Podcasts about Nature Medicine

It is now known that the Covid 19 epidemic of early 2020 resulted from an accidental release of the virus from the Wuhan lab funded by the US Defense Department and Tony Fauci through the EcoHealth Alliance. Join our Happy Warrior community www.WeHappyWarriors.com But eminent scientists wrote in Lancet Magazine and in Nature Medicine magazine early in 2020 that Covid came from the so-called Wet Market in Wuhan and thinking otherwise is crazy conspiracy theory. Take a look at the wonderful Tower of Power course:  https://www.wehappywarriors.com/offers/L6KwuaXh?coupon_code=MEMORIAL15 .  As late as October 2023 the New York Times was still insisting that the Wuhan Virology Lab escape story was nonsense. For Memorial Day, America's Real War eBook – only $10. America's Real War (Paperback) – now just $15  Wuhan was operating with the same biosecurity levels you'd find at your dentist instead of hi level security needed for lethal viruses.  Learn more about your ad choices. Visit megaphone.fm/adchoices

It is now known that the Covid 19 epidemic of early 2020 resulted from an accidental release of the virus from the Wuhan lab funded by the US Defense Department and Tony Fauci through the EcoHealth Alliance. Join our Happy Warrior community www.WeHappyWarriors.com. But eminent scientists wrote in Lancet Magazine and in Nature Medicine magazine early in 2020 that Covid came from the so-called Wet Market in Wuhan and thinking otherwise is crazy conspiracy theory. Take a look at the wonderful Tower of Power course:  https://www.wehappywarriors.com/offers/L6KwuaXh?coupon_code=MEMORIAL15 . As late as October 2023 the New York Times was still insisting that the Wuhan Virology Lab escape story was nonsense. For Memorial Day, America's Real War eBook – only $10. America's Real War (Paperback) – now just $15. Wuhan was operating with the same biosecurity levels you'd find at your dentist instead of hi level security needed for lethal viruses.

How important is one's family history when determining Alzheimer's risk? Returning guests Drs. Jessica Langbaum and Sterling Johnson discuss the latest research on family history and genetic risk factors and share their perspectives on the topic, specifically focusing on the role of the APOE gene as a risk factor. Guests: Sterling Johnson, PhD, leader, Wisconsin Registry for Alzheimer's Prevention (WRAP), associate director, Wisconsin Alzheimer's Disease Research Center, associate director, Wisconsin Alzheimer's Institute, lead principal investigator, ADRC Consortium for Clarity in ADRD Research Through Imaging (CLARiTI), Jean R. Finley Professor of Geriatrics and Dementia, UW School of Medicine and Public Health, and Jessica Langbaum, PhD, senior director of research strategy, Banner Alzheimer's Institute, overseer, Observational Research Program, Clinical Trials Program, Alzheimer's Prevention Initiative, director, Alzheimer's Prevention Registry, director, Arizona Alzheimer's Disease Research Center Show Notes Read Dr. Langbaum's viewpoint, “The Risk of Alzheimer Disease in APOE4 Homozygotes,” on the Journal of American Medical Association (JAMA) website. Read Dr. Johnson's article, “APOE4 homozygosity represents a distinct genetic form of Alzheimer's disease,” on Nature Medicine's website. Read Dr. Chin's opinion piece, “What to do if your family has a history of Alzheimer's,” mentioned at 2:04 on the Wisconsin State Journal's website. Please note there is a paywall to access the article. Read Dr. Tobey Betthauser's paper, “Multi-method investigation of factors influencing amyloid onset and impairment in three cohorts,” mentioned by Dr. Johnson at 16:50, on the National Library of Medicine's website. Learn more about the Banner Alzheimer's Institute on their website.  Read about the GeneMatch program from the Alzheimer's Prevention Registry on their website.  Learn more about the Arizona Alzheimer's Disease Research Center on their website.  Connect with us Find transcripts and more at our website. Email Dementia Matters: dementiamatters@medicine.wisc.edu Follow us on Facebook and Twitter. Subscribe to the Wisconsin Alzheimer's Disease Research Center's e-newsletter. Enjoy Dementia Matters? Consider making a gift to the Dementia Matters fund through the UW Initiative to End Alzheimer's. All donations go toward outreach and production.

Antimicrobial resistance is a rising global threat. When these become ineffective, infections can become difficult or impossible to treat, leading to an increase in the spread and severity of disease. In a new study, published in Nature Medicine, a team of researchers at the Center for Phage Biology and Therapy at Yale discovered a novel approach that may revolutionize the fight against antimicrobial resistance. In the study, the research team investigated the use of phage therapy—the use of viruses, or phages, to target and kill bacteria—to help patients with cystic fibrosis, a disease in which antimicrobial resistance is a significant issue. The team pioneered a strategy to select phages that not only kill bacteria that cause infections but also weaken surviving bacteria to become less virulent or less resistant to antibiotics. Joining me today to discuss phage therapy and their research is Jon Koff, MD, Dr. Koff is an associate professor in Yale School of Medicine's Section of Pulmonary, Critical Care, and Sleep Medicine and medical director of the Center for Phage Biology and Therapy.   Check out the paper: Phage Therapy May Treat Drug Resistance in Patients With Cystic Fibrosis, Study Finds   Watch the video version at Outbreak News TV

Join us on the latest episode, hosted by Jared S. Taylor!Our Guest: Ross Harper, CEO & Co-Founder at Limbic.What you'll get out of this episode:Scaling Mental Healthcare with AI: Limbic uses regulated AI agents to bridge the gap between mental health needs and clinical supply, enabling autonomous intake, triage, diagnostics, and care delivery.Largest Deployment of Generative AI in UK Healthcare: Adopted by 40% of the UK's NHS, supporting over 420,000 patients.Proven Clinical Impact: Peer-reviewed research in top journals (e.g., Nature Medicine) shows improved outcomes, reduced wait times, and better access—especially for underserved communities.Rapid U.S. Expansion: In just 9 months, Limbic has gone live in 13 states with a roadmap to reach all 50.Next-Gen AI Tools Incoming: Limbic is introducing voice capabilities and deeper clinical insights to further improve engagement and care delivery.To learn more about Limbic: Website https://limbic.ai Linkedin https://www.linkedin.com/company/limbic-ai/Our sponsors for this episode are:Sage Growth Partners https://www.sage-growth.com/Quantum Health https://www.quantum-health.com/Show and Host's Socials:Slice of HealthcareLinkedIn: https://www.linkedin.com/company/sliceofhealthcare/Jared S TaylorLinkedIn: https://www.linkedin.com/in/jaredstaylor/WHAT IS SLICE OF HEALTHCARE?The go-to site for digital health executive/provider interviews, technology updates, and industry news. Listed to in 65+ countries.

Trump dijo que "no está contento" después de que Rusia lanzó su ola de ataques más mortíferos contra Kyiv en nueve meses, diciéndole al presidente Vladimir Putin que "¡SE DETENGA!", mientras intenta presionar a Ucrania para que acepte una polémica propuesta de alto al fuego. Luego de que el miércoles hubo bloqueos y actos violentos en Michoacán, Guanajuato y Jalisco, Harfuch salió a decir que fue por un enfrentamiento entre bandas criminales. Se sabe que dos policías murieron y aún no hay detenidos.Además… Sheinbaum aseguró que no hay censura en la reforma a la ley de Telecomunicaciones que envió al Congreso; Asesinaron a la madre buscadora María del Carmen Morales, y su hijo en Jalisco; El Vaticano dejó abierta toda la noche la Basílica de San Pedro; Las tensiones entre la India y Pakistán están escalando; Grupo Modelo invertirá 3,600 millones de dólares en México; Y Dos personas resultaron heridas por el colapso de unas gradas en el Palacio de los Deportes durante el concierto de Quevedo.Y para #ElVasoMedioLleno… Un estudio publicado en Nature Medicine mostró que controlarse la presión, fortalece un 15% al cerebro frente a la demencia.Para enterarte de más noticias como estas, síguenos en redes sociales. Estamos en todas las plataformas como @telokwento. Hosted on Acast. See acast.com/privacy for more information.

The NACE Journal Club with Dr. Neil Skolnik, provides review and analysis of recently published journal articles important to the practice of primary care medicine. In this episode Dr. Skolnik and guests review the following publications:1. Adverse Outcomes Associated With Inhaled Corticosteroid Use in Individuals With Chronic Obstructive Pulmonary Disease. Annals of Family Medicine 2025. Discussion by:Guest:Barbara Yawn, MD, MSc, MPHAdjunct Professor, Department of Family and Community HealthUniversity of Minnesota Former Chief Scientific Officer at the COPD Foundation2. Optimal dietary patterns for healthy aging. Nature Medicine. Discussion by:Guest:Jessica Stieritz, MD Resident– Family Medicine Residency Program Jefferson Health – Abington3. Amount and intensity of daily total physical activity, step count and risk of incident cancer. British Journal of Sports Medicine. Discussion by:Guest:William Callahan, D.O. Associate Director – Family Medicine Residency ProgramJefferson Health – AbingtonMedical Director and Host, Neil Skolnik, MD, is an academic family physician who sees patients and teaches residents and medical students as professor of Family and Community Medicine at the Sidney Kimmel Medical College, Thomas Jefferson University and Associate Director, Family Medicine Residency Program at Abington Jefferson Health in Pennsylvania. Dr. Skolnik graduated from Emory University School of Medicine in Atlanta, Georgia, and did his residency training at Thomas Jefferson University Hospital in Philadelphia, PA. This Podcast Episode does not offer CME/CE Credit. Please visit http://naceonline.com to engage in more live and on demand CME/CE content.

In this episode, we're joined by the brilliant Dr. Tim Spector—Professor of Genetic Epidemiology, founder of the renowned TwinsUK study, and co-founder of the science-driven nutrition company ZOE. Known for his groundbreaking research featured in the Netflix documentary Hack Your Health and over 900 published studies, Dr. Spector dives into the fascinating science of the gut microbiome, why identical twins don't respond the same to food, and how ZOE's massive nutrition study (published in Nature Medicine) is transforming how we understand personalized health. We unpack the science behind fiber (why he eats 30 different plants a week), what improves or damages your microbiome, and how gut health ties directly to mood, sleep, and metabolic health. Dr. Spector also shares his thoughts on mental well-being, the real issue behind the rise of protein, and offers an early peek at the new Processed Food Risk Scale. If you're looking to go beyond basic nutrition advice and get into the real science of food, microbes, and health, this is the episode for you.Follow Dr. Tim Spector on InstagramZOE Gut Microbiome Test LINKZOE Fiber Supplement LINK

Welcome to today's episode, where we're diving into the delicious world of diet choices that not only make living longer more feasible but also turn the journey into an enjoyable experience. Modern medicine has undeniably extended our lifespan, yet it's crucial to ensure those extra years are filled with vitality and health. Fortunately, more and more people are recognising the power of smart dietary decisions.The foundation of this revelation isn't particularly new, echoing what naturopathic experts have been advocating for years. A balanced diet and lifestyle aren't just keys to longevity, they're essential for enjoying those golden years in full health and energy.A fascinating study, recently published in Nature Medicine, highlights the profound impact that careful food choices have on "healthy aging”, with findings suggesting a staggering 86% increase in the odds of achieving this. Today, we'll explore these insights, focusing on dietary guidelines such as the Mediterranean diet and the MIND diet, which combine nutritious elements to bolster cognitive and physical health.The study, led by Harvard T.H. Chan School of Public Health in collaboration with global researchers, delved into the effects of long-term adherence to various eating patterns. Their research spanned 30 years and included over 100,000 health care practitioners. It examined how these dietary habits influence the likelihood of living a healthier life into old age.So, is there a one-size-fits-all solution for dieting to achieve longevity? Not quite. As you'll hear, personalised approaches to diet are crucial for optimal results. Stay tuned as we unpack how you can tailor your eating habits to extend your years and truly enjoy life's later stages.GoodBad

In this episode Dr's J and Santhosh once again round up the latest in medical news this time with an emphasis on some surprising stories related to healthcare. Along the way they cover a peek behind the curtain of our production, cello scrotum, a new form of airline screening, Ro and contagion numbers,, the health benefits of scratching itches, the inflammatory response, permission to eat boogers, new methods to grow teeth, a rant about George Washingtons dentures, transgenic experiments tooth in eye surgery and more! So sit back and relax as we discuss things that will make you say, what the health??Further ReadingJournal reference Nature Medicine DOI: 10.1038/s41591-025-03501-4Science DOI: 10.1126/science.adn9390https://academic.oup.com/stcltm/article/14/2/szae076/7933795?login=truehttps://www.vice.com/en/article/surgeons-just-put-a-tooth-in-a-blind-patients-eye-to-restore-their-sight/Support Us spiritually, emotionally or financially here! or on ACAST+travelmedicinepodcast.comBlueSky/Mastodon/X: @doctorjcomedy @toshyfroTikotok: DrjtoksmedicineGmail: travelmedicinepodcast@gmail.comSpotify: https://open.spotify.com/show/28uQe3cYGrTLhP6X0zyEhTPatreon: https://www.patreon.com/travelmedicinepodcast Supporting us monthly has all sorts of perks! You get ad free episodes, bonus musical parody, behind the scenes conversations not available to regular folks and more!! Your support helps us to pay for more guest interviews, better equipment, and behind the scenes people who know what they are doing! https://plus.acast.com/s/travelmedicinepodcast. Hosted on Acast. See acast.com/privacy for more information.

What if one psychedelic plant could change how we approach trauma, addiction, and even neurodegenerative diseases?In this eye-opening episode of Keeping It Real, Jillian sits down with Bryan Hubbard, a leading voice in the psychedelic therapy space, to explore the power of Ibogaine therapy.Together, they take a deep dive into:How ibogaine works in the brain to disrupt addiction cycles, rewire trauma pathways, and stimulate neuroplasticity to help people with everything from sobriety to weight loss. The powerful potential of ibogaine therapy to address depression, anxiety, PTSD, and stress-related illnessWhy ibogaine may offer hope for those experiencing cognitive decline, and how it's being studied for conditions like Parkinson's disease, multiple sclerosis (MS), and Lyme diseaseThe recent Stanford University–Ambio study, published in Nature Medicine, showing remarkable improvements in veterans with traumatic brain injuries — and no serious adverse eventsWhy veterans, trauma survivors, and chronic illness patients are turning to alternative, plant-based healing modalitiesWhile ibogaine therapy remains unapproved by the FDA and is only legal in certain countries, this episode brings awareness to a growing global movement pushing the boundaries of how we understand and treat human suffering.Disclaimer: This episode is for educational and informational purposes only. Ibogaine is not FDA-approved and should not be considered medical advice. Always consult with a qualified healthcare provider.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

În cadrul ediției de pe 18 martie a emisiunii Știința360 de pe Radio România Cultural, Dr. Marius Geantă, Președintele Centrului pentru Inovație în Medicină, a comentat ultimele noutăți din domeniul sănătății. Un studiu publicat în Nature Medicine a raportat remisia pe termen lung la pacienții cu neuroblastom tratați cu terapie CAR-T direcționată către GD2. Unii pacienți au rămas fără semne de cancer timp de peste un deceniu, marcând un progres semnificativ în tratamentul tumorilor solide. Această cercetare oferă noi perspective asupra potențialului terapiei CAR-T dincolo de cancerele hematologice, aplicațiilor lor extinzându-se la tumori solide precum neuroblastomul.Terapia cu celule T cu receptor antigenic chimeric (CAR-T) este o metodă inovatoare de tratare a cancerului. Aceasta implică extragerea celulelor T ale pacientului—o componentă esențială a sistemului imunitar—modificarea lor genetică pentru a exprima receptori speciali (CAR) care vizează celulele canceroase și apoi, reinfuzarea CAR-T în organism. Aceste celule T modificate recunosc proteinele specifice de pe celulele canceroase și le atacă.Neuroblastomul este un cancer rar care afectează în principal copiii sub cinci ani. Acesta își are originea în celulele nervoase imature și este cunoscut pentru rata ridicată de recidivă, ceea ce face tratamentul deosebit de dificil. Între 2004 și 2009, cercetătorii au desfășurat un studiu clinic de fază I pentru a testa o terapie CAR-T inovatoare direcționată către GD2, o proteină supraexprimată în celulele de neuroblastom. Această terapie a utilizat două tipuri de celule T modificate: celule T activate (ATC) și celule T specifice virusului Epstein-Barr (VST), ambele concepute pentru a recunoaște și distruge celulele tumorale.Mai multe detalii despre subiectele discutate - ▶ Noi variante genetice asociate fibrilației atriale, descrise în cel mai amplu studiu de până acum▶ Noile recomandări NCCN pentru testarea ADN-ului tumoral circulant ca marker de prognostic pentru cancerul de colon, rect și carcinomul cu celule Merkel▶ Testul MyProstateScore 2.0, validat clinic pentru depistarea cancerului agresiv de prostată din probe de urină▶ Remisiune de 15 ani la pacienții cu neuroblastom tratați cu terapia CAR-T anti-GD2Ascultă emisiunea pe Radio România Cultural.

Richard Gaster, M.D., Ph.D., is a Managing Partner at venBio with experience as a physician, entrepreneur, and life science investor. Now, a cancer dad. He has helped to launch, invest, and serve on the board of or as board observer of a number of venBio companies. Prior to joining venBio, Dr. Gaster served as the head of translational medicine at Pliant Therapeutics. As a key member of the founding management team, Dr. Gaster was instrumental in the formation and launch of Pliant Therapeutics from Third Rock Ventures where he previously served as a Senior Associate.Dr. Gaster has published numerous articles in top-tier peer-reviewed journals including Nature Medicine and Nature Nanotechnology, holds more than a dozen patents, was awarded first prize in the IEEE Change the World Competition, and was named one of Forbes “30 Under 30” in Science and Healthcare.Dr. Gaster holds a B.S.E in Bioengineering from the University of Pennsylvania where he graduated summa cum laude and was a University Scholar. He received his M.D. and Ph.D. in Bioengineering from Stanford University in the Medical Scientist Training Program.On March 1, 2024, my daughter, Claire experienced a seizure. She was diagnosed with a type of brain cancer called AT/RT (atypical teratoid rhabdoid tumor), a highly aggressive grade IV glioma..... tune in for the rest of the story!You can also get involved with the Gold Ribbon Kids Cancer Foundation or the National Pediatric Cancer Foundation through fundraising, volunteering, promoting awareness, or contributing to pediatric cancer research. Visit goldribbon-kids.org or nationalpcf.org for more informationTo contact Tiffany, please email info@goldribbon-kids.orgTo contact Kelly, please email kgoddard@nationalpcf.orgSupport the show

As we move further into the year, 2025 brings further changes to The Psych Review team. This special episode is Shakira's last with the podcast, and we try to mark the occasion with a couple of very interesting and novel articles. Greg walks us through some exciting developments around the potential for GLP-1 receptor antagonists to treat psychosis, and Alanna digs into the complexity of delusions in psychosis and how things may be more complex than they seem. Goodbye Shakira, the team won't be the same without you!The references for this episode are:Greg: Yan Xie, Taeyoung Choi & Ziyad Al-Aly. Mapping the effectiveness and risks of GLP-1 receptor agonists. Nature Medicine (2025). Published online on 20 January 2025Alanna: Pappa, E., Baah, F., Lynch, J., Shiel, L., Blackman, G., Raihani, N., & Bell, V. (2025). Delusional Themes are More Varied Than Previously Assumed: A Comprehensive Systematic Review and Meta-Analysis. Schizophrenia bulletin, sbae225. Advance online publication. https://doi.org/10.1093/schbul/sbae225The Psych Review was brought to you by Call to Mind, a telepsychiatry service that you can learn more about at www.calltomind.com.au. The original music in our podcast was provided by the very talented John Badgery, and our logo was designed by the creative genius of Naz.

durée : 00:04:52 - Avec sciences - par : Alexandre Morales - Une nouvelle étude parue dans Nature Medicine fait le point sur l'évolution des cancers du sein à travers le monde et met en évidence de gros écarts de survie selon les niveaux socio-économique des pays.

