Podcasts about Framingham Heart Study

Send us a textIn this final episode of 2024, I explore why taking proper holidays isn't just a luxury—it's a biological necessity. Drawing from leading research, including the Framingham Heart Study and findings from Ernst & Young, I reveal how extended breaks significantly impact our health, wellbeing and professional performance, with evidence showing that even small increases in holiday time can improve performance ratings by 8%.The science is clear: taking regular holidays once or twice a year is essential for our cognitive health and professional success. Even planning a holiday can reduce stress and help us cope better with challenges. With this research in mind, I'm taking my own advice, and I'm taking a much needed break too! The podcast will be taking a break over summer and be returning in early 2025 with fresh perspectives on leadership and wellbeing.For the full show notes and transcript, click here.Find out more about Rob Hills: www.robhills.com.auRob Hills Instagram: https://www.instagram.com/robhills_Rob Hills Facebook Page: https://www.facebook.com/iamrobhillsRob Hills LinkedIn: https://www.linkedin.com/in/rob-hills/

This week's episode of The Metabolic Classroom focuses on the potential of continuous glucose monitors (CGMs) as a valuable tool not only for individuals with diabetes but also for anyone interested in gaining deeper insights into their metabolic health.CGMs, which measure glucose levels continuously by detecting interstitial glucose, provide real-time feedback on how diet, exercise, stress, and sleep impact blood sugar, making them useful beyond their traditional application for managing diabetes.Dr. Bikman highlights studies that showcase the variability in individual glucose responses to the same foods, which can be attributed to factors like gut microbiome composition. Ben cites a prominent 2015 study from Israel that revealed individuals' glucose reactions to identical foods varied widely, showing the personal nature of glycemic responses and the role of CGMs in helping people manage their blood glucose variability.Another study, from Stanford University, further illustrates how CGMs can reveal “hidden” glucose spikes, leading people to make more informed dietary and lifestyle decisions.Dr. Bikman touches on the idea that, beyond personal use, CGMs have clinical benefits as well. Studies from the Scripps Research Institute and the Framingham Heart Study show that CGMs can detect early signs of prediabetes and diabetes in individuals who may otherwise go undiagnosed, providing a valuable tool for early intervention.While there are critiques about CGMs, including concerns about potential overemphasis on glucose levels, costs, and possible psychological impacts, Dr. Bikman asserts that the advantages—such as improving insulin sensitivity, reducing glycemic variability, and empowering users to make healthier choices—outweigh these concerns.Ben concludes by encouraging those curious about their metabolic health to consider CGMs as a practical tool for self-monitoring, with potential for significant long-term health benefits.visit: https://www.insuliniq.comBen's favorite meal-replacement shake: https://gethlth.com (discount: BEN10)Ben's favorite electrolytes (and more): https://redmond.life (discount: BEN15)Ben's favorite allulose source: https://rxsugar.com (discount: BEN20)Ben's favorite health check-up for women: https://choosejoi.co/drben15 (discount: DRBEN15)Ben's favorite health check-up for men: https://blokes.co/drben15 (discount: DRBEN15)Ben's favorite exogenous ketone: https://www.americanketone.com (discount: Ben10)Show Notes/References:Due to character length constraints, references are not posted here. However, for a complete list, we respond quickly. Please email: support@insuliniq.com with your request, and be sure to mention which Metabolic Classroom episode you are referring to, which in this case is “Episode 76 - Using a Continuous Glucose Monitor (CGM) to Help You Improve Insulin Sensitivity”.#InsulinResistance #CGM #MetabolicHealth #BloodSugar #DrBenBikman #ContinuousGlucoseMonitor #InsulinSensitivity #GlycemicVariability #Microbiome #Prediabetes #SelfMonitoring #HealthTech #DiabetesPrevention #MetabolicInsights #NutritionalScience #Hyperglycemia #Glycation #HealthOptimization Hosted on Acast. See acast.com/privacy for more information.

The Framingham Heart Study is on the block this time. Some major health guidelines came from this ongoing study since 1948. Pity there is no mention of what we really need to focus on. https://linktr.ee/steve.andelkovic#Conciergehealthadvisor #micronutrients #nutrition #health #metabolicsyndrome

El riesgo cardiovascular se mide mediante una combinación de factores clínicos, antecedentes médicos, estilos de vida y pruebas de laboratorio. Existen varias herramientas y modelos que los profesionales de la salud utilizan para evaluar este riesgo de manera integral. A continuación, se describen los métodos más comunes:Herramientas y Puntuaciones de RiesgoFramingham Risk Score:Desarrollada a partir del estudio Framingham Heart Study.Estima el riesgo a 10 años de desarrollar enfermedades cardiovasculares.Factores incluidos: edad, sexo, colesterol total, HDL, presión arterial sistólica, tratamiento antihipertensivo, tabaquismo y diabetes.SCORE (Systematic COronary Risk Evaluation):Utilizada en Europa.Estima el riesgo a 10 años de muerte por enfermedad cardiovascular.Factores incluidos: edad, sexo, tabaquismo, colesterol total, presión arterial sistólica.QRISK:Utilizada en el Reino Unido.Estima el riesgo a 10 años de desarrollar enfermedades cardiovasculares.Factores incluidos: edad, sexo, etnia, índice de masa corporal (IMC), colesterol total/HDL, presión arterial sistólica, diabetes, enfermedad renal crónica, migrañas, enfermedades inflamatorias, uso de esteroides, antecedentes familiares de enfermedad cardiovascular.ASCVD Risk Calculator:Utilizada en Estados Unidos.Estima el riesgo a 10 años de desarrollar aterosclerosis, enfermedad coronaria, infarto de miocardio o accidente cerebrovascular.Factores incluidos: edad, sexo, raza, colesterol total, HDL, presión arterial sistólica, tratamiento antihipertensivo, diabetes y tabaquismo.Factores Clínicos y Pruebas de LaboratorioAdemás de las herramientas de puntuación de riesgo, los médicos también evalúan otros factores:Perfil Lipídico:Colesterol total, LDL, HDL y triglicéridos.Las pruebas de laboratorio pueden identificar dislipidemias que aumentan el riesgo cardiovascular.Glucosa y HbA1c:Glucosa en ayunas y hemoglobina glicosilada (HbA1c) para evaluar la presencia de diabetes o prediabetes.Proteína C Reactiva de Alta Sensibilidad (PCR-hs):Indicador de inflamación sistémica que puede predecir el riesgo cardiovascular.Presión Arterial:La hipertensión es un factor de riesgo mayor para las enfermedades cardiovasculares.Índice de Masa Corporal (IMC) y Circunferencia de Cintura:Evaluación de la obesidad y distribución de grasa corporal.Historia Clínica y Familiar:Antecedentes personales y familiares de enfermedades cardiovasculares.Hábitos de Vida:Tabaquismo, dieta, actividad física y consumo de alcohol.Otros Exámenes DiagnósticosEn algunos casos, se pueden realizar pruebas adicionales para evaluar el riesgo cardiovascular:Electrocardiograma (ECG):Para detectar anomalías en el ritmo y la estructura cardíaca.Ecocardiograma:Evaluación de la función y estructura del corazón.Prueba de Esfuerzo:Para evaluar cómo responde el corazón al ejercicio.Tomografía Computarizada de Calcio Coronario (CAC):Medición de la cantidad de calcio en las arterias coronarias, que puede indicar aterosclerosis.Análisis de la Función Renal:Evaluación de la creatinina y la tasa de filtración glomerular (TFG) para detectar enfermedad renal crónica, que es un factor de riesgo cardiovascular.Interpretación y PlanificaciónEl riesgo cardiovascular se clasifica generalmente en bajo, moderado, alto o muy alto, basado en los resultados de las herramientas y pruebas mencionadas. Una vez que se determina el nivel de riesgo, los profesionales de la salud pueden recomendar estrategias de prevención y tratamiento, que pueden incluir:Cambios en el estilo de vida (dieta, ejercicio, dejar de fumar).Medicación para controlar la presión arterial, el colesterol y la glucosa.Monitoreo regular y seguimiento médico.La evaluación del riesgo cardiovascular es un proceso integral y continuo que requiere la cooperación entre el paciente y el equipo de atención médica para lograr los mejores resultados posibles.Conviértete en un seguidor de este podcast: https://www.spreaker.com/podcast/comiendo-con-maria-nutricion--2497272/support.

หนึ่งในงานวิจัยที่สำคัญและมีอิทธิพลใน Nutrition Science ก็คืองานวิจัยของ Ancel Keys และคณะ The Seven Countries Study (SCS) ซึ่งเป็น observational cohort study เริ่มต้นในปีค.ศ.1957 เพื่อสำรวจความสัมพันธ์ระหว่างไลฟ์สไตล์ biomarkers และโรคหัวใจ SCS เป็นโครงการระดับอภิมหาโปรเจคซึ่งต้องการความร่วมมือระหว่างนักวิทยาศาสตร์ทั่วโลก การเก็บและวิเคราะห์ข้อมูลกินเวลาหลายสิบปี SCS จุดประกายให้มีการทำงานวิจัยเชิงสังเกตุการที่สำคัญออกมาหลายโครงการ ที่สำคัญมากคือ The Framingham Heart Study ในที่สุด SCS ก็ได้ข้อสรุปว่า มีความเชื่อมโยงระหว่างการบริโภคไขมันอิ่มตัวและโรคหัวใจ Ancel Keys กับ SCS ถูกวิพากษ์วิจารณ์หลังจากการเสียชีวิตของเขาในปีค.ศ. 2004 และมักจะเป็นการใช้เรื่องเล่าโดย Health Influencers ทางโซเชียลมีเดีย กล่าวหา Ancel Keys และ SCS ว่าผิดพลาดอย่างมโหฬาร ทำให้เป็นต้นกำเนิดของอาหารไขมันต่ำ มีอิทธิพลต่อการจัดทำ Nutrition Guidelines รวมถึงนโยบายโภชนาการของประเทศ ซึ่งไม่เป็นความจริงเลย ข้อกล่าวหา Ancel Keys กับ SCS มีอยู่ 4 ประเด็น ซึ่งพี่ปุ๋มจะนำข้อมูลจากแหล่งข้อมูลที่ดีมากหลายแหล่ง เพื่อคืนความเป็นธรรมให้กับ Ancel Keys กับ SCS ค่ะ 1. ประเทศที่ถูกเลือกและคัดออกจาก SCS ทำโดยพื้นฐานของอคติที่ Keys อยากให้ผลลัพธ์ออกมาตามที่ตัวเองต้องการ 2. ข้อมูลประเทศฝรั่งเศสถูกเอาออกไปจาก SCS โดยเจตนา 3. ข้อมูลโภชนาการของประเทศกรีซได้รับมาในช่วงเวลาถือศีลอดทำให้ข้อมูลของ SCS เกิดการบิดเบือน 4. น้ำตาลไม่ถูกนำมาพิจารณาใน SCS ว่าเป็นตัวการที่เป็นไปไปได้ในการเกิดโรคหลอดเลือดหัวใจ มาคืนความเป็นธรรมให้ Ancel Keys กัน วันพฤหัสที่ 11 ก.ค. เวลา 20.00 น.ค่ะ

Send us a Text Message.Is your breakfast making you an 'alpha' or a 'beta'? Discover why the steak-and-eggs versus oatmeal debate is far more than just what's on your plate! Join me, Rob Maxwell, as I dissect the flood of misinformation swamping social media and challenge the binary thinking promoted by so-called nutrition 'gurus'. We'll explore how influential voices can mislead the masses and why it's crucial to look beyond loud opinions to evidence-based research for your dietary choices. This isn't just about breakfast; it's about reclaiming your ability to think critically about what you eat.In this episode, we also tackle common myths about healthy eating and set the record straight. From understanding the true role of pesticides in agriculture to the dietary habits of omnivorous animals, I unravel the science behind why humans thrive on a balanced diet. Drawing insights from the Framingham Heart Study, I delve into the health benefits of combining meat and plant-based foods, emphasizing the importance of moderating saturated fat intake and boosting fiber for heart health. Balance is key, and I'll show you how to navigate through the noise to make well-informed decisions for your well-being.

Plus Is AI Funnier Than The Onion? (subscribe below) Like this? Get AIDAILY, delivered to your inbox, every weekday. Subscribe to our newsletter at https://aidaily.us AI Lie Detectors Are Better Than Humans at Spotting Lies AI-based lie detectors are outperforming humans, detecting lies with 67% accuracy compared to human accuracy of around 50%. However, reliance on these tools led to increased accusations, potentially undermining trust. While AI offers benefits in identifying misinformation, its widespread use could have significant social impacts and necessitates careful regulation.  AI Outshines Humans in Humor: Study Finds ChatGPT is as Funny as The Onion A study in PLOS ONE reveals AI-generated humor, using ChatGPT 3.5, is rated as funny or funnier than jokes by humans, including professional satirists from The Onion. ChatGPT excelled in creating humorous acronyms, fill-in-the-blank statements, and roast jokes, posing a potential employment threat to comedy writers. Nintendo Boss Says They Won't Use Generative AI for Game Creation Nintendo president Shuntaro Furukawa announced that the company will not use generative AI in developing new games, citing intellectual property concerns and a desire to maintain unique gaming experiences. While acknowledging AI's role in controlling character movements, Furukawa emphasized the importance of creativity that cannot be achieved through AI alone. He noted that longer development cycles are unavoidable due to increasing complexity and advancing technology. AI Approach Optimizes Antibody Drugs Stanford scientists have developed a method using a ChatGPT-like AI model combined with protein 3D structures to enhance antibody drug development. This approach improves the prediction of beneficial mutations, exemplified by a 25-fold enhancement of a SARS-CoV-2 antibody. By integrating structural constraints, the model accelerates drug optimization, reducing reliance on extensive lab experiments and enabling faster responses to emerging diseases. The research, published in Science, showcases AI's potential to revolutionize protein engineering and drug development.  AI Model for Alzheimer's Prediction Using Speech Patterns An AI model utilizing speech patterns to predict Alzheimer's progression from mild cognitive impairment (MCI) has shown 78.5% accuracy. Based on data from the Framingham Heart Study, it integrates natural language processing techniques, offering a cost-effective, accessible tool for remote cognitive assessment. This AI model could revolutionize early Alzheimer's diagnosis, making it more inclusive and accessible, particularly through smartphone apps for those in underserved areas. Researchers aim to enhance the model with data from natural conversations and daily life patterns for better accuracy. AI Blunders Mar Brands' Reputations Brands rushing to embrace AI have faced notable missteps. Examples include Toys "R" Us' creepy AI video, McDonald's AI drive-through failures, Air Canada's erroneous chatbot, and Sports Illustrated's fake author scandal. These incidents highlight the risks of adopting AI hastily without proper oversight.

