray, over time, those prayers shape us into a certain kind of person. The prayers themselves can change, in maturity and clarity, but basically we all become the kind of person who prays the way we do.Maybe a better way to say it is that our prayers stay with us. When we pray about something, we don't ever just ‘check the box' and move on — because prayer is not ‘one and done' sort of thing. The way we pray, even in private, gets represented by us everywhere we go. Everywhere we go, we go as persons who are praying a certain way.And we even talk this way as a church. A lot of times we'll say something like “Yeah, I'm praying about that” or “I'm praying for you” — we use the present tense. We understand that our prayers stay with us. That's true of us … and that's true of Jesus, like right now.I want you to know that the prayer Jesus prayed in John 17 is still operative. It's not a mere record of the way he prayed once upon a time. It's not left behind in the dust of history. But this is a prayer that reflects the heart of Jesus this morning. Jesus carries this prayer with him, and he wants all of this for us now like he wanted it when he first prayed it. We know the word of God is living and active! — I want you to know this prayer in the word of God is living and active!I want you to know that Jesus is praying this for you today!There are three things he's praying that I want to show you.1. Jesus is praying for us to be kept. I'm not sure what you think when you hear the word “kept” but it's got a rich biblical meaning. And it's really an image. For God to “keep you” means he holds onto you and cares for you. He doesn't let you go and he provides for what you need. That's what we hear in Psalm 121 when the psalmist says: The Lord is your keeper; the Lord is your shade on your right hand.The sun shall not strike you by day, nor the moon by night. The Lord will keep you from all evil; he will keep your life. (Verses 5–7)Or it's like when God says of his servant in Isaiah 42, verse 6:“I am the Lord; I have called you in righteousness; I will take you by the hand and keep you …” That's an image. He's saying: I'm looking out for you. I'm protecting you. I'm gonna get you where I'm leading you. In the New Testament, we see this in places like 1 Peter 1:5, “by God's power [we] are being guarded [or kept] through faith …” Or Jude 24, which we sing sometimes, “Now to him who is able to keep you … be glory!”Theologically, this idea of being kept is about endurance. It is part of a doctrine known as the “perseverance of the saints.” That doctrine teaches that those whom God truly saves he faithfully preserves. If you are in Christ, you will make it! That's the doctrine, and we see it in action in this prayer. Doctrine in ActionNotice first how Jesus describes who he's talking about. Jesus calls believers those whom the Father has given him. We can see that right away in verse 6. Jesus says, “I have manifested your name [Father] to the people whom you gave me out of the world. Yours they were, and you gave them to me …”Jesus says that's who he's praying for. Verse 9:“I am praying for them. I am not praying for the world but for those whom you have given me, for they are yours.”This is a big deal. Jesus is doubling-down on a distinction: there is the world here, and then there are those out of the world that the Father claims as his own and gives them to the Son.Where Are You?Here's an important question: How do you know where you are? Are you of the world? Or has the Father given you to Jesus out of the world?That's a good question. I was thinking about this the other day. I was on the road, sitting at red light, and there were seven cars at the intersection turning left in front of me, and I decided I would just look at the face of each person as they drove by. I think people are fascinating. So I'm looking at each person, and they're all different; they're all going somewhere; they all got stories, and I thought: “I wonder which of these people have been given to Jesus?” That one? That one? That one?Here's the thing: you can't really tell by just looking at people, but I know the answer: The ones who are given to Jesus are the ones who believe in him. That's what it means to keep Jesus's word in verse 6. Or, in verse 8, to “know in truth” who Jesus is. We're asking the wrong question if we're asking: “Have I been given to Jesus or not?”The question is: “Do you believe him?” If you believe in Jesus, you are given to Jesus, and if you are given to Jesus, you are kept by Jesus. Because he's praying for that. Right now. This means, for Christians in the room, we are gonna make it! We need to remind each other of this more often, especially in the face of hostility. Church, we will endure. We will make it through. Jesus is praying for us to be kept. 2. Jesus is praying for us to glorify him. This is a very simple sentence in verse 10, but I'd love for you to see it. Everybody help me out and find verse 10. Chapter 17, verse 10.“All mine are yours, and yours are mine, and I am glorified in them.”This is the first time Jesus has ever said this. Now he's talked about his glory before, at some key places in the Gospel. He opens verse 1 of this prayer asking the Father to glorify the Son so that the Son may glorify the Father. We saw that last week. Jesus is saying:Father, make me shine, so that you shine!Magnify me so that people see you! And Jesus is referring to the cross and resurrection. That is the most vivid revelation of God's heart! It's what the entire ministry of Jesus was been building toward — when Jesus was lifted up as our sacrifice and then raised from dead to defeat sin and death! Jesus is glorified in his cross and resurrection! He's told us that. But verse 10 is the first time Jesus has ever said that he's glorified in his disciples. It's a remarkable statement. Now Mediated Glory!Last week, Pastor David Mathis walked through “the story of Jesus's glory.” He showed us that Jesus has: Pre-world glory, Incarnate glory, Crucified glory, and Resurrected glory.Today, we add one more: Mediated glory. Now, like today — after his resurrection or because of his resurrection — Jesus shines through the work he does in his disciples. Including us.Because he's not here anymore, remember? But we are. That's what he says in verse 11 — Jesus is now in heaven with the Father, but we are here, with his Spirit. And that means that now we have become the living theater of his glory in this world. Jesus is now seen and heard, and known and loved, through the nature and witness of his church.That is how he is glorified in us. We might have the impression that to glorify Jesus means we must accomplish some grandiose thing; we might think we must do something super radical that gets people's attention — but that's not the case at all.We glorify Jesus, first, simply by the reality of who we are as believers. We trust him. We are born again to a living hope.I told you last week, church, we are living miracles. Our very being — and our being together — is because of the work of Jesus Christ. He is glorified in us by our existence.And then, also, he is glorified in us when we bear witness to him — when we join his mission to make his glory known. This part is astounding. …We get to really and truly display Jesus to others. We get to acknowledge him by our lifestyles, and give him in our relationships. We get to point to him and tell of him. Our Eager Expectation and HopeChristian, look: Jesus can be glorified in you through what you do. Isn't that amazing? You can make your Savior shine! You can show him, in all kinds of ways — starting with the meditations of your heart … to the words of your mouth, from serving your family well … to sharing the gospel with the lost, from small acts of faith … to costly acts of love, from resisting temptation … to enduring hostility with a smile on your face — we can do things that glorify Jesus. And don't you want to? Just for the wondrous fact that Jesus is happy about it. That he truly shines.I believe that if we could see the smile of Jesus upon us, we could do anything. I pray as a church that our ambition would become like the apostle Paul's, who said in Philippians 1:20, “it is my eager expectation and hope that … Christ be honored in my body, whether by life or by death.”That's it. Whatever it takes! Jesus be glorified in us — and Jesus is praying that! Jesus is praying for us to glorify him. 3. Jesus is praying for us to have his joy.Take a look at verse 12. Jesus prays:“While I was with them, I kept them in your name, which you have given me. I have guarded them, and not one of them has been lost except the son of destruction, that the Scripture might be fulfilled. 13 But now I am coming to you, and these things I speak in the world, that they may have my joy fulfilled in themselves.”Jesus says again here what we've already seen — he keeps his own. He guards his people. Judas, however, ‘went out from them because he was never truly of them' (1 John 2:19). It was foretold in the Scripture. Jesus was not surprised by this. It was no failure on his part.He has been faithful to the mission the Father gave him, and he says again in verse 13 what he's been saying this whole time: I'm coming home. Another Purpose StatementJesus is going back to his Father, and we're staying here — and he wants something for us here.In fact, Jesus makes another purpose statement about the Farewell Discourse.Notice in verse 13 he says, “these things I speak in the world that they may have…” — it's a purpose statement.The “these things” includes this prayer he's praying, but he's thinking about everything he's been teaching. Jesus is praying that everything he's been teaching will accomplish a purpose. I want you to tell me what it is. Everybody look at verse 13, Jesus says: “these things I speak in the world, that they may have my joy.” He already told us he wanted us to have his peace, now he tells us he wants us to have his joy!Now you gotta go back to those people who asked you about the Farewell Discourse a couple of weeks ago, and you gotta tell them that Jesus wants us to have peace and joy! That's what he says. He wants his joy fulfilled in us.He said the same thing in Chapter 15, verse 11. He said there:“These things I have spoken to you, that my joy may be in you, and that your joy may be full.” He wants our joy to get filled up with his joy. The Joy of JesusWe can say for sure here that Jesus is not talking about generic joy. He says “my joy.” So what does that mean?What is the joy of Jesus that he wants us to have?The joy of Jesus that he wants us to have is joy in the glory of the Trinity. It's joy in the love that the Father has for the Son, and the Son for the Father, and Spirit who is the very presence of that joy. The joy of Jesus is truly joy in God himself — it is non-derivative, infinite, independent, and inexhaustible. That's why it's so good. It's what we could call “big picture joy” — and I mean that in the most profound way you could ever imagine it. Biggest possible picture joy.Which means: it's a joy that has the ability to look beyond the immediate. It can look beyond even pain and suffering. Now this is really important: I'm not saying that this joy ignores pain and suffering. It does not pretend those things don't exist. They do. This joy can say: “Father, it if be possible, let the cup pass from me!” (Matthew 26:39).This joy can say: “My God, my God, why have you forsaken me?” (Matthew 27:46)This joy can say: Father, this hurts. I don't want it. Make it stop. Bring me through it. This joy doesn't ignore pain and suffering, but it's able to see to the other side. “For the joy that was set before him he endured the cross” (Hebrews 12:2). Big picture joy — the joy of Jesus — is a joy in front of us so glorious that it reaches back into our lives now and makes us make it. We're gonna make it because of this joy — and if I keep going, I'm describing the ministry of the Holy Spirit. But let me say this: Jesus wants you to have his joy — He prays for you to be kept. He prays for you to glorify him. He prays for you to have his joy.The InvitationAnd this morning, I would like for us to close with an invitation: Would you open your heart to the joy of Jesus?I mean this, first, for non-Christians: If you're here and you've never put your faith in Jesus, you are currently without this joy. You do not have Christ, but I'm inviting you to have him. Right now, you can pray: Jesus, I'm done walking down this path I've been on, save me. Trust in Jesus Christ. And for all the Christians in the room, for Cities Church: don't we want more of the joy of Jesus? For many of us, the burdens have piled up. We're weighed down. Life is heavy. We need that big picture joy! We need the joy of Jesus — and I'm inviting you: open your heart to him again. Ask for a fresh filling of his joy this morning. And you can do that at this Table. The TableAt this Table we remember the death of Jesus for us! He welcomes us again into his fellowship, into his joy. If you are a Christian, this is for you. Receive his bread and cup today and may the Lord Jesus restore to you the joy of his salvation. He's praying for you.