La risposta a questa domanda arriva da uno studio pubblicato su Nature Medicine dei ricercatori dell'Università di Oxford che commentiamo con il professore Giovanni Scapagnini, Ordinario di Nutrizione Umana all’Università degli Studi del Molise e vicepresidente SINUT Società Italiana Nutraceutica,

This week, Kim and Grandma Gail bring it back to their early days of the podcast via video call. After a few hours of technical difficulties, they caught up on Kim's birthday celebrations, the hottest things coming to Palm Beach, how it's impossible to eat in NYC (let Kim and Gail know how to score a reservation at Chez Fifi), and fake Hermes bags. In honor of International Women's Day, the female founders of Excuse My Grandma give advice and recognition to all the amazing women pursuing their dreams! In the Drama Club, Kim recaps the Oscars. Grandma was in it for the fashion and red carpet, while Kim was there for the awards and the “Defying Gravity” performance (which she watches on repeat). In the Grandma Report, they discuss a recent Nature Medicine study (read the article here) about what really ages you. From loneliness to lifestyle habits, certain factors are in your control. Grandma recommends eating healthy, staying active, and enjoying life! Based on “The Kardashians,” biohacking and a vampire lifestyle might be the answer to longevity. Kim's latest obsession in The Rewind is “The White Lotus” (on Max). She's three episodes into Season 3, and already loving the drama. It's a murder mystery based in Thailand –what's not to like?!The women answer a listener's email, who is still thinking about a kiss she had 50 years ago! Would you tell your twin sister her boyfriend “accidentally” kissed you? Grandma and Kim give their honest thoughts. Do you have family drama you need opinions on? Write to team@excusemygrandma.com or DM us with a voicemail! To finish the episode, they play Should We Bring It Back: 1950s Slang Edition. Who else is calling their new crush a dreamboat instead of a smokeshow? They also answer your questions about snowbirding, fashion, and staying positive about dating in a round of Ask Grandma Anything. Follow us onInstagram @excusemygrandma TikTok @excusemygrandma Watch on YouTubeSpotifyMusic By: Guy Kelly(00:00) Intro(10:35) The Drama Club(15:25) The Grandma Report(18:57) The Rewind(20:08) Grandma Gail's Voicemail (22:53) Should We Bring It Back? (24:34) Ask Grandma Anything

A Northwestern Medicine study published in Nature Medicine, used a new technique called spatial transcriptomics to examine the brain's response to Alzheimer's therapies, revealing new molecular targets that could enhance the effectiveness of current therapies and not just slow the disease, but potentially improve patient outcomes. David Gate, PhD, assistant professor of Neurology in the Ken and Ruth Davee Department of Neurology and director of the Abrams Research Center on Neurogenomics, led this research. 

William Sauer, MD, FHRS, CCDS, Brigham and Women's Hospital is joined by Tobias Reichlin, MD, University Hospital Basel, Switzerland, and Nikolas Nozica, MD, Brigham and Women's Hospital, to discuss the Nature Medicine article Safety of pulsed field ablation in more than 17,000 patients with atrial fibrillation in the MANIFEST-17K study. The following is a brief summary of the study covered in the article. Pulsed field ablation (PFA) is an emerging technology for the treatment of atrial fibrillation (AF), for which pre-clinical and early-stage clinical data are suggestive of some degree of preferentiality to myocardial tissue ablation without damage to adjacent structures. Here in the MANIFEST-17K study, we assessed the safety of PFA by studying the post-approval use of this treatment modality. Of the 116 centers performing post-approval PFA with a pentaspline catheter, data were received from 106 centers (91.4% participation) regarding 17,642 patients undergoing PFA (mean age 64, 34.7% female, 57.8% paroxysmal AF, and 35.2% persistent AF). No esophageal complications, pulmonary vein stenosis, or persistent phrenic palsy was reported (transient palsy was reported in 0.06% of patients; 11 of 17,642). Major complications, reported for ~1% of patients (173 of 17,642), were pericardial tamponade (0.36%; 63 of 17,642) and vascular events (0.30%; 53 of 17,642). Stroke was rare (0.12%; 22 of 17,642) and death was even rarer (0.03%; 5 of 17,642). Unexpected complications of PFA were coronary arterial spasm in 0.14% of patients (25 of 17,642) and hemolysis-related acute renal failure necessitating hemodialysis in 0.03% of patients (5 of 17,642). Taken together, these data indicate that PFA demonstrates a favorable safety profle by avoiding much of the collateral damage seen with conventional thermal ablation. PFA has the potential to be transformative for the management of patients with AF.  https://www.hrsonline.org/education/TheLead https://doi.org/10.1038/s41591-024-03114-3 Host Disclosure(s): W. Sauer: Honoraria/Speaking/Consulting: Biotronik, Biosense Webster, Inc., Abbott, Boston Scientific, Research: Medtronic   Contributor Disclosure(s): N. Nozica: Nothing to disclose. T. Reichlin: Nothing to disclose. This episode has .25 ACE credits associated with it. If you want credit for listening to this episode, please visit the episode page on HRS365 https://www.heartrhythm365.org/URL/TheLeadEpisode93

On this week's episode, Chris Garabedian, Tim Opler, Sam Fazeli, Brian Skorney and Luba Greenwood begin with breaking news on the obesity front with Novo Nordisk's next-gen program, amycretin. The conversation transitions to post-JPM public market sentiment and a reluctance in capital markets. On the flip side, the hosts suggest a positive outlook for venture capital investments despite the public market challenges. The group also highlights the active M&A and licensing deal market, including the significant role of Chinese biotechs in licensing deals. The hosts also discusses the impact of Trump's administration's actions on the biotech sector, including the freeze on NIH activities and the potential withdrawal from the WHO. Other topics include potential of AI in healthcare, Biogen's strategic shifts, Nature Medicine paper on GLP-1 drugs effects, and more. This episode aired on January 24, 2025.

Una mujer con neuroblastoma que fue tratada con células CAR-T cuando era una niña, permanece en remisión 18 años después. Es el caso de mayor duración tras una terapia de este tipo descrito hasta la fecha. Los resultados se publican en la revista Nature Medicine. Diego Sánchez, investigador ARAID en el Instituto de Investigación Sanitaria Aragón, explica este caso, y las perspectivas de Aragón en estas terapias. Además, Ágora conversa con Martín Resano, coordinador del grupo Métodos Rápidos de Análisis con Técnicas Espectroscópicas (MARTE) e investigador del I3A reconocido en Europa por su labor en el ámbito de la espectroquímica del plasma.

Una mujer con neuroblastoma que fue tratada con células CAR-T cuando era una niña, permanece en remisión 18 años después. Es el caso de mayor duración tras una terapia de este tipo descrito hasta la fecha. Los resultados se publican en la revista Nature Medicine. Diego Sánchez, investigador ARAID en el Instituto de Investigación Sanitaria Aragón, explica este caso, y las perspectivas de Aragón en estas terapias. Además, Ágora conversa con Martín Resano, coordinador del grupo Métodos Rápidos de Análisis con Técnicas Espectroscópicas (MARTE) e investigador del I3A reconocido en Europa por su labor en el ámbito de la espectroquímica del plasma.

Raidījumu esam veltījuši Valentīna dienas noskaņām dzīvnieku pasaulē. Cilvēks ir radījis sarežģītu sociālo shēmu, kā iepazīstas, dibina kontaktus, draudzības, vēlāk arī partnerattiecības. Dzīvnieku pasaulē katrai sugai ir savi paradumi un stingri rakstīti likumi, kuriem sekot. Taču kā dzīvnieki nonāk viens otra uzmanības lokā, dzīvojot slēgtā vidē, piemēram, zooloģiskajā dārzā? Dabā stiprākais ir iekārojamāks pretēja dzimuma acīs, bet ģimenes dibināšana sākas ar skaistu gada parādi - riestu. Kā tas notiek ierobežotā vidē, piemēram, zooloģiskajā dārzā? Kā speciālisti darbojas par dzīvnieku "savedējiem" un kā rodas pēcnācēji šādos kontrolētos apstākļos? Raidījumā Zināmais nezināmajā atklāj Rīgas Nacionālā Zooloģiskā dārza pārstāvis Māris Lielkalns un ihtiologs, Zinātniskā institūta "BIOR" Jūras nodaļas vadītājs Ivars Putnis. Raidījuma ievadā zinātnes ziņas Afantāzija skar 2 līdz 4 procentus iedzīvotāju Mēs mēdzam lietot tādus teicienus kā “pafantazēsim - kā būtu, ja mēs tagad atrastos vienā vai otrā vietā”, “manās fantāzijās es dažkārt mēdzu darīt vienu vai otru lietu” un tamlīdzīgi. Bet izrādās, ka nelielai daļai pasaules iedzīvotāju ir afantāzija, un tas nozīmē, ka viņi nespēj neko vizuāli iztēloties, un par to tad vietnē “Live Science”. Tātad, ja cilvēkam ar afantāziju liek iedomāties, ka viņš, piemēram, atrodas pludmalē un redz rietošas saules starus, kas jūras virsmu oranžā un zeltainā krāsā, tad viņš visticamāk neko tādu neredzēs. Afantāzija skar 2 līdz 4 procentus iedzīvotāju, tomēr pētījumi par šo parādību vēl ir visai ierobežotā skaitā. Kafija nāk par labu cilvēka zarnu mikrobiomam Ja par afantāziju vēl daudz kas nav zināms, tad gadsimtiem ilgi daudz ir zināms par aromātisko dzērienu kafiju. Tajā pašā laikā ir parādījies daudz un dažādu versiju gan par kafiju, gan citiem produktiem, piemēram, šokolādi vai vīnu un to, kā tie atsaucas uz cilvēka organismu. Uzticēties var speciālistiem - ārstiem, kuri, ja runājam kafiju, ir teikuši, ka divas līdz trīs kafijas tases dienā organismam nekaitē un pat nāk pat labu, piemēram, sirds veselībai, un šoreiz apstājāmies pie raksta vietnē “Scientific American”, kurā vēstīts par kafijas labvēlīgo ietekmi uz zarnu baktēriju darbību - par šo aspektu nudien līdz šim nekas plaši nav bijis zināms. Mikro- un nanoplastmasa spēj uzkrāties cilvēka galvas smadzenēs Vēl īpaši pēdējo gadu laikā ir bijis daudz publikāciju par mikroplastmasu - plastmasas daļiņām, kas mazākas par pieciem milimetriem un var būt pat ar izmēru viens nanometrs, ko mēs ar aci tad redzēt nevaram. Ir bijuši skaidrojumi, ka mikroplastmasa nu jau pilnīgi noteikti nonāk mūsu organismā, ņemot vērā, kādi plastmasas kalni peld gan jūrās un okeānos, gan vienkārši ir kaut kur izsviesti. “CNN” publicēts raksts, kur minētas atsauces uz dažādos laikos veiktiem pētījumiem, tostarp uz pavisam nesen publicētu pētījumu žurnālā “Nature Medicine”. Šajā pētījumā zinātnieki analizējuši smadzeņu, nieru un aknu audus, kas jau agrākos gados iegūti no cilvēkiem, kuriem veikta tiesu ekspertīze. Smadzeņu audos salīdzinājumā ar aknām un nierēm konstatētas lielākas polietilēna proporcijas, un, kas vēl būtiski, lielāka mikro- un nanoplastmasas koncentrācija novērota to mirušo cilvēku smadzeņu paraugos, kuriem ir bijusi fiksēta demence, attiecīgi mikro- un nanoplastmasa ievērojami nogulsnējusies uz smadzeņu asinsvadu sieniņām un imūnajās šūnās.    

Die Themen in den Wissensnachrichten: +++ Omega-3-Fettsäuren könnten Altersveränderungen bremsen +++ Altsteinzeit-Menschen hatten wohl schon Piercings +++ Koffein schützt vermutlich Mate-Pflanze +++**********Weiterführende Quellen zu dieser Folge:Individual and additive effects of vitamin D, omega-3 and exercise on DNA methylation clocks of biological aging in older adults from the DO-HEALTH trial, Nature Aging, 03.02.2025Probable Use of Labrets Among the Mid Upper Paleolithic Pavlovian Peoples of Central Europe, Journal of Paleolithic Archaeology, 23.01.2025Yerba mate (Ilex paraguariensis) genome provides new insights into convergent evolution of caffeine biosynthesis, Elife, 08.01.2025Bioaccumulation of microplastics in decedent human brains, Nature Medicine, 03.02.2025Local chemical heterogeneity enabled superior zero thermal expansion in nonstoichiometric pyrochlore magnets, National Science Review, 17.12.2024Alle Quellen findet ihr hier.**********Ihr könnt uns auch auf diesen Kanälen folgen: TikTok auf&ab , TikTok wie_geht und Instagram .

In this milestone 50th episode, co-hosts Donna LaLonde and Ron Wasserstein continue their tradition of introducing the American Statistical Association’s incoming president. Ji-Hyun Lee, the ASA’s 120th president, joins them to share her vision for 2025, which is centered on “building bridges.” As she begins her presidential year, Lee shares both her excitement and jitters, reflecting, “This presidency is the honor of a lifetime—and with that honor comes an incredible sense of responsibility.” Several promising initiatives are already underway. One example is her groundbreaking collaboration with Nature Medicine, which by integrating statistical ... The post Practical Significance | Episode 50: Building Bridges with ASA 2025 President Ji-Hyun Lee first appeared on Amstat News.

Trump rilancia sui palestinesi fuori da Gaza e considera DeepSeek “un campanello d’allarme”. Intanto oggi inauguriamo “Il mondo di Trump”, progetto in collaborazione con Il Sole 24 Ore e Radiocor che scandaglia vari aspetti della politica del nuovo presidente americano, con un primo appuntamento dedicato a multinazionali e fisco. Con noi oggi Alessandro Galimberti de Il Sole 24 Ore. Il maltempo si abbatte su Liguria e Toscana. Nel 2099 il cambiamento climatico potrebbe far aumentare le morti per caldo in Europa: lo indicano le stime di una ricerca pubblicata sulla rivista Nature Medicine e condotta dalla London School of Hygiene & Tropical Medicine. Sentiamo Serena Giacomin, climatologa e meteorologa, direttrice scientifica di Italian Climate Network. Migranti: mentre la nave Cassiopea attracca in Albania, i dati di gennaio mostrano un aumento di sbarchi dalla Libia rispetto all’anno scorso. Ne parliamo con Federica Saini Fasanotti, ricercatrice associata ISPI.

Join us this episode for a conversation with Dr. James D. Guest, MD, PhD, of The Miami Project to Cure Paralysis, for a conversation about the paper titled "Non-invasive spinal cord electrical stimulation for arm and hand function in chronic tetraplegia: a safety and efficacy trial" published in the journal Nature Medicine. This paper is the culmination of commercialization efforts to bring to market a transcutaneous ("noninvasive") electrical spinal cord simulator for the purpose of recover of upper extremity motor strength. We trust you will enjoy our conversation with Dr. Guest, who was a site-Principal Investigator (PI) for the Up-LIFT trial sponsored by Onward Medical Inc., in the timely wake of the exciting FDA approval of the now-titled ARC-EX® device that was studied in this pivotal clinical trial.

Join us this episode for a conversation with Dr. James D. Guest, MD, PhD, of The Miami Project to Cure Paralysis, for a conversation about the paper titled "Non-invasive spinal cord electrical stimulation for arm and hand function in chronic tetraplegia: a safety and efficacy trial" published in the journal Nature Medicine. This paper is the culmination of commercialization efforts to bring to market a noninvasive ("transcutaneous ") electrical spinal cord simulator for the purpose of recover of upper extremity motor strength. We trust you will enjoy our conversation with Dr. Guest, who was a site-Principal Investigator (PI) for the Up-LIFT trial sponsored by Onward Medical Inc., in the timely wake of the exciting FDA approval of the now-titled ARC-EX® device that was studied in this pivotal clinical trial.

Raymond Tallis is Professor Emeritus of Geriatric Medicine at the University of Manchester. He is a philosopher, poet, novelist, cultural critic, and a retired physician and clinical neuroscientist. He trained in medicine at Oxford University and at St Thomas' in London and has 4 honorary degrees: DLitt (Hull, 1997) and Litt.D. (Manchester, 2001) for contributions to the humanities; and DSc (St George's Hospital Medical School, 2015; University of East Anglia, 2017) for contributions to medicine. He was an editor and major contributor to two key textbooks in the field, The Clinical Neurology of Old Age and Textbook of Geriatric Medicine and Gerontology and author of over 200 original scientific articles, including papers in Nature Medicine, Brain, Lancet. He has published fiction, poetry, and over 30 books on the philosophy of mind, metaphysics, philosophical anthropology, and literary and cultural criticism. Lecture Title: "Rescuing the Self from the Philosophers" EPISODE LINKS: - Raymond's Podcast: https://www.youtube.com/watch?v=6F7gsOs5JBI - Raymond's Website: https://tinyurl.com/2nentc3x - Raymond's Work Site: https://tinyurl.com/32p9fpvc - Raymond's Books: https://tinyurl.com/3s5b9f98 CONNECT: - Website: https://tevinnaidu.com - Podcast: https://creators.spotify.com/pod/show/mindbodysolution - YouTube: https://youtube.com/mindbodysolution - Twitter: https://twitter.com/drtevinnaidu - Facebook: https://www.facebook.com/drtevinnaidu - Instagram: https://www.instagram.com/drtevinnaidu - LinkedIn: https://www.linkedin.com/in/drtevinnaidu ============================= Disclaimer: The information provided on this channel is for educational purposes only. The content is shared in the spirit of open discourse and does not constitute, nor does it substitute, professional or medical advice. We do not accept any liability for any loss or damage incurred from you acting or not acting as a result of listening/watching any of our contents. You acknowledge that you use the information provided at your own risk. Listeners/viewers are advised to conduct their own research and consult with their own experts in the respective fields.

En Alemania, un estudio cientifico deterinó que el uso de inteligencia artificial en programas de tamizado mamográfico puede aumentar la tasa de detección de casos de cáncer sin incrementar los falsos positivos. Según la revista Nature Medicine, incluyeron a más de 460.000 mujeres de entre 50 y 69 años y se llevó a cabo en 12 centros de cribado en Alemania entre julio de 2021 y febrero de 2023.