En lo último en salud y fitness edición de junio 2024, damos un paseo por las últimas tendencias, investigaciones y noticias en el mundo de la salud y el fitness. Con un enfoque en la ciencia y la práctica, vamos a platicar sobre algunos temas que van desde la eficacia de los suplementos pre-entrenamiento hasta los últimos descubrimientos en biomecánica cerebral. Atajos del Episodio 02:47 - ¿Es un suplemento pre-entrenamiento mejor que solo cafeína para mejorar el rendimiento en ejercicios de resistencia?1 06:10 - ¿Es la cafeína efectiva para aumentar la fuerza y resistencia muscular?2 09:10 - ¿Son efectivas las técnicas avanzadas de entrenamiento de resistencia para el crecimiento muscular?3 13:19 - Proteínas vegetales al nivel de la proteína de suero de leche4 16:08 - Crecimiento Cerebral en el Siglo XX: Un Fenómeno en Evolución5   Referencias:  1.      Snyder, M., Brewer, C. & Taylor, K. Multi-Ingredient Preworkout Supplementation Compared With Caffeine and a Placebo Does Not Improve Repetitions to Failure in Resistance-Trained Women. … Journal of Sports … (2024). 2.      Wu, W. et al. Effects of Acute Ingestion of Caffeine Capsules on Muscle Strength and Muscle Endurance: A Systematic Review and Meta-Analysis. Nutrients (2024). 3.      Fonseca, P. A. B., Ide, B. N. & Oranchuk…, D. J. Comparison of Traditional and Advanced Resistance Training Paradigms on Muscle Hypertrophy in Trained Individuals: A Systematic Review and Meta‐Analysis. Translational Sports … (2023). 4.      Heijden, I. V. D. & Monteyne…, A. J. Plant Protein Blend Ingestion Stimulates Post-Exercise Myofibrillar Protein Synthesis Rates Equivalently to Whey in Resistance-Trained Adults. … & Science in … (2024). 5.      DeCarli, C., Maillard, P., Pase, M. P. & Beiser…, A. S. Trends in intracranial and cerebral volumes of Framingham Heart Study participants born 1930 to 1970. JAMA … (2024).

Savage speaks with Dr. Richard Fleming to learn the latest in preventing and living with cardiac disease. Dr. Fleming is a Nuclear and Preventive Cardiologist who has published more than 50 papers in peer-reviewed medical journals, over 50 presentations at scientific conferences throughout the U.S., Europe and Asia and written 3 independent books on healthcare. Find out what you can do to improve your heart health and the current breakthroughs in cardiac care. Is the Framingham Heart Study still relevant based on modern research? Is the Ornish diet still recommended? What are its drawbacks? How does diet and lifestyle influence heart disease? Can atherosclerosis be reversed? Do women have better outcomes than men with heart disease? What is coronary artery disease? What role does alcohol play in heart disease? What preventative measures do we have? Learn about the SHOCKING starvation study conducted by the US government! Savage explains the three elements of health... lifestyle, genetics, and unknown. Learn more about your ad choices. Visit podcastchoices.com/adchoices

The Framingham Heart Study is the longest running cohort study on cardiovascular health in human history. Last fall, the study turned 75 — we speak with two generations of participants and the study's research director about its impacts.

Today, you'll learn about the traits most people value in romantic partners, a new link between a particular gut bacteria and cardiovascular health, and why dogs might make your kids healthier. Romantic Traits “Intelligence and kindness are the most valued traits in romantic partners, study finds.” by Eric W. Dolan. 2024. “What Do Different People Look for in a Partner? Effects of Sex, Sexual Orientation, and Mating Strategies on Partner Preferences.” by Joao Francisco Goes Braga Takayanagi, et al. 2024. Heart & Gut “Scientists link certain gut bacteria to lower heart disease risk.” by Allessandra DiCorato. 2024. “7 Crazy Facts About The Microbiome And Gut Bacteria.” by Ross Carver-Carter. N.d. “Gut microbiome and metabolome profiling in Framingham heart study reveals cholesterol-metabolizing bacteria.” by Chenhao Li, et al. 2024. “Cholesterol Metabolism by Uncultured Human Gut Bacteria Influences Host Cholesterol Level.” by Douglas J. Kenny, et al. 2020. “About the Framingham Heart Study.” n.a. N.d. Canine Play “The Serious Side of Kid And Canine Play.” UMass Amherst. 2024. “America's Pandemic, Physical Inactivity.” PHIT America. 2023. “Physical Activity: Children.” CDC. 2023. “The KID Study (Kids Interacting With Dogs): Piloting a Novel Approach for Measuring Dog-Facilitated Youth Physical Activity.” by Colleen J. Chase, et al. 2024. Hosted on Acast. See acast.com/privacy for more information.

Discover the shocking truth about seed oils and the diet-heart hypothesis. This episode blows the lid off the saturated fat controversy using the Framingham Heart Study, Minnesota Coronary Experiment, and more. 4:54 The history of food production and the impact of new technologies on the industry. 10:30 The history of heart disease research and the influence of Ancel Keys. 20:29 Limitations of Seven Countries Study, a flawed observational epidemiology study on saturated fat and heart disease. 24:43 Flaws in the diet-heart hypothesis, including ignored mortality data. 34:03 Dietary heart hypothesis study with unexpected results. 38:40 Reducing seed oil intake for better health. Website Show Notes Page David's Book The Christian's Guide to Holistic Health

Today, you'll learn about why our brains are getting bigger and why that's a good thing, how the sweet songs of the reef could help save it, and an AI device that gives a voice to the voiceless. Bigger Brains “Human brains are getting larger. That may be good news for dementia risk.” UC David Health. 2024. “Trends in Intracranial and Cerebral Volumes of Framingham Heart Study Participants Born 1930 to 1970.” by Charles DeCarli, MD, et al. 2024. “Framingham Heart Study.” Framingham Heart Study. N.d. “Study examines factors behind decline in dementia incidence.” NIH. 2016. Reef Songs “Sounds appealing - reef recordings entice coral larvae to start building.” by Ben Coxworth. 2024. “Life Below Water.” UN. n.d. “Status of Coral Reefs.” Reef Resilience Network. N.d. “Soundscape enrichment increases larval settlement rates for the brooding coral Porites astreoides.” by Nadege Aoki, et al. 2024. AI Speech “Speaking without vocal cords, thanks to a new AI-assisted wearable device.” by Christine Wei-li Lee. 2024. “Speaking without vocal folds using a machine-learning-assisted wearable sensing-actuation system.” by Ziyuan Che, et al. 2024. Follow Curiosity Daily on your favorite podcast app to get smarter with Calli and Nate — for free! Still curious? Get exclusive science shows, nature documentaries, and more real-life entertainment on discovery+! Go to https://discoveryplus.com/curiosity to start your 7-day free trial. discovery+ is currently only available for US subscribers. Hosted on Acast. See acast.com/privacy for more information.

Ready to reclaim sovereignty over your mind and rewrite your narrative? Join us as we explore simple yet profound practices to combat anxiety and cultivate resilience. “There is all this stuff that can stress us out and we can have these high levels of anxiety and depression.  But if we take care of ourselves, if we find ways to calm ourselves, soothe ourselves… be present with your breath. As simple a method as mindful breathing can help extricate us from that kind of conditioning.”  - Dawson Church, best-selling science writer, author of three award-winning books, and today's guest on Quantum Revolution. Prepare to explore the fascinating realms of healing and personal transformation with Dawson Church in this enlightening episode. As we journey through the intersection of science and spirituality, discover the profound impact of mindfulness, meditation, and compassion on our mental and emotional well-being. Through engaging discussions and real-life examples, Dawson demonstrates how these practices can lead to profound shifts in our brain's structure and function, paving the way for greater joy and fulfillment in our lives. Join us as we uncover the transformative power of embracing our innate potential and creating lives filled with purpose and abundance. Check out the video interview on YouTube! https://youtu.be/uUVMGktfR5Y Links: Dawson Church: http://dawsongift.com/ Quantum Revolution Get your free Quantum Human Design™ Chart at https://freehumandesignchart.com/ For more information and for full transcripts (starting with season 6), please go to our website at https://quantumrevolutionpodcast.com/ Produced by Number Three Productions, https://numberthreeproductions.com/ Timestamps: [0:00] Introduction to this episode, “Rewire Your Brain for Bliss with Dawson Church”, with Karen Curry Parker. [3:29] Are we actually thriving right now as humanity? [6:06] We seem to be addicted to being miserable. [8:25] Our communication seems to be getting more negative as well. Why is that happening when we're actually getting better? [14:05] Our kids, emotional regulation, and executive functioning. [20:04] The brain vs. the mind. [27:56] The Framingham Heart Study and Mind to Matter. [30:30] How to connect with Dawson Church. [31:59] Outro to this episode, “Rewire Your Brain for Bliss with Dawson Church”, with Karen Curry Parker.

Once again it is time for our (mostly) monthly Instagram Q&A episode. This week we have 25 questions that we answer. These episodes are always a favorite of ours to record so a big thank you to all the listeners who submitted questions. TIMESTAMPS0:00 - Life/Episode updates11:27 - If moving to hypertrophy / machine focused can that negatively affect other activity areas such as hiking, biking, etc? 13:51 - With all the volume studies lately and so much per session volume, are we ready to throw junk volume out?...17:26 - When returning to an exercise after months away, does NOT starting at the same weight/reps as prior indicate that no progress has been made?20:18 - How long to stick with a movement? Until plateau?23:53 - Does Creatine really show benefits maintaining LBM while cutting or is it all marketing hype?25:04 - Are alternating limb movements underrated?...30:04 - Can you elaborate on the Omega 3 index being tied to longevity? https://www.lifeextension.com/magazine/2022/3/omega-3-levels-healthy-years (Framingham Heart Study)34:41 - Updates on your Tongkat experiment? 36:06 - As an intermediate, can you still add muscle eating at maintenance or is a bulk required at some point? ...42:28 - Is it ok to rotate movements...44:20 - Cardio destroys muscle? 47:04 - Tips for improvements in digestion?48:08 - Top fallacies/lessons you learned about starting a business? (see Episode 142 at 1:16:00 mark (question on business lessons/growth))49:31 - If you were going to rewrite the T-nation article on strength standards for beginner to advanced... https://forums.t-nation.com/t/strength-standards-are-you-strong/28463353:10 - If you can't secure yourself down for movements like pulldowns/rows in a home gym or DIY at a Globo gym...54:09 - How to know when to give another macro increase in a growth phase?55:39 - Do you think metabolic adaptation occurs faster with a larger deficit?57:02 - At what point does all the optimization stuff get in the way of just being tough?....1:01:39 - Daily Supplements for a natty (see Episode 148)1:01:56 - It feels like Rhonda Patrick is gaining a lot of steam in the space. Thoughts?  https://www.emedevents.com/speaker-profile/rhonda-patrick 1:05:31 - Better to have a second home in San Diego or Costa Rica? 1:07:53 - Hurt my back and could only train arms 4x/week. Now how do I train to keep the gains?1:09:59 - Would it be ideal to train 7x a week given no recovery issues?  Coaching with Aaron ⬇️https://strakernutritionco.com/nutrition-coaching-apply-now/Done For You Client Check-In System for Online Coaches ⬇️https://strakernutritionco.com/macronutrient-reporting-check-in-template/Paragon Training Methods Programming ⬇️https://paragontrainingmethods.comFollow Bryan's Evolved Training Systems Programming ⬇️https://evolvedtrainingsystems.comFind Us on Social Media ⬇️IG | @Eat.Train.ProsperIG | @bryanboorsteinIG | @aaron_strakerYT | EAT TRAIN PROSPER PODCAST

According to Alzheimer's Disease International, the number of people around the world with the condition will reach 78 million in 2030, and 139 million in 2050. As of 2024, there is no known cure for Alzheimer's, dementia, or similar degenerative brain conditions. So, how are those testing for these diseases using data and technology to help improve health outcomes?Today's guest is Rhoda Au, Professor of Anatomy & Neurobiology, Neurology, and Epidemiology at Boston University, and Director of Neuropsychology at the Framingham Heart Study. She's also the Director of Global Cohort Development at the Davos Alzheimer's Collaborative.We discuss Rhoda's experience of paper-and-pen Alzheimer's testing in the early 90s, her switch to voice capture in 2005, and her thoughts about how medical data should be shared. 00:00 - Intro02:02 - The pen-and-paper days of Altizmer's testing12:34 - The ethics of voice capture20:20 - Why we need to open up health data to the community26:07 - Dan's final thoughtsLINKS:Rhoda Au: https://www.linkedin.com/in/rhoda-au-1687277/Boston University School of Medicine & Public Health: https://www.bu.edu/sph/Framingham Heart Study: https://www.framinghamheartstudy.org/Alzheimer's Disease International: https://www.alzint.org/Alzheimer's Disease Data Initiative: https://www.alzheimersdata.org/Dan Klein: https://uk.linkedin.com/in/dplkleinZühlke: https://www.zuehlke.com/enWelcome to Data Today, a podcast from Zühlke.We're living in a world of opportunities. But to fully realise them, we have to reshape the way we innovate.We need to stop siloing data, ring-fencing knowledge and looking at traditional value chains. And that's what this podcast is about. Every two weeks, we're taking a look at data outside the box to see how amazing individuals from disparate fields and industries are transforming the way they work with data, the challenges they are overcoming, and what we can all learn from them.Zühlke is a global innovation service provider. We envisage ideas and create new business models for our clients by developing services and products based on new technologies – from the initial vision through development to deployment, production and operation.