This week we are jointed By Professor Maya Buch, Chief Investigator of the UK Cardio-IMID partnership to talk about the cutting edge of cardio-rheumatology. If you are interested in the link between inflammation and heart disease you won't want to miss out on this weeks episode!

Most major newsrooms have now moved beyond early experimentation with AI. The main challenge now is determining how to govern effectively, scale consistently, and strategically position AI across the entire organization—while maintaining public trust as a central priority.This week on Newsroom Robots, host Nikita Roy sits down with Uli Köppen, Chief AI Officer at Bavarian Broadcasting (BR), to talk about what it really looks like to lead AI strategy inside one of Europe's largest public broadcasting networks.Uli makes a compelling case for why every newsroom should establish a dedicated AI leadership function, backed by an interdisciplinary governance structure. They also dig into a question defining the next phase of AI strategy for many newsrooms: in a world of AI overviews, zero-click search, and agent-driven information retrieval, how do you maintain your brand as a recognizable, trustworthy source? Uli shares why BR opted out of AI crawling and what they are building instead, including a vision for a verified content data pool that could power new products across multiple media organizations.In this episode, they cover:02:09 — What it means to be Chief AI Officer at a public broadcaster06:30 — Why every newsroom needs an interdisciplinary AI board, not just a single AI leader09:06 — The skills newsrooms need to build for an AI-driven environment11:00 — Why reinventing workflows starts before adding any technology16:28 — Inside the Oktoberfest Chatbot and the collaborative content pool powering it23:40 — Using AI for smarter community engagement and real-time moderation26:30 — The personalized audio news briefing that users love and where it's headed36:00 — How BR's AI guidelines evolved from broad guardrails to clear, example-based rules41:40 — The strategic question: be part of AI platforms, or build recognizable products of your own? Hosted on Acast. See acast.com/privacy for more information.