The Chief Scientific Advisor at Novo Nordisk, Lotte Bjerre Knudsen, was the key force who pushed hard to develop GLP-1 drugs for treating obesity and subsequently for Alzheimer's. She was recently recognized by the 2024 Lasker Medical Research Award, and the 2024 AAAS Bhaumik Breakthrough of the Year Award. That recognition is richly deserved, since it is unclear if the GLP-1 drug path to obesity treatment, and all of the associated benefits, would have been seen at this time without her influence. That's especially true given the mystery for why people with Type 2 diabetes (for which these drugs were used for many years) did not exhibit much in the way of weight loss. We discussed that and the future of these drugs, including their potential to prevent neurodegenerative diseases. And about dressing up in pink!The Ground Truths podcasts are also available on Apple and Spotify.Our entire conversation can also be seen by video at YouTube along with all of the Ground Truths podcasts. If you like the video format, please subscribe to this channel. Even if you prefer video, please take a look at the transcript with graphics and useful links to citations.A Video Clip below on the barriers of a woman scientist to push Novo Nordisk to develop GLP-1 for obesity. “I was always just been a nerdy little scientist who kind of found home here in this company for 35 years.”—Lotte Bjerre Knudsen, 60 MinutesTranscript with Links to audio and external referencesEric Topol (00:06):Well, hello, it's Eric Topol with Ground Truths, and I have with me a special guest. She's the Chief Science Officer of Novo Nordisk and it's Lotte Bjerre Knudsen, and we're delighted to have her. She's a recent recipient of the Lasker Award, which I think is considered like the pre-Nobel Award here in the United States. And I was involved with her in terms of researching who was the principal person who brought the GLP-1 drugs to the forefront for obesity, and it turned out to be Lotte. So welcome, Lotte.Lotte Bjerre Knudsen (00:48):Thank you very much. And also very, very happy to be here. I'm not the Chief Science Officer for Novo Nordisk, I'm the Chief Scientific Advisor of working for the Chief Science Officer of Novo Nordisk, but maybe too many people, not so different, right?From Laundry Detergents to GLP-1 DrugsEric Topol (01:06):Yes. Thank you, I actually meant to say advisor, but yes, I'm glad you cleared that up. I know from speaking to some of your colleagues, I actually spoke to Robin yesterday that you are looked to very highly, the most highly regarded person in science there, so not surprisingly. What I want to do is first talk about the glucagon-like peptide-1 (GLP-1) that got its legs back in, I guess 1984. So we're going way back. And what's also interesting is that you go way back at Novo Nordisk to 35 years in 1989. And so, there had been this work with this extraordinary hormone and neurotransmitter with a very short half-life that you knew about. But when you first started in Novo Nordisk, you weren't working on this. As I understand it, you're working on laundry detergent enzymes. How did you make this pivot from the laundry enzymes to getting into the GLP-1 world?Lotte Bjerre Knudsen (02:16):Yeah, thank you for that question. I'm from the technical University of Denmark, so I'm trained in biotechnology, and we're a small country, so not that many companies to work for. And I always had my mind set on, I wanted to work for Novo as it was called back then, and it just happened to be in the industrial enzyme part that I got my foot in first. And then I had a very interesting boss at the time. Unfortunately, he's not alive anymore, but he was both a medical doctor as well as a chemist. So he was actually put in charge of actually, let's see if we can do something new in diabetes. And then since he hired me and I had not been there that long, I simply tagged along as the youngest scientist on the team, and then suddenly I became a diabetes researcher. Around the same time, I think you remember that all of pharma was interested in obesity in the early 90s, everyone wanted to do diabetes as well as obesity, but they were separate teams and they all wanted to do small molecules, but it just happens to be so that the best idea we could find at that time was actually GLP-1, because we actually had clinical data relatively early that GLP-1 was a really good candidate as a treatment for diabetes because of the glucose sensitivity of the actions.(03:43):So you'd have efficient lowering of glucose through a dual mechanism with increasing insulin, lowering glucagon, and then it was safe because there wasn't this hypoglycemia you get from insulin. But then I had other colleagues who were working on obesity, and I was just kind of listening, right, what's going on there? And then also a colleague that I had, we had, I don't know if you remember the old Hagedorn Research Institute, but Novo actually had kind of like an academic research institute that was affiliated with us. And there was this group that were working on this glucagon tumor model that produced high levels of glucagon, GLP-1 and PYY. And these rats, they starved themselves to death. And I knew about that from 1994. So that actually inspired my thinking. So when Stephen Bloom's paper came out in January of 1996, and he was the first one to call GLP-1 a neurotransmitter, I think, but I was already way into actually screening these kind of molecules that later then became liraglutide.No One Else Thought About This [Obesity](04:54):And then I thought, why on earth should we not actually do both things at the same time? If we have an idea that can both work in diabetes in a much safer way than in insulin, and then also at the same time work in obesity. But the reality is that no one else thought about this, or if they thought about it, they didn't really think that it would a good idea. But I think I had the luxury of being in a biotech company, so everyone was working with peptides and proteins. So I don't think I got the same challenge that the other people in the other pharma's got when they all wanted small molecules.Eric Topol (05:36):Well, also just to set the foundation here, which you alluded to, there had been so many attempts to come up with a drug that would work, not just of course in diabetes where there are many classes of drugs, but moreover, to treat the condition of obesity. Actually, I was involved with one of them, Rimonabant and did the large trial, which as you know, led to having to stop the drug, discontinue it because it was associated with suicidal ideation and actual some suicide. So there had been such a long history of checkered inability to come up with a drug. But what was striking is the challenge, and this is one of the first important questions about, when you had the extended half-life of the first GLP-1 drug, that instead of having to take multiple times a day, you could actually, with liraglutide get to a point where you were starting to get to an extended half-life. This is now going back to 1997 with approval in 2010, still 14 years ago. But when you came up with this drug, because this was certainly one of your great contributions, this drug was just a step along the way in this kind of iterative process, wouldn't you say? It wasn't the long half-life and the potency that eventually got us to where we are today. Is that true?Lotte Bjerre Knudsen (07:15):Yeah, it was a stepwise process. And what's super interesting about this class of medicines is that they're actually so different. If you talk about a class of medicine where small molecules, they can be different, but they're usually more alike than they're different. And when it comes to this class with these medium-sized peptides, people tried a whole bunch of different things. So they're actually really, really different. Some are simple peptides. So the idea that I came up with was to use this fatty acid isolation principle, and that's then a subclass in the class. And then the first, once weekly, for example, was an antibody-based molecule liraglutide. So they're much, much, much larger molecule compared to the small peptides. So they're very different. And neither the simple peptides nor the really big antibody derived molecules, they don't give a lot of weight loss. So we actually get more weight loss with these kinds of molecules, which is also why you can now see that it has actually kind of inspired a whole industry to kind of try and go and make similar kinds of molecules.Eric Topol (08:27):Well, inspired a whole industry is an understatement. It's become the most extraordinary class of drugs, I think in medical history, having been a student of various, I mean obviously statins have been a major contribution, but this seems to have transcended that already. We're going to talk about more about where things are headed, but this fatty acid acetylation was a major step forward in extending the half-life of the drug, whereby today you can give semaglutide once a week. And this, I think, of course, there are many ways that you might've been able to extend the half-life, but you were starting with a hormone, a natural hormone neurotransmitter that had such an exquisitely short half-life of basically second or minutes rather than that you could give for a week. So I know there were many different ways you could have protected or extended the half-life one way or another, but this seemed to be a breakthrough of many along the chain of breakthroughs. But the question I have is when you were giving this to the diabetics, which was the precedent, that was really what these drugs were first intended, they didn't lose that much weight, and they never, still today when it's looked at for obese non-diabetics versus diabetics, there's a gap in weight loss. Why is that at the exact same dose, with the exact same peptide that the weight loss differs for people with type 2 diabetes as compared to those who have pure obesity?The Mystery of Why People With Type 2 Diabetes Don't Lose Weight Like Those With Obesity Lotte Bjerre Knudsen (10:09):Yeah, I can't give you a molecular answer to that, right. But I think the notion, I think it's the same for example with metformin, even though it gives less weight loss because that has also been tried in both people with diabetes and people without diabetes. So I think it's just for somehow people with diabetes are more resistant to weight loss. I think it's a really good question that I'm hoping maybe we could get through, for example, with proteomics and actually comparing people with diabetes and people without diabetes and looking at people who have the similar kind of weight loss. That could be really interesting. But I really don't have a good molecular answer for you, but it's just a really, really strong fact. But it also leads me to wanting to say it's interesting, because if that had been our motivation to actually say, oh, there's weight loss in diabetes, let's pursue it in people with obesity, I don't think we would've done that because the weight loss in people with diabetes wasn't that impressive. So it was very important for our chain of thought and decision early on that we actually knew that GLP-1 had these separate effects and that they could work in the brain and have a separate effect on well-known pathways in the brain. And that was more our motivation to actually continue to invest in obesity.Eric Topol (11:42):Yeah, no, I think this is when we did the research on the committee for the American Association for Advancement of Science (AAAS) award, the Mani L. Bhaumik Award, that you were recognized for the breakthrough of the year, this year. We tried to scour all the work and we actually had to hit Danish translations and all sorts of other papers they reviewed. And we learned through that process working on this committee that you were the one to be the champion of pushing this towards obesity, and it would've easily been missed because as we've been discussing, the weight loss in people with diabetes was small, but you push for it. And this was an extraordinarily important push because what it has resulted in, of course, has been spectacular. And obviously as we're going to get into much more than just obesity and obesity related conditions. But before we get to those other conditions, and as you've been known in the medical community as “the mother of GLP-1”, you were dubbed that term. The GLP-1 receptor is expressed in many parts of the body. Maybe you could just tell us about the distribution because this, I think is tied into these central nervous system effects that are not just related to the gut hormone type of axis.GLP-1 Receptors and the BrainLotte Bjerre Knudsen (13:17):So I spent a lot of time on that together with my amazing colleague, Charles Pyke, who's an histology expert because it turned out to be so very important. In general, when you're trying to make new medicines, understanding the mechanism, sometimes people say, yeah, who cares? But actually, it should matter, I think because where it becomes really important can be an understanding what they do not do. We've had to do a lot of proving the negatives for GLP-1. We went through these issues with thyroid cancer, pancreatitis, pancreas cancer. In all of that work, it was actually really important that we could show where the GLP-1 receptor was not expressed. So in the pancreas, we know that it's primarily on the insulin producing cells, and then we also have them in the intestine where they're probably involved in regulating inflammation and really creating a much healthier gut.(14:15):And then we have a lot of receptors in the brain. They're typically expressed on neurons, but they're also on astrocytes, they're also on smooth muscle cells. We have them on the heart and the sinus node. That's why there's a small increase in heart rate. We have them in the kidney, on again some smooth muscle cells that are renin positive. So there we can start thinking blood pressure and other things. So it turns out that you can go around the body and there are all of these specific GLP-1 receptor population, that you can see how they tie into the pharmacology. But obviously in physiology, they're not as important as they have turned out to be in pharmacology when we suddenly come with 24 hours a day exposure for a day or a week or for as long as the administration interval is. So, but specifically for obesity, I think it's in the vein, it's hard to, you should always be careful.(15:18):That's something I've learned to never say never. Of course, there could be a contribution from the peripheral nervous system as well to the effects in obesity. But I do think there are so many important and well described neuronal populations that have the GLP-1 receptor and which are accessible from the periphery. So just to mention, maybe one of the most, well-known is a POMC/CART neuron in the hypothalamus. They have the GLP-1 receptor, they're activated, but there also is an inhibitory tone on the AgRP and NPY neurons, and it fits very well with that. We know that people report that they feel more sated, they feel less hungry. But then there are also effects in the hindbrain and in some of the reward centers also have GLP-1 receptors. And we know that also now, we have really good actually clinical studies that show that there is a change in food choice and people can control their food intake better. So I think that fits very well with effects on the reward system. So it's a whole myriad, or maybe you could say that GLP-1 orchestrates a number of different neuronal populations to have these overall effects that reduce energy intake.Eric Topol (16:42):Yeah, it's pretty striking. It's almost like we're all walking around with GLP-1 deficiency, that if we had this present at higher levels around the clock, and of course eventually we'll see things that are well beyond obesity, how well this has an impact. Now, there was an extraordinary review in Cell Metabolism on the brain and GLP-1, and not just the brain, but the essential nervous system, the neurovascular, it's called the “GLP-1 programs and neurovascular landscape.”(17:20):And in this review, it got into the brain effects that were well beyond, I think what are generally appreciated. Not only the protection of the integrity of the blood-brain barrier, this whole neuroglial vascular unit, the myelin sheath protection, reducing inflammation within the brain, improving the glymphatic flow, which is of course critical for clearing waste and promoting cerebral vascular remodeling and more, so the brain effects here is what it seems to be. You mentioned the reward circuit, of course, but the brain effects here seem to be diverse, quite a bit of breath and extraordinary. And as we've seen in the clinic now with the work that's been done, we're seeing things about addiction, even gambling, alcohol, drugs, I mean neuropsychiatric impact, it's pretty profound. Maybe you could comment about that.On to Alzheimer's and Parkinson's DiseasesLotte Bjerre Knudsen (18:23):Yeah. I haven't read that paper yet, but I just saw it earlier. And I have been following this for about actually more than 10 years because when I was kind of over the big work of actually getting the approval for diabetes and obesity. I thought I had a little bit of capacity to actually look at Alzheimer's and Parkinson's disease because I just thought there's such an insane unmet need and what if GLP-1 could actually make a difference? And the first big paper that talked about this was actually in Nature Medicine in 2003, and it was originally, I think I should credit Nigel Greig. Greig, he's from NIH or from NIA, I can't remember, right. But he was actually the first one, I think to say if GLP-1 has all of these important effects in the pancreas and to protect cells, and there are all these GLP-1 receptors in the brain, maybe it also protects neurons.(19:25):So that was the first hypothesis. And the paper on Nature Medicine in 2003 describes how the GLP-1 receptor in the hippocampus is involved in cognition. And then we did a couple of studies in different animal models, and I was, to be honest, really confused. But then there was a new paper in Nature Medicine in 2018 that started to focus in on neuroinflammation. And by that time, I knew much more about inflammation and knew GLP-1 actually lower CRP by about 50% in the different trials. So I was really tuned into the potential importance of that in cardiovascular and kidney disease. But I was like, oh, what if that's also something that is important in the brain? Then it made more sense to me to try and build some evidence for that. So that was how we actually started looking at a hypothesis for Alzheimer's and Parkinson's.(20:21):And we now have a really large phase three study ongoing, but of course, it's a hypothesis, right? And no one has yet, I think, proven that GLP-1 has really important effects on these indications, but we are testing it in 4,000 people with Alzheimer's disease. So our hypothesis is around neuroinflammation, but defined in a way where you could say it's both peripheral inflammation and the effect it has on the vasculature, it's the effect on the blood-brain barrier. It's the astrocytes and the microglia, and there are probably also some T cells that have the GLP-1 receptor that could be important. And then couple that up also with some of the new information from neurons, because there are two papers to think in the last year that has highlighted neurons either in the hindbrain or a little bit further on. Both of them are probably hindbrain populations that actually seem to be really important in regulating both peripheral as well as central information.(21:27):So what if neurons are actually also an overlooked mechanism here, and both of these neuronal populations have the GLP-1 receptor and are accessible from the periphery, even though the child super paper in Nature doesn't mention that, but they do have the GLP-1 receptor. So there are all these different mechanisms that GLP-1 can have an impact on the broad definition maybe of neuroinflammation. And maybe the way one should start thinking about it is to say it's not an anti-inflammatory agent, but maybe it induces homeostasis in these systems. I think that could maybe be a good way to think about it, because I think saying that GLP-1 is anti-inflammatory, I think that that's wrong because that's more for agents that have a really strong effect on one particular inflammatory pathway.Eric Topol (22:22):That's a very important point you're making because I think we conceive of these drugs as anti-inflammatory agents from these more diverse actions that we've just been reviewing. But I like this restoring homeostasis. It's an interesting way to put it. This brings us, you mentioned about the Parkinson's, and when I reviewed the three randomized Parkinson's trials, they're all small, but it appears to be the first disease modifying drug ever in Parkinson's. Of course, these were done with different drugs that were older drugs. We haven't seen the ones that yet to be with semaglutide or other agents. And I wondered if you pushed, just like you did for obesity within Novo Nordisk, you pushed to go into obesity. Did you also force to push for Alzheimer's?Lotte Bjerre Knudsen (23:19):Yes. So that is also me who had to argue for that. I'm happy to do these things. I was born brave. I am happy to do these things.Eric Topol (23:31):That's wonderful. Without you, we would be way behind, and it took decades to get to this point. But look where we are now, especially with all the rigorous trials, the large clinical trials. You're into one right now of some 20,000 participants to see whether not just people with prior heart disease, but people without known heart disease to see whether or not this will have an effect. And there's so much data now, of course, already a completed trial with reduction of heart attacks and strokes. But now to extend this to people who are not such high risk, but these large trials, we keep learning more. Like for example, the reduction of inflammatory markers is occurring even before the weight loss that starts to manifest. So we learned a lot from the trials that are just even beyond some of the major primary outcomes. Would you agree about that?Lotte Bjerre Knudsen (24:34):So I'm not sure we can say that it comes before the weight loss because the energy intake reduction happens instantly. The glycemic response happens instantly. And all of these improvements will of course also have an effect to dampen inflammation. We do not have data that supports that it comes before because we haven't sampled that much in the beginning.Eric Topol (25:04):Okay.Lotte Bjerre Knudsen (25:05):I wouldn't be able to say that, and I don't think there are any, well, it's hard to keep up that the entire literature on GLP-1 these days, but I don't think anyone has actually shown that there is a separation because it's super hard to separate when things are occurring at the same time.Eric Topol (25:24):Yeah, I'm just citing the heart disease trial where in the New England Journal that point was made. But I think your point also that there was already a change in energy intake immediately is apropos for sure. Now, when we get into this new paper of yours, the proteomics, can you tell us about that because that's really exciting. We're in a high throughput proteomics era right now that we can analyze thousands of plasma proteins in any given individual. What are you learning about proteomics with the GLP-1 drug?The GLP-1 Drug Impact on ProteomicsLotte Bjerre Knudsen (26:07):Yeah, yeah. So I'm also the super excited about omics, right? Because I have worked in a wonderful organization of people who can do these large scale clinical trials, and we used to not collect a lot of samples for future use, but we've done that for some years now. So now we have this amazing collection of samples we can learn from and actually both inform the patients and the physicians, but also inform future research. So we have been doing that in our semaglutide trials, and we've just published the proteomics data from the step one and step two trials. So the phase 3a trials that supported the approval of semaglutide for the treatment of obesity. So one of them in people with obesity and one in people with obesity and diabetes, and those data are now published in Nature Medicine. [3 January 2025]. And we were learning a lot of things because you can compare the proteome effects to what has been done in the decode cohort.(27:11):So they have all these disease signature. So that's one thing that you can for sure see, and you can see a lot of things there with hints towards addiction. And then also you can take more predefined signatures also to look into what actually might be driving the cardiovascular risk. So I think there are so many things that you can learn from this, and of course it can also inform when you look at what's actually mediating the effect and probably something around inflammation is important. We have already also shown a more standard mediation analysis that shows that actually the most explainable factor for the effect on MACE [major adverse cardiovascular events] in the select trial is inflammation. It doesn't explain everything, but it actually looks like it's more important than BMI and weight loss. So that's really interesting how much we can learn from there. We're making the data are available at the summary statistic level so people can go and play with them ourselves.(28:23):And I think as we have more different kinds of medicines available in obesity, it's also a way to kind of compare how these different medicines work. And as we get more and more better at maybe also characterizing people with obesity, because I think that's a great thing that's going to happen now is there's going to be more funding for obesity research. Because I think that's what the attention that we are seeing right now is also giving. Then we can better start to understand. We always, we've been saying that people probably have different kinds of obesity, but we don't really know. So now we can actually start to understand that much better and maybe also understand how these different classes of medicines will work if we have the proteome data from different trials.Eric Topol (29:10):No, I'm absolutely fascinated about the proteomics. I call it a quiet revolution because many people don't know about it. [My recent post on this topic here.](29:18):The ability to assess thousands of proteins in each individual, and it's giving us new insights about cause and effect as you alluded to, the relationship with as you said, MACE (major adverse cardiovascular events) and the actions of this drug class. I mean, there's just so much we can learn here from the proteomics. Another thing that's fascinating about the GLP-1 is its effect on epigenetic clocks. And recently at one of the meetings it was presented, this is Steven Horvath that we had on Ground Truths not long ago. He talked about at this talk that for the first time to see that you could basically slow the epigenetic clock with a GLP-1. Is there any further information about that?Lotte Bjerre Knudsen (30:16):Yeah, no. We've never had enough of a sample size to actually be able to look at it, so unfortunately, no. But there is something else, right, because there is this group at the Stanford, Tony Wyss-Coray or something.Eric Topol (30:33):Yes, Tony Wyss-Coray.Lotte Bjerre Knudsen (30:35):Now he published a paper, is it two years ago? Where he did it using proteomics. He defined an anti-aging signature for various different organs.Lotte Bjerre Knudsen (30:46):We are in the process of trying to see if we could take those signatures and apply them on to our data.Eric Topol (30:55):Well, what's interesting is we're pretty close friends, and he, not only that paper you mentioned on organ clocks, which is a phenomenal contribution, but he has a paper coming out soon in Nature Medicine, the preprint is up, and what he showed was that the brain and the immune system was the main organ clocks that were associated with longevity. And so, it takes another step further and it's looking at 11,000 plasma proteins. So it's really interesting how this field is evolving because the omics, as you put it, whether it's proteomics, and now we're learning also about the epigenome and what brings us to the potential that this class of drugs would have an impact on health span in all people, not just those who are obese. Would you project that's going to be possible in the years ahead?Lotte Bjerre Knudsen (32:02):I don't know about health span, but because certainly there's been so many studies with metformin and there's been a lot of wonderful data showing an effect on the epigenetic clocks, but not really an effect on lifespan because that metformin is so widely used. If that was the case, it would be easy to dig those data out of different registries. But certainly a healthier aging is the most obvious one because when you have one class of medicine that actually has so many different effects. Right now we are looking at them at a one by one case, but we really should be looking at them so you are getting the benefits on the heart and the vasculature on the brain and the kidneys and the diabetes and the knees. You're getting all of that at the same time, and that certainly should lead to much, much healthier lives. And then of course, we just need to get people to eat healthier. Also, maybe we should talk a little bit about the food industry. I heard you did that in some of your podcast, right?Eric Topol (33:17):Yes. That is the big food, if you will. It's a big problem, a very big problem, and the ultra-processed foods. And so, lifestyle is not good and trying to compensate for that with a drug intervention strategy is like chasing your tail. So you're absolutely right about that. I mean, I guess what I'm getting into here is that whereas today we keep seeing the effects, whether it's the liver, the kidney, the heart, obesity, and people with diabetes. But for example, in the Alzheimer's trial, do you have to be obese to be enrolled in the Alzheimer's trial, or is it just people who are at risk for developingAlzheimer's?Lotte Bjerre Knudsen (34:01):Yeah, no, you do not have to be obese. It's a standard Alzheimer's trial.GLP-1 PillsEric Topol (34:07):So this will be one of the really important trials to get a readout in people who are not having an obesity background. Now, the future, of course, gets us to oral GLP-1 drugs, which obviously you have there at Novo Nordisk. And it seems to me once that happens, if it can simulate the effects we see with the injectables, that would be another big step forward. What do you think about that?Lotte Bjerre Knudsen (34:39):Yeah. Isn't it interesting, what we've learned is that people actually don't mind the injections, right? Also, because I think it's simple, once a week injection and the needles are so small, obviously there are people who really have needle phobia, but take those aside, it's relatively few. I would argue if you close your eyes and somebody else used this needle on you, you would not be able to feel where it was inserted, right? They're so small. So it becomes maybe a personal preference. Would you like to have once a day or maybe twice a day tablets, or are you fine with once a week injection? And I think there probably will be quite a few once they've tried it. And now so many have tried it and they actually, maybe it gives us a simple lifestyle. You don't have to do it every day, right? You can just have a weekly reminder.Eric Topol (35:46):Yeah, no, I think that's really interesting what you're bringing up. I never thought we would evolve to a point where injectables were becoming some common, and I even have some physician colleagues that are taking three different injectable drugs.Lotte Bjerre Knudsen (36:00):That's also just mentioned Richard DiMarchi, who I shared the Breakthrough Prize with, and also Svetlana Mojsov, who I was one of the other two recipients for the Lasker prize because they both been at Rockefeller, and they both have worked a lot with peptides, and they both say the same thing. They were told so many times, this is not medicines, these kinds of molecules just they're not medicines. Forget about it. It turns out people were wrong. And peptides can be medicines, and they can even be produced also in a sustainable manner with fermentation, which is not a bad way of producing medicines. And people actually don't mind. Maybe some people actually even like it because it's once a week and then it's done.Confronting BarriersEric Topol (36:58):Yeah, no, that's a very important point. And the quest for the oral, which have more issues with bioavailability versus the peptides that are having such pronounced impact is really interesting to ponder. Well, before we wrap up, it's very clear the impact you've had has been profound, not just obviously at Novo Nordisk, but for the world of advancing health and medicine. And you've mentioned some of the key other people who have made seminal contributions, but I think you stand out because when we went deep into who took this field forward into obesity and who might also wind up being credited for Alzheimer's, it was you. And as a woman in science, especially in an era that you've been at Novo now for three and a half decades, there weren't many women in science leaders. And for one to be, as you said, you're brave for the good old boys to listen to the woman in science. Tell us about that challenge. Was this ever an issue in your career? Because obviously we want to have this whole landscape change. It is in the midst of change, but it's certainly still a ways to go. So maybe you can give us insight about that.Lotte Bjerre Knudsen (38:27):Yeah. Well, it for sure was a thing. It was a very male dominated world, and in a way, it might have prevented other people from doing it. But then, as I said, I was born brave for some reason. I'm not really sure why. It actually motivated me to kind of like, yeah, I'm going to show them. I'm going to show them. So it never really got to me that people, not everyone was nice to say. There was the first 10 years of my career, I think they were quite lonely, but then I was really inspired. I was so happy to be allowed to work on this. I thought it was super fun. And I did find people who wanted to play with me. And I also have to say that the CSO back then, Mads Krogsgaard Thomsen, he always supported me. So maybe I didn't get everything I wanted, but I always got what I needed in order to progress.(39:29):So on the women's side, and I think that yes, and there's still a change to be made, and I'm actually a little bit on behalf of my generation, maybe not too proud of the change we made because we didn't do a lot of change. It was all the women coming from the arts and the culture. They were the ones who actually make the big change here like 5 or 10 years ago. So I've also started to be more open about sharing my journey and advocating for women in science. So that's why I show up in pink to some of these award sessions just to be a little bit different and to maybe also just show that you don't have to be a certain type in order to fit into a certain job. But there is still a change to be made where people should be better at listening to what a person say and what ideas they say.(40:28):And they should be mindful about not always labeling women as passionate. When people call me passionate, I say like, no, thank you. I'm actually not too happy about the mother of either, because men always are being told. They're being told that they're brave and ambitious and courageous and strategic, whereas we we're, oh, you're so passionate. No, thank you. I'm also brave and strategic and ambitious and all of that. So we simply put different vocabulary on. I don't think people don't do it on purpose. I think we need to be better at actually giving people at work the same kind of vocabulary for their contributions. And I think that would mean that we get listened to in the same way. And that would be important. And then I also have to say that science, whether it comes from men or women, doesn't really matter.(41:32):Successful science is always the work of many. And I hope that some of you will actually listen to my last speech because that's what I speak about, how it's always the work of the many. And also, how if you want to do something novel, then you actually have to do it at a time when no one else is doing it, and you should believe in your ideas. So believe in it, listen to the critique, but believe in it, and then come back with new arguments or give up if you can't come up with any new arguments, right?Eric Topol (42:05):Well, we'll definitely put a link to the Lasker Awards speech that you gave. And I just want to say that the parallels here, for example, with Kati Karikó , my friend who had the Nobel Award for mRNA, she spent three decades trying to get people to listen to her and never got a grant from the NIH or other places [our conversation here]. And it was a really tough battle. And as you already touched on Svetlana Mojsov, who did some of the seminal work at Rockefeller to isolate the portion of GLP-1, that really was the key part peptide, and it was overlooked for years. And so, it's a tough fight, but you're paving the way here. And I think the contributions you've made are just so extraordinary. And I hope that over the years we will continue to see this momentum because people like what you've done, deserve this extraordinary recognition. I'm glad to see. And the Lasker Award is really capping off some of that great recognition that is so well deserved. We've covered a lot of ground today, and I want to make sure if I missed anything that you wanted to get into before we wrap up.Lotte Bjerre Knudsen (43:30):I think we've been around all the exciting biology of GLP-1, both in diabetes, obesity, cardiovascular, kidney, potential in Alzheimer's and addiction. We'll see, we need the clinical data and we've put out a message to inspire people to do new science. There's still a lot of unmet need out there. There's a lot of diseases that don't have good treatments. Even in the diseases we've talked about there's a lot of money for diabetes. There are no disease modifying therapies for diabetes. It's not really changing the course of the disease. So there's a lot of things that needs great scientists.Eric Topol (44:17):And I guess just in finishing the discovery of this class of drugs and what it's led to, tells us something about that, there's so much more to learn that is, this has taken on perhaps the greatest obstacle in medicine, which was could you safely treat obesity and have a marked effect. Which decades, many decades were devoted to that and gotten nowhere. It's like a breakthrough in another way is that here you have an ability to triumph over such a frustrating target, just like we've seen with Alzheimer's, of course, which may actually intersect with Alzheimer's, with a graveyard of failed drugs. And the ones that it were approved so far in certain countries, like the US are so questionable as to the safety and efficacy. But it gives us an inspiration about what is natural that can be built on the basic science that can lead to with people like you who push within the right direction, give the right nudges and get the support you need, who knows what else is out there that we're going to be discovering in the years ahead. It's a broad type of lesson for us.Lotte Bjerre Knudsen (45:38):Yeah, there is another hormone that's also in phase three clinical development, right? The amylin hormone. We've had pramlintide on the market for years, but we have this long-acting version that is in phase three clinical development. That could be the same kind of story because there's also additional biology on that one.Eric Topol (45:58):Yeah, this is what grabs me Lotte, because these gut hormone, we've known about them, and there's several more out there, of course. And look what they're having. They're not just gut hormones, like you said, they're neurotransmitters and they're body-wide receptors waiting to be activated, so it's wild. It's just wild. And I'm so glad to have had this conversation with you. Now, congratulations on all that you've done, and I know the Nature Medicine paper that just came out is going to be just one of many more to come in your career. So what a joy to have the chance to visit with you, and we'll be following the work that you and your colleagues are doing with great interest.Lotte Bjerre Knudsen (46:45):And thank you very much, and thank you for your wonderful podcast. They're really great to listen to on the go. Very easy listening.*****************************************Please complete the quick poll question above.Thank you for reading, listening and subscribing to Ground Truths.If you found this podcast informative please share it!All content on Ground Truths—its newsletters, analyses, and podcasts, are free, open-access.Paid subscriptions are voluntary and of course appreciated. All proceeds from them go to support Scripps Research. Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. I welcome all comments from paid subscribers and will do my best to respond to each of them and any questions.Thanks to my producer Jessica Nguyen and to Sinjun Balabanoff for audio and video support at Scripps Research.Ground Truths now has subscribers in 203 countries! Get full access to Ground Truths at erictopol.substack.com/subscribe