Deepthy Varghese, MSN, ACNP, FNP, of Northside Hospital, is joined by guests Sandeep K. Goyal, MD, FHRS, Piedmont Heart Institute, and Andrea M. Russo, MD, FHRS, Cooper University Hospital. to discuss the article explores that development and validation of the HARMS2-AF score, a novel lifestyle risk assessment tool for identifying atrial fibrillation (AF) risk in the general population. Using data from the UK Biobank and Framingham Heart Study, the score, derived through Cox proportional hazards regression, includes variables like hypertension, age, body mass index, sex, sleep apnea, smoking, and alcohol. Physical inactivity and diabetes were not significant predictors. The score demonstrated effective predictive performance in both cohorts, outperforming existing models like Framingham-AF and ARIC, and comparable to CHARGE-AF. In conclusion, the HARMS2-AF score is a valuable tool for lifestyle-related AF risk identification, aiding in population screening and potential early intervention. https://www.hrsonline.org/education/TheLead https://academic.oup.com/eurheartj/article/44/36/3443/7205602 Host Disclosure(s): D. Varghese: No relevant financial relationships with ineligible companies to disclose. Contributor Disclosure(s): A. Russo: Honoraria, Speaking, and Consulting: Pacemate, AtriCure, Inc., Bayer Healthcare Pharmaceuticals, Sanofi, Medtronic, Biosense Webster, Inc., Biotronik, Abbott Medical, Boston Scientific, BMS/PFizer Alliance, Royalty Income: UpToDate, Inc., Research: Medtronic, Boston Scientific, Fellowship Support: Medtronic, Board Membership: ABIM.  S. Goyal: Honoraria, Speaking, and Consulting: Biosense Webster, Inc., Medtronic 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/TheLeadEpisode50

MedLink Neurology Podcast is delighted to feature selected episodes from BrainWaves, courtesy of James E Siegler MD, its originator and host. BrainWaves is an academic audio podcast whose mission is to educate medical providers through clinical cases and topical reviews in neurology, medicine, and the humanities, and episodes originally aired from 2016 to 2021. Originally released: June 7, 2018 Depression and dementia are, unfortunately, two very common disorders in mental health. But the fact that they occur together is not explained by their overall prevalence. The relationship is a bit more complicated. Joan Dietz joins Jim Siegler in a discussion on how she counters these common conditions. Produced by James E Siegler. Music by Lee Rosevere, Jason Shaw, Chris Zabriskie, Kai Engel, and Scott Holmes. BrainWaves' podcasts and online content are intended for medical education only and should not be used for clinical decision-making. REFERENCES Alexopoulos GS, Murphy CF, Gunning-Dixon FM, et al. Microstructural white matter abnormalities and remission of geriatric depression. Am J Psychiatry 2008;165(2):238-44. PMID 18172016Byers AL, Yaffe K. Depression and risk of developing dementia. Nat Rev Neurol 2011;7(6):323-31. PMID 21537355Dotson VM, Beydoun MA, Zonderman AB. Recurrent depressive symptoms and the incidence of dementia and mild cognitive impairment. Neurology 2010;75(1):27-34. PMID 20603482Korczyn AD, Halperin I. Depression and dementia. J Neurol Sci 2009;283(1-2):139-42. PMID 19345960Lee CW, Lin CL, Sung FC, Liang JA, Kao CH. Antidepressant treatment and risk of dementia: a population-based, retrospective case-control study. J Clin Psychiatry 2016;77(1):117-22; quiz 122. PMID 26845268Sachdev PS, Smith JS, Angus-Lepan H, Rodriguez P. Pseudodementia twelve years on. J Neurol Neurosurg Psychiatry 1990;53(3):254-9. PMID 2324757Saczynski JS, Beiser A, Seshadri S, Auerbach S, Wolf PA, Au R. Depressive symptoms and risk of dementia: the Framingham Heart Study. Neurology 2010;75(1):35-41. PMID 20603483  We believe that the principles expressed or implied in the podcast remain valid, but certain details may be superseded by evolving knowledge since the episode's original release date.

Welcome to the Olink® Proteomics in Proximity podcast! Below are some useful resources mentioned in this episode: Olink tools and software• Olink® 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 articles• Dhindsa, R.S., Burren, O.S., Sun, B.B. et al. Rare variant associations with plasma protein levels in the UK Biobank. 2023 Nature, DOI: 10.1038/s41586-023-06547-xhttps://www.nature.com/articles/s41586-023-06547-x• Sun, B.B., Chiou, J., Traylor, M. et al.  Plasma proteomic associations with genetics and health in the UK Biobank. 2023 Nature, DOI: 10.1038/s41586-023-06592-6 https://www.nature.com/articles/s41586-023-06592-6• Ticau S, Sridharan G, Tsour S, et al. Neurofilament Light Chain as a Biomarker of Hereditary Transthyretin-Mediated Amyloidosis 2021 Neurology, DOI: 10.1212/WNL.0000000000011090https://n.neurology.org/content/96/3/e412.long• Zannad F, Ferreira JP, Butler J, et al.  Effect of Empagliflozin on Circulating Proteomics in Heart Failure: Mechanistic Insights from the EMPEROR Program. 2022 European Heart Journal, DOI: 10.1093/eurheartj/ehac495                https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehac495/6676779• Eldjarn GH, et al. Large-scale plasma proteomics comparisons through genetics and disease associations. Nature. 2023 Oct;622(7982):348-358. doi: 10.1038/s41586-023-06563-xhttps://www.nature.com/articles/s41586-023-06563-x#Sec44• [PREPRINT] Carrasco-Zanini et al 2023 Proteomic prediction of common and rare diseases MedRxiv https://www.medrxiv.org/content/10.1101/2023.07.18.23292811v1• Michaëlsson E, Lund LH, Hage C, et al. Myeloperoxidase Inhibition Reverses Biomarker Profiles Associated With Clinical Outcomes in HFpEF. 2023 JACC. Heart Failure, DOI: 10.1016/j.jchf.2023.03.002https://www.sciencedirect.com/science/article/pii/S2213177923001257• Girerd N, Levy D, Duarte K, et al.  Protein Biomarkers of New-Onset Heart Failure: Insights From the Heart Omics and Ageing Cohort, the Atherosclerosis Risk in Communities Study, and the Framingham Heart Study. 2023 Circulation Heart Failure, DOI: 10.1161/CIRCHEARTFAILURE.122.009694https://www.ahajournals.org/doi/abs/10.1161/CIRCHEARTFAILURE.122.009694Subscribe 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: https://podcastaddict.com/podcast/409... Deezer: https://www.deezer.com/show/5178787 Player FM: https://player.fm/series/series-3396598 In case you were wondering, Proteomics in Proximity refers to the principle underlying Olink technology called the Proximity Extension Assay (PEA). More information about the assay and how it works can be found here: https://bit.ly/3Rt7YiY For any questions regarding information about Olink Proteomics, please email us at info@olink.com or visit our website: https://www.olink.com/Interested in a specific podcast topic or guest? Reach out to us at PIP@olink.comWHAT IS PROTEOMICS IN PROXIMITY?Proteomics in Proximity discusses the intersection of proteomics with genomics for drug target discovery, the application of proteomics to reveal disease biomarkers, and current trends in using proteomics to unlock biological mechanisms. Co-hosted by Olink's Cindy Lawley and Sarantis Chlamydas.

BUFFALO, NY- November 14, 2023 – A new #researchpaper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 20, entitled, “Alcohol consumption and epigenetic age acceleration across human adulthood.” The alcohol-associated biological aging remains to be studied across adulthood. In their new study, researchers Mengyao Wang, Yi Li, Meng Lai, Drew R. Nannini, Lifang Hou, Roby Joehanes, Tianxiao Huan, Daniel Levy, Jiantao Ma, and Chunyu Liu from Boston University School of Public Health, Northwestern University Feinberg School of Medicine, National Institutes of Health, Framingham Heart Study, and Tufts University conducted linear regression analyses to investigate the associations between alcohol consumption and two DNA methylation-based biological age acceleration metrics in 3823 Framingham Heart Study participants (24–92 years and 53.8% women) adjusting for covariates. “We also investigated whether the two epigenetic aging metrics mediated the association of alcohol consumption with hypertension.” They found that higher long-term average alcohol consumption was significantly associated with biological age acceleration assessed by GrimAge acceleration (GAA) and PhenoAge acceleration (PAA) in middle-aged (45–64 years, n = 1866) and older (65–92 years, n = 1267) participants while not in young participants (24–44 years, n = 690). For example, one additional standard drink of alcohol (~14 grams of ethanol per day) was associated with a 0.71 ± 0.15-year (p = 2.1e-6) and 0.60 ± 0.18-year (p = 7.5e-4) increase in PAA in middle-aged and older participants, respectively, but the association was not significant in young participants (p = 0.23). One additional standard serving of liquor (~14 grams of ethanol) was associated with a greater increase in GAA (0.82-year, p = 4.8e-4) and PAA (1.45-year, p = 7.4e-5) than beer (GAA: 0.45-year, p = 5.2e-4; PAA: 0.48-year, p = 0.02) and wine (GAA: 0.51-year, p = 0.02; PAA: 0.91-year, p = 0.008) in middle-aged participant group. “We observed that up to 28% of the association between alcohol consumption and hypertension was mediated by GAA or PAA in the pooled sample. Our findings suggest that alcohol consumption is associated with greater biological aging quantified by epigenetic aging metrics, which may mediate the association of alcohol consumption with quantitative traits, such as hypertension.” DOI - https://doi.org/10.18632/aging.205153 Corresponding authors - Jiantao Ma - jiantao.ma@tufts.edu, and Chunyu Liu - liuc@bu.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205153 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, alcohol consumption, epigenetic aging, DNA methylation, hypertension About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Leading American poverty researcher Mark Robert Rank joins the Utterly Moderate Podcast to discuss his Poverty Risk Calculator, the record-low poverty rates that the U.S. saw in 2021, Dr. Rank's research on the risk Americans face of experiencing poverty throughout their lives, a new book he has coming out on luck, and more! Rank has spent his career studying poverty, economic inequality, and social policy in America and teaching about these topics at Washington University in St. Louis, where he has been a faculty member since 1985. Much of his research has focused on the life course risk of poverty in America. Using data from hundreds of thousands of Americans taken from a longitudinal study that began in the 1960s, Dr. Rank and his research collaborators have been able to estimate the likelihood that the average American will experience poverty at some point in their lives. This research shows that around 59% of Americans will experience at least one year under the official poverty line at some point in their lives. While Rank has published his research findings in a number of academic articles and books over the years, it occurred to him that it might be possible to use this body of poverty research in order to develop a tool that would allow individuals to estimate their own risk of poverty. The idea is similar to a doctor's ability to predict your risk of heart disease. Using several pieces of information (blood pressure, cholesterol, etc.), your doctor can make a reasonable estimate of your chances of having a heart attack in the next decade. These numbers are based on statistical patterns derived from a very large sample of families that make up the Framingham Heart Study, the longitudinal study of cardiovascular health that began in 1948. Could this be done with poverty data? Working with his colleagues over the course of hundreds of hours of programming and designing, Rank developed the Poverty Risk Calculator. You can try it for yourself. Using the calculator, individuals enter background information on five dimensions (age, race, gender, education, and marital status), and receive a 5-, 10-, and 15-year probability that they will experience at least one year of poverty during these time periods. Individuals can also calculate their odds of experiencing near-poverty and extreme poverty. The calculator is designed so that individuals can also easily compare their profile with others' side-by-side in the same graph to examine how the risk of poverty varies by different characteristics. The impact of each variable is profound, and one can readily see how poverty is affected by, for example, changes to one's race, education, or marital status. This allows users to observe the impact of key social dimensions on life chances. Try it for yourself and see how even a single change can drastically alter your personal risk of poverty. By utilizing the calculator you can see that the risk of poverty for many Americans is significant. While the likelihood of poverty may be low during any single year, across multiple years, individuals observe that their risk can rise substantially.  Visit us at CONNORSINSTITUTE.ORG and sign up for our free newsletter! Episode Audio: "Air Background Corporate" by REDCVT (Free Music Archive) "Please Listen Carefully" by Jahzzar (Free Music Archive) "Last Dance" by Jahzzar (Free Music Archive) “Happy Trails (To You)” by the Riders in the Sky (used with artist's permission) See omnystudio.com/listener for privacy information.

It's a study that laid the foundation of many more studies. The now famous Framingham Heart Study asked a simple question: Who is at risk for heart disease? Answers poured in over the years. Dr. Castelli was its third director and shares what's been learned.

We are re-releasing an episode from 2021 in remembrance of Ralph D'Agostino, Sr.  Ellie Murray and Lucy D'Agostino McGowan chat with Ralph D'Agostino Sr. and Ralph D'Agostino Jr. about their careers in statistics, looking back at how things have developed and forward at where they see the world of statistics and epidemiology going.  Ralph D'Agostino Sr. was a professor of Mathematics/Statistics, Biostatistics, and Epidemiology at Boston University. He was the lead biostatistician for the Framingham Heart Study, a biostatistical consultant to The New England Journal of Medicine, an editor of Statistics in Medicine and lead editor of their Tutorials, and a member and consultant on FDA committees. His major fields of research were clinical trials, prognostic models, longitudinal analysis, multivariate analysis, robustness, and outcomes/effectiveness research.  Ralph D'Agostino Jr. is a professor in the Department of Biostatistics and Data Science at Wake Forest University where he is the Director of the Biostatistics Core of the Comprehensive Cancer Center. Methodologically his research includes developing statistical techniques for evaluating data from observational settings, handling missing data in applied problems, and developing predictive functions to identify prospectively patients at elevated risk for future negative outcomes. Some of his recent work includes the development of methods using propensity score models to identify safety signals in large retrospective databases. 