Iran's president says Tehran isn't pursuing nuclear weapons and has no intention of doing so, as a third round of crucial talks with the US continues in Geneva. Also: former US secretary of state and first lady, Hillary Clinton, appears before a Congressional committee investigating the late paedophile Jeffrey Epstein. North Korean leader Kim Jong-un says his country "could get along well" with the United States, if Washington recognises Pyongyang as a nuclear power. US condemns the use of drones by both sides in the conflict in Sudan. And a new study reveals why some older people's minds are as sharp as they were when they were young.

David Kavanagh, MBChB, PhD, FRCP - A Clinically Considered Real-World Case Series: Practice Essentials From Biopsy To Diagnosis in Immune-Mediated Glomerular Diseases

David Kavanagh, MBChB, PhD, FRCP - A Clinically Considered Real-World Case Series: Practice Essentials From Biopsy To Diagnosis in Immune-Mediated Glomerular Diseases

In this episode, interventional spine physician Dr. Abhishek Gupta and spine surgeon Dr. Matthew Cunningham team up to tackle the tricky diagnosis and management of axial low back pain. They break down how to spot the differences between muscle issues, disc problems, and facet joint pain, using simple clues like whether a patient hurts more while standing or sitting. The duo also chats about why MRIs don't always tell the whole story and why diagnostic blocks can be a game-changer for pinpointing the source of pain. From conservative rehab and radiofrequency ablation to surgery, they outline a collaborative approach to finding patients lasting relief.

Dr. Niyati Borkar chats with Dr. Marissa Guttenberg about her article, "Tissue-Resident Alveolar Macrophages Reduce Ozone-induced Inflammation via MerTK-mediated Efferocytosis."

AP correspondent Laurence Brooks reports on indirect talks between the U.S. and Iran in Oman.

Dr. Daniel Stone (Associate Editor-in-Chief, Molecular Therapy Advances) sits down with Dr. Krishanu Saha, Anna Tommasi, and Dr. Dan Cappabianca from the University of Wisconsin-Madison. Join them as they discuss their team’s recent publication, Efficient nonviral integration of large transgenes into human T cells using Cas9-CLIPT, and learn more about their novel method to improve the manufacturing of multifunctional, genome-edited immune cell therapies. Music: 'Electric Dreams' by Scott Buckley - released under CC-BY 4.0. www.scottbuckley.com.auShow your support for ASGCT!: https://asgct.org/membership/donateSee omnystudio.com/listener for privacy information.

In this episode of Chasing Leviathan, PJ is joined by Dr. Eric Jacobsen, senior pastor of First Presbyterian Church in Tacoma, Washington, to discuss his book Three Pieces of Glass: Why We Feel Lonely in a World Mediated by Screens. Together they explore how modern life, shaped by smartphones, automobiles, and screen-mediated environments, quietly reshapes our relationships, our neighborhoods, and our sense of belonging. Rather than treating loneliness as only a personal or psychological problem, Jacobsen reframes it as a civic and cultural issue rooted in how we build and inhabit our shared spaces.The conversation moves through the hidden costs of car-centered development, the loss of walkable neighborhoods, and the rise of placeless places that fail to hold human stories. Jacobsen explains how habits formed since the mid-twentieth century have trained us to see others as obstacles rather than neighbors, while also hollowing out the everyday relationships that once created social trust and connection. Drawing on urban theory, theology, and lived experience, he makes the case that loneliness is not only about missing close friendships but also about losing meaningful ties to place, community, and civic life.Throughout the episode, PJ and Dr. Jacobsen discuss placemaking, social capital, and the importance of ordinary relationships with neighbors, shopkeepers, and strangers who slowly become acquaintances. They also reflect on how Christian theology, common grace, and the pursuit of the common good can help believers collaborate with their wider communities for the flourishing of shared spaces. This episode will resonate with anyone interested in technology and culture, urban design, Christian theology, or the growing crisis of loneliness in modern society.Make sure to check out Jacobsen's book: Three Pieces of Glass: Why We Feel Lonely in a World Mediated by Screens

In this episode, we review the high-yield topic of⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) ⁠⁠⁠ from the Immunology section.Follow⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Medbullets⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ on social media:Facebook: www.facebook.com/medbulletsInstagram: www.instagram.com/medbulletsofficialTwitter: www.twitter.com/medbullets