Die Themen in den Wissensnachrichten: +++ Forschende haben 200 Dino-Fußabdrücke entdeckt +++ So lassen sich hochansteckende Erreger-Varianten schneller identifizieren +++ Verloren geglaubter Satellit geht wieder - dank eines Hackers +++**********Weiterführende Quellen zu dieser Folge:Major new footprint discoveries on Britain's ‘dinosaur highway', 02.01.2025Learning the fitness dynamics of pathogens from phylogenies, in: Nature, 01.01.202538C3: Hacker kapert und repariert Beesat-1-Satelliten vom Boden ausBrain-wide cell-type-specific transcriptomic signatures of healthy ageing in mice, in: Nature, 01.01.2025An evaluation framework for clinical use of large language models in patient interaction tasks, in: Nature Medicine, 02.01.2025Alle Quellen findet ihr hier.**********Ihr könnt uns auch auf diesen Kanälen folgen: TikTok auf&ab , TikTok wie_geht und Instagram .

The FiltrateJoel TopfSwapnil HiremathAC GomezJordy CohenNayan AroraSpecial Guest Brendon NuenEditing bySimon Topf and Nayan AroraShow NotesFINEARTS-HF in NEJM FINEARTS Kidney outcomes in JACCFINE-HEART pooled analysis of cardiovascular, kidney and mortality outcomes in Nature Medicine discussion in NephJC BARACH-D: Low-dose spironolactone and cardiovascular outcomes in moderate stage chronic kidney disease: a randomized controlled trial (Nature Medicine)Live Freely Filtered at KidneyWkSwapnil comes out as a SpiroStan post to NephJC TOPCATTOPCAT primary publication TOPCAT North American results TOPCAT funny business explained AHA/ACC/HFSA Heart Failure Guidelines (PDF)SGLT2i are 2aMRA are a 2bARBs are a 2bARNI are a 2bClinical Phenogroups in Heart Failure With Preserved Ejection Fraction: Detailed Phenotypes, Prognosis, and Response to SpironolactoneKansas city cardiomyopathy questionnaire in patients with CKD without a diagnosis of heart failure: https://pubmed.ncbi.nlm.nih.gov/21187260/GFR slope with steroidal MRAs in HF: https://onlinelibrary.wiley.com/doi/10.1002/ejhf.2635Why Has it Been Challenging to Modify Kidney Disease Progression in Patients With Heart Failure? (JACC)Tubular SecretionsSwap: Disclaimer on Apple TVAC: Duo Lingo Plushy (Amazon)Nayan: The Puzzle BoxJordy: Project Hail MaryBrendon has a podcast, The Kidney Compass with Shikha Wadhwani. And he recommends singer-songwriter, Maggie Rogers (YouTube)Joel: The Singularity Is Nearer: When We Merge with AI by Ray KurzweilClosing music, Tim Yau with The Kidney Connection