House Republicans began an impeachment inquiry against President Joe Biden Thursday with an initial hearing. USA TODAY Congress and Campaigns Reporter Ken Tran has a recap.A New York court rejects former President Donald Trump's request to delay a civil trial.CVS pharmacists return to their stores after a walkout over working conditions.Teachers take to TikTok to express concerns about students falling behind.USA TODAY Health Reporter Karen Weintraub explains the significance of the Framingham Heart Study on its 75th anniversary.Episode Transcript available hereAlso available at art19.com/shows/5-ThingsSee Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Welcome to Olink Proteomics in Proximity Podcast!  Below are some useful resources from this episode:  Highlighted publication:Girerd N, et al. Protein Biomarkers of New-Onset Heart Failure: Insights From the Heart Omics and Ageing Cohort, the Atherosclerosis Risk in Communities Study, and the Framingham Heart Study. Circ Heart Fail. 2023 May;16(5):e009694. doi: 10.1161/CIRCHEARTFAILURE.122.009694 https://pubmed.ncbi.nlm.nih.gov/37192292/ Large-scale cardiovascular studies:·         Heart “OMics” in AGEing (HOMAGE), a European-based consortium investigating biomarkers to predict heart failure and as drug targets for prevention: https://www.homage-hf.eu/·         Atherosclerosis Risk in Communities (ARIC) consortium, a prospective epidemiologic study to investigate the causes of atherosclerosis and its clinical outcomes: https://sites.cscc.unc.edu/cscc/projects/ARIC·         Framingham Heart Study, a study identifying common factors or characteristics that contribute to cardiovascular disease across three generations: https://www.framinghamheartstudy.org/'·         EMPEROR-Preserved trial, a cohort of patients who had chronic heart failure and a left ventricular ejection fraction of more than 40% : https://www.wikijournalclub.org/wiki/EMPEROR-Preserved High-throughput platforms mentioned during the podcast or used in this study that measure tens to thousands of proteins simultaneously: ·         Olink® Target 96: https://olink.com/products-services/target/ ·         Olink® Explore 3072: https://olink.com/products-services/explore/·         Olink® Explore HT: https://olink.com/products-services/exploreht/ Podcast mentioned during this podcast:Cooper, Peter M, host. Easter Island – Where Giants Walked. Fall of Civilizations, Episode 6, July 2019, https://fallofcivilizationspodcast.com/ Books mentioned during the podcast:·         Attia, Peter. Outlive: the science & art of longevity. New York: Harmony, 2023. https://www.goodreads.com/en/book/show/61153739·         Hood, Leroy and Price, Nathan. The Age of Scientific Wellness: Why the Future of Medicine Is Personalized, Predictive, Data-Rich, and in Your Hands. Cambridge, MA and London, England: Harvard University Press, 2023. https://doi.org/10.4159/9780674293465 Would you like to subscribe to the podcast on your favorite player or app? You can do so here:  Apple Podcasts: https://apple.co/3T0YbSm  Spotify Podcasts: https://open.spotify.com/show/2sZ2wxO...  Google Podcasts: https://podcasts.google.com/feed/aHR0...  Amazon Music: https://music.amazon.com/podcasts/d97...  Podcast Addict: https://podcastaddict.com/podcast/409...  Deezer: https://www.deezer.com/show/5178787  Player FM: https://player.fm/series/series-3396598   In case you were wondering, Proteomics in Proximity refers to the principle underlying Olink Proteomics assay technology called the Proximity Extension Assay (PEA), and more information about the assay and how it works can be found here: https://bit.ly/3Rt7YiY  For any questions regarding information Olink Proteomics, please email us at info@olink.com or visit our website: https://www.olink.com/ WHAT IS PROTEOMICS IN PROXIMITY?Proteomics in Proximity discusses the intersection of proteomics with genomics for drug target discovery, the application of proteomics to reveal disease biomarkers, and current trends in using proteomics to unlock biological mechanisms. Co-hosted by Olink's Dale Yuzuki, Cindy Lawley and Sarantis Chlamydas.

Frailty and Flavonols Episode 1141 JUN 2023 Other subclasses showed no association (P values range: 0.12–0.99), but every 10 mg/d of higher quercetin intake was associated with 35% lower odds of frailty onset (OR: 0.65; 95% CI: 0.48–0.88). #Frailty #quercetin #flavonols Oei, S., Millar, C. L., Nguyen Lily, T. N., Mukamal, K. J., Kiel, D. P., Lipsitz, L. A., Hannan, M. T., & Sahni, S. (2023). Higher intake of dietary flavonols, specifically dietary quercetin, is associated with lower odds of frailty onset over 12 years of follow-up among adults in the Framingham Heart Study. The American Journal of Clinical Nutrition. https://doi.org/10.1016/j.ajcnut.2023.04.013 Frailty, falling, weakness, quercetin, flavonols, osteoporosis, sarcopenia. kaempferol , myricetin, aging, elderly, fisetin, strength, balance --- Support this podcast: https://podcasters.spotify.com/pod/show/ralph-turchiano/support

Frailty and Flavonols Episode 1141 JUN 2023 Frailty and Flavonols Other subclasses showed no association (P values range: 0.12–0.99), but every 10 mg/d of higher quercetin intake was associated with 35% lower odds of frailty onset (OR: 0.65; 95% CI: 0.48–0.88). #Frailty #quercetin #flavonols Oei, S., Millar, C. L., Nguyen Lily, T. N., Mukamal, K. J., Kiel, D. P., Lipsitz, L. A., Hannan, M. T., & Sahni, S. (2023). Higher intake of dietary flavonols, specifically dietary quercetin, is associated with lower odds of frailty onset over 12 years of follow-up among adults in the Framingham Heart Study. The American Journal of Clinical Nutrition. https://doi.org/10.1016/j.ajcnut.2023.04.013 Frailty, falling, weakness, quercetin, flavonols, osteoporosis, sarcopenia. kaempferol , myricetin, aging, elderly, fisetin, strength, balance --- Support this podcast: https://podcasters.spotify.com/pod/show/ralph-turchiano/support

​​Contributor: Travis Barlock MD Educational Pearls The QT interval represents phases 2 and 3 of ventricular plateau and repolarization, respectively. As the QT interval lengthens, more sodium and calcium channels are available and susceptible to action potentials. Prolonged QT interval is more concerning in the setting of bradycardia. This scenario increases the likelihood of R on T phenomenon.  R on T phenomenon occurs due to an early afterdepolarization event in which a premature ventricular contraction (PVC) occurs during the repolarization period (superimposed on the T wave), leading to an aberrant re-entry circuit. The re-entry circuit leads to Torsades de Pointes (polymorphic ventricular tachycardia with prolonged QT) and subsequent ventricular fibrillation. Treatment for Torsades de Pointes is 2g MgSO4. The preferred antiarrhythmic for VTach is IV lidocaine 1.5 mg/kg over 2 minutes. Avoid amiodarone due to risk of further QT prolongation. A heart rate under 80 does not need QT correction Corrected QT interval is used in the setting of tachycardia due to an abnormally small T wave Correction for the QT interval in tachycardia: 472 ms for males vs. 482 ms for females References 1. Banai S, Schuger C, Benhorin J, Tzivoni D. Treatment of torsade de pointes with intravenous magnesium. Am J Cardiol. 1989;63(20):1539-1540. doi:10.1016/0002-9149(89)90033-7 2. Gorgels APM, Van Den Dool A, Hofs A, et al. Comparison of procainamide and lidocaine in terminating sustained monomorphic ventricular tachycardia. Am J Cardiol. 1996;78(1):43-46. doi:10.1016/S0002-9149(96)00224-X 3. Liu MB, Vandersickel N, Panfilov A V., Qu Z. R-From-T as a Common Mechanism of Arrhythmia Initiation in Long QT Syndromes. Circ Arrhythmia Electrophysiol. 2019;12(12):1-15. doi:10.1161/CIRCEP.119.007571 4. Sagie A, Larson MG, Goldberg RJ, Bengtson JR, Levy D. An improved method for adjusting the QT interval for heart rate (the Framingham Heart Study). Am J Cardiol. 1992;70(7):797-801. doi:10.1016/0002-9149(92)90562-D 5. Vandenberk B, Vandael E, Robyns T, et al. Which QT correction formulae to use for QT monitoring? J Am Heart Assoc. 2016;5(6). doi:10.1161/JAHA.116.003264 6. Zipes DP, Camm AJ, Borggrefe M, et al. ACC/AHA/ESC 2006 Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death - Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines. Vol 114.; 2006. doi:10.1161/CIRCULATIONAHA.106.178104 Summarized by Jorge Chalit, OMSII | Edited by Meg Joyce & Jorge Chalit, OMSII

As we age, our immune system undergoes changes that influence our susceptibility to various diseases. Certain factors, such as smoking, viruses, age, and sex can have differential impacts on our various circulating immune cells. How changes to these immune cells contribute to cardiovascular disease and other age-related diseases is not yet fully understood. More research is needed to fully understand the underlying mechanisms and implications. “Understanding the composition of circulating immune cells with aging and the underlying biologic mechanisms driving aging may provide molecular targets to slow the aging process and reduce age-related disease.” In a new study, researchers Yuan Fang, Margaret F. Doyle, Jiachen Chen, Jesse Mez, Claudia L. Satizabal, Michael L. Alosco, Wei Qiao Qiu, Kathryn L. Lunetta, and Joanne M. Murabito from Boston University, Boston Medical Center, University of Vermont, and University of Texas Health Science Center aimed to characterize the circulating innate and adaptive immune system by profiling immune cell phenotypes from a community-based cohort. Their research paper was published in Aging's Volume 15, Issue 10, on April 27, 2023, entitled, “Circulating immune cell phenotypes are associated with age, sex, CMV, and smoking status in the Framingham Heart Study offspring participants.” “We hypothesize that we will identify immune cell phenotype and ARIP [age-related immune phenotype] measure associations with CMV serostatus, age, and sex, as well as associations with cardiovascular risk factors.” Full blog - https://aging-us.org/2023/06/the-impact-of-age-sex-cmv-and-smoking-on-circulating-immune-cells/ Paper DOI - https://doi.org/10.18632/aging.204686 Corresponding author - Yuan Fang - yfang8@binghamton.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204686 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, immune cell, CMV, T cells, smoking About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

 Is Happiness Contagious (New Research Says Yes) What if our happiness influences the people around us?  Could you imagine the positive changes we could have on others?  A recent study suggested that not only does our jollity help others feel happiness, but this happiness also spreads to others.  Explore the power of our joyful state. Harvard Medical School. (2008, December 5). Happiness Is 'Infectious' In Network Of Friends: Collective -- Not Just Individual -- Phenomenon. ScienceDaily. Retrieved April 23, 2023 from www.sciencedaily.com/releases/2008/12/081205094506.htm James H Fowler, Nicholas A Christakis. Dynamic spread of happiness in a large social network: longitudinal analysis over 20 years in the Framingham Heart Study. British Medical Journal, December 4, 2008 New Happiness Podcast episode with Dr. Robert Puff, Newport Beach Psychologist