This week, we're joined by Dr. Brooke Ingersoll, a leading autism researcher and Director of the MSU Autism Research Lab. She'll be sharing insights on parent-mediated interventions, Project ImPACT, and the RISE study. These topics offer valuable support for families and individuals in the autism community. Download latest episode to learn more! Resources  Project Impact Resources Link to the official Project Impact website or resources where families can learn more about the program, access materials, and explore training opportunities. 2. MSU Autism Research Lab A link to Dr. Brooke Ingersoll's research lab at Michigan State University, where families can explore her work and related studies. ............................................................... Autism weekly is now found on all of the major listening apps including apple podcasts, stitcher, Spotify, amazon music, and more. Subscribe to be notified when we post a new podcast. Autism weekly is produced by ABS Kids. ABS Kids is proud to provide diagnostic assessments and ABA therapy to children with developmental delays like Autism Spectrum Disorder. You can learn more about ABS Kids and the Autism Weekly podcast by visiting abskids.com.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/TWU865. CME credit will be available until December 16, 2026.Beneath the Surface of Sjögren's Disease: Understanding Systemic Impact and B-Cell–Mediated PathwaysThe University of Cincinnati is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.The University of Cincinnati and PVI, PeerView Institute for Medical Education, are both accredited by the ACCME to provide continuing medical education for physicians and have collaborated to design and execute this activity. For accreditation purposes, the University of Cincinnati is responsible for certification and documentation of attendance for this activity.SupportThis activity is supported by an educational grant from Novartis Pharmaceuticals Corporation.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/TWU865. CME credit will be available until December 16, 2026.Beneath the Surface of Sjögren's Disease: Understanding Systemic Impact and B-Cell–Mediated PathwaysThe University of Cincinnati is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.The University of Cincinnati and PVI, PeerView Institute for Medical Education, are both accredited by the ACCME to provide continuing medical education for physicians and have collaborated to design and execute this activity. For accreditation purposes, the University of Cincinnati is responsible for certification and documentation of attendance for this activity.SupportThis activity is supported by an educational grant from Novartis Pharmaceuticals Corporation.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/TWU865. CME credit will be available until December 16, 2026.Beneath the Surface of Sjögren's Disease: Understanding Systemic Impact and B-Cell–Mediated PathwaysThe University of Cincinnati is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.The University of Cincinnati and PVI, PeerView Institute for Medical Education, are both accredited by the ACCME to provide continuing medical education for physicians and have collaborated to design and execute this activity. For accreditation purposes, the University of Cincinnati is responsible for certification and documentation of attendance for this activity.SupportThis activity is supported by an educational grant from Novartis Pharmaceuticals Corporation.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/TWU865. CME credit will be available until December 16, 2026.Beneath the Surface of Sjögren's Disease: Understanding Systemic Impact and B-Cell–Mediated PathwaysThe University of Cincinnati is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.The University of Cincinnati and PVI, PeerView Institute for Medical Education, are both accredited by the ACCME to provide continuing medical education for physicians and have collaborated to design and execute this activity. For accreditation purposes, the University of Cincinnati is responsible for certification and documentation of attendance for this activity.SupportThis activity is supported by an educational grant from Novartis Pharmaceuticals Corporation.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/TWU865. CME credit will be available until December 16, 2026.Beneath the Surface of Sjögren's Disease: Understanding Systemic Impact and B-Cell–Mediated PathwaysThe University of Cincinnati is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.The University of Cincinnati and PVI, PeerView Institute for Medical Education, are both accredited by the ACCME to provide continuing medical education for physicians and have collaborated to design and execute this activity. For accreditation purposes, the University of Cincinnati is responsible for certification and documentation of attendance for this activity.SupportThis activity is supported by an educational grant from Novartis Pharmaceuticals Corporation.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/TWU865. CME credit will be available until December 16, 2026.Beneath the Surface of Sjögren's Disease: Understanding Systemic Impact and B-Cell–Mediated PathwaysThe University of Cincinnati is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.The University of Cincinnati and PVI, PeerView Institute for Medical Education, are both accredited by the ACCME to provide continuing medical education for physicians and have collaborated to design and execute this activity. For accreditation purposes, the University of Cincinnati is responsible for certification and documentation of attendance for this activity.SupportThis activity is supported by an educational grant from Novartis Pharmaceuticals Corporation.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/TWU865. CME credit will be available until December 16, 2026.Beneath the Surface of Sjögren's Disease: Understanding Systemic Impact and B-Cell–Mediated PathwaysThe University of Cincinnati is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.The University of Cincinnati and PVI, PeerView Institute for Medical Education, are both accredited by the ACCME to provide continuing medical education for physicians and have collaborated to design and execute this activity. For accreditation purposes, the University of Cincinnati is responsible for certification and documentation of attendance for this activity.SupportThis activity is supported by an educational grant from Novartis Pharmaceuticals Corporation.Disclosure information is available at the beginning of the video presentation.

Julie A. Parsons, MDHaberfield Endowed Chair in Pediatric Neuromuscular DisordersProfessor of Clinical Pediatrics and NeurologyUniversity of Colorado School of Medicine, Children's Hospital ColoradoAurora, CO, USAThe gene transfer trials for musculoskeletal disorders, if we look at musculoskeletal and neurologic disorders, we really do have the highest success rate in terms of treatment, but we also carry the highest incidence of treatment-emergent severe adverse events. And why is that true? Yesterday, when we were hearing about Donovan as well, we looked and said, When the first gene transfer therapies were started, he had a single muscle that was injected.When we look at Luxturna, we injected the retina. Now, what is happening with these disorders is that we're giving these huge, massive doses of viral vector to patients. There haven't been a lot of gene transfer therapies that have reached the market. But you saw yesterday, so many gene transfer therapies being worked on, but there are very few that have actually come to market. There are a couple of reasons for that.One is with the indications that we have, we know that the musculoskeletal disorders are most likely to achieve benefit, but there are the high risk of severe adverse events. Route of Administration, IV, for most of our disorders is the way we're going. We may end up having some Intrathecal therapies as well that are coming on board, but right now it's IV, and that means, a huge dose of this viral vector and antigenic risk that is being administered.In the vector design now, we actually have more specific vectors as well as promoters that are being utilized to really target specific tissues, so that we're able to focus in a little bit more on the tissues that we want to have affected. And then the dose has gone from these little tiny local injections to really systemic, much broader. And now our patients, are larger. So we're giving a viral genome per kilo dose that is just massive as we look at that.Then there really are challenges in terms of the translation of clinical trials to commercial treatment with these agents. And we don't always know, we're not always great when we do tests in clinical trials in small populations, about when that's broadened to the commercial availability and we hit larger heterogeneous populations.There are safety issues arising from these therapies, and I think that we have some experience now, certainly with the three diseases that I mentioned at the beginning, in terms of collecting some data and information to have a little bit more of an idea what to expect. Although to me, the recurring esteem is always, expect the unexpected. Because we still are learning about this. Hepatotoxicity. We know that transaminitis is something that we see in almost every gene transfer therapy that has been delivered, and we have to watch really, really closely and follow our patients closely for this. We also have to select patients that we don't think have risk for additional liver injury or underlying liver pathology, because as we found out in the XLMTM boys, we missed that. Thrombotic Microangiopathy. We look at this disorder. We've had deaths in SMA from TMA. We have Duchenne patients that have had TMA.This is scary because as many of us as clinicians who have treated patients, you know that we end up getting thrombocytopenia. So is that it this time, or are they going to be fine, or the platelet is going to go back to normal? This is another one that we have to watch really, really closely for. Cardiac Toxicity. We have had cardio myositis. We've had deaths from cardiac toxicity.Something really, really important for us to think about. In little kids, vomiting could be a sign of cardiac myositis. And for most of us who've treated patients with gene transfer therapy, what's one of the first issues that you get?You get nausea of vomiting, they don't feel good. So is that myocarditis or is it just a standard side effect that we're seeing with treatment? Importantly, as we discovered, there actually can be an immune response to the transgene. It's not just the viral vector capsid, it's actually the transgene as well. That was discovered in patients who were treated for Duchenne. So that's a really important thing in terms of looking now at what's our patient's selection and how do we pick the right patients.Next part, Dr. Parsons will discuss understanding and preparing risk factors associated with AAV gene therapies.