A leader for conducting rigorous randomized trials of humans along with animal models for understanding nutrition and metabolism, Dr. Kevin Hall is a Senior Investigator at the National Institutes of Health, and Section Chief of the Integrative Physiology Section, NIDDK. In this podcast, we reviewed his prolific body of research a recent publications. The timing of optimizing our diet and nutrition seems apropos, now that we're in in the midst of the holiday season!Below is a video snippet of our conversation on his ultra-processed food randomized trial.Full videos of all Ground Truths podcasts can be seen on YouTube here. The current one is here. If you like the YouTube format, please subscribe! The audios are also available on Apple and Spotify.Note: I'll be doing a Ground Truths Live Chat on December 11th at 12 N EST, 9 AM PST, so please mark your calendar and join!Transcript with links to publications and audioEric Topol (00:05):Well, hello. This is Eric Topol with Ground Truths, and I'm really delighted to have with me today, Dr. Kevin Hall from the NIH. I think everybody knows that nutrition is so important and Kevin is a leader in doing rigorous randomized trials, which is not like what we usually see with large epidemiologic studies of nutrition that rely on food diaries and the memory of participants. So Kevin, it's really terrific to have you here.Kevin Hall (00:34):Thanks so much for the invitation.Ultra-Processed FoodsEric Topol (00:36):Yeah. Well, you've been prolific and certainly one of the leaders in nutrition science who I look to. And what I thought we could do is go through some of your seminal papers. There are many, but I picked a few and I thought we'd first go back to the one that you published in Cell Metabolism. This is ultra-processed diets cause excessive caloric intake and weight gain. (Main results in graph below.) So maybe you can take us through the principle findings from that trial.Kevin Hall (01:10):Yeah, sure. So that was a really interesting study because it's the first randomized control trial that's investigated the role of ultra-processed foods in potentially causing obesity. So we've got, as you mentioned, lots and lots of epidemiological data that have made these associations between people who consume diets that are very high in ultra-processed foods as having greater risk for obesity. But those trials are not demonstrating causation. I mean, they suggest a strong link. And in fact, the idea of ultra-processed foods is kind of a new idea. It's really sort of appeared on the nutrition science stage probably most prominently in the past 10 years or so. And I first learned about this idea of ultra-processed foods, which is really kind of antithetical to the way most nutrition scientists think about foods. We often think about foods as nutrient delivery vehicles, and we kind of view foods as being the fraction of carbohydrates versus fats in them or how much sodium or fiber is in the foods.Kevin Hall (02:17):And along came this group in Brazil who introduced this new way of classifying foods that completely ignores the nutrient composition and says what we should be doing is classifying foods based on the extent and purpose of processing of foods. And so, they categorize these four different categories. And in the fourth category of this so-called NOVA classification scheme (see graphic below) , they identified something called ultra-processed foods. There's a long formal definition and it's evolved a little bit over the years and continues to evolve. But the basic ideas that these are foods that are manufactured by industries that contain a lot of purified ingredients made from relatively cheap agricultural commodity products that basically undergo a variety of processes and include additives and ingredients that are not typically found in home kitchens, but are typically exclusively in manufactured products to create the wide variety of mostly packaged goods that we see in our supermarkets.Kevin Hall (03:22):And so, I was really skeptical that there was much more about the effects of these foods. Other than that they typically have high amounts of sugar and saturated fat and salt, and they're pretty low in fiber. And so, the purpose of this study was to say, okay, well if there's something more about the foods themselves that is causing people to overconsume calories and gain weight and eventually get obesity, then we should do a study that's trying to test for two diets that are matched for these various nutrients of concern. So they should be matched for the macronutrients, they should be matched for the sugar content, the fat, the sodium, the fiber, and people should just be allowed to eat whatever they want and they shouldn't be trying to change their weight in any way. And so, the way that we did this was, as you mentioned, we can't just ask people to report what they're eating.Kevin Hall (04:19):So what we did was we admitted these folks to the NIH Clinical Center and to our metabolic ward, and it's a very artificial environment, but it's an environment that we can control very carefully. And so, what we basically did is take control over their food environment and we gave them three meals a day and snacks, and basically for a two-week period, they had access to meals that were more than 80% of calories coming from ultra-processed foods. And then in random order, they either received that diet first and give them simple instructions, eat as much as little as you want. We're going to measure lots of stuff. You shouldn't be trying to change your weight or weight that gave them a diet that had no calories from ultra-processed foods. In fact, 80% from minimally processed foods. But again, both of these two sort of food environments were matched for these nutrients that we typically think of as playing a major role in how many calories people choose to eat.Kevin Hall (05:13):And so, the basic idea was, okay, well let's measure what these folks eat. We gave them more than double the calories that they would require to maintain their weight, and what they didn't know was that in the basement of the clinical center where the metabolic kitchen is, we had all of our really talented nutrition staff measuring the leftovers to see what it was that they didn't eat. So we knew exactly what we provided to them and all the foods had to be in our nutrition database and when we compute what they actually ate by difference, so we have a very precise estimate about not only what foods they chose to ate, but also how many calories they chose to eat, as well as the nutrient composition.And the main upshot of all that was that when these folks were exposed to this highly ultra-processed food environment, they spontaneously chose to eat about 500 calories per day more over the two-week period they were in that environment then when the same folks were in the environment that had no ultra-processed foods, but just minimally processed foods. They not surprisingly gained weight during the ultra-processed food environment and lost weight and lost body fat during the minimally processed food environment. And because those diets were overall matched for these different nutrients, it didn't seem to be that those were the things that were driving this big effect. So I think there's a couple of big take homes here. One is that the food environment really does have a profound effect on just the biology of how our food intake is controlled at least over relatively short periods of time, like the two-week periods that we were looking at. And secondly, that there's something about ultra-processed foods that seem to be driving this excess calorie intake that we now know has been linked with increased risk of obesity, and now we're starting to put some of the causal pieces together that really there might be something in this ultra-processed food environment that's driving the increased rates of obesity that we've seen over the past many decades.Eric Topol (07:18):Yeah, I mean I think the epidemiologic studies that make the link between ultra-processed foods and higher risk of cancer, cardiovascular disease, type 2 diabetes, neurodegenerative disease. They're pretty darn strong and they're backed up by this very rigorous study. Now you mentioned it short term, do you have any reason to think that adding 500 calories a day by eating these bad foods, which by the way in the American diet is about 60% or more of the average American diet, do you have any inkling that it would change after a few weeks?Kevin Hall (07:54):Well, I don't know about after a few weeks, but I think that one of the things that we do know about body weight regulation and how it changes in body weight impact both metabolism, how many calories were burning as well as our appetite. We would expect some degree of moderation of that effect eventually settling in at a new steady state, that's probably going to take months and years to achieve. And so the question is, I certainly don't believe that it would be a 500 calorie a day difference indefinitely. The question is when would that difference converge and how much weight would've been gained or lost when people eventually reached that new plateau? And so, that's I think a really interesting question. Some folks have suggested that maybe if you extrapolated the lines a little bit, you could predict when those two curves might eventually converge. That's an interesting thought experiment, but I think we do need some longer studies to investigate how persistent are these effects. Can that fully explain the rise in average body weight and obesity rates that have occurred over the past several decades? Those are open questions.Eric Topol (09:03):Yeah. Well, I mean, I had the chance to interview Chris van Tulleken who wrote the book, Ultra-Processed People and I think you might remember in the book he talked about how he went on an ultra-processed diet and gained some 20, 30 pounds in a short time in a month. And his brother, his identical twin brother gained 50, 60 pounds, and so it doesn't look good. Do you look at all the labels and avoid all this junk and ultra-processed food now or are you still thinking that maybe it's not as bad as it looks?Kevin Hall (09:38):Well, I mean I think that I certainly learned a lot from our studies, and we are continuing to follow this up to try to figure out what are the mechanisms by which this happen. But at the same time, I don't think we can throw out everything else we know about nutrition science. So just because we match these various nutrients in this particular study, I think one of the dangers here is that as you mentioned, there's 60% of the food environment in the US and Great Britain and other places consist of these foods, and so they're unavoidable to some extent, right? Unless you're one of these privileged folks who have your backyard garden and your personal chef who can make all of your foods, I'm certainly not one of those people, but for the vast majority of us, we're going to have to incorporate some degree of ultra-processed foods in our day-to-day diet.Kevin Hall (10:24):The way I sort of view it is, we really need to understand the mechanisms and before we understand the mechanisms, we have to make good choices based on what we already know about nutrition science, that we should avoid the foods that have a lot of sugar in them. We should avoid foods that have a lot of saturated fat and sodium. We should try to choose products that contain lots of whole grains and legumes and fruits and vegetables and things like that. And there's some of those, even in the ultra-processed food category. I pretty regularly consume a microwavable ready meal for lunch. It tends to be pretty high in whole grains and legumes and low in saturated fat and sugar and things like that. But to engineer a food that can heat up properly in a microwave in four minutes has some ultra-processing technology involved there. I would be pretty skeptical that that's going to cause me to have really poor health consequences as compared to if I had the means to eat homemade French fries every day in tallow. But that's the kind of comparison that we have to think about.Eric Topol (11:36):But I think what you're touching on and maybe inadvertently is in that NOVA class four, the bad ultra-processed foods, there's a long, long list of course, and some of those may be worse than others, and we haven't seen an individual ranking of these constituents. So as you're alluding to what's in that microwave lunch probably could be much less concerning than what's in these packaged snacks that are eaten widely. But I would certainly agree that we don't know everything about this, but your study is one of the most quoted studies ever in the ultra-processed food world. Now, let me move on to another trial that was really important. This was published in Nature Medicine and it's about a plant-based diet, which is of course a very interesting diet, low-fat versus an animal-based ketogenic diet. Also looking at energy intake. Can you take us through that trial?Plant-Based, Low Fat Diet vs Animal-Based, Low Carbohydrate Ketogenic DietKevin Hall (12:33):Sure. So it's actually interesting to consider that trial in the context of the trial we just talked about because both of these diets that we tested in this trial were relatively low in ultra-processed foods, and so both of them contained more than a kilogram of non-starchy vegetables as a base for designing these, again, two different food environments. Very similar overall study design where people again were exposed to either diets that were vegan plant-based diet that was really high in starches and was designed to kind of cause big insulin increases in the blood after eating the meals. And the other diet had very, very few carbohydrates of less than 10% in total, and we built on that kind of non-starchy vegetable base, a lot of animal-based products to kind of get a pretty high amount of fat and having very low carbohydrates. Both diets in this case, like I mentioned, were pretty low in ultra-processed foods, but what we were really interested in here was testing this idea that has come to prominence recently, that high carbohydrate diets that lead to really large glucose excursions after meals that cause very high insulin levels after meals are particularly obesogenic and should cause you to be hungrier than compared to a diet that doesn't lead to those large swings in glucose and insulin and the prototypical case being one that's very low in carbohydrate and might increase the level of ketones that are floating around in your blood, which are hypothesized to be an appetite suppressant. Same sort of design, these minimally processed diets that one was very high in carbs and causes large swings in insulin and the other that's very low in carbs and causes increases in ketones.Kevin Hall (14:22):We ask people, again, while you're in one food environment or the other, don't be trying to gain weight or lose weight, eat as much or as little as you'd like, and we're going to basically measure a lot of things. They again, don't know what the primary outcome of the study is. We're measuring their leftovers afterwards. And so, the surprise in this particular case was that the diet that caused the big swings in glucose and insulin did not lead to more calorie consumption. In fact, it led to about 700 calories per day less than when the same people were exposed to the ketogenic diet. Interestingly, both food environments caused people to lose weight, so it wasn't that we didn't see the effect of people over consuming calories on either diet, so they were reading fewer calories in general than they were when they came in, right. They're probably eating a pretty ultra-processed food diet when they came in. We put them on these two diets that varied very much in terms of the macronutrients that they were eating, but both were pretty minimally processed. They lost weight. They ended up losing more body fat on the very low-fat high carb diet than the ketogenic diet, but actually more weight on the ketogenic diet than the low-fat diet. So there's a little bit of a dissociation between body fat loss and weight loss in this study, which was kind of interesting.Eric Topol (15:49):Interesting. Yeah, I thought that was a fascinating trial because plant-based diet, they both have their kind of camps, you know.Kevin Hall (15:57):Right. No, exactly.Immune System Signatures for Vegan vs Ketogenic DietsEric Topol (15:58):There are people who aren't giving up on ketogenic diet. Of course, there's some risks and some benefits and there's a lot of interest of course with the plant-based diet. So it was really interesting and potentially the additive effects of plant-based with avoidance or lowering of ultra-processed food. Now, the more recent trial that you did also was very interesting, and of course I'm only selecting ones that I think are particularly, there are a lot of trials you've done, but this one is more recent in this year where you looked at vegan versus ketogenic diets for the immune signature, immune response, which is really important. It's underplayed as its effect, and so maybe you can take us through that one.[Link to a recent Nature feature on this topic, citing Dr. Hall's work]Kevin Hall (16:43):Yeah, so just to be clear, it's actually the same study, the one that we just talked about. This is a secondary sort of analysis from a collaboration we had with some folks at NIAID here at the NIH to try to evaluate immune systems signatures in these same folks who wonder what these two changes in their food environment. One is vegan, high carbohydrate low-fat diet and the other, the animal-based ketogenic diet. And again, it was pretty interesting to me that we were able to see really substantial changes in how the immune system was responding. First of all, both diets again seem to have improved immune function, both adaptive and innate immune function as compared to their baseline measurements when they came into the study. So when they're reading their habitual diet, whatever that is typically high in ultra-processed foods, they switched to both of these diets.Kevin Hall (17:39):We saw market changes in their immune system even compared to baseline. But when we then went and compared the two diets, they were actually divergent also, in other words, the vegan diet seemed to stimulate the innate immune system and the ketogenic diet seemed to stimulate the adaptive immune system. So these are the innate immune system can be thought of. Again, I'm not an immunologist. My understanding is that this is the first line defense against pathogens. It happens very quickly and then obviously the adaptive immune system then adapts to a specific pathogen over time. And so, this ability of our diet to change the immune system is intriguing and how much of that has to do with influencing the gut microbiota, which obviously the gut plays a huge role in steering our immune system in one direction versus another. I think those are some really intriguing mechanistic questions that are really good fodder for future research.Eric Topol (18:42):Yeah, I think it may have implications for treatment of autoimmune diseases. You may want to comment about that.Kevin Hall (18:51):Yeah, it's fascinating to think about that the idea that you could change your diet and manipulate your microbiota and manipulate your gut function in a way to influence your immune system to steer you away from a response that may actually be causing your body damage in your typical diet. It's a fascinating area of science and we're really interested to follow that up. I mean, it kind of supports these more anecdotal reports of people with lupus, for example, who've reported that when they try to clean up their diet for a period of time and eliminate certain foods and eliminate perhaps even ultra-processed food products, that they feel so much better that their symptoms alleviate at least for some period of time. Obviously, it doesn't take the place of the therapeutics that they need to take, but yeah, we're really interested in following this up to see what this interaction might be.Eric Topol (19:46):Yeah, it's fascinating. It also gets to the fact that certain people have interesting responses. For example, those with epilepsy can respond very well to a ketogenic diet. There's also been diet proposed for cancer. In fact, I think there's some even ongoing trials for cancer of specific diets. Any comments about that?Kevin Hall (20:10):Yeah, again, it's a really fascinating area. I mean, I think we kind of underappreciate and view diet in this lens of weight loss, which is not surprising because that's kind of where it's been popularized. But I think the role of nutrition and how you can manipulate your diet and still you can have a very healthy version of a ketogenic diet. You can have a very healthy version of a low-fat, high carb diet and how they can be used in individual cases to kind of manipulate factors that might be of concern. So for example, if you're concerned about blood glucose levels, clearly a ketogenic diet is moderating those glucose levels over time, reducing insulin levels, and that might have some positive downstream consequences and there's some potential downsides. Your apoB levels might go up. So, you have to kind of tune these things to the problems and the situations that individuals may face. And similarly, if you have issues with blood glucose control, maybe a high carbohydrate diet might not be for you, but if that's not an issue and you want to reduce apoB levels, it seems like that is a relatively effective way to do that, although it does tend to increase fasting triglyceride levels.Kevin Hall (21:27):So again, there's all of these things to consider, and then when you open the door beyond traditional metabolic health markers to things like inflammation and autoimmune disease as well as some of these other things like moderating how cancer therapeutics might work inside the body. I think it's a really fascinating and interesting area to pursue.Eric Topol (21:55):No question about it. And that also brings in the dimension of the gut microbiome, which obviously your diet has a big influence, and it has an influence on your brain, brain-gut axis, and the immune system. It's all very intricate, a lot of feedback loops and interactions that are not so easy to dissect, right?Kevin Hall (22:16):Absolutely. Yeah, especially in humans. That's why we rely on our basic science colleagues to kind of figure out these individual steps in these chains. And of course, we do need human experiments and carefully controlled experiments to see how much of that really translates to humans, so we need this close sort of translational partnership.On the Pathogenesis of Obesity, Calories In and Calories OutEric Topol (22:35):Yeah. Now, you've also written with colleagues, other experts in the field about understanding the mechanisms of pathogenesis of obesity and papers that we'll link to. We're going to link to everything for what we've been discussing about calories in, calories out, and that's been the longstanding adage about this. Can you enlighten us, what is really driving obesity and calories story?Kevin Hall (23:05):Well, I co-organized a meeting for the Royal Society, I guess about a year and a half ago, and we got together all these experts from around the world, and the basic message is that we have lots of competing theories about what is driving obesity. There's a few things that we all agree on. One is that there is a genetic component. That adiposity in a given environment is somewhere between 40% to 70% heritable, so our genes play a huge role. It seems like there's certain genes that can play a major role. Like if you have a mutation in leptin, for example, or the leptin receptor, then this can have a monogenic cause of obesity, but that's very, very rare. What seems to be the case is that it's a highly polygenic disease with individual gene variants contributing a very, very small amount to increased adiposity. But our genes have not changed that much as obesity prevalence has increased over the past 50 years. And so, something in the environment has been driving that, and that's where the real debates sort of starts, right?Kevin Hall (24:14):I happen to be in the camp that thinks that the food environment is probably one of the major drivers and our food have changed substantially, and we're trying to better understand, for example, how ultra-processed foods which have risen kind of in parallel with the increased prevalence of obesity. What is it about ultra-processed foods that tend to drive us to overconsume calories? Other folks focus maybe more on what signals from the body have been altered by the foods that we're eating. They might say that the adipose tissue because of excess insulin secretion for example, is basically driven into a storage mode and that sends downstream signals that are eventually sensed by the brain to change our appetite and things like that. There's a lot of debate about that, but again, I think that these are complementary hypotheses that are important to sort out for sure and important to design experiments to try to figure out what is more likely. But there is a lot of agreement on the idea that there's something in our environment has changed.Kevin Hall (25:17):I think there's even maybe a little bit less agreement of exactly what that is. I think that there's probably a little bit more emphasis on the food environment as opposed to there are other folks who think increased pollution might be driving some of this, especially endocrine disrupting chemicals that have increased in prevalence. I think that's a viable hypothesis. I think we have to try to rank order what we think are the most likely and largest contributors. They could all be contributing to some extent and maybe more so in some people rather than others, but our goal is to try to, maybe that's a little simple minded, but let's take the what I think is the most important thing and let's figure out the mechanisms of that most important thing and we'll, number one, determine if it is the most important thing. In my case, I think something about ultra-processed foods that are driving much of what we're seeing. If we could better understand that, then we could both advise consumers to avoid certain kinds of foods because of certain mechanisms and still be able to consume some degree of ultra-processed foods. They are convenient and tasty and relatively inexpensive and don't require a lot of skill and equipment to prepare. But then if we focus on the true bad guys in that category because we really understand the mechanisms, then I think that would be a major step forward. But that's just my hypothesis.Eric Topol (26:43):Well, I'm with you actually. Everything I've read, everything I've reviewed on ultra-processed food is highly incriminating, and I also get frustrated that nothing is getting done about it, at least in this country. But on the other hand, it doesn't have to be either or, right? It could be both these, the glycemic index story also playing a role. Now, when you think about this and you're trying to sort out calories in and calories out, and let's say it's one of your classic experiments where you have isocaloric proteins and fat and carbohydrate exactly nailed in the different diets you're examining. Is it really about calories or is it really about what is comprising the calorie?Kevin Hall (27:29):Yeah, so I think this is the amazing thing, even in our ultra-processed food study, if we asked the question across those people, did the people who ate more calories even in the ultra-processed diet, did they gain more weight? The answer is yes.Kevin Hall (27:44):There's a very strong linear correlation between calorie intake and weight change. I tend to think that I started my career in this space focusing more on the metabolism side of the equation, how the body's using the calories and how much does energy expenditure change when you vary the proportion of carbs versus fat, for example. The effect size is there, they might be there, but they're really tiny of the order of a hundred calories per day. What really struck me is that when we just kind of changed people's food environments, the magnitude of the effects are like we mentioned, 500 to 700 calories per day differences. So I think that the real trick is to figure out how is it that the brain is regulating our body weight in some way that we are beginning to understand from a molecular perspective? What I think is less well understood is, how is that food intake control system altered by the food environment that we find ourselves in?The Brain and GLP-1 DrugsKevin Hall (28:42):There are a few studies now in mice that are beginning to look at how pathways in the brain that have been believed to be related to reward and not necessarily homeostatic control of food intake. They talk to the regions of the brain that are related to homeostatic control of food intake, and it's a reciprocal sort of feedback loop there, and we're beginning to understand that. And I think if we get more details about what it is in our foods that are modulating that system, then we'll have a better understanding of what's really driving obesity and is it different in different people? Are there subcategories of obesity where certain aspects of the food environment are more important than others, and that might be completely flipped in another person. I don't know the answer to that question yet, but it seems like there are certain common factors that might be driving overall changes in obesity prevalence and how they impact this reward versus homeostatic control systems in the brain, I think are really fascinating questions.Eric Topol (29:43):And I think we're getting much more insight about this circuit of the reward in the brain with the food intake, things like optogenetics, many ways that we're getting at this. And so, it's fascinating. Now, that gets me to the miracle drug class GLP-1, which obviously has a big interaction with obesity, but of course much more than that. And you've written about this as well regarding this topic of sarcopenic obesity whereby you lose a lot of weight, but do you lose muscle mass or as you referred to earlier, you lose body fat and maybe not so much muscle mass. Can you comment about your views about the GLP-1 family of drugs and also about this concern of muscle mass loss?Kevin Hall (30:34):Yeah, so I think it's a really fascinating question, and we've been trying to develop mathematical models about how our body composition changes with weight gain and weight loss for decades now. And this has been a long topic, one of the things that many people may not realize is that people with obesity don't just have elevated adiposity, they also have elevated muscle mass and lean tissue mass overall. So when folks with obesity lose weight, and this was initially a pretty big concern with bariatric surgery, which has been the grandfather of ways that people have lost a lot of weight. The question has been is there a real concern about people losing too much weight and thereby becoming what you call sarcopenic? They have too little muscle mass and then they have difficulties moving around. And of course, there are probably some people like that, but I think what people need to realize is that folks with obesity tend to start with much higher amounts of lean tissue mass as well as adiposity, and they start off with about 50% of your fat-free mass, and the non-fat component of your body is skeletal muscle.Kevin Hall (31:45):So you're already starting off with quite a lot. And so, the question then is when you lose a lot of weight with the GLP-1 receptor agonist or with bariatric surgery, how much of that weight loss is coming from fat-free mass and skeletal muscle versus fat mass? And so, we've been trying to simulate that using what we've known about bariatric surgery and what we've known about just intentional weight loss or weight gain over the years. And one of the things that we found was that our sort of expectations for what's expected for the loss of fat-free mass with these different drugs as well as bariatric surgery, for the most part, they match our expectations. In other words, the expected amount of fat loss and fat free mass loss. The one outlier interestingly, was the semaglutide study, and in that case, they lost more fat-free mass than would be expected.Kevin Hall (32:44):Now, again, that's just raising a little bit of a flag that for whatever reason, from a body composition perspective, it's about a hundred people underwent these repeated DEXA scans in that study sponsored by Novo Nordisk. So it's not a huge number of people, but it's enough to really get a good estimate about the proportion of weight loss. Whether or not that has functional consequences, I think is the open question. There's not a lot of reports of people losing weight with semaglutide saying, you know what? I'm really having trouble actually physically moving around. I feel like I've lost a lot of strength. In fact, it seems to be the opposite, right, that the quality of the muscle there seems to be improved. They seem to have more physical mobility because they've lost so much more weight, that weight had been inhibiting their physical movement in the past.Kevin Hall (33:38):So it's something to keep an eye on. It's an open question whether or not we need additional therapies in certain categories of patients, whether that be pharmacological, there are drugs that are interesting that tend to increase muscle mass. There's also other things that we know increase muscle mass, right? Resistance exercise training, increase this muscle mass. And so, if you're really concerned about this, I certainly, I'm not a physician, but I think it's something to consider that if you go on one of these drugs, you might want to think about increasing your resistance exercise training, maybe increasing the protein content of your diet, which then can support that muscle building. But I think it's a really interesting open question about what the consequences of this might be in certain patient populations, especially over longer periods of time.Dietary Protein, Resistance Exercise, DEXA ScansEric Topol (34:30):Yeah, you've just emphasized some really key points here. Firstly, that resistance exercise is good for you anyway. And get on one of these drugs, why don't you amp it up or get it going? The second is about the protein diet, which it'd be interesting to get your thoughts on that, but we generally have too low of a protein diet, but then there are some who are advocating very high protein diets like one gram per pound, not just one gram per kilogram. And there have been studies to suggest that that very high protein diet could be harmful, but amping up the protein diet, that would be a countering thing. But the other thing you mentioned is a DEXA scan, which can be obtained very inexpensively, and because there's a variability in this muscle mass loss if it's occurring, I wonder if that's a prudent thing or if you just empirically would just do the things that you mentioned. Do you have any thoughts about that?Kevin Hall (35:32):Yeah, that's really a clinical question that I don't deal with on a day-to-day basis. And yeah, I think there's probably better people suited to that. DEXA scans, they're relatively inexpensive, but they're not readily accessible to everyone. I certainly wouldn't want to scare people away from using drugs that are now known to be very effective for weight loss and pretty darn safe as far as we can tell, just because they don't have access to a DEXA scanner or something like that.Eric Topol (36:00):Sure. No, that makes a lot of sense. I mean, the only reason I thought it might be useful is if you're concerned about this and you want to track, for example, how much is that resistant training doing?Kevin Hall (36:13):But I think for people who have the means to do that, sure. I can't see any harm in it for sure.Continuous Glucose Sensors?Eric Topol (36:19):Yeah. That gets me to another metric that you've written about, which is continuous glucose tracking. As you know, this is getting used, I think much more routinely in type one insulin diabetics and people with type 2 that are taking insulin or difficult to manage. And now in recent months there have been consumer approved that is no prescription needed, just go to the drugstore and pick up your continuous glucose sensor. And you've written about that as well. Can you summarize your thoughts on it?Kevin Hall (36:57):Yeah, sure. I mean, yeah, first of all, these tools have been amazing for people with diabetes and who obviously are diagnosed as having a relative inability to regulate their glucose levels. And so, these are critical tools for people in that population. I think the question is are they useful for people who don't have diabetes and is having this one metric and where you target all this energy into this one thing that you can now measure, is that really a viable way to kind of modulate your lifestyle and your diet? And how reliable are these CGM measurements anyway? In other words, do they give the same response to the same meal on repeated occasions? Does one monitor give the same response as another monitor? And those are the kinds of experiments that we've done. Again, secondary analysis, these trials that we talked about before, we have people wearing continuous glucose monitors all the time and we know exactly what they ate.Kevin Hall (37:59):And so, in a previous publication several years ago, we basically had two different monitors. One basically is on the arm, which is the manufacturer's recommendation, the other is on the abdomen, which is the manufacturer's recommendation. They're wearing them simultaneously. And we decided just to compare what were the responses to the same meals in simultaneous measurements. And they were correlated with each other thankfully, but they weren't as well predictive as you might expect. In other words, one device might give a very high glucose reading to consuming one meal and the other might barely budge, whereas the reverse might happen for a different meal. And so, we asked the question, if we were to rank the glucose spikes by one meal, so we have all these meals, let's rank them according to the glucose spikes of one device. Let's do the simultaneous measurements with the other device.Kevin Hall (38:53):Do we get a different set of rankings? And again, they're related to each other, but they're not overlapping. They're somewhat discordant. And so, then the question becomes, okay, well if I was basically using this one metric to kind of make my food decisions by one device, I actually start making different decisions compared to if I happen to have been wearing a different device. So what does this really mean? And I think this sort of foundational research on how much of a difference you would need to make a meaningful assessment about, yeah, this is actionable from a lifestyle perspective, even if that is the one metric that you're interested in. That sort of foundational research I don't think has really been done yet. More recently, we asked the question, okay, let's ignore the two different devices. Let's stick to the one where we put it on our arm, and let's ask the question.Kevin Hall (39:43):We've got repeated meals and we've got them in this very highly regimented and controlled environment, so we know exactly what people ate previously. We know the timing of the meals, we know when they did their exercise, we know how much they were moving around, how well they slept the night before. All of these factors we could kind of control. And the question that we asked in that study was, do people respond similarly to the same meal on repeated occasions? Is that better than when you actually give them very different meals? But they match overall for macronutrient content, for example. And the answer to that was surprisingly no. We had as much variability in the glucose response to the same person consuming the same meal on two occasions as a whole bunch of different meals. Which suggests again, that there's enough variability that it makes it difficult to then recommend on for just two repeats of a meal that this is going to be a meal that's going to cause your blood glucose to be moderate or blood glucose to be very high. You're going to have to potentially do this on many, many different occasions to kind of figure out what's the reliable response of these measurements. And again, that foundational research is typically not done. And I think if we're really going to use this metric as something that is going to change our lifestyles and make us choose some meals other than others, then I think we need that foundational research. And all we know now is that two repeats of the same meal is not going to do it.Eric Topol (41:21):Well, were you using the current biosensors of 2024 or were you using ones from years ago on that?Kevin Hall (41:27):No, we were using ones from several years ago when these studies were completed. But interestingly, the variability in the venous measurements to meal tests is also very, very different. So it's probably not the devices per se that are highly variable. It's that we don't really know on average how to predict these glucose responses unless there's huge differences in the glycemic load. So glycemic load is a very old concept that when you have very big differences in glycemic load, yeah, you can on average predict that one kind of meal is going to give rise to a much larger glucose excursion than another. But typically these kind of comparisons are now being made within a particular person. And we're comparing meals that might have quite similar glycemic loads with the claim that there's something specific about that person that causes them to have a much bigger glucose spike than another person. And that we can assess that with a couple different meals.Eric Topol (42:31):But also, we know that the spikes or the glucose regulation, it's very much affected by so many things like stress, like sleep, like exercise. And so, it wouldn't be at all surprising that if you had the exact same food, but all these other factors were modulated that it might not have the same response. But the other thing, just to get your comment on. Multiple groups, particularly starting in Israel, the Weizmann Institute, Eran Segal and his colleagues, and many subsequent have shown that if you give the exact same amount of that food, the exact same time to a person, they eat the exact same amount. Their glucose response is highly heterogeneous and variable between people. Do you think that that's true? That in fact that our metabolism varies considerably and that the glucose in some will spike with certain food and some won't.Kevin Hall (43:29):Well, of course that's been known for a long time that there's varying degrees of glucose tolerance. Just oral glucose tolerance tests that we've been doing for decades and decades we know is actually diagnostic, that we use variability in that response as diagnostic of type 2 diabetes.Eric Topol (43:49):I'm talking about within healthy people.Kevin Hall (43:53):But again, it's not too surprising that varying people. I mean, first of all, we have a huge increase in pre-diabetes, right? So there's various degrees of glucose tolerance that are being observed. But yeah, that is important physiology. I think the question then is within a given person, what kind of advice do we give to somebody about their lifestyle that is going to modulate those glucose responses? And if that's the only thing that you look at, then it seems like what ends up happening, even in the trials that use continuous glucose monitors, well big surprise, they end up recommending low carbohydrate diets, right? So that's the precision sort of nutrition advice because if that's the main metric that's being used, then of course we've all known for a very long time that lower carbohydrate diets lead to a moderated glucose response compared to higher carbohydrate diets. I think the real question is when you kind of ask the issue of if you normalize for glycemic load of these different diets, and there are some people that respond very differently to the same glycemic load meal compared to another person, is that consistent number one within that person?Kevin Hall (45:05):And our data suggests that you're going to have to repeat that same test multiple times to kind of get a consistent response and be able to make a sensible recommendation about that person should eat that meal in the future or not eat that meal in the future. And then second, what are you missing when that becomes your only metric, right? If you're very narrowly focused on that, then you're going to drive everybody to consume a very low carbohydrate diet. And as we know, that might be great for a huge number of people, but there are those that actually have some deleterious effects of that kind of diet. And if you're not measuring those other things or not considering those other things and put so much emphasis on the glucose side of the equation, I worry that there could be people that are being negatively impacted. Not to mention what if that one occasion, they ate their favorite food and they happen to get this huge glucose spike and they never eat it again, their life is worse. It might've been a complete aberration.Eric Topol (46:05):I think your practical impact point, it's excellent. And I think one of the, I don't know if you agree, Kevin, but one of the missing links here is we see these glucose spikes in healthy people, not just pre-diabetic, but people with no evidence of glucose dysregulation. And we don't know, they could be up to 180, 200, they could be prolonged. We don't know if the health significance of that, and I guess someday we'll learn about it. Right?Kevin Hall (46:36):Well, I mean that's the one nice thing is that now that we have these devices to measure these things, we can start to make these correlations. We can start to do real science to say, what a lot of people now presume is the case that these spikes can't be good for you. They must lead to increased risk of diabetes. It's certainly a plausible hypothesis, but that's what it is. We actually need good data to actually analyze that. And at least that's now on the table.Eric Topol (47:04):I think you're absolutely right on that. Well, Kevin, this has been a fun discussion. You've been just a great leader in nutrition science. I hope you'll keep up your momentum because it's pretty profound and I think we touched on a lot of the uncertainties. Is there anything that I didn't ask you that you wish I did?Kevin Hall (47:23):I mean, we could go on for hours, I'm sure, Eric, but this has been a fascinating conversation. I really appreciate your interest. Thank you.Eric Topol (47:30):Alright, well keep up the great stuff. We'll be following all your work in the years ahead, and thanks for joining us on Ground Truths today.**************************************Footnote, Stay Tuned: Julia Belluz and Kevin Hall have a book coming out next September titled “WHY WE EAT? Thank you for reading, listening and subscribing to Ground Truths.If you found this fun and informative please share it!All content on Ground Truths—its newsletters, analyses, and podcasts, are free, open-access.Paid subscriptions are voluntary. All proceeds from them go to support Scripps Research. Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. I welcome all comments from paid subscribers and will do my best to respond to them and any questions.Thanks to my producer Jessica Nguyen and to Sinjun Balabanoff for audio and video support at Scripps Research.Note on Mass Exodus from X/twitter:Many of you have abandoned the X platform for reasons that I fully understand. While I intend to continue to post there because of its reach to the biomedical community, I will post anything material here in the Notes section of Ground Truths on a daily basis and cover important topics in the newsletter/analyses. You can also find my posts at Bluesky: @erictopol.bsky.social, which is emerging as an outstanding platform for sharing life science. Get full access to Ground Truths at erictopol.substack.com/subscribe