This month on Episode 48 of Discover CircRes, host Cynthia St. Hilaire highlights three original research articles featured in the April 28th issue of Circulation Research. This Episode also includes a discussion between Dr Mina Chung, Dr DeLisa Fairweather and Dr Milka Koupenova, who all contributed to manuscripts to the May 12th Compendium on Covid-19 and the Cardiovascular System.     Article highlights:   Heijman, et al. Mechanisms of Enhanced SK-Channel Current in AF   Chen, et al. IL-37 Attenuates Platelet Activation   Enzan, et al. ZBP1 Protects Against Myocardial Inflammation   Compendium on Covid-19 and the Cardiovascular System.   Cindy St. Hilaire: Hi, and welcome to Discover CircRes, the podcast of the American Heart Association's journal, Circulation Research. I'm your host, Dr Cindy St. Hilaire, from the Vascular Medicine Institute at the University of Pittsburgh. Today, I'm going to be highlighting articles from our April 28th and May 12th issues of Circulation Research. I'm also going to have a chat with Dr Mina Chung, Dr DeLisa Fairweather and Dr Milka Koupenova, who all contributed to articles in the May 12th COVID Compendium. But before we have that interview, let's first talk about some highlights.   The first article I want to present is titled Enhanced Calcium-Dependent SK-Channel Gating and Membrane Trafficking in Human Atrial Fibrillation. This article is coming from the University of Essen by Heijman and Zhou, et al. Atrial fibrillation is one of the most common forms of heart arrhythmia in humans and is characterized by irregular, often rapid heartbeats that can cause palpitations, dizziness and extreme fatigue. Atrial fibrillation can increase a person's risk of heart failure, and though treatments exist such as beta blockers, blood thinners and antiarrhythmia medications, they can have limited efficacy and side effects. A new family of drugs in development are those blocking small-conductance calcium-activated potassium channels called SK channels, which exhibit increased activity in animal models of AF and suppression of which attenuates the arrhythmia. In humans however, the relationship between SK channels and atrial fibrillation is less clear, at least in terms of SK channel mRNA levels. Because mRNA might not reflect actual channel activity, this group looked at just that and they found indeed that channel activity was increased in cardiomyocytes from atrial fibrillation patients compared to those from controls even though the mRNA and protein levels themselves were similar. The altered currents were instead due to changes in SK channel trafficking and membrane targeting. By confirming that SK channels play a role in human atrial fibrillation, this work supports the pursuit of SK channel inhibitors as possible new atrial fibrillation treatments.   The next article I want to present is titled IL-37 Attenuates Platelet Activation and Thrombosis Through IL-1R8 Pathway. This article comes from Fudan University by Chen and Hong, et al. Thrombus formation followed by the rupture of a coronary plaque is a major pathophysiological step in the development of a myocardial infarction. Understanding the endogenous antithrombotic factors at play could provide insights and opportunities for developing treatments. With this in mind, Chen and Hong, et al. investigated the role of interleukin-1 receptor 8, or IL-1R8, which suppresses platelet aggregation in mice, and of IL-37, a newly discovered human interleukin that forms a complex with IL-1R8 and is found at increased levels in the blood of patients with myocardial infarction. Indeed, the amount of IL-37 in myocardial infarction patients negatively correlates with platelet aggregation. They also show that treatment of human platelets in vitro with IL-37 suppresses the cell's aggregation and does so in a concentration-dependent manner. Moreover, injection of the protein into the veins of mice inhibits thrombus development and better preserves heart function even after myocardial infarction. Such effects were not seen in mice lacking IL-1R8. This suggests IL-37's antithrombotic action depends on its interaction with the receptor. Together, the results suggest IL-37 could be developed as a antithrombotic agent for use in MI patients or indeed perhaps other thrombotic conditions.   The last article I want to present before our interview is titled ZBP1 Protects Against Mitochondrial DNA-Induced Myocardial Inflammation in Failing Hearts. This article is coming from Kyushu University and is by Enzan, et al. Myocardial inflammation is a key factor in the pathological progression of heart failure and occurs when damaged mitochondria within the stricken cardiomyocyte release their DNA, triggering an innate inflammatory reaction. In a variety of cells, DNA sensors such as Z-DNA-binding protein 1 or ZBP1 are responsible for such mitochondrial DNA-induced inflammation. In theory then, it's conceivable that therapeutic suppression of ZBP1 might reduce myocardial inflammation in heart failure and preserve function. But as Enzan and colleagues have now discovered to their surprise, mice lacking ZBP1 exhibited worse, not better heart inflammation and more failure after induced myocardial infarction. Indeed, the test animals' hearts had increased infiltration of immune cells, production of inflammatory cytokines and fibrosis together with decreased function compared with the hearts of mice with normal ZBP1 levels. Experiments in rodent cardiomyocytes further confirmed that loss of ZBP1 exacerbated mitochondrial DNA-induced inflammatory cytokine production while overexpression of ZBP1 had the opposite effect. While the reason behind ZBP1's opposing roles in different cells is not yet clear, the finding suggests that boosting ZBP1 activity in the heart might be a strategy for mitigating heart inflammation after infarction.   Cindy St. Hilaire:         The May 12th issue of Circulation Research is our COVID compendium, which consists of a series of 10 reviews on all angles of COVID-19 as it relates to cardiovascular health and disease. Today, three of the authors of the articles in this series are here with me. Dr Mina Chung is a professor of medicine at the Cleveland Clinic. She and Dr Tamanna Singh and their colleagues wrote the article, A Post Pandemic Enigma: The Cardiovascular Impact of Post-Acute Sequelae of SARS-CoV-2. Dr DeLisa Fairweather, professor of medicine, immunology and clinical and translational science at the Mayo Clinic, and she and her colleagues penned the article, COVID-19 Myocarditis and Pericarditis. Dr Milka Koupenova is an assistant professor of medicine at the UMass Chan School of Medical and she led the group writing the article, Platelets and SARS-CoV-2 During COVID-19: Immunity, Thrombosis, and Beyond. Thank you all for joining me today.   DeLisa Fairweather:    Thank you so much for having us.   Mina Chung:   Thank you.   Milka Koupenova:       Thank you for having us, Cindy.   Cindy St. Hilaire:         In addition to these three articles, we have another seven that are on all different aspects of COVID. Dr Messinger's group wrote the article, Interaction of COVID-19 With Common Cardiovascular Disorders. Emily Tsai covered cell-specific mechanisms in the heart of COVID-19 patients. Mark Chappell and colleagues wrote about the renin-angiotensin system and sex differences in COVID-19. Michael Bristow covered vaccination-associated myocarditis and myocardial injury. Jow Loacalzo and colleagues covered repurposing drugs for the treatment of COVID-19 and its cardiovascular manifestations. Dr Stephen Holby covered multimodality cardiac imaging in COVID, and Arun Sharma covered microfluidic organ chips in stem cell models in the fight against COVID-19.   Cindy St. Hilaire          As of today, worldwide, there have been over six hundred million individuals infected with the virus and more than six and a half million have died from COVID-19. In the US, we are about a sixth of all of those deaths. Obviously now we're in 2023, the numbers of individuals getting infected and dying are much, much lower. As my husband read to me this morning, one doctor in Boston was quoted saying, "People are still getting wicked sick." In 75% of deaths, people have had underlying conditions and cardiovascular disease is found in about 60% of all those deaths. In the introduction to the compendium, you mentioned that the remarkable COVID-19 rapid response initiative released by the AHA, which again is the parent organization of Circ Research and this podcast, if I were to guess when that rapid response initiative started, I would've guessed well into the pandemic, but it was actually March 26th, 2020. I know in Pittsburgh, our labs have barely shut down. So how soon after we knew of SARS-CoV-2 and COVID, how soon after that did we know that there were cardiovascular complications?   Mina Chung:               I think we saw cardiovascular complications happening pretty early. We saw troponin increases very early. It was really amazing what AHA did in terms of this rapid response grant mechanism. You mentioned that the RFA was announced, first of all, putting it together by March 26th when we were just shutting down in March was pretty incredible to get even the RFA out. Then the grants were supposed to be submitted by April 6th and there were 750 grants that were put together and submitted. They were all reviewed within 10 days from 150 volunteer reviewers. The notices were distributed April 23rd, less than a month out.   Cindy St. Hilaire:         Amazing.   Mina Chung:               So this is an amazing, you're right, paradigm for grant requests and submissions and reviews.   DeLisa Fairweather:    For myocarditis, reports of that occurred almost immediately coming out of China, so it was incredibly rapid.   Cindy St. Hilaire:         Yeah, and that was a perfect lead up to my next question. Was myocarditis, I guess, the first link or the first clue that this was not just going to be a respiratory infection?   DeLisa Fairweather:    I think myocarditis appearing very early, especially it has a history both of being induced by viruses, but being strongly an autoimmune disease, the combination of both of those, I think, started to hint that something different was going to happen, although a lot of people probably didn't realize the significance of that right away.   Cindy St. Hilaire:         What other disease states, I guess I'm thinking viruses, but anything, what causes myocarditis and pericarditis normally and how unique is it that we are seeing this as a sequelae of COVID?   DeLisa Fairweather:    I think it's not surprising that we find it. Viruses around the world are the primary cause of myocarditis, although in South America, it's the parasite Trypanosoma cruzi. Really, many viruses that also we think target mitochondria, including SARS-CoV-2, have an important role in driving myocarditis. Also, we know that SARS-CoV-1 and MERS also reported myocarditis in those previous infections. We knew about it beforehand that they could cause myocarditis.   Cindy St. Hilaire:        Is it presenting differently in a COVID patient than say those South American patients with the... I forget the name of the organism you said, but does it come quickly or get worse quickly or is it all once you get it, it's the same progression?   DeLisa Fairweather:    Yeah. That's a good question. Basically, what we find is that no matter what the viral infection is, that myocarditis really appears for signs and symptoms and how we treat it identically and we see that with COVID-19. So that really isn't any different.   Cindy St. Hilaire:         Another huge observation that we noticed in COVID-19 patients, which was the increased risk of thrombic outcomes in the patients. Dr Koupenova, Milka, you are a world expert in platelets and viruses and so you and your team were leading the writing of that article. My guess is knowing what you know about platelets and viruses, this wasn't so surprising to you, but could you at least tell us the state of the field in terms of what we knew about viruses and platelets before COVID, before Feb 2020?   Milka Koupenova:       Before Feb 2020, we actually knew that influenza gets inside in platelets. It leads to not directly prothrombotic events, but it would lead to release of complement 3 from them. That complement 3 would actually increase the immunothrombosis by pushing neutrophils to release their DNA, forming aggregates. In cases when you have compromised endothelium and people with underlying conditions, you would expect certain thrombotic outcomes. That, we actually published 2019 and then 2020 hit. The difference between influenza and SARS-CoV-2, they're different viruses. They carry their genome in a different RNA strand. I remember thinking perhaps viruses are getting inside in platelets, but perhaps they do not. So we went through surprising discoveries that it seemed like it is another RNA virus. It also got into platelets. It was a bit hard to tweak things surrounding BSL-3 to tell you if the response was the same. It is still not very clear how much SARS or rather what receptor, particularly when it gets inside would induce an immune response. There are some literature showing the MDA5, but not for sure, may be responsible. But what we found is that once it gets in platelets, it just induces this profound activation of programmed cell death pathways and release of extracellular vesicles and all these prothrombotic, procoagulant form of content that can induce damage around, because platelets are everywhere. So that how it started in 2019 and surprisingly progressed to 2021 or 2020 without the plan of really studying this virus.   Cindy St. Hilaire:         How similar and how different is what you observe in platelets infected, obviously in the lab, so I know it's not exactly the same, but how similar and how different is it between the flu? Do you know all the differences yet?   Milka Koupenova:       No offense here, they don't get infected.   Cindy St. Hilaire:         Okay.   Milka Koupenova:       Done the proper research. The virus does not impact platelets, but induces the response.   Cindy St. Hilaire:         Okay.   Milka Koupenova:       That goes back to sensing mechanism. Thank goodness platelets don't get infected because we would be in a particularly bad situation, but they remove the infectious virus from the plasma from what we can see with function.   Cindy St. Hilaire:         Got it. So they're helping the cleanup process and in that cleaning up is where the virus within them activates. That is a really complicated mechanism.    Milka Koupenova:       Oh, they're sensing it in some form to alert the environment. It's hard to say how similar and how different they are unless you study them hint by hint next to each other. All I can tell is that particularly with SARS-C, you definitely see a lot more various kinds of extracellular vesicles coming out of them that you don't see the same way or rather through the same proportion with influenza. But what that means in how platelet activates the immune system with one versus the other, and that goes back to the prothrombotic mechanisms. That is exactly what needs to be studied and that was the call for this COVID compendium is to point out how much we have done as a team. As scientists who put heads together, as Mina said, superfast response, it's an amazing going back and looking at what happened to think of what we achieved. There is so much more, so much more that we do not understand how one contributes to all of these profound responses in the organs themselves, such as myocarditis. We see it's important and that will be the problem that we're dealing from here on trying to figure it out and then long COVID, right?   Cindy St. Hilaire:         Yeah. Related to what you just said about the mechanism, this cleanup by the platelets or the act of cleaning up helps trigger their activation, is that partly why the antiplatelet and anticoagulant therapies failed in patients? Can you speculate on that? I know the jury's still out and there's a lot of work to be done, but is that part of why those therapies weren't beneficial?   Milka Koupenova:       The answer to that in my personally biased opinion is yes. Clearly, the antiplatelet therapies couldn't really control the classical activation of a platelet. So what I think we need to do from here on is to look at things that we don't understand that non-classically contribute to the thrombotic response downstream. If we manage to control the immune response in some way or the inflammation of the infection or how a platelet responds to a virus, then perhaps we can ameliorate a little bit of the downstream prothrombotic effect. So it's a lot more for us to trickle down and to understand in my personal opinion.   DeLisa Fairweather:    There is one thing that was really remarkable to me in hearing your experience, Milka, is that I had developed an autoimmune viral model of myocarditis in mice during my postdoc. So I've been studying that for the last 20 years. What is unique about that model is rather than using an adjuvant, we use a mild viral infection so it doesn't take very much virus at all going to the heart to induce it. I also, more recently, started studying extracellular vesicles really as a therapy, and in doing that, inadvertently found out that actually, the model that I'd created where we passage the virus through the heart to induce this autoimmune model, we were actually injecting extracellular vesicles into the mice and that's what was really driving the disease. This is really brought out. So from early days, I did my postdoc with Dr Noel Rose. If you've heard of him, he came up with the idea of autoimmune disease in the '50s. We had always, in that environment, really believed that viruses were triggering autoimmune disease and yet it took COVID before we could really prove that because no one could identify them. Here we have an example and I think the incidence rates with COVID were so high for myocarditis because for the first time, we had distinguished symptoms of patients going to the doctor right at the beginning of their infection having an actual test to examine the virus, knowing whether it's present or not, whether PCR or antibody test, and then being able to see when myocarditis happened.   Cindy St. Hilaire:         Yeah. I think one thing we can all appreciate now is just some of the basic biology we've learned on the backend of this. Actually, those last comments really led well to the article that your team led, Dr Chung, about what we call long COVID, which I guess I didn't realize has an actual name, post-acute sequelae of SARS-CoV-2 or PASC is the now more formal name for long COVID. But what is it? We hinted at it that there's these bits about autoimmune and things like that. What counts as long COVID?   Mina Chung:   Yeah. Our article was led by Tamanna Singh. She did a fantastic job of putting this together. We've had, and others, theorized that the huge palette of symptoms that you can experience post-COVID, they can affect all these organ systems with brain fog, these atypical chest pains, postural orthostatic tachycardia, a lot of palpitations, atrial fibrillation, many weakness and fatigue. To us, really, you can get GI symptoms. We've been very interested in, is this an autoimmune phenomenon directed against nerves and all those things. It's also very interesting because many of the non-COVID syndromes that existed pre-COVID like POTS and chronic fatigue syndrome and a lot of other syndromes are associated with autoantibodies. So that is a very interesting area to explore. Is there a persistence of viral fragments. Is there autoimmunity? Is it also a component of persistence of the damage from the initial infection? So it's an area that still needs a lot of work and a lot of work is going into it, but this is like a post or inter pandemic of itself, so hopefully we'll get more insights into that.   Cindy St. Hilaire:         Yeah, it's really interesting. I have a friend who has very debilitating long COVID and one of her doctors had said, "If I didn't know any better, I would just describe this as a autoimmune type X." What do we know, I guess, about the current hypothesis of the pathogenesis of PASC? Are there any prevailing theories right now as to why it's occurring? Is the virus still active or is it these domino effects that are leading to multi-organ collapse of some sort?   Mina Chung:   Yeah. In some people, persistent viral particles can be identified for months, but whether or not that's what's triggering it, it's hard to know. We see more autoimmune disease that's been reported and various antibodies being reported. So those are clearly processes to be investigated. The microthrombosis is still up there in terms of potentially playing a role in long COVID.   Milka Koupenova:       Mina, you probably know better because you see patients, but to all I have been exposed to, long COVID does not really have a homogeneous symptom presentation and then a few theories as to what may be going on in these patients. Not everybody has a microthrombosis. Not everybody have a D-dimer elevated, but some people do. Some people have, as you pointed out, these spectacularly profound brain fog. People can't function. It's probably your friend, Cindy, right?   Cindy St. Hilaire:         Yeah.   Milka Koupenova:       So one of the theories that I have been, from a viral perspective, very interested in is that a lot of the symptoms in certain individuals such as fatigue, brain fog, sensitivity to light and skin can very well be explained by a flare-up of Epstein-Barr virus that may be what SARS-CoV-2 somehow is inducing. I don't know, DeLisa, what your experience with long COVID is as a scientist. I hope only. But I would like to hear your perspective too because it's so heterogeneous and it is amazing what happens.   DeLisa Fairweather:    I have a very interesting perspective from a number of different directions. One, as I mentioned before, my long history with Dr Rose and I've written many articles theorizing how viruses could cause autoimmune disease. This has grown and really, I think this has been extremely revealing during COVID for many of those theories. One thing that I write about in the review for this article is that mast cells, from all the research I've done with myocarditis in our model, mast cells are central to what is driving everything. We show they're the first innate immune cell acting as an antigen-presenting cell, completely driving the response in a susceptible pattern. One of the things that's very important in autoimmune disease is both sex and race. I'd say one of the big weaknesses we have in myocarditis pre-COVID and post-COVID has been ignoring what's going on with race. In the United States, myocarditis is 90%, 95% white men that are under 50 years of age and most of the cases are under 40 or some of the ones really associated with sudden cardiac death are under 30. So it's very specific. I've been studying sex and race differences and we see those exact differences in our animal models. In animal models, whether you're susceptible or not depends on how many mast cells you have. Well, I've proposed from the beginning, looking, I've written a lot of different sex difference reviews looking at viruses and autoimmune disease with different autoimmune diseases and hypothesizing and really seeing that mast cells do a lot of the things we're talking about. They have all of the receptors, the whole group of them that have been related to SARS-CoV-2 so they can be activated or stimulated by the virus itself. They act as a antigen-presenting cell. They're critical in the complement pathway as well as macrophages. We see the dominant immune phenotype really being macrophages. Mast cells just are usually not counted anywhere. And of course, these receptors, a lot of them have to do with enzymes and things that are all related to mast cells pathways. Then how they activate the immune response and lead it towards the pathway that leads to chronic autoimmune disease with increased autoantibodies in females, mast cells are very different by sex. This has to do also when we talked in the Review about myocarditis and pericarditis. It's both those appearing. Although clinically, we have really boxed them as separate things, because there is some definite clinical pericarditis phenotypes that are different, myocarditis in animal models is always myopericarditis. It always then, in that outer pericardial areas where mast cells sit, they sit around the vascular area in most concentrated. So when they degranulate, we see inflammation coming in the vessel, but really concentrated with fibrosis there and along the pericardium. So that's very typical of what's going on. When we shift anything that shifts that, it changes whether you have more pericarditis or less pericarditis and the vascular inflammation by altering anything that affects the mast cells. I talk a little bit about in the review, I think there's only been a few recent things looking at it in COVID, but I think mast cells and certain susceptibility to autoimmune diseases that occur more often in women can really predispose.We need to pay more attention to mast cells and what they might indicate for all these pathways.   Milka Koupenova:       I think we should study the platelet mast cell access at this point.   DeLisa Fairweather:    Yes.   Milka Koupenova:       Because as you're talking about these sex differences, which is spectacular, these things to me are so mind-boggling how one, the infection itself would be more prevalent in men, but then long COVID is more prevalent in women. All of these things and why we understand so very little, what we found about a few years ago in the Framingham Heart Study in the platelets from those people is that all toll-like receptors are expressed at the higher level in women and they associate with different things between men and female. For instance, toll-like receptors in women will associate more with a prothrombotic response while in male with pro-inflammatory response. I think they grossly underestimate the amount of our sex differences from cell to cell.   DeLisa Fairweather:    It is, yeah.   Mina Chung:   One other thing that I learned about the sex differences from this compendium is Mark Chappell also notes, you mentioned TLR and TLR7 and ACE2 are X chromosome in an area that he says escapes X-linked inactivation. So it could very well be involved in further.   DeLisa Fairweather: Further, yeah. And ACE2 is expressed more highly in male cells for what's been researched because of the sex difference in COVID, both the COVID infection   Cindy St. Hilaire:         So a variety of organ systems are impacted in patients with PASC, also referred to as long COVID, the lungs, the heart, the pancreas, the GI system, pretty much any system, the brain, nervous system. We've just been talking about the mast cell impact. I was really thinking in my head, well, the one thing that connects all of it is the vasculature. I'm a vascular biologist, so I have certain biases, I'm sure, but how much of the sequelae that we see is a function of vascular phenotypes?       Milka Koupenova:       I do think the vasculature is super important. It's clear that not all endothelial cells, for instance, will pick up the virus and respond to it. That's why you have this patchy breakage when you look at autopsies. Hence, platelets will respond according to what's local. That's why you find these micro thrombotic events at certain places. Why does it happen in each organ? How does the virus get to each organ to respond? Or is it just inflammation, but why is it in specific places? That's what we don't understand. That's where we need to go. Perhaps, as DeLisa points out, perhaps it's a lot more complicated than how we traditionally think of thrombosis. Actually, my personal bias, again 100% sure that it is a lot more complicated than the traditional mechanisms that we have understood, and that's where the immune system comes and autoimmunity perhaps stems from and they probably speak to each other, right? It's not just one thing.   DeLisa Fairweather:    Yeah. I think really, EVs are bringing lots of understanding. A lot of things we used to just think were maybe free-floating and the serum are inside EVs. I think that the immune response is perhaps even more specific than we ever thought and more regulated than we ever understood.   When an EV comes through a cardiomyocyte, whether it's from the mitochondria or through a lysosome, is part of what goes into its outer membrane, something that tells the immune system that that came from the heart, so it knows to go. This will solve a lot of our questions with autoimmune disease if it's very specific like that. It doesn't just have to be the release of free-floating cardiac myosin. We know cardiac myosin is the driver of the autoimmune response in myocarditis, but they're probably  much more fine-tuned.   Cindy St. Hilaire:         Yeah. I just would love to end with hearing from each of you. You each have your own domain of specialty. If I gave you a massive pot of money, what would be the question you would want to tackle? What's the gap you would love to answer?   Milka Koupenova:       We still don't understand specifically what kind of vesicles are coming out, what are their contents in addition to those vesicles. We don't understand. When it comes to platelets, what comes from their granules? We see these breakages of the membrane. Those are non-granule proteins, and non-granule proteins, they serve as dangerous associated molecular pattern signals and can be profoundly inflammatory to the surrounding environment, can be procoagulant. What are those? How are they affecting the surrounding environment? Ultimately, why is there a microthrombi? Why is there not a profound thrombosis everywhere? Thank goodness there isn't, but why isn't? That's what I would do with my money.   DeLisa Fairweather:    I think I would do something very similar. All of our research in our animal model, on the one side, we are looking in this viral myocarditis animal model and finding the EVs that come from that are driving myocarditis. On the other hand, we're using EVs that come from healthy human plasma or fat, and we're seeing a profound downregulation of everything if you give it early and we're trying to see how late you can give it and still get an effect. So looking at those and really understanding the components in the context of COVID and COVID vaccines to understand those components, I really think that's the future of where we're going to find what's causing disease and also how we can find therapies. They may be able to reverse this.   Mina Chung:   Yeah, I'm interested very much in the autoimmunity and the autoantibodies that are    and how they may react with those microthrombi. Perhaps there's autoantibodies within a lot of that material. We're looking at using human and pluripotent stem cell-derived cell models to study the effects of those. That is what I would use our money for.   Cindy St. Hilaire:        Well, Dr Mina Chung, Dr DeLisa Fairweather, Dr Milka Koupenova, thank you all so much for joining me today and talking about not only the articles that you wrote and with your colleagues, but also other articles in this amazing compendium. I do think this is one of the first all-encompassing compendiums or group of articles that focus specifically on COVID and cardiovascular disease. So thank you all so much.   Mina Chung:   Thank you.   DeLisa Fairweather:    Thank you.   Milka Koupenova:       You're welcome.   Cindy St. Hilaire:         That's it for highlights from the April 28th and May 12th issues of Circulation Research. Thank you for listening. Please check out the CircRes Facebook page and follow us on Twitter and Instagram with the handle @circres and #DiscoverCircRes. Thank you to our guests, Dr Mina Chung, Dr DeLisa Fairweather and Dr Milka Koupenova. This podcast is produced by Ishara Ratnayaka, edited by Melissa Stoner and supported by the editorial team of Circulation Research. Some of the copy text for the highlighted articles is provided by Ruth Williams. I'm your host, Dr Cindy St. Hilaire, and this is Discover CircRes, your on-the-go source for the most exciting discoveries in basic cardiovascular research. This program is copyright of the American Heart Association 2023. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more information, visit ahajournals.org.    