Alan Beggs, PhDDirector of the Manton Center for Orphan Disease ResearchSir Edwin and Lady Manton Professor of Pediatrics, Boston Children's HospitalHarvard Medical School, Boston, MA, USA Julie A. Parsons, MDHaberfield Endowed Chair in Pediatric Neuromuscular DisordersProfessor of Clinical Pediatrics and NeurologyUniversity of Colorado School of Medicine, Children's Hospital ColoradoAurora, CO, USADoctors Beggs and Parsons discuss the current status of gene therapies in rare neuromuscular disorders in this eight part podcast series. This is derived from the symposium that was presented at the MDA 2025 conference in Dallas, Texas, in March 2025 and is intended for healthcare professionals only. This podcast includes information about investigational compounds that do not yet have a regulatory approval or authorization for a specific indication. The safety and efficacy of the agents under investigation have not been established. In contents of this podcast, shall not be used in any manner to directly or indirectly promote or sell the product for unapproved uses. The ASPIRO clinical trial is on clinical hold since September 2021.In this part, Doctor Beggs will provide an explanation of AAV-mediated gene therapies.Alan Beggs, PhDAAV vectors, which I'm going to be talking about more today, or Adeno associated viral vectors are small viruses. Their DNA gets delivered into the cell and remains extrachromosomal. There are very rare occasional integrations, but the risk of oncogenesis as a result is significantly lower as a consequence of remaining extrachromosomal, though, we do have to think about what happens as the cells divide and potentially the durability of treatment is more limited.There have been a lot of movement and development over the years, starting back in the 1980s when the first AAV genomes were isolated and sequenced. This led to a development of methods to produce recombinant AAVs that would lack the genes necessary for viral replication, but contain a therapeutic gene you wish to deliver. Through this, the structure of AAVs have been developed. There have been isolation of a number of naturally occurring variants. You've heard of AAV8, AAV9, also RH 74, derived from a rhesus monkey for the RH. These have all been used in clinical trials. Then at the end I'll talk a little bit about directed evolution methods to actually engineer capsids with particular properties that are beneficial.Throughout this we've identified some of the issues that arise in this. It was initially thought that AAV vectors were non-immunogenic, but in fact there are immune responses not just to the viral payload to the therapeutic protein, but also to the viral vectors, and you're going to hear about that from Doctor Parsons. Over time, as we've come to understand these challenges, we've also been developing approaches to mitigate them. In terms of clinical trials and treatments, the very first studies were done back in the 1970s.By the early 2000, the very first clinical therapeutic was approved in China. It was actually an oncolytic virus carrying a p53 gene to treat head and neck cancers. By now there are over 40 approved treatments for various types of AAV delivered gene therapies. Of course, the ones we know a lot about are Zolgensma, which was approved in 2019, and Elevidys, which was approved last year. A number of challenges and then also a number of approaches to overcome those challenges. First of all, the preclinical data are not always sufficient to predict the response of a human patient.For example, in X-linked myotubular myopathy we had mouse and dog models that exhibited a myopathy but nothing else, and yet when we treated human patients, we discovered that patients with X-linked myotubular myopathy actually had a previously only poorly recognized hepatopathology that led to potential liver consequences following gene therapy. The animal models don't always predict the clinical outcome in humans.Also, we have small disease populations. These are rare diseases. It's important to understand the natural history of these diseases, understand the heterogeneity among the clinical population. It's very important to engage with families and with patients and communities, understand who might be at increased risk to treatment with one of these. This feeds into safety considerations. We need to think also about some of the immune responses. I think we're starting to learn, for example, with the gene therapies for Duchenne, and we know this from SMA that some patients get into trouble and others don't. We need to understand why that may be, and we don't know about the long term effects. This has been very recent.

Julie A. Parsons, MD Haberfield Endowed Chair in Pediatric Neuromuscular DisordersProfessor of Clinical Pediatrics and NeurologyUniversity of Colorado School of Medicine, Children's Hospital ColoradoAurora, CO, USAAs we talk about the gene transfer therapies and the modalities that we have to use, it's really interesting. Yesterday, with our keynote speaker, you could see this logarithmic growth of the use of gene transfer therapies for these disorders. If you look at the Venn diagram, you can see that really 27% almost of gene transfer therapies that are used are in musculoskeletal and neurology. For many of us as neurologists, we also take care of metabolic disorders.We really own right now this landscape, and of course, our two approved modalities are Onasemnogene and Delandistrogene. We're going to look at three different disorders, monogenic disorders, monogenic diseases, to typify what we look at in terms of some of the risks and benefits of these treatments. SMA, Duchenne, and X-linked myotubular myopathy are all rare disorders. They're all diseases that have a high unmet medical need and a significant disease burden.I think they're all good in terms of typifying where we are clinically with these disorders. The first question is, is it worth it? Are these effective treatments? We know from looking at the information about SMA that just looking early on, we know that if we treat kids early, that we do see a marked improvement in motor scores for kids that are treated early with Onasemnogene.In Duchenne, we have information that there is at least some improvement in the 4-5-year-olds in terms of motor skills treated with Delandistrogene. In terms of X-linked MTM, which was a very dramatic improvement, you could see that for boys who were basically traked, vented, and had no mobility, the bottom line, the blue line, is actually looking at ventilator dependence. Are they effective? Yeah, they're effective, but then we have to say, okay, what's the downside?The downside is that there's tremendous risk associated with treatment with these agents. If we really look at the sobering facts, we know that with SMA, there have been deaths, there have been fatalities related to thrombotic microangiopathy to patients who have liver failure, a couple of patients have died. With Onasemnogene, this is 4,000 plus doses that have so far been given. With Duchenne, unfortunately, many of us got the letter yesterday talking about an additional death in a patient treated with commercial Delandistrogene.We also know with some of the other agents, like fordadistrogene, patient died of heart failure, cardiac arrest, another patient who had acute respiratory syndrome with pulmonary edema. Again, we look at this and say this is significant. With X-linked MTM, as Alan said, there were some unanticipated deaths, four deaths from patients who ended up having cholestatic liver diseases that really wasn't anticipated prior to the patients being treated with the animal models and all that we had. Then many of you have heard about the patient with Rett syndrome who had a systemic hyperinflammatory syndrome. Again, these are rare disorders. They have a high disease burden, but the risk of treatment is significant.In the next part, Dr. Parsons discuss factors impacting safety and efficacy of AAV-mediated gene therapies.