Já faz tempo que não fazemos uma leitura crítica de artigo científico sobre ensaio clínico controlado aqui no PQU Podcast. E achei um muito bom: bem escrito, sucinto, publicado em revista prestigiosa, sobre tema muito atual e pertinente. Seu título é “Comprimidos de cetamina de ação estendida para depressão resistente ao tratamento: um ensaio randomizado fase 2 controlado por placebo”. Ele foi publicado em julho de 2024 na Nature Medicine. No episódio 297 do PQU Podcast fazemos sua leitura passo a passo, de acordo com nosso método testado e aprovado. Você não se arrependerá de escutá-lo com atenção. Modéstia à parte, ficou muito bom.

Welcome to the Olink® Proteomics in Proximity podcast! Below are some useful resources mentioned in this episode:  Olink tools and softwareOlink® Explore 3072, the platform utilized by the UK Biobank to measure ~3000 proteins in plasma: https://olink.com/products-services/explore/Olink® Explore HT, Olink's most advanced solution for high-throughput biomarker discovery, measuring 5400+ proteins simultaneously with a streamlined workflow and industry-leading specificity: https://olink.com/products-services/exploreht/  UK Biobank Pharma Proteomics Project (UKB-PPP), one of the world's largest scientific studies of blood protein biomarkers conducted to date, https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/news/uk-biobank-launches-one-of-the-largest-scientific-studies  Research articlesThe support of human genetic evidence for approved drug indicationsMatthew R Nelson et al,  Nature Genetics 2015https://www.nature.com/articles/ng.3314 Proteomic aging clock predicts mortality and risk of common age-related diseases in diverse populationsM. Austin Argentieri et al,  Nature Medicine 2024https://www.nature.com/articles/s41591-024-03164-7 Plasma protein-based organ-specific aging and mortality models unveil diseases as accelerated aging of organismal systemsLudger J.E. Goeminne et al, Cell Metabolism 2024, in presshttps://www.sciencedirect.com/science/article/abs/pii/S1550413124004017?via%3Dihub Plasma proteomic associations with genetics and health in the UK BiobankBenjamin B. Sun et, Nature 2023https://www.nature.com/articles/s41586-023-06592-6 Rare variant associations with plasma protein levels in the UK BiobankRyan S. Dhindsa; Nature 2023https://www.nature.com/articles/s41586-023-06547-x Disease prediction with multi-omics and biomarkers empowers case–control genetic discoveries in the UK BiobankManik Garg, Nature Genetics, 2024https://www.nature.com/articles/s41588-024-01898-1 China Kadoorie Biobank: https://www.ckbiobank.org/publicationsPublications: https://www.ckbiobank.org/publications Subscribe to the podcast on your favorite player or app:Apple Podcasts: https://apple.co/3T0YbSm  Spotify Podcasts: https://open.spotify.com/show/2sZ2wxO...  Google Podcasts: https://podcasts.google.com/feed/aHR0...   Amazon Music: https://music.amazon.com/podcasts/d97...   Podcast Addict:

The BENEFIT trial, which studied isatuximab, lenalidomide, dexamethasone, and bortezomib in transplant-ineligible multiple myeloma, was published earlier this year in Nature Medicine. I'll be talking about this as if it was one of my patients coming to me with a copy of this paper in their hand that a friend or loved one forwarded to them. What do I tell them?

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma and Biotech world.## Breakthrough in Cancer ResearchIn a groundbreaking study published in Nature Medicine, researchers have identified a new potential target for cancer therapy. This discovery could lead to more effective treatments for a wide range of cancers, offering hope to patients around the world.## COVID-19 Vaccine UpdateThe latest data on COVID-19 vaccine effectiveness shows promising results. Several vaccines have been shown to provide high levels of protection against the virus, with some offering more than 90% efficacy. This news brings us one step closer to ending the pandemic.## Drug Approval AnnouncementThe FDA has approved a new drug for the treatment of a rare genetic disorder. This medication has been shown to significantly improve patient outcomes and quality of life. The approval marks a major milestone in the fight against rare diseases.## Biotech Startup Success StoryA small biotech startup has made waves in the industry with their innovative approach to drug development. Their recent success in securing funding and partnerships has put them on the map as a key player to watch in the coming years. ## Pharma Company MergerTwo major pharmaceutical companies have announced plans to merge, creating a powerhouse in the industry. The merger is expected to result in increased resources for research and development, leading to the development of new and improved treatments for patients worldwide.## Clinical Trial ResultsExciting results from a phase III clinical trial show promising outcomes for a new treatment for Alzheimer's disease. The drug has been found to significantly slow the progression of the disease, offering hope to millions of patients and their families.## Regulatory Approval UpdateA new drug seeking regulatory approval has passed a major milestone in the approval process. The FDA has granted priority review status to the medication, which could expedite its availability to patients in need. This news is a significant step forward in bringing this potentially life-saving treatment to market.That's all for today's episode. Stay tuned for more updates on the latest news in Pharma and Biotech. Thank you for listening.