Synopsis: Sekar Kathiresan is the Co-Founder, CEO and Board Member of Verve Therapeutics, a clinical-stage biotechnology company developing gene editing medicines to treat patients with cardiovascular disease. Sekar discusses Verve's work developing single-course, in vivo liver-directed gene editing medicines for patients with and at risk of cardiovascular disease and what the company pipeline looks like. He talks about the evolution of his pitch after years of experience with fundraising, how he approaches team building, and his perspective on why people are leaving academia for biotech. He also discusses what he's learned about being a board member and what a good board for a pre-revenue biotech looks like. Biography: Dr. Sekar Kathiresan is co-founder and CEO of Verve Therapeutics, a biotechnology company pioneering a new approach to the care of cardiovascular disease, transforming treatment from chronic management to single-course gene editing medicines. Dr. Kathiresan is a cardiologist and scientist who has focused his career on understanding the inherited basis for heart attack and leveraging those insights to improve the care of cardiovascular disease. Based on his groundbreaking discoveries in human genetic mutations that confer resistance to cardiovascular disease, Dr. Kathiresan co-founded Verve Therapeutics with a vision to create a pipeline of single-course, gene editing therapies focused on addressing the root causes of this highly prevalent and life-threatening disease. Today, Verve is advancing two initial programs that target PCSK9 and ANGPTL3, respectively – genes that have been extensively validated by Dr. Kathiresan and others as targets for lowering blood lipids, such as low-density lipoprotein cholesterol, which is a major driver of cardiovascular disease. Prior to joining Verve, Dr. Kathiresan's roles included director of the Massachusetts General Hospital (MGH) Center for Genomic Medicine, director of the Cardiovascular Disease Initiative at the Broad Institute and professor of medicine at Harvard Medical School. There, Dr. Kathiresan's research laboratory focused on understanding the inherited basis for blood lipids and myocardial infarction. For his research contributions, he has been recognized by the American Heart Association with its highest scientific honor – a Distinguished Scientist Award and by the American Society of Human Genetics with the 2018 Curt Stern Award. Dr. Kathiresan graduated summa cum laude with a B.A. in history from the University of Pennsylvania and received his M.D. from Harvard Medical School. He completed his clinical training in internal medicine and cardiology at MGH and his postdoctoral research training in human genetics at the Framingham Heart Study and the Broad Institute.