Sadanand Dhume examines the shift in US foreign policy, where President Trump now favors Pakistan and its military chief, General Munir. This followed intense combat between India and Pakistan after a horrific terrorist attack. When the US mediated a ceasefire, Trump took credit, which embarrassed Indian Prime Minister Modi. Pakistan cleverly thanked Trump and nominated him for a Nobel Peace Prize, securing his favor over India. India now needs a trade deal. Guest: Sadanand Dhume.

Systematic Review Examines Periodontitis and DevelopmentRisk of Immune-Mediated ConditionsBy Today's RDH ResearchOriginal article published on Today's RDH: https://www.todaysrdh.com/systematic-review-examines-periodontitis-and-development-risk-of-immune-mediated-conditions/Need CE? Start earning CE credits today at https://rdh.tv/ce Get daily dental hygiene articles at https://www.todaysrdh.com Follow Today's RDH on Facebook: https://www.facebook.com/TodaysRDH/Follow Kara RDH on Facebook: https://www.facebook.com/DentalHygieneKaraRDH/Follow Kara RDH on Instagram: https://www.instagram.com/kara_rdh/

The Need to Heed God's Mediated Word: A Sermon on Deuteronomy 5:1–33 by Jason S. DeRouchie

In this episode of the Epigenetics Podcast, we talked with Mo Motamedi from the Center for Cancer Research at Massachusetts General Hospital about his work on RNA-mediated epigenetic regulation. The Interview starts with Dr. Motamedi sharing his personal journey into the realm of biology, sparked by a familial inclination towards science and a challenge to excel in a field that initially felt daunting. His passion was ignited during a genetics class, as he recognized the quantitative nature of the discipline amidst the evolution of modern techniques like qPCR and high-throughput sequencing. Dr. Motamedi goes on to articulate the importance of understanding the interplay between genetics and broader biological systems, emphasizing that an insightful grasp of evolution is vital for decoding cellular mechanisms. He reflects on his time in a postdoctoral lab under Danish Moazet, investigating RNA interference (RNAi) and its unexpected nuclear roles, contributing significantly to the understanding of how RNAi is involved in gene silencing via chromatin interaction. As his narrative unfolds, Dr. Motamedi provides deep insights into his own lab's work, which focuses on the establishment and maintenance of epigenetic states and their implications in cancer epigenetics. He discusses groundbreaking discoveries related to RNAi and heterochromatin, detailing experiments that unveil how specific proteins contribute to transcriptional and post-transcriptional gene silencing. A pivotal theme emerges: the complex dynamics of genome evolution and chromatin organization can be reshaped under various biological contexts, including the quiescent state of cells under stress. Moreover, the discussion traverses recent publications from Dr. Motamedi's lab, revealing how they identify long non-coding RNAs that function as silencers at centromeres, an essential mechanism that aids in the establishment of heterochromatin independently of RNAi. His findings advocate for the idea that well-structured genome organization can lead to more efficient gene regulation, which can also be crucial in therapeutic contexts for various cancers. References Motamedi, M. R., Hong, E. J., Li, X., Gerber, S., Denison, C., Gygi, S., & Moazed, D. (2008). HP1 proteins form distinct complexes and mediate heterochromatic gene silencing by nonoverlapping mechanisms. Molecular cell, 32(6), 778–790. https://doi.org/10.1016/j.molcel.2008.10.026 Joh, R. I., Khanduja, J. S., Calvo, I. A., Mistry, M., Palmieri, C. M., Savol, A. J., Ho Sui, S. J., Sadreyev, R. I., Aryee, M. J., & Motamedi, M. (2016). Survival in Quiescence Requires the Euchromatic Deployment of Clr4/SUV39H by Argonaute-Associated Small RNAs. Molecular cell, 64(6), 1088–1101. https://doi.org/10.1016/j.molcel.2016.11.020 Joh, R. I., Lawrence, M. S., Aryee, M. J., & Motamedi, M. (2021). Gene clustering drives the transcriptional coherence of disparate biological processes in eukaryotes. Systems Biology. https://doi.org/10.1101/2021.04.17.440292 Related Episodes Evolutionary Forces Shaping Mammalian Gene Regulation (Emily Wong) Chromatin Evolution (Arnau Sebé-Pedrós) The Role of lncRNAs in Tumor Growth and Treatment (Sarah Diermeier) Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: podcast@activemotif.com

Join Professor Iain McInnes for the latest episode of Discussing RA on The Immune-Mediated Inflammatory Disease Forum. In this episode, he highlights two papers: risk of MACE, VTE, and malignancies in patients with RA or UC treated with filgotinib and frequency of reporting of MACE, MI, and stroke between JAKis and anti-TNFα.