Superimposed on an impressive body of work on the blood-brain-barrier and immune system, Prof Akassoglou and her collaborators just published an elegant study in Nature that centered on the direct binding os the SARS-CoV-2 spike protein to fibrin with marked downstream pro-inflammatory effects. The findings and potential treatments have implications beyond Covid, Long Covid to other neurologic diseases.Full videos of all Ground Truths podcasts can be seen on YouTube here. The audios are also available on Apple and Spotify.Transcript with links to audio and to relevant papers, graphicsEric Topol (00:07):Well, hello this is Eric Topol with Ground Truths, and with me today is Katerina Akassoglou. She is at the Gladstone Institute and she is a remarkable neuroimmunologist who has been doing extraordinary work for three decades to unravel the interactions between the brain, blood vessels and the role of inflammation. So Katerina, there's a lot to discuss, so welcome.Katerina Akassoglou (00:40):Thank you. Thank you so much. It's a great pleasure to join.By Way of BackgroundEric Topol (00:43):It's really interesting going back in your career. First of all, we're thankful that you immigrated here from Greece, and you have become one of the leading scientists in this discipline of important discipline of neuroimmunology, which is not just about Covid that we're going to talk about, but Alzheimer's and neurodegenerative diseases. This is a really big hot area and you're definitely one of the leaders. And what I was impressed is that all these years that you've been working on the integrity of the blood-brain barrier, the importance of fibrinogen and fibrin, and then comes along the Covid story. So maybe what we can do is start with that, which is you've made your mark in understanding this whole interaction between what can get into the brain, through the blood-brain barrier and incite inflammation. So this has been something that you've really taken to the extreme knowledge base. So maybe we can start with your work there before we get into the important seminal Nature paper that you recently published.Katerina Akassoglou (01:57):Yes, of course. So since very early on, I was still a graduate student when we made the first discovery and at the time was like mid-90s, so it was really ahead of its time. That dysregulation of cytokine expression in the brain of mice was sufficient to induce the whole cascade of events, triggering neurodegeneration, demyelination in pathological alterations, very reminiscent of multiple sclerosis pathology. And it was really hard to publish that study at the time because it was not yet accepted that this regulation of the immune system modeling the brain can be linked to neurodegeneration. So that was 1995 when we made that discovery, and I became really interested, what are the pathogenic triggers that actually polarized the immune cells in the brain? So with this, of course, this transgenic animal was expressing TNF, it was an artificially made animal that we made, but naturally what were the triggers that would polarize the innate immune cells? So I looked really early on in this mice and what I found was that the very first event was leaks of blood-brain barrier. It was opening of the blood-brain barrier in this mouse before inflammation, before demyelination, before neuronal loss. And this is really what shaped the question that, is it possible that these blood leaks that happened very early in the pathology, could this be the instigators of pathogenic inflammation in the brain?Eric Topol (03:34):Yeah. So in a way, you got at this question because of the chicken-and-egg and what happens first, and you got to the temporal saying, which happened first as you said, the leak before you could see evidence of inflammation and being able to study this of course in the experimental model, which you couldn't really do in people. And what I love about the description of your career, which has been quite extraordinary contributions is connecting the dots between the blood, the inflammatory response and the brain. Perhaps no one has done that like you have. And before we get into the recent paper, a lot of people are not aware that a year ago, a group in the UK known as PHOSP-COVID, they published a really important paper in Nature Medicine of over 1,800 people who were hospitalized with Covid and they found that fibrinogen was the best marker for cognitive deficits at 6 and 12 months (Figure below)(04:40):So that's just one of many papers, but it's a particularly well done study that already before you got into this work that recently published had emphasized fibrinogen. And by the way, again, having spent a lot of years in clots in the arteries, for me, we have to just get it down to fibrinogen plus thrombin gets you to fibrin. Okay, so fibrin is a major player here when fibrinogen is cleaved. So here we have the basis that you established, which is the fibrinogen leakage into the brain, activating inflammation, activating microglia, which like the macrophages of the brain and inciting the whole process. And before we close, I want to not just talk about Covid, but Alzheimer's too. But now let's get into the study that you did, [Fibrin drives thromboinflammation and neuropathology in COVID-19] which is striking, I mean really striking. And can you kind of take us through, because you not only demonstrated the importance of fibrin in inciting neuroinflammation in this model, but also how you could reverse it or prevent it. So this, and you looked at it in many different ways, this was a systematic approach. Maybe you can take us through how you were able to make such compelling evidence.The Multimodal EvidenceKaterina Akassoglou (06:09):Yes, thank you. First of all, thank you for bringing up the human relevance because this was also our inspiration for the work that we did in the Covid study. So as you mentioned in Covid patients, fibrinogen unbiased mass spec analysis was identified as the predictive biomarker for cognitive impairment in Long Covid patients. And this was in addition to also neuropathology data about the abundance of fibrin deposition in the brain. And these were studies that were done by NIH that have found deposition of fibrin in the brain and the reports for the abnormal and puzzling coagulation in Covid that is not setting other infections and also in many cases not always relating with the severity of symptoms. So even mild cases of Covid also had increased coagulation. I was really intrigued by this human, all this evidence in human data, and I thought that maybe the way that we're thinking about this, that it's systemic inflammation that drives the clotting.(07:24):Maybe there's another aspect to this. Maybe there is a direct effect of the virus with the coagulation cascade, and in this way maybe this can be an instigator of inflammation. So this was the original idea to be able to reconcile this data from the clinic about why do we have this prevalence of coagulopathy in Covid. And of course, the second question is, could this also be a driver of the disease? And of course, we're in a unique position because we have been studying this pathway now for over 20 years to have all the toolbox, the genetic toolbox, the pharmacologic toolbox to be able to actually really address these questions with genetic loss of function studies, with a blood innate immunity multiomics pipeline that we have set up in the lab. And of course, with preclinical pharmacology in our ABSL3 facility. So we had the infrastructure in place and the source in place to actually really dissect this question with both genetic tools as well as also technology platforms.Eric Topol (08:29):And you had in vivo imaging, you're the director of in vivo imaging for Gladstone and UCSF. So you do have the tools to do this.Katerina Akassoglou (08:38):Yes. The imaging that you mentioned is really important because this is, we employed that very early in our studies over now 15 years ago. And the reason was sometimes from snapshots of histopathology, you cannot really understand the sequence of events. So by being able to image these processes, both neuronal activity, microglia activation, infiltration of peripheral cells in the brain, this is how we could see the steps that what happens early on and to be able to answer these chicken-and-egg questions that you mentioned. So these were very, they're very important experiments, especially at the beginning because they were hypothesis driving and we were able to ask the right questions to drive our research program.Eric Topol (09:26):Now was the binding of the spike protein to one key site in fibrinogen, was that known before? [See outstanding Figure below from Trends in Immunology]Katerina Akassoglou (09:36):No, this was not known. So there was evidence that there are abnormal clots in Covid, but it was not known whether the spike protein would directly bind to protein to the coagulation cascade. So one of the key discoveries in our study was to use peptide array mapping and be able to identify not only the binding, but exactly the domains on fibrin that spike binds too. And what we found was two key domains, one the inflammatory domain and the other the plasmin binding site, which is important for fibrin degradation. So this suggested a potential dual deleterious role for this interaction, both by maybe affecting inflammation, but also delaying fibrinolysis, which is the degradation of this toxic protein from the brain. And indeed, we found that this interaction was responsible for all these two aspects, including decreased degradation, more inflammation, but also at the same time increased, increased coagulation. So it was a really pathogenic interaction.Eric Topol (10:47):Yeah, actually it's pretty striking. You have these two sites, the plasmin cleavage site of fibrinogen, which as you say, we knew there was a problem with clots. We knew that, but we didn't know exactly the spike protein how exactly it was implicated, particularly with fibrinogen. And then this other site, the CD11b-C18, now that's fancy for surface receptors of macrophages. And basically, this is critical because it's this microglia activation in the brain, and I know you saw it in the lungs as well through this other site that spike protein activated. So you had a twofer here of things that you discovered that the SARS-CoV-2 spike protein was capable of doing. This was a really big revelation. And then you also looked at mice that were genetically manipulated. So maybe you can, because before we get to your antibody monoclonal, the ways that you proved this were, I mean, one thing after another is really systematic. So maybe you can teach us about that.Thanks for reading Ground Truths! This post is public so feel free to share it.Establishing CausalityKaterina Akassoglou (12:08):Yeah, sure. So the first was about chemistry experiment. So this of course, we had to get to the next step to see is there any causality for this pathway. So we employed genetic loss of function studies and we had knockout mice, either fibrinogen knockout mice, this mice have all blood proteins except fibrinogen, and they have a delay in coagulation so they don't clot properly. But we also had a mutant mouse, which is a fibrinogen NK mouse. And this was a mutation only within this inflammatory domain that you mentioned, inflammatory domain that binds to C11b-C18. Other names for this is of course complement receptor 3, Mac-1 (αMβ2). It's the same, many names for this receptor, that as you mentioned, is expressed not only in microglial in the brain, but also peripheral immune cells including macrophages as well as also neutrophils which are CD11b expressing.(13:12):So we now have genetic models to be able to look at both complete depletion of fibrinogen, but also a very specific mutation and very selective mutation that only blocks the inflammatory properties without affecting the properties of fibrin in hemostasis. And these mice were made many years ago by a very close collaborator, Jay Degen at the University of Cincinnati. So what we found is that when we block either the inflammatory domain or we completely deplete fibrinogen, there was this profound protection after infection in internasal infection with the virus in lung inflammation. And this was both suppression of oxidative stress and this pathogenic inflammation in the lung, but also decreasing fibrosis, which has been associated with also Long Covid. And the surprise came from the transcriptomic data. So when we did transcriptomic analysis in this mice in the lungs, we found perhaps the expected decrease in the immune signatures in macrophages. This was in line with our previous work in, as you mentioned, Alzheimer's models, multiple sclerosis models. But what also was really surprising is there was that genes that are associated with activation of NK cells were upregulated. And of course this was the first time we had infected these mice, previously we had not done an infection before. So I think that maybe because of this region we had not seen before in our data this immunomodulatory role of fibrin that not only surprises the macrophage response, but also increases these NK cells that are important for viral clearance.Eric Topol (15:00):So again, the finding another important unique finding is the natural killer (NK) cells and effect there from the activation of this, as you said, the inflammation site or the CD11b-C18 that we've been talking about. So now another layer of this, a dimension of your Nature paper was that you tested an antibody that you already had developed so-called 5B8. A monoclonal that specifically binds to the domain of the one we're talking about this inflammation domain of fibrinogen. So can you tell us about what that showed?Katerina Akassoglou (15:45):Yes, so we tested this antibody in different models of Covid, which were both models with neuroinvasion and models without neuroinvasion. So we used both transgenic mice for hACE2, the human ACE2 infected with Delta, but we also use mouse adapted viruses like Beta that is just in the wild type mice with no transgenic being involved that these are without neuroinvasion. And we wanted to see if the antibody had any potential protective effects. And what we found is that the antibody protected from inflammation in the lung. So the data looked so similar with a genetic mutation of this pathway, protection from inflammation, decreased fibrosis, increased viral clearance, so decreased spike and viral proteins in the lungs. But we also found a protection in the brain. So the brains of this mice, including both the models we used with neuroinvasion and without, they both have had microglia activation in the brain. And we also found neuronal loss in the Delta infected mice and the antibody protected from both neuroinflammation but also improved neuronal survival in the mice. Showing that there can be this despite regardless of which model we used, there was this protective effect suggesting that by blocking fibrin, either the periphery or in the brain, this could be protected for these models.Eric Topol (17:28):Yeah, so I mean this is fascinating because until now, until this report of yours and your colleagues at Gladstone, there was knowledge that there would be neuroinflammation from Covid, both in patients from various biomarkers and imaging as well as in experimental model. But what this did was take it to the fibrin story, and I guess that's one of the questions you nailed that how important fibrin is, but that doesn't necessarily rule out other triggers of neuroinflammation, right?Katerina Akassoglou (18:04):Oh, absolutely not. So I think that this is one of the mechanisms that can be very important, especially in some patients. But we know that there are additional of course mechanisms of neuroinflammation including auto-antibody responses, as well as also endotheliopathy that are persistent endotheliopathy, this can be interacting also with each other. So I think that it's important for future research that we understand how do these mechanisms feed into each other? Are there a positive feedback loops between autoimmune mechanisms and coagulopathy and endothelial dysfunction with inflammation? But I think most importantly, I think that if we're thinking of this in the context of patients, can we identify patients with mechanism that might be more prevalent in specific cases of Long Covid and tailor our potential future clinical trials towards the needs of Long Covid patients?Towards TreatmentEric Topol (19:06):Absolutely. I did interview some months back on Grounds Truths, Michelle Monje at Stanford, who I'm sure and interact with, and she's also works not so much on the fibrin side, but on neuroinflammation and the likeness between this condition in people and chemo brain because of the inflammation that's seen there. So we've talked about the multiple triggers that could contribute to brain inflammation, which I think most people would say in Long Covid this is one of the most, besides obviously the lack of energy, the profound fatigue and disability, but the cognitive function hit, not just brain fog is often profound. And we've just seen some reports about that, and particularly in hospitalized patients, how bad that can be. So that gets us to a potential treatment. Now, one of the things that's out there dangling, there's many things that people have talked about in terms of why can't we have a treatment for Long Covid?(20:13):And now of course this fibrin pathway, if you will, lends itself to many possibilities, whether it's anticoagulants or fibrinolytics like a tPA or things like nattokinase, which is a Japanese food enzyme that you could get at the nutrition centers or whatever. What are your thoughts? Because we don't have any good studies. There are all these little, tiny studies and they don't provide much conclusion, and you have an antibody that could potentially be effective. As I understand it, you set up a company some years ago, Therini Bio and used to be called MedaRed. You're the first woman scientist at Gladstone to develop a spin out company, which is another point of congratulations on that. But could the antibody be tested in patients or what do you think about these other possibilities?Katerina Akassoglou (21:15):Yes, yes. These are great questions. So first of all, the different approaches that you mentioned have very different mechanism of action. So degrading fibrin, the degradation products of fibrin also can have deleterious effects. The dimer, for example, can be very pro-inflammatory. So at the same time, blocking coagulation can also have a diverse effects because this can lead to excessive hemorrhage. So the approach that we took was to selectively block the inflammatory properties of fibrin without affecting beneficial effects of the molecule in normal hemostasis. So the challenge when I made the antibody was to be able to dissect these two functions of fibrin. It's our most important clotting factor, but at the same time, a molecule with profound pro-inflammatory capacity. So the observation that these two domains, the clotting domain and inflammatory domain were not overlapping, was really the foundation of this invention was that we could maybe create this antibody to be able to target them in a selective way.Other Neurologic Conditions (22:31):So the antibody I developed is neutralizing blood toxicity by blocking the inflammatory domain of fibrin without adverse coagulation effects. And it's now completing phase one trials. So it has already completed the single ascending dose at 40 milligram per kilogram. It's interim data were announced already for this trial, with no safety signals. So if the antibody completes this year, the phase one trials, then it should be possible to be tested in different patient populations. You mentioned before chemo brain, and I think it's important that we think that blood-brain barrier disruption occurs among many neurological conditions, and it's an early event associated with early disease onset and worse prognosis in multiple sclerosis, Alzheimer's disease, traumatic injuries. So I think that it's by developing a strategy, therapeutic strategy to neutralize blood toxicity, this can have applications in a wide range of neurological conditions with vascular dysfunction.Eric Topol (23:54):Yeah, no. In your Nature Immunology 2020 piece [Figure below], you started with the 1883 identification of multiple sclerosis (MS) lesions were “engorged with blood”, the first link between blood leaks and brain inflammation. So this has enormous potential. And what I like about this Katerina is that you've dissected the clot component versus the inflammatory trigger of the fibrinogen and fibrin story. And this is so vital because if you keep throwing these things that just going to work on the clot and not deal with the pro-inflammatory consequences, then you're going to get the wrong impression that clots are not that important. And by the way, you did mention, and I want to come back to that too, endothelial inflammation, which is another feature of Long Covid is another kind of interactive part of this because when the lining of the blood vessel is inflamed, it will attract microthrombi and also be a participant in this whole affair. What do you think about Alzheimer's and the prospects of being able to interfere with Alzheimer's? We have 20 years in someone before this process takes hold and meets clinical manifestations. Would an antibody like this ever be useful along the way?Katerina Akassoglou (25:29):Yeah, so well, our antibody was tested first in Alzheimer's, this models when it was originally published, and we performed reversal trials in Alzheimer's models. So we dosed mice when they have established amyloid plaques, microglia activation, neuronal loss, and we could reverse this effect so it could increase cholinergic neurons in mice, reduce inflammation in a very selective way, only the neurotoxic part of inflammation and for genetic depletion of this pathway with akin mice in Alzheimer's disease. Also, improves from cognitive impairment, and we now have a new paper in Cell Press that is showing this effects also with really nice and unbiased machine learning models for behavioral segmentation [Figure below].So I think that there is the data both from genetic studies and the antibody show projection in Alzheimer's disease. And of course, as you might have read the recent Lancet report from the Lancet committee on dementia that identified the vascular risk factors as the key contributors, especially post sporadic cases of Alzheimer's disease that is over 90% of Alzheimer's disease that is not genetically linked.(26:58):So I think that there is a real need in Alzheimer's disease to be able to block this vascular induced pathology. And an antibody like the fibrin neutralizing therapy could be positioned to be protective from the vascular induced immune-mediated neurodegeneration in this disease as well. I mean, ultimately, I think that we need to be thinking the terms of efficacy. So we want to have a drug that is efficacious, but we also want it to be selective. And the selectivity is really important because the immune system has so many protective functions. So if we block phagocytosis, we end up with more debris, decrease of neurorepair, anti-myelination. So by blocking a ligand here and not blocking, not eliminating a cell type or blocking a global pathway in this cell, but biologic a single ligand, I think we have been able to achieve this balance between efficacy, but also safety because we only block this neurotoxic populations and not the entire innate immune response that also has been beneficial for metastatic functions in the brain.Blocking NeuroinflammationEric Topol (28:19):So you're bringing up another critical concept about targeting the inflammation, this kind of goldilocks story of how much you interfere with the immune response and how much you are able to reduce the adverse pro-inflammatory effects. So that gets me to what if we don't know in any given patient how much fibrin is having a role in their Long Covid. Although we know it has to be a prominent feature because we saw it in, not just a hospitalized patient series that I mentioned we reviewed, but other papers as well. But what about if you just try to take on inflammation like through a GLP-1 drug or cGAS–STING or any of these really strong anti-inflammatory pathways. Do you see a difference in a generalized approach versus a specific approach that is really fibrin centered?Katerina Akassoglou (29:22):Yeah, so we have a focus actually on both because we wanted to dissect the downstream intracellular pathways of fibrin, and it's interesting that we can find specific inflammatory mediators that potentially can also be targeted as well, to be able to preserve that specificity, which I think is really important because if we don't preserve the specificity, we'll end up with a lot of adverse effects by eliminating major immune responses. But the point that you raised I think is really important because it's not enough to have an efficacious and selective drug if you don't know the patient population that will benefit from this drug. So I think that in addition to the drug discovery studies, it's important to develop also biomarker programs with both fluid biomarkers, but also imaging biomarkers to be able to identify the patient populations that will benefit from such treatment.(30:25):So if for example, a patient population has a fibrin deposition, blocking only downstream might not be enough, and it might be really important to neutralize this fibrin toxicity in the brain of patients. And with our target engagement studies, we show that at least in animal models, the antibody can be there. So I'm very encouraged by also programs that are going on now in the scientific community to develop noninvasive ligands to be able to image fibrin in the brain that are already tested in different patient populations like multiple sclerosis. Because I think we're going to learn so much from the biology as we start interrogating and asking these questions now in different patient populations.Eric Topol (31:14):I think that's a vital point you're making because the success of a clinical trial here in a clinical syndrome that is mosaic with lots of different types of pathways. If you can nail down the patients that would have the most to stand to benefit from a particular intervention, that the chance of you not missing the benefit that is matching the marker, what image marker or other markers is so vital. Well, we've talked, I think, about some fascinating discoveries that you and your colleagues have made. I mean, it's really extraordinary, and obviously we need this in Long Covid. But you know what, Katerina, it's almost made me think that you were warming up to this for three decades, that somehow or other you were working on all this stuff and then came Covid. Is that how you see it, that somehow or other you didn't know that all the work you were doing was going to wind up in this space?Katerina Akassoglou (32:18):Oh, I never thought I would work in a virology project. This collaboration started over Zoom with Warner Greene. We were both sheltering in place. It was the beginning of the pandemic, and the first reports were coming out about this puzzling coagulopathy. And our labs were hardly operational at the time, as you know, we had to close down our labs for a while. And however, this was a very big problem, and we thought that this is our role as scientists. If we feel that we can contribute and we have the tools to contribute, we felt that it's important that we pivot some part of our research, and even we wouldn't be doing this before, but it was important to pivot a part of our research and collaborate. And I think studies like this, this study would have been impossible without a team of collaborators. As you know, there were over 50 scientists involved at Gladstone, UCSF, UCLA, UCSD, Stanford University. Without collaboration, this study wouldn't be possible. So I'm really grateful to everyone who came together to solve this problem because I think that's what scientists should be doing. We should be solving problems as they arise.Eric Topol (33:41):Well, and also, I think a lot of people don't realize that, for example, when the Covid vaccines came along, people think, oh, well, it all got done in 10 months since the sequence of the virus, when in fact it took 30 years at least between all the factors that went into having an mRNA and sequencing virus and nanoparticles. And in many ways, your arc of this work is like that because it took three decades to have all the tools and the basic understanding, the antibody that you had developed for different reasons and this fascinating unraveling of what's going on in the model and undoubtedly in some patients at least as well. So before we wrap up, have I missed anything about this just remarkable work you've done?Katerina Akassoglou (34:33):Oh, thank you. I just want to thank you for this discussion and thank you for emphasizing the different areas and the different decisions that this pathway can have implications both for our understanding, our basic understanding of the blood brain immune interface, as well as also potential translation. And I think that the curiosity sometimes of how things work, I never thought it would work on Covid, like you mentioned at the beginning, but I think that basic science and curiosity driven science can sometimes lead to discoveries with translational implications that hopefully might benefit patients one day.Eric Topol (35:21):Yeah, well, undoubtedly it will. We're indebted to you, Katerina and all the folks that you have teamed up with, connecting the dots at the neurovascular interface. Phenomenal work and will follow the subsequent with great interest and it will likely not just a story about Long Covid, but other areas as well, so thank you.*********************************Thanks for listening, reading or watching!The Ground Truths newsletters and podcasts are all free, open-access, without ads.Please share this post/podcast with your friends and network if you found it informative!Voluntary paid subscriptions all go to support Scripps Research. Many thanks for that—they greatly help fund our summer internship programs.Thanks to my producer Jessica Nguyen and Sinjun Balabanoff for audio and video support at Scripps Research.Note: you can select preferences to receive emails about newsletters, podcasts, or all I don't want to bother you with an email for content that you're not interested in. Get full access to Ground Truths at erictopol.substack.com/subscribe

Ellen Kamhi talks with Dr. Friedemann Schaub, a physician, researcher, personal development coach, and the author of the award-winning book The Fear and Anxiety Solution. His research and advice have been featured in many publications, including Nature Medicine, Oprah Magazine, Huffington Post, Reader's Digest, Teen Vogue, and Shape. He is the host of the “Empowerment Solutions” podcast and lives between Seattle, Washington, and the South of France. They discuss his book, The Empowerment Solution.

A Nobel prize for understanding how genes are turned on and offThe early-morning call from Sweden came on Monday to American molecular biologist Gary Ruvkun for his work in discovering microRNAs, which are essential for regulating genetic activity in plants and animals. Ruvkun says that research based on this work helps us understand basic biology, but has also provided significant insight into disease and might even help us understand whether there is life on other planets. Biologists discover a new microbial world in your bathroomResearchers have found a new biodiversity hotspot. Environmental microbiologist Erica Hartmann and her team sampled showerheads and toothbrushes in ordinary bathrooms, and found a host of bacteria and hundreds of previously unknown viruses. But don't panic: much of this new life are bacteriophages — viruses that infect bacteria — which are harmless to humans and could be potential weapons against the bacteria that can cause human disease. The study was published in the journal Frontiers in Microbiomes.How we might zap an asteroid on a collision course with EarthA new experiment using the world's most powerful radiation source has shown the way to deflecting asteroids with X-rays. The X-rays were used to vaporize some of the surface of a model asteroid, creating a rocket-like effect. Dr Nathan Moore, a physicist at the Sandia National Laboratories in New Mexico, says it's a proof of principle for the concept of deflecting a real asteroid using X-rays generated by a powerful nuclear explosion. The study was published in the journal Nature Physics. Exploring the origins of Australia's iconic, if controversial, wild dogThe Australian Dingo has a fierce reputation as a predator, leading to European settlers attempting to exterminate it in the 19th century. But the dingo's origin story has not been well understood. For years, it was assumed the dingo originated from India, given its similarities to the Indian pariah dog, or from New Guinea. Dr. Loukas Koungolos, a research associate at the University of Sydney, led the study looking at dingo fossils and found out where it likely came from, and how the domestic dogs of ancient people became a wild predator down under. The study was published in the journal Scientific Reports. Can we treat autoimmune disease by manipulating the immune system? Autoimmune diseases like Lupus can be a result of critical immune cells attacking our own bodies. New advances are pointing to ways we might be able to reverse this. Researchers have repurposed a relatively new cancer treatment, called CAR-T therapy that can reprogram immune cells to attack cancer cells, to reset the immune system in patients with lupus to neutralize its autoimmune attack. Dr. Georg Schett and his colleagues, from the Friedrich Alexander University of Erlangen in Germany, were the first to use this immunotherapy to successfully treat lupus patients. That research appeared in the journal Nature Medicine with a follow-up in The New England Journal of Medicine.Other researchers are focussing on understanding — and possibly reversing — what triggers the immune cells to go awry in the first place. Dr. Jaehyuk Choi, from Northwestern University, said they found a molecule that lupus patients are deficient in. In cell culture they demonstrated that correcting this deficiency can reprogram certain immune T-cells to stop directing the attack on the body which they hope could potentially reverse the effects of lupus. His research was published in Nature.