This week, please join authors Marc Sabatine and Prakriti Gaba, as well as Associate Editor Amit Khera, as they discuss the article "Association Between Achieved Low-Density Lipoprotein Cholesterol Levels and Long-Term Cardiovascular and Safety Outcomes: An Analysis of FOURIER-OLE." Dr Greg Hundley: Welcome listeners, to this April 18th issue of Circulation on the Run and I am Dr. Greg Hundley, Associate Editor, Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr Peder Myhre: And I'm Dr. Peder Myhre, Social Media Editor from Akershus University Hospital and University of Oslo. Dr Greg Hundley: Peder, today's feature discussion, very interesting. We're going to evaluate the association between what's achieved with LDL cholesterol lowering, and then also long-term cardiovascular and safety outcomes. But before we get to that, how about we grab a cup of coffee and discuss some of the other articles in the issue? Would you like to go first? Dr Peder Myhre: Yes, Greg. I would love to. And the first paper is from the World of Preclinical Science and it comes to us from corresponding author, Jan Magnus Aronsen from University of Oslo in Norway. And perhaps, as you know, Greg, cardiomyocyte contraction and relaxation depend on the activity of the sarcoplasmic reticulum CA+2 ATPase 2, abbreviated SERCA2, and lowered levels or reduced activity of SERCA2, as seen in chronic heart failure, weakens contractile force and delays relaxation and no available therapy involves direct manipulation of the SERCA2 activity. And Greg, phosphodiesterase 3A is proposed to be present in the SERCA2 interactome limit SERCA2 activity and disruption of phosphodiesterase 3A from SERCA2 might thus be a strategy to develop SERCA2 activators. And in this study, the authors investigated and mapped SERCA2 and phosphodiesterase 3A and assessed this in experiments assessing the binding between these two in cardiomyocytes and in vesicles. Dr Greg Hundley: Wow Peder, sounds very interesting. So what did they find and how about the clinical implications of the findings? Dr Peder Myhre: So Greg phosphodiesterase 3A bounded directly to SERCA2 in the cardiomyocyte. So that's the first finding. Second, they demonstrated that SERCA2 phosphodiesterase 3A disruption increased SERCA2 activity independently of the catalytic activity of phosphodiesterase 3A in both normal and failing cardiomyocytes. And third, SERCA2 activity by the optimized SERCA2 phosphodiesterase 3A disruptor peptide OPT F reduced mortality and improved contractility after aortic binding in mice. So the clinical implication is that direct targeting of phosphodiesterase 3A binding to SERCA2 could be a novel approach to increase SERCA2 activity and thus cardiac contractility in patients with heart failure. Dr Greg Hundley: Very nice Peder. What a great new finding in the world of preclinical science. Well my paper is going to delve into the world of clinical science and involves patients with stroke. So Peder in this study led by corresponding author, Dr. Dileep Yavagal from University of Miami Miller School of Medicine performed a survey in 75 countries through the Mission Thrombectomy 2020+ Global Network between November of 2020 and February of 2021 to determine the availability of mechanical thrombectomy for large vessel occlusion in patients with stroke. Now Peder, the primary endpoints were the current annual mechanical thrombectomy availability, the mechanical thrombectomy operator availability and the mechanical thrombectomy center availability. All of these availabilities were defined as the proportion of estimated large vessel occlusion for patients receiving mechanical thrombectomy in a given region annually. Dr Peder Myhre: Okay, Greg, so this is really an access question. So in essence, what is the availability of mechanical thrombectomy worldwide? So what did they find? Dr Greg Hundley: Right, great Peder. So what they found, the authors received 887 responses from 67 countries and low-income countries had 88% lower mechanical thrombectomy availability compared to high-income countries. The global mechanical thrombectomy operator availability was 16.5% of optimal, and the mechanical thrombectomy center availability was only 20.8% optimal. And with these results, the authors indicate that global cooperation and targeted region-specific public health interventions, including all stakeholders involved in stroke care delivery, are really needed to rapidly increase access to this brain-saving and disability-sparing treatment with mechanical thrombectomy really worldwide. Dr Peder Myhre: Oh wow. What a beautiful summary, Greg. Thank you so much. And we also have some other interesting papers in the mailbag today. We have an exchange of letters between Dr. Yang and Dr. O'Donoghue regarding the article “Long Term evolocumab in Patients with Established Atherosclerotic Cardiovascular Disease.” Dr Greg Hundley: Great Peder, and also Professor Perera has a Frontiers article entitled “Unloading the Left Ventricle in Venoarterial ECMO in Who, When and How?” and then finally there's a Research Letter from Professor Verma entitled “Prevalence of Diabetes and Cardiovascular Risk in the Middle East and Africa: The Primary results of the PACT-MEA Study.” Well Peder, how about we jump to that feature discussion? Dr Peder Myhre: Can't wait. Dr Greg Hundley: Welcome listeners to this feature discussion on April 18th and we have with us today Prakriti Gaba and Marc Sabatine from Brigham and Women's Hospital and our own associate editor, Dr. Amit Khera. Welcome everyone. Well Marc, we'll start with you. Can you describe for us some of the background information that really helps constitute the preparation of your study and what was the hypothesis that you wanted to address? Dr. Marc Sabatine: Yeah, thanks Greg and thanks for having us. So we've seen in a variety of epidemiologic cohorts the association between LDL cholesterol and the risk of adverse cardiovascular events like in Framingham Heart Study and UK Biobank. But in those cohorts, in these industrial societies, we don't have the benefit of lots of data in individuals with very low levels of LDL cholesterol and so we had the opportunity with the FOURIER study that was the randomized comparison of evolocumab PCSK9 inhibitor versus placebo to get patients down to extremely low levels of LDL cholesterol and evolocumab. We were able to get individuals down to about 30 mg/dL. And so in addition to all the studies we've done showing the comparison of evolocumab to placebo, we also then had the chance to use FOURIER, and as you'll hear from PK, FOURIER-OLE, the open-label extension, as a cohort to then examine patients' new baseline, if you will, their new achieved LDL cholesterol and then it's association not only with cardiovascular events but safety events. And so the hypothesis is that there would be a relationship with the lower the LDL cholesterol, the lower the risk of cardiovascular events and we wanted to explore how far down that went. And then the second one for safety would be that there wouldn't be any association between low levels of LDL cholesterol and a variety of safety outcomes that rightly or wrongly people have ascribed to low levels of LDL cholesterol. Dr Greg Hundley: Thanks so much, Marc. Well listeners, now we're going to turn to PK, the first author, on this very interesting paper and PK, Marc mentioned to us the FOURIER-OLE study. Maybe describe for us here your study design and then what specifically was your study population? Dr. Prakriti Gaba (PK): Yeah, definitely. Thanks so much for the introduction. So the study population included 27,564 patients with stable atherosclerotic cardiovascular disease and LDL cholesterol levels that were greater than or equal to 70 mg/dL or non-HDL cholesterol greater than or equal to a 100 mg/dL on statin therapy. The patients who then went on to the FOURIER-OLE or the open-label extension part of the trial consisted of about 6,635 patients. And so in this study we essentially evaluated the combination of those populations in 2 separate analyses. We then categorized patients according to 6 pre-specified bins based on their achieved LDL cholesterol levels at designated time points and those ranged from LDL levels of less than 20 mg/dL all the way up to 100 mg/dL. And then we looked at their baseline characteristics and evaluated the cardiovascular and safety outcomes that Dr. Sabatine mentioned earlier. Dr Greg Hundley: Very nice PK. Well we've got a great listening audience today and they're anxious to hear your study results, so can you share those with us please? Dr. Prakriti Gaba (PK): Definitely. So over the course of more than 77,000 patient years of follow-up, we found that there was a monotonic relationship between achieving lower LDL cholesterol levels down to very low levels of less than 20 mg/dL and a lower annualized risk of the primary efficacy endpoint, which was a composite of 5 individual endpoints. We also found that there was a similar relationship observed between lower LDL achieved, LDL cholesterol levels and a lower annualized risk of the secondary efficacy endpoint, and then when we looked at safety, there were actually no clear monotonic trends between lower achieved LDL levels and the risk of any of the 8 adverse events and these included things like serious adverse events, hemorrhagic stroke or muscle related events. Dr Greg Hundley: Very nice PK and I'm sure our listeners are wanting to know, did you find any discrepancy in your results based on either age or gender? Dr. Prakriti Gaba (PK): That's an excellent question, and we did look at age and gender throughout. I think across the board the results were pretty consistent, but additional subanalyses will further address this question. Dr Greg Hundley: Very good. Well listeners now we're going to turn to one of our associate editors, Dr. Amit Khera, who has helped move this article through the process of evaluation with the editorial team. Amit, you have many papers come across your desk, what attracted you to this paper and then how do we put this study's results really in the context of other studies that have sought to dramatically lower LDL cholesterol? Dr. Amit Khera: Well first thanks a lot Greg for allowing me to participate today. I want to congratulate Drs. Gaba and Sabatine on a fantastic paper and the minute I saw it, and you know can tell when you've done this for a while what's a great paper, and this one certainly is and we work closely with them to try to make it better and enhance the analyses and as a group, I think we achieved that. I was fortunate to write an accompanying editorial that you'll see. So I got to take a pretty deep dive in this paper and I want to just talk about sort of what's important here, why is this important, and I think as Dr. Gaba mentioned, there's two sides to this. There's the efficacy side where you talk about LDL lowering and getting to very low levels. Now mind you, they got to, what I call, ultra low levels, even explored for a down to a median of 7 mg/dL, so really, really low. And first I think what our listeners need to know when we look at guidelines, these numbers of 70 or 55, these are completely arbitrary and they're based on what was observed in clinical trials, what was achieved in high intensity versus moderate intensity statins in IMPROVE-IT. There's no biology behind that, and I think what this study does is reminds us there is no biology behind how low we need to go. This group previously published their shorter-term data approximately 2 years with this construct of lower is better and I think that's fine, but people worry, particularly on the safety side about extension, and we'll get to that in a minute, so where this fits is it gives us even more reassurance that lower is better, reminds us there's no biologic basis of that even down to very low levels. And so what does that mean? I think that comes back to guidelines. We have some discrepancy between European, ACC, Multisociety Guidelines that are around 55 and so from a guideline perspective, I think we'll see a little bit more enthusiasm about lower cut points or lower thresholds. And from a clinical standpoint, as a clinician it reminds me that when I see someone that's very high risk, there's no magic to achieving a number that if the risk is high, we need to be quite intensive and get their LDL down as low as possible and as safely as possible. I do want to also acknowledge, there's not, to your point about context, the IMPROVE-IT study also showed very low levels show additional efficacy and there's also a lot of other data, genetics and ecologic data supporting this. So this is... we look at Bayesian analysis that this is consistent that we're seeing across different platforms. I do want to talk about safety too, Greg. That's really important because honestly this is when it comes to patient level, the safety part of it. We as clinicians may have comfort with very low levels, but the safety is important. I also want to, just from a steady design, this is post-hoc, so those that achieve very low levels are different. You can see that in their table 1, but these investigators did lots of things. They did pretty extensive multi-variable analysis, they looked at time-dependent LDLs, they looked at it multiple different ways, but as mentioned, there really did not seem to be a safety signal. And this is where time matters. Safety in two years, interesting, but safety 5 to 8 years really offers us much more reassurance. So I think that's where this really comes in about that safety piece with the extended analysis. So again, I think from a guideline perspective, from a clinical perspective, there's so many implications from this paper and I really hope people take the time to take a deep dive and also put it in context, like you said, to the other literature where this is not standalone, but it's corroborating what we're seeing. Dr Greg Hundley: Very nice, amit. Marc, I want to come back to you, just two quick questions thinking about the preparation of your study. One, did you sample cognition? One thing we hear about frequently in dramatic lowering of LDL cholesterol are questions around cognition, particularly in the elderly? Dr. Marc Sabatine: Yeah, it's a great question Greg. So first of all, in the FOURIER study itself, there was an embedded study called EBBINGHAUS that Bob Giugliano from our group led that actually did formal neurocognitive testing in individuals using basically a iPad-like test. We also collected the usual neurocognitive adverse events as part of safety collecting. So 2 ways, the general asking about any adverse events and then the specific neurocognitive testing. We had previously reported out the results of EBBINGHAUS that there wasn't any relationship between evolocumab and the low LDL cholesterol and the risk of any neurocognitive AEs. We just were able to recently do this OLE analysis over time for the major adverse cardiovascular events and for the general safety events including cognition, so all that looked good. As PK indicated, we're now digging into the EBBINGHAUS formal neurocognitive testing, which was also extended out. So stay tuned for those results. Dr Greg Hundley: Very nice. And then eligibility, maybe just walk us through that really quickly. Patients that are going to be randomized to this form of therapy, were they already on high-dose statins? Who exactly did we randomize in this trial? Dr. Marc Sabatine: Yeah, so at the get-go, as PK indicated, these are patients with atherosclerotic cardiovascular disease, so they had a prior MI, prior stroke, symptomatic PAD. They were to be on an optimized lipid-lowering regimen, optimized statin therapy, so for close to 70%, that was a high-intensity statin. We had a small percentage on ezetimibe, but that's because we hadn't yet published the results of the IMPROVE-IT trial that Amit mentioned when we were enrolling in FOURIER, but it was a well-treated population on statin therapy. So these results would apply to your typical patient with ASCVD who's on a good statin regimen. Dr Greg Hundley: Very nice. Well, listeners now we're going to go back to both of our authors and investigators, as well as Dr. Khera. PK we'll start with you. What do you see as the next study to really be performed in this sphere of research? Dr. Prakriti Gaba (PK): I think that's an excellent question. I think with the data presented here now we know that the lower the LDL, the lower the risk of adverse cardiovascular events and that having a low LDL is safe in the long term. I think moving forward, as Dr. Khera mentioned, there needs to be a shift of these recommendations into the guidelines. So I think additional studies confirming these findings is what we need, but we do have the evidence available. Dr Greg Hundley: Very nice. And Marc? Dr. Marc Sabatine: Yeah, and I agree with PK of course. I think there's a couple things that we want to look at. We had looked in the parent FOURIER trial and found some groups who were higher risk, who seemed to have a bigger benefit early on, and those by and large were people who had a lot of athero. But as Amit indicated that the parent FOURIER trial was relatively short at about in two and a quarter years median follow up, and so now we have the benefit of an additional half decade of follow up in a subset of people and so now we're starting to look through and see the subgroups where we saw some differential benefit and this was a paper we published in circulation soon after we published the primary results of FOURIER. Now we have the ability to go through and look at those same subgroups and see what happens now with an additional 5 years. And so that'll be quite interesting, I think, to see how those groups play out now over time. I think as Amit indicated, time is critical. We know the benefit of lipid lowering really tends to grow with time. We saw that in FOURIER, we saw that in FOURIER-OLE and then as Amit indicated, I think for safety also it's now very reassuring, being able to go out to not two and a half years, but 5, 6, 7, 8 years of safety follow up. Dr Greg Hundley: Very nice. Well, listeners we're next going to turn to Dr. Khera. I'm going to put him on the spot a little bit. I don't know if many of you know he's a cardiologist with expertise in primary prevention. So here we've really focused today, I think, on a very unique set of results in secondary prevention. Amit, as you think about studies to be performed in the future, is there a role for really lowering LDL cholesterol as a primary prevention target? Dr. Amit Khera: The short answer is absolutely. I think, to be fair, you can't necessarily directly extrapolate these results 'cause it's a secondary prevention population, but I think if we step back for a second, is there any reason I think this wouldn't work in primary prevention, there's not, and I think there's tons of genetic data, tons of other long-term data that suggests that lower is better than primary prevention. I think the challenge, as you know, is just from primary prevention is it's just about the number that you need to treat and primary prevention is pretty profound in terms of to lower events. So this is where the trade-off comes. I think even in their study, we do have to appreciate while lower is better, when you have very low levels and you're going to even lower, let's say when you go from in secondary prevention from 50 to 40, as much as that sounds valuable, that delta's pretty small and then the absolute risk reduction is still going to be pretty small for those individuals and that's only magnified in primary prevention. So the short answer is I have no reason to believe that lower is better is not applicable in primary prevention, but I do know that the cost and what entails to get there, you don't get as much return on investment. I do want to say one last thing though. We're talking about lower is better, and I know these investigators know this well, but it's not only just how low but how long and I think that's where primary prevention about to go to clinic and I play the long game for primary prevention that we know we've magnified these benefits over the long term and even a little bit early in life can pay off long dividends. So that's how I look at it. Dr Greg Hundley: Very nice. Well, listeners we want to thank Dr. Prakriti Gaba, Dr. Marc Sabatine, both from Brigham and Women's Hospital and also our own associate editor, Dr. Amit Khera from University of Texas Southwestern Medical Center for bringing us this study involving patients with arteriosclerotic cardiovascular disease indicating that long-term achievement of lower LDL cholesterol levels down to values less than 20 mg/dL was associated with a lower risk of cardiovascular outcomes and not and not an increase in the risk of significant safety related events. Well, on behalf of Peder, Carolyn and myself, we want to wish you a great week and we will catch you next week on the run. Dr. Greg Hundley: This program is copyright of the American Heart Association 2023. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit ahajournals.org.