Interview with Sharmili Edwin Thanarajah, MD, author of Soft Drink Consumption and Depression Mediated by Gut Microbiome Alterations. Hosted by John Torous, MD. Related Content: Soft Drink Consumption and Depression Mediated by Gut Microbiome Alterations GLP-1 Receptor Agonists for Pharmacologically Induced Weight Gain

Interview with Sharmili Edwin Thanarajah, MD, author of Soft Drink Consumption and Depression Mediated by Gut Microbiome Alterations. Hosted by John Torous, MD. Related Content: Soft Drink Consumption and Depression Mediated by Gut Microbiome Alterations GLP-1 Receptor Agonists for Pharmacologically Induced Weight Gain

Our 21st century digital age provides countless and unprecedented opportunities for identity development and cultural engagement. But how might these new means of social interaction impact religious institutions and their public image?On today's episode of Scholars & Saints, host Nicholas Shrum seeks out these answers with the help of Oklahoma State University's Professor of Media and Strategic Communications Rosemary Avance. In her recent book, Mediated Mormons: Shifting Religious Identities in the Digital Age, Avance explores how the Church of Jesus Christ of Latter-day Saints created and negotiated its public image during the "Mormon Moment" of the 2010's. Avance and Shrum discuss the different media focuses during this period, including Mitt Romney's 2012 presidential campaign, online discussions around caffeine, the Gospel Topics Essays, and more.You can learn more about Rosemary Avance, her research, and her academic interests by visiting her faculty page.

Join Professor Iain McInnes as he discusses the top publications in the world of RA. This month's discussion covered the ‘Efficacy and safety of upadacitinib for patients with immune-mediated inflammatory diseases: a systematic review and meta-analysis'. Read the full paper summary online at www.imidforum.com.

In this episode, host Alyssa Watson, DVM, welcomes back John M. Thomason, DVM, MS, DACVIM (SAIM), to talk about his recent Clinician's Brief article, “Top 4 Primary Immune-Mediated Disorders in Dogs.” In part 2 of this 2-part conversation, Dr. Thomason focuses on immune-mediated polyarthritis (IMPA) and pemphigus foliaceus. He covers some diverse presentations for IMPA and makes joint taps sound highly doable. You'll also be reminded about those fabled “fried egg cells.”Resources:https://www.cliniciansbrief.com/article/anemia-thrombocytopenia-immune-disorder-dogshttps://www.apoquel.comContact:podcast@instinct.vetWhere To Find Us:Website: CliniciansBrief.com/PodcastsYouTube: Youtube.com/@clinicians_briefFacebook: Facebook.com/CliniciansBriefLinkedIn: LinkedIn.com/showcase/CliniciansBrief/Instagram: @Clinicians.BriefX: @CliniciansBriefThe Team:Alyssa Watson, DVM - HostAlexis Ussery - Producer & Multimedia Specialist

Suruchi Mazumdar's book addresses the complex relationship between India's evolving, emerging media landscape, the political and economic interests of diverse media actors, and movements opposing contentious issues such as market-based economic reforms and religious nationalism. In the mid-2000s, Singur and Nandigram, nondescript semi-urban and rural areas in the east Indian state of West Bengal, suddenly became the center of national and international media attention and debates on state-led neoliberal agenda. The point of controversy were local agitations provoked by the then state government's plans to acquire agricultural land for large scale corporate industrial projects. The movements by farmers to protect their agricultural land were described variously as challenges to neoliberal initiatives and widespread social tension that put a temporary brake to state-led market reforms. In traditional liberal narratives, the triumph of economic reforms was expected to replace value-based ideology with global economic principles, perceived as objective and neutral.  But the forces of neoliberalism became strongly entrenched in India alongside religious nationalism. Such political economic developments paralleled with the simultaneous expansion of India's digital and traditional media sectors, consolidation of market forces, the co-option of both old and new media by powerful actors, and opportunities of mediated democratization and activism. While narratives of economic liberalization and global trends of commercialized journalism have been amply documented, this book addresses the tension between mainstream media's political and commercial logic, movements and citizen-led activisms questioning dominant development and religious nationalist agenda, and the possibilities of political diversity and democratic participation in the Indian city of Kolkata. By focusing on the hybridities, commonalities, differences, and complexities in Kolkata's mainstream news media and emerging digital space, this book captures the regional and linguistic variations in the studies of media, movements, and politics in India. Dr Suruchi Mazumdar is an Associate Professor at Jindal School of Journalism and Communication, O.P. Jindal Global University in India. Dr Priyam Sinha is an Alexander Von Postdoctoral Research Fellow at the Institute for Asian and African Studies, Humboldt University in Berlin. 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

Suruchi Mazumdar's book addresses the complex relationship between India's evolving, emerging media landscape, the political and economic interests of diverse media actors, and movements opposing contentious issues such as market-based economic reforms and religious nationalism. In the mid-2000s, Singur and Nandigram, nondescript semi-urban and rural areas in the east Indian state of West Bengal, suddenly became the center of national and international media attention and debates on state-led neoliberal agenda. The point of controversy were local agitations provoked by the then state government's plans to acquire agricultural land for large scale corporate industrial projects. The movements by farmers to protect their agricultural land were described variously as challenges to neoliberal initiatives and widespread social tension that put a temporary brake to state-led market reforms. In traditional liberal narratives, the triumph of economic reforms was expected to replace value-based ideology with global economic principles, perceived as objective and neutral.  But the forces of neoliberalism became strongly entrenched in India alongside religious nationalism. Such political economic developments paralleled with the simultaneous expansion of India's digital and traditional media sectors, consolidation of market forces, the co-option of both old and new media by powerful actors, and opportunities of mediated democratization and activism. While narratives of economic liberalization and global trends of commercialized journalism have been amply documented, this book addresses the tension between mainstream media's political and commercial logic, movements and citizen-led activisms questioning dominant development and religious nationalist agenda, and the possibilities of political diversity and democratic participation in the Indian city of Kolkata. By focusing on the hybridities, commonalities, differences, and complexities in Kolkata's mainstream news media and emerging digital space, this book captures the regional and linguistic variations in the studies of media, movements, and politics in India. Dr Suruchi Mazumdar is an Associate Professor at Jindal School of Journalism and Communication, O.P. Jindal Global University in India. Dr Priyam Sinha is an Alexander Von Postdoctoral Research Fellow at the Institute for Asian and African Studies, Humboldt University in Berlin. Learn more about your ad choices. Visit megaphone.fm/adchoices Support our show by becoming a premium member! https://newbooksnetwork.supportingcast.fm/political-science