In this weeks episode of "Pushing the Limits" , Dr. David Furman, Director of the 1000 immunomes project, the world's largest longitudinal population-based study of immunology and aging at Stanford University and Associate Professor at the Buck Institute for Aging, Founder of Edifice Health and Cosmica Biosciences, discusses his extensive research in immunology, particularly focusing on the 1000 Immunomes Project, which aims to understand the immune system's role in aging.  He emphasizes the importance of studying human biology over traditional animal models and introduces the concept of the Inflammation Age Clock as a new biomarker for aging.  The discussion also covers the implications of systemic chronic inflammation in aging, the role of nutrition, and the potential for interventions to improve health span. Additionally, Dr. Furman shares insights into his work with NASA on accelerated aging in astronauts, highlighting the broader applications of his research in combating age-related diseases.   Takeaways:    Dr. Furman aims to have a massive impact on human health. The immune system plays a crucial role in aging. Human studies provide better insights than animal models. The Inflammation Age Clock is a new biomarker for aging. Chronic inflammation is a key factor in age-related diseases. Nutrition significantly affects inflammation and aging. Reliable biomarkers are needed for effective aging interventions. NASA's research on astronauts reveals accelerated aging in space. The convergence of technologies is revolutionizing health research. Future research will focus on protecting astronauts and advancing aging studies. Titles: System Chronic Inflammation: The Hidden Driver of Aging Nutrition and Inflammation: Key Factors in Health span   About the 1000 immunomes Project: The Stanford 1000 Immunomes Project (KIP) is a collaborative ongoing study at Stanford University that aims to define the biological basis of aging and disease using state-of-the-art 'omics' platforms and advanced artificial intelligence (AI) methods. The main focus of 1KIP is to establish biomarkers for healthy versus sub-functional immune systems. They do this by identifying the interactions between genetic and environmental factors, which contribute to the observed heterogeneity of biological responses in human beings.  To this end, 1000 individuals of different age groups (9-96 years old) were recruited between 2007-2017. Their blood samples were screened using multiple state-of-the-art technologies at a single facility, the Human Immune Monitoring Center (HIMC) to measure circulating proteins, cell types, cellular functions, whole-genome blood gene expression and subjects' haplotypes using deep sequencing technologies. The 1KIP dataset has enabled us for the first time to identify reliable biomarkers of aging and disease in a longitudinal population-based study of immunology and aging. 1KIP provides reference values for thousands of immune variables and identifies clusters of individuals sharing similar health versus disease immune profiles. BIO Dr. David Furman is an academic entrepreneur deeply committed to addressing intricate challenges within human biology, systems medicine, translational immunology, preventative healthcare, aging, and precision longevity. Holding positions as the Director of the Stanford 1000 Immunomes Project at the Stanford School of Medicine and as an Associate Professor and Director of the Bioinformatics and Data Science Core at the Buck Institute for Research on Aging, Dr. Furman leads research endeavors that leverage multi-scale biology ('omics') platforms and advanced AI/ML methodologies. He identifies biomarkers and integrative biological clocks essential for monitoring individual health statuses. Groundbreaking technologies originating from the Furman lab now facilitate the application of descriptive and mechanistic biomarkers to detect and combat accelerated aging and disease progression. With over 15 years of specialization in inflammation's role in aging mechanisms, Dr. Furman's expertise includes various domains, including neuroscience, cardiovascular health, metabolic diseases, and immune system function. Notably, in 2022, NASA's Human Research Program sought Dr. Furman's collaboration, leading to partnerships with SpaceX and Cornell University. Dr. Furman's entrepreneurial initiatives include the founding of the Inflammaging Institute, aimed at democratizing biological aging diagnosis, and the establishment of Stanford spin-off Edifice Health Inc., and Buck Institute spin-off Cosmica Biosciences Inc., both focused on innovative approaches to combat aging-related ailments and precision longevity interventions. Dr. Furman has published over 50 scientific articles in top-tier journals such as Cell, Nature Medicine, PNAS, The Lancet, and others, and is the inventor of over 25 patents.     Personalised Health Optimisation Consulting with Lisa Tamati Lisa offers solution focused coaching sessions to help you find the right answers to your challenges. Topics Lisa can help with:  Lisa is a Genetics Practitioner, Health Optimisation Coach, High Performance and Mindset Coach. She is a qualified Ph360 Epigenetics coach and a clinician with The DNA Company and has done years of research into brain rehabilitation, neurodegenerative diseases and biohacking. She has extensive knowledge on such therapies as hyperbaric oxygen,  intravenous vitamin C, sports performance, functional genomics, Thyroid, Hormones, Cancer and much more. She can assist with all functional medicine testing. Testing Options Comprehensive Thyroid testing DUTCH Hormone testing Adrenal Testing Organic Acid Testing Microbiome Testing Cell Blueprint Testing Epigenetics Testing DNA testing Basic Blood Test analysis Heavy Metals  Nutristat Omega 3 to 6 status and more  Lisa and her functional medicine colleagues in the practice can help you navigate the confusing world of health and medicine . She can also advise on the latest research and where to get help if mainstream medicine hasn't got the answers you are searching for whatever the  challenge you are facing from cancer to gut issues, from depression and anxiety, weight loss issues, from head injuries to burn out to hormone optimisation to the latest in longevity science. Book your consultation with Lisa    Join our Patron program and support the show Pushing the Limits' has been free to air for over 8 years. Providing leading edge information to anyone who needs it. But we need help on our mission.  Please join our patron community and get exclusive member benefits (more to roll out later this year) and support this educational platform for the price of a coffee or two You can join by going to  Lisa's Patron Community Or if you just want to support Lisa with a "coffee" go to  https://www.buymeacoffee.com/LisaT to donate $3   Lisa's Anti-Aging and Longevity Supplements  Lisa has spent years curating a very specialized range of exclusive longevity, health optimizing supplements from leading scientists, researchers and companies all around the world.  This is an unprecedented collection. The stuff Lisa wanted for her family but couldn't get in NZ that's what it's in her range. Lisa is constantly researching and interviewing the top scientists and researchers in the world to get you the best cutting edge supplements to optimize your life.   Subscribe to our popular Youtube channel  with over 600 videos, millions of views, a number of full length documentaries, and much more. You don't want to miss out on all the great content on our Lisa's youtube channel. Youtube   Order Lisa's Books Lisa has published 5 books: Running Hot, Running to Extremes, Relentless, What your oncologist isn't telling you and her latest "Thriving on the Edge"  Check them all out at  https://shop.lisatamati.com/collections/books   Perfect Amino Supplement by Dr David Minkoff Introducing PerfectAmino PerfectAmino is an amino acid supplement that is 99% utilized by the body to make protein. PerfectAmino is 3-6x the protein of other sources with almost no calories. 100% vegan and non-GMO. The coated PerfectAmino tablets are a slightly different shape and have a natural, non-GMO, certified organic vegan coating on them so they will glide down your throat easily. Fully absorbed within 20-30 minutes! No other form of protein comes close to PerfectAminos Listen to the episode with Dr Minkoff here:    Use code "tamati" at checkout to get a 10% discount on any of their devices.   Red Light Therapy: Lisa is a huge fan of Red Light Therapy and runs a Hyperbaric and Red Light Therapy clinic. If you are wanting to get the best products try Flexbeam: A wearable Red Light Device https://recharge.health/product/flexbeam-aff/?ref=A9svb6YLz79r38   Or Try Vielights' advanced Photobiomodulation Devices Vielight brain photobiomodulation devices combine electrical engineering and neuroscience. To find out more about photobiomodulation, current studies underway and already completed and for the devices mentioned in this video go to www.vielight.com and use code “tamati” to get 10% off     Enjoyed This Podcast? If you did, subscribe and share it with your friends! If you enjoyed tuning in, then leave us a review and share this with your family and friends. Have any questions? You can contact my team through email (support@lisatamati.com) or find me on Facebook, Twitter, Instagram and YouTube. For more episode updates, visit my website. You may also tune in on Apple Podcasts.  To pushing the limits, Lisa and team

Dr. Will Bulsiewicz, affectionately known as "Dr. B," is a distinguished gastroenterologist, globally renowned gut health authority, and a bestselling author of "Fiber Fueled" and "The Fiber Fueled Cookbook" recognized by the New York Times, Wall Street Journal, and USA Today. He is an Adjunct Assistant Professor of Medicine at Emory School of Medicine and the visionary Founder of 38TERA, a leading gut health supplement company.Dr. B is dedicated to democratizing health knowledge as the U.S. Medical Director of ZOE. His scholarly work includes over twenty articles in top-tier scientific journals like Nature Medicine, and he has delivered more than forty presentations at national forums, including sessions with Congress and the USDA. He has educated over 10,000 students on enhancing gut health.His academic credentials include a Bachelor's degree from Vanderbilt University, a medical degree from Georgetown University, and a Master's in Clinical Investigation from Northwestern University. Dr. B was the chief medical resident at Northwestern and the chief gastroenterology fellow at The University of North Carolina, and received the highest award given by both his residency and fellowship. He completed an epidemiology fellowship on a grant from the National Institutes of Health at UNC's prestigious Gillings School of Global Public Health.Dr. B resides in Charleston, South Carolina with his family. Connect with him on Instagram and Facebook at @theguthealthmd, on TikTok at @theguthealthmd_, or visit his website at theplantfedgut.com to join his free email list explore more about his work and insights on gut health.www.theplantfedgut.comhttps://www.facebook.com/theguthealthmd/https://www.instagram.com/theguthealthmd/https://www.tiktok.com/@theguthealthmdThank you so much for listening! I use fitness and movement to help women prevent and overcome pelvic floor challenges like incontinence and organ prolapse. There is help for women in all life stages! Every Woman Needs A Vagina Coach! Please make sure to LEAVE A REVIEW and SUBSCRIBE to the show for the best fitness and wellness advice south of your belly button. *******************I recommend checking out my comprehensive pelvic health education and fitness programs on my Buff Muff AppYou can also join my next 28 Day Buff Muff Challenge https://www.vaginacoach.com/buffmuffIf you are feeling social you can connect with me… On Facebook https://www.facebook.com/VagCoachOn Instagram https://www.instagram.com/vaginacoach/On Twitter https://twitter.com/VaginaCoachOn The Web www.vaginacoach.comGet your Feel Amazing Vaginal Moisturizer Here

Episode 032 | Tofunmi Omiye, MD, MS is an incoming dermatology resident (class of 2028) at Stanford and is currently a postdoctoral scholar at Stanford University where he works in the Daneshjou (shout out Roxana!) and Zaba (shout out Lisa!) Labs that are part of the departments of Dermatology and Biomedical Data Science.Dr. Omiye works at the nexus of artificial intelligence, healthcare, and policy. His research covers computer vision, foundation models, and AI bias. His projects have been published in journals like Nature Medicine and featured in media outlets like the Washington Post and AP news.Before Stanford, Tofunmi earned his medical degree from the University of Ibadan, Nigeria, where he was privileged to be a Federal Govt. and Shell University Scholar. He later pursued an MS in Health Policy at Stanford while focusing on AI and working in a surgery-AI lab. Here, he explored the utility of machine learning algorithms in clinical settings and how macroeconomic policies influence mortality.Dr. Omiye has previously collaborated on global health projects with the WHO and Gates foundation and had a stint in venture capital supporting early stage investments in the San Francisco Bay Area. He is passionate about helping ensure that AI benefits all patients, and enjoys concerts, and the real Football. ⚽️This episode was recorded in June 2024.Connect with and learn more about Dr. Omiye

Dr. Schwartz received his undergraduate and medical degrees from Harvard University, where he graduated Magna Cum Laude. After completing his residency and chief residency in Neurosurgery at The Neurological Institute of NewYork at Columbia-Presbyterian Medical Center, Dr. Schwartz spent a year at Yale-New Haven Medical Center receiving advanced fellowship training. Dr. Schwartz specializes in the surgical treatment of brain tumors, pituitary tumors, and epilepsy using the latest techniques in computer-guided surgical navigation, minimally invasive endoscopy, and microsurgery. Dr. Schwartz was recently named David and Ursel Barnes Professor in Minimally Invasive Surgery, the first endowed professorship in the department.Dr. Schwartz has provided commentary for numerous television shows on ABC, NBC, CBS, and Larry King, in addition to national radio shows. His expertise has been sought through interviews, quoted and published, in the Wall Street Journal, The New York Post, The New York Daily News, and Crain's New York Business; he is asked to lecture throughout the country and world. Dr. Schwartz has published many scholarly articles for the Journal of Neurosurgery, Neurosurgery, Epilepsia, Clinical Neurosurgery the Journal of Neuro-Oncology, Nature Medicine, NeuroImage and the Journal of Neuroscience.Dr. Schwartz has been named one of New York's Super Doctors, Best Doctors in New York Magazine, America's Top Surgeons, America's Best Doctors and America's Best Doctors for Cancer. He is the co-author of two books on endoscopic skull base surgery and endoscopic pituitary surgery.

Getting help for depression can be like purgatory. Setting aside for a moment the stigma and other barriers to seeking treatment in the first place, finding the right combination of medication and/or therapy can be a months- or years-long process of trial and error. And for about one third of people, nothing seems to work.Today we're talking with Dr. Leanne Williams, the founding director of the Stanford Center for Precision Mental Health and Wellness and Vincent V.C. Woo Professor in the Stanford Department of Psychiatry and Behavioral Sciences. Williams and her team have recently used brain imaging and machine learning techniques to identify six distinct "biotypes" of depression — each of which may require a different approach to treatment. Beyond setting the stage for more targeted therapies, better understanding the biology behind the disease could finally cut through the stigma of one of the world's most common brain disorders.Learn moreWilliams' Personalized and Translational Neuroscience Lab (PANlab)The Stanford Center for Precision Mental Health and WellnessSix distinct types of depression identified in Stanford Medicine-led study(Stanford Medicine, 2024)Personalized brain circuit scores identify clinically distinct biotypes in depression and anxiety (Nature Medicine, 2024)Brain scans could help personalize treatment for people who are depressed or suicidal (Science, 2022)Williams' scientific publicationsEpisode CreditsThis episode was produced by Michael Osborne, with production assistance by Morgan Honaker, and hosted by Nicholas Weiler. Art by Aimee Garza.Send us a text!Thanks for listening! If you're enjoying our show, please take a moment to give us a review on your podcast app of choice and share this episode with your friends. That's how we grow as a show and bring the stories of the frontiers of neuroscience to a wider audience. Learn more about the Wu Tsai Neurosciences Institute at Stanford and follow us on Twitter, Facebook, and LinkedIn.

New polling estimates independent presidential candidate Robert F. Kennedy Jr. is at around 6% of the national vote, which could make a difference in battleground states. He spoke to CBS News about his campaign and his controversies.Dr. Celine Gounder, a CBS News medical contributor, discusses a new study that says the latest shingles vaccination may also help delay dementia. According to a study published in the journal "Nature Medicine," researchers found people who received that vaccine lived on average 164 additional days without dementia, compared to those who got the previous shingles vaccines.Engineers say they're still troubleshooting issues discovered aboard the Boeing Starliner spacecraft that took NASA astronauts Butch Wilmore and Suni Williams into space. They were originally supposed to spend eight days aboard the International Space Station. They've now been up there for almost eight weeks.CBS News business analyst Jill Schlesinger discusses how American consumers are helping to boost the economy. The latest numbers show economic growth doubled to an annual rate of 2.8% in the last three months from 1.4% in the first quarter of 2024.Global soccer stars Christian Pulisic, who is the captain of the U.S. National team and currently plays for the iconic Italian club AC Milan, and Zlatan Ibrahimovic, a former player and now senior adviser to AC Milan, talk about its U.S. summer tour, which kicks off Saturday with a preseason match against Manchester United in New York City.Nyjah Huston is one of the world's best street skaters and a favorite in the men's street event at the Olympics. He talks about his journey through the sport and getting redemption at the Paris Olympics after he left Tokyo without a medal.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

An early study found that electrical stimulation could improve hand and arm function in people with spinal cord injuries. Also, for thousands of years, Indigenous communities in Guatemala have used observations and mathematics to track astronomical events.Zapping Nerves Into RegrowthResults of an early trial published this week in the journal Nature Medicine found that people with cervical spinal cord damage showed some improvements both in strength and movement in arm and hand function after they received electrical stimulation near the site of their injury. The improved function persisted even after the stimulation stopped, indicating that the treatment may be inducing nerve cells to regrow in the damaged area.Sophie Bushwick, senior news editor at New Scientist, joins Ira to talk about the work and what it could mean for people with severe spinal cord injuries. They also talk about other stories from the week in science, including creating the most powerful X-ray pulse ever reported, investigations into the microbiome of the scalp, and some epic cosplay—testing out the practicality of some ancient Greek armor in combat scenarios.Celebrating the Maya Calendar In Guatemala's HighlandsEvery 260 days, Indigenous communities in the highlands of Guatemala celebrate a new cycle of the Maya calendar. This ceremony has persisted for thousands of years, from pre-Columbian times to today. The latest of these ceremonies happened in early May.Joining Ira to talk about the importance of astronomical ceremony is Willy Barreno, a Maya calendar keeper based in Quetzaltenango, Guatemala, and Dr. Isabel Hawkins, astronomer and senior scientist at the Exploratorium in San Francisco, California.Transcripts for each segment will be available after the show airs on sciencefriday.com. Subscribe to this podcast. Plus, to stay updated on all things science, sign up for Science Friday's newsletters.

Stanford University's Dr. Nolan Williams is one of the world's leading researchers on psychedelic medicine. He joined Rep. Crenshaw to talk about the revolutionary clinical trial he recently conducted with the psychedelic ibogaine to treat veterans suffering from PTSD, Traumatic Brain Industry, and addiction. The clinical trial showed a phenomenal 83% remission rate for participants after just one treatment. Dr. Williams explains what ibogaine is, the experiences patients have while taking it, what we know about how it affects the brain, and how it differs from classic psychedelics like MDMA and psylocibin. They also discuss the potential for ibogaine treatments to combat America's addiction epidemic. Nolan Williams, MD, is an Associate Professor of neurology and psychiatry at Stanford University and the Director of the Stanford Brain Stimulation Lab. He is one of leading researchers in the study of how psychedelics can impact the human brain and be used to successfully treat various health challenges such as post-traumatic stress disorder, traumatic brain injury, and major depression. Read his study in Nature Medicine: https://www.nature.com/articles/s41591-023-02705-w and follow him on X at @NolanRyWilliams.