ReferencesAnal Cell Pathol (Amst).2018; 2018: 787.1814J. Biol. Chem. 2018;293:2422-2437Current Opinion in Structural BiologyVolume 83, December 2023, 102707The Journal of Biological Chemistry 2016.291, 23756-23768Mann, Martinez, O'Neill. 1979 "Angels at My Gate" Manfred Mann EB.https://open.spotify.com/track/2A9wPXzu7uijsOhIpbAH6e?si=2226c50bc7ab4a45Tchaikovsky, PI . 1880. Capricio Italiane" Romeo and Juliet; Nutcracker. https://open.spotify.com/album/0t5AVxOQO5GqqlZW0AeL0c?si=Fwd2uqTtQpqlzhILsRWXQA

In this episode, host Alyssa Watson, DVM, is joined by John M. Thomason, DVM, MS, DACVIM (SAIM), to talk about his recent Clinician's Brief article, “Top 4 Primary Immune-Mediated Disorders in Dogs.” In part 1 of this 2-part conversation, Dr. Thomason focuses on the diagnosis and management of IMHA and IMTP. You'll hear vital details for both conditions including the right way to handle blood smears and slide agglutination, which IMHA cases are hypercoagulable (spoiler: all of them), and if vincristine actually helps in IMTP (spoiler again: it does).Resources:https://www.cliniciansbrief.com/article/anemia-thrombocytopenia-immune-disorder-dogshttps://www.zoetisus.com/products/dogs/librelaContact:podcast@instinct.vetWhere To Find Us:Website: CliniciansBrief.com/PodcastsYouTube: Youtube.com/@clinicians_briefFacebook: Facebook.com/CliniciansBriefLinkedIn: LinkedIn.com/showcase/CliniciansBrief/Instagram: @Clinicians.BriefX: @CliniciansBriefThe Team:Alyssa Watson, DVM - HostAlexis Ussery - Producer & Multimedia Specialist

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TWiV reviews cuts in National Science Foundation budgets, cuts to Harvard University grants, judge blocks ban on Harvard enrolling international students, DOGE ordered cuts of NIH grants, endemic coronavirus infection induces Fc receptor binding antibodies to SARS-CoV-2, and inherited IFNAR1 deficiency causing adverse reactions to measles and yellow fever infectious vaccines. Hosts: Vincent Racaniello, Alan Dove, and Angela Mingarelli Subscribe (free): Apple Podcasts, RSS, email Become a patron of TWiV! Links for this episode Support science education at MicrobeTV NSF funding cut to lowest level (NY Times) 1,000 grants cut at Harvard University (Nature) Administration ban on international students at Harvard blocked (CNN) DOGE killed NIH grants (Nature) Endemic coronavirus infection induces FcR binding antibodies to SARS-CoV-2 (J Virol) IFNAR1 deficiency and severe reaction to measles and yellow fever vaccines (J Exp Med) Letters read on TWiV 1221 Timestamps by Jolene Ramsey. Thanks! Weekly Picks Angela – Contact lenses that give people infrared vision — even with their eyes shut (one, two) Alan –  Autocrats are afraid of you – see the graphic, especially. Vincent – How One Company Secretly Poisoned The Planet Intro music is by Ronald Jenkees Send your virology questions and comments to twiv@microbe.tv Content in this podcast should not be construed as medical advice.

From the BBC World Service: The Yemeni group started attacking shipping lanes around the Red Sea after the war in Gaza began. It's hoped the ceasefire will stop disruptions to major trade routes. Then, China and the U.S. are set to hold their first trade talks since sweeping tariffs were announced. Later: Spanish Prime Minister Pedro Sánchez on last week's massive power outage and former U.S. President Joe Biden on defense and international trade.

From the BBC World Service: The Yemeni group started attacking shipping lanes around the Red Sea after the war in Gaza began. It's hoped the ceasefire will stop disruptions to major trade routes. Then, China and the U.S. are set to hold their first trade talks since sweeping tariffs were announced. Later: Spanish Prime Minister Pedro Sánchez on last week's massive power outage and former U.S. President Joe Biden on defense and international trade.

Bret Weinstein speaks with Laura Delano, the author of “Unshrunk: A Story of Psychiatric Treatment Resistance” on the subject of today's mental health treatment and psychotropic medications.Find Laura Delano on X at https://x.com/LauraDelano  and her book, “Unshrunk: A Story of Psychiatric Treatment Resistance” at  https://unshrunkthebook.com.*****This episode is sponsored by:Jolie: For your best skin & hair guaranteed head to http://jolieskinco.com/DARKHORSE to try it out for yourself with FREE shipping.VanMan: Tallow and honey balm, deodorant, and many other amazing animal based personal care products.Go to http://www.vanmanscompany.com/darkhorse and use code darkhorse10 for 10% off your first order.*****Join DarkHorse on Locals! Get access to our Discord server, exclusive live streams, live chats for all streams, and early access to many podcasts: https://darkhorse.locals.com Check out the DHP store! Epic tabby, digital book burning, saddle up the dire wolves, and more: https://www.darkhorsestore.orgTheme Music: Thank you to Martin Molin of Wintergatan for providing us the rights to use their excellent music.*****Mentioned in this episode:- The Challenge of Going Off Psychiatric Drugs https://www.newyorker.com/magazine/2019/04/08/the-challenge-of-going-off-psychiatric-drugs- A Hunter-Gatherer's Guide to the 21st Century https://amzn.to/3AGANGg (commission earned)Support the show

Joe kicks off this week's show by sharing aspects of his "rough week" with the audience. Once he's done venting, he begins his training talk :) During the 1st half of the show he shares an online interaction he recently had with an ignorant "science-based" lifter... This discussion is centered around "stretch mediated hypertrophy" and Joe's biggest pet peeve with the current "lengthened training" obsession. The 2nd half of the show is dedicated to balance training. Joe reveals the SECRET to improving balance in the "real world" as well as the most overrated balance training techniques! *For a full list of Show Notes + Timestamps visit www.IndustrialStrengthShow.com. IMPORTANT LINKS Team Forever Strong [1-Week Free Trial] CPPS certification [code: JOED30] Joe's Instagram