Should you go carnivore? If you ask that question to my next guest on the Smart Nutrition Made Simple Show, the answer would be a resounding yes. In today's podcast, I have the pleasure of chatting with my former rugby teammate turned neurosurgeon, Anthony Chaffee, MD. Dr. Chaffee is a fierce advocate of the carnivore diet and has completely eliminated all plant-based foods from his repertoire citing them as toxic and carcinogenic.  No fruits. No vegetables. No carbohydrates. No sugar. No artificial sweeteners. His diet consists entirely of meat and water, and he says he feels incredible. In today's conversation, we talk about:

This week, please join author Xuerong Wen, Associate Editor Sandeep Das, and Guest Host Mercedes Carnethon as they discuss the article "Comparative Effectiveness and Safety of Direct Oral Anticoagulants and Warfarin in Patients With Atrial Fibrillation and Chronic Liver Disease: A Nationwide Cohort Study." Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass of the journal and its editors. We're your co-hosts. I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, associate editor, Director of the Poly Heart Center at VCU Health in Richmond, Virginia. Dr. Carolyn Lam: Greg, I'm so excited about today's feature paper. It deals with the important condition where atrial fibrillation exists in patients with chronic liver disease and what do we do for anticoagulation in these patients. It's a comparative effectiveness and safety study of direct oral anticoagulants compared with warfarin in these patients. A huge, wonderful, important study that we're going to discuss. But before we get there, I'd like to tell you about some papers in this issue and I'd like you to tell me about some too. You got your coffee? Dr. Greg Hundley: Absolutely. Dr. Carolyn Lam: All right. I'll go first In this paper that describes a quantitative prognostic tool for the mitral valve prolapse spectrum and it's derived from the new mitral regurgitation international database quantitative or MIDA-Q registry, which enrolled more than 8,000 consecutive patients from North America, Europe, Middle East. And these were patients all diagnosed with isolated mitral valve prolapse or MVP in routine clinical practice of academic centers, all of which also did prospective degenerative mitral regurgitation quantification. The MIDA-Q score was calculated based on characteristics collected in routine practice combining the established MIDA score, which integrated guideline based markers of outcomes like age, New York Heart Association status, atrial fibrillation, LA size, pulmonary artery pressure left ventricular and systolic, I mentioned, and ejection fraction. Integrating that with scoring points based on the degenerative mitral regurgitation quantitation that is measuring effective regurgitant orifice and volume. Dr. Greg Hundley: Very interesting Carolyn. So a scoring system that combines clinical information with what we might assess with echocardiography like regurgitant volume or regurgitant orifice area. So how well did this mortality risk score perform? Dr. Carolyn Lam: So the new score was associated with an extreme range of predicted survival under medical management and that ranged from 97% to 5% at five years for the extreme score ranges. And it was strongly, independently and incrementally associated with long-term survival over all the markers of outcomes. So the authors concluded, and these by the way were authors led by Dr. Maurice Serrano from Mayo Clinic, Rochester, Minnesota. These authors concluded that the score should allow integrated risk assessment of patients with mitral valve prolapse to refine clinical decision making in routine practice and ultimately reduce degenerative mitral regurgitation under treatment. Dr. Greg Hundley: Wonderful description Carolyn. Well I'm going to switch to the world of electrophysiology, Carolyn. And so as you know, the Brugada syndrome is an inherited arrhythmia syndrome caused by loss of function variants in the cardiac sodium channel gene SCN5A and that occurs in about 20% of subjects. And these authors led by Dr. Dan Roden at Vanderbilt University School of Medicine identified a family with four individuals diagnosed with Brugada syndrome, harboring a rare missense variant in the cardiac transcription factor, TBX5, but no SCN5A variant. And upon identifying these individuals, their objective was to establish TBX5 as a causative gene in Brugada syndrome and to define the underlying mechanisms by which it would be operative. Dr. Carolyn Lam: Oh wow. So a new gene variant. So what was the relationship? Dr. Greg Hundley: Right Carolyn? So using induced pluripotent stem cell derived cardiomyocytes from members of the affected family, multiple electrophysiologic abnormalities were detected in these cardiomyocytes including decreased peak and enhanced late cardiac sodium current. In these cells these abnormalities were entirely corrected by CRISPR/Cas9 mediated editing of that TBX5 variant and transcriptional profiling and functional assays in unedited and edited pluripotent stem cell derived cardiomyocytes showed direct SCN5A down regulation caused decreased peak sodium current and that reduced PDGF receptor expression and blunted signal transduction to phosphoinositide-3-kinase. And interestingly, PDGF receptor blockade markedly prolonged normal induced pluripotent stem cell derived cardiomyocyte action potentials. And also Carolyn interestingly in this study they did a separate analysis. It reviewed plasma levels of PDGF in the Framingham Heart Study and they found that they were inversely correlated with the QT corrected interval. And so Carolyn, these results established decrease SCN5A transcription by the TBX5 variant as a cause of Brugada syndrome and also reveal a new general transcriptional mechanism of arrhythmogenesis of enhanced late sodium current caused by reduced PDGF receptor mediated phosphoinositide-3-kinase signaling. Dr. Carolyn Lam: Wow. Wow, that's significant. Thanks Greg. So this next paper is also really important and could change the practice in the field of cardiac resynchronization therapy or CRT. You see, it suggests that the practice of what we do now, which is combining right bundle branch block with intraventricular conduction delay patients into a single non-left bundle branch block category when we select patients for CRT, that this may not be the way to go. So let's go back a bit and remember that benefit from CRT varies with QRS characteristics and individual trials are actually underpowered to assess the benefit for relatively small subgroups. So the current authors led by Dr. Friedman from Duke University Hospital and colleagues, therefore performed a patient level meta-analysis of randomized trials of CRT to assess the relationship between QRS duration and morphology with outcomes. Dr. Greg Hundley: Very interesting Carolyn. So another wonderful paper from the world of electrophysiology in trying to understand optimal mechanisms to resynchronize the ventricle in patients with differing bundle branch blocks or intraventricular conduction delays. So what did they find? Dr. Carolyn Lam: They found that patients with intraventricular conduction delays and a QRS duration of 150 milliseconds or more, CRT was associated with lower rates of heart failure hospitalizations and all cause mortality. The magnitude of CRT benefit among these patients with the interventricular conduction delay of 150 milliseconds or more and those with the left bundle branch block of 150 milliseconds or more were similar. In contrast, there was no clear CRT benefit for patients with a right bundle branch block of any QRS duration, although the authors could not rule out the potential for benefit at a markedly prolonged QRS duration. So they concluded that the practice of combining right bundle branch block with intraventricular conduction delay patients into a single non-left bundle branch block category when we make patient selections for CRT is not supported by the current data. And in fact, patients with an intraventricular conduction delay of 150 milliseconds or more should be offered CRT as is done for patients with a left bundle branch block of 150 milliseconds or more. Dr. Greg Hundley: Wow, Carolyn, so really interesting point. No clear CRT benefit for patients with right bundle branch block regardless of the QRS duration. Well we've got some other articles in the issue. I'll describe a couple from the mail bag. There's a Research Letter from Professor Lassen entitled "Risk of Incident Thromboembolic and Ischemic Events Following COVID-19 Vaccination Compared with SARS-COV2 Infection." Also Bridget Kuhn has a wonderful Cardiology News piece entitled "Collaborative Care Model Helps Heart Failure Patients Meet End-of-Life Goals." Dr. Carolyn Lam: There's an exchange of letters between Doctors Donzelli and Hippisley-Cox regarding that risk of myocarditis after sequential doses of COVID-19 vaccine, there's an AHA Update by Dr. Churchwell on continuous Medicaid eligibility, the lessons from the pandemic. There's an On My Mind paper by Dr. Parkhomenko on Russia's war in Ukraine and cardiovascular healthcare. Wow, what an issue. Thanks so much, Greg. Shall we go on to the feature discussion? Dr. Greg Hundley: You bet. Dr. Mercedes Carnethon: Well welcome to this episode of Circulation on the Run podcast. I'm Mercedes Carnethon, associate editor of the journal Circulation and Professor and Vice Chair of Preventive Medicine at the Northwestern University Feinberg School of Medicine. I'm very excited to be here today with Xuerong Wen and Sandeep Das, my fellow associate editor here at Circulation to talk about a wonderful piece by Dr. Wen and colleagues from the University of Rhode Island. So welcome this morning Xuerong and thank you so much for sharing your important work with us. Dr. Xuerong Wen: Thank you Dr. Carnethon. It was great meeting you all and I'm the Associate Professor of Pharmacoepidemiology and Health Outcomes at the University of Rhode Island. I'm happy to introduce my study to everyone. Dr. Mercedes Carnethon: Well thank you so much and thank you as well Sandeep for identifying this fantastic article and bringing it forth. Dr. Sandeep Das: Thanks Mercedes. It's great to be with you. Dr. Mercedes Carnethon: Great. Well let's go ahead and get into it. There's so much here to talk about. So Dr. Wen and colleagues studied the comparative effectiveness and safety of direct oral anticoagulants or DOACs and warfarin in patients with atrial fibrillation and chronic liver disease. So this is such an important topic. Can you tell us a little bit about what your study found? Dr. Xuerong Wen: So our study is a comparative effectiveness and the safety analysis using a national health administrative data from private health plans. So we compared the risk of hospitalized ischemic stroke, systemic embolism and major bleeding between DOACs and warfarin in patients with atrial fibrillation and chronic liver disease. So we also had to had compare to these primary outcomes between apixaban and rivaroxaban in the study population. So our studies show that among patients with atrial fibrillation and chronic liver disease, DOACs as a class was associated with lower risk of hospitalization of ischemic stroke and systemic embolism and major bleeding, compared with warfarin. And when compared risk outcomes between individuals apixaban has lower risks as compared to rivaroxaban. So that's our study results. Dr. Mercedes Carnethon: Well thank you so much. This seems like such an important question. We hear a lot about DOACs and some of their risks as well as their considerable benefits. I think what leaves me the most curious is why did you choose to pursue this question and in particular in patients with both atrial fibrillation and liver disease. So why was the intersection of these two particular conditions of interest to your study team? Dr. Xuerong Wen: That's a great question. So the liver actually plays a central role in both the synthesis of coagulation factors and the metabolism of anticoagulant drugs. And the clearance of the anticoagulants in liver ranges from 20% to 100% for DOACs and warfarin. So in clinical practice anticoagulation abnormalities and elevated risk of spontaneous or unprovoked venous thrombotic complications have been reported in patients with liver disease. While these patients with cirrhosis were excluded from the clinical trials of DOACs and also population based, the real world experience is very limited. So that is why we initiated this retrospective cohort study and based on the real world data in this specific population. Dr. Mercedes Carnethon: Oh, thank you so much for explaining that. I definitely learned a lot and really enjoyed reading the piece. I think it was very well organized and well written and I know that our readership will appreciate it. It obviously stood out to you as well, Sandeep. Can you tell me a little bit about why you thought that this would be an excellent piece for circulation? Dr. Sandeep Das: Yeah, absolutely. Thanks for the question. So in the broad field of what we call observational comparative effectiveness research, so basically that's using large observational data sets to try to answer important clinical questions and it's a really challenging thing to do. I mean we're all very familiar with the idea of using randomized trials to assess important clinical questions because of the structure of that design allows you to mitigate some of the effects of confounding. Here, it has to be done analytically. So what's the important factor that really drives you towards a great observational comparative effectiveness piece? So first the clinical importance. I feel a little guilty because I'm old enough to remember when warfarin was the only option available, but really as a clinician, or every patient, I really prefer DOACs over warfarin just for ease of use and lifestyle. So there's a huge sort of importance to the question. Second, the patients with chronic liver disease were excluded from the larger RCTs and the DOAC trials. So really we don't have the answer to the question already. It's an important question. Obviously the bleeding risk is tied up with the liver, warfarin directly antagonizes vitamin K, so there's real questions about safety and so this is the perfect storm and then on top of it was a really well done and well executed study. So when this came across my desk, the very first thing I thought was not, "Is this something that we're interested?" But rather, "How do we make it better? How do we make it more useful to the reader?" This had me from hello. Dr. Mercedes Carnethon: Well thanks so much. We rarely have the opportunity when we read an article to be able to ask the authors questions. So Sandeep, I know that you had mentioned that you had some follow up questions as well. Dr. Sandeep Das: Yeah. So the real thought that I have then is would you argue based on this that we know enough that we should change our practice? And that do you feel comfortable advocating that people now prescribe DOACs to these patients? Dr. Xuerong Wen: I would say yes. Okay. Although this is not a clinical trial, but our study is actually systematically compare the effectiveness and safety between DOAC users and also the warfarin users. And if you look at our table one, we compare with so many variables between these two users and we use the propensity score adjustment and we after propensity score weighting and the two control group almost balanced. And I know right now FDA actually suggested that emulate the trial using the large real world data to do the emulated trial. So our study actually conducted is based on the large population using large data and we use the propensity score weighting to control all this potential compounding factors. Although there are still some limitations in this study. I think we mentioned that in the discussion section and we discussed all potential compounding factors that still may exist. And also there are some misclassifications and out of all this limitations and we still found the two drugs performed differently in this specific population. So we feel that comfortable to say that a DOAC drug performs better than warfarin. And also I think based on other studies that based on the clinical trial in the general population, DOAC drug is performs much better than warfarin and considering that the clearance in liver for DOAC is less than warfarin. So plus all this information together, I think DOAC may be safer than wafarin in the patients with AF and chronic liver disease. Dr. Sandeep Das: Yeah, I would say that I agree that these data, even if you're skeptical about observational CT generally, which I admit that I tend to be, these are really reassuring data that at least the DOACs are... There's absolutely nothing that suggests that they're any worse than warfarin and all of the sort of soft indications for ease of use and patient happiness really would seem to favor DOACs. So I think this is the sort of rare observational CT paper that may actually change my practice. Dr. Mercedes Carnethon: I have a follow-up question, Xuerong, related to the design and as well your strategy to address differences between the groups. So inverse probability weighting is certainly a standard in the field to be able to manage differences between groups when you have a situation where can't, where it's not a randomized trial. Do you as well, and educate me, I admit I'm an epidemiologist whose methodological skills are sometimes challenged. Do you have the opportunity using this design and with inverse probability weighting to evaluate subgroup effects? So my specific question is were you able to determine whether or not these associations were similar based on age and gender in particular? Dr. Xuerong Wen: That's a great question. We did conducted a lot of subgroup study but not by age or gender. We conducted I think this study in a lot of subgroups using the propensity score weighting, but the subgroup that I think we did a subgroup like a patient with a different chronic liver disease. So that's what we did. And we also tested different methods inverse probability score weighting. So we did trimming and we used a different percentage of trimming and to see how that affect the study results. So we have done a lot of subgroup studies. We did not check the age and the gender, but that's a very good point. Maybe later, well I'll ask my student to do that. Dr. Mercedes Carnethon: Well, you're a good mentor. So I think that is a really certainly an appropriate approach. Sandeep, did you have additional questions? Dr. Sandeep Das: No, I wish I had thought of yours before you did. I think exactly the older age, women, racial ethnic groups that are underrepresented historically in trials. I think that that's really, again, the sweet spot of this observational research. We definitely, and NH definitely working on trying to increase enrollment of all these groups in our CTs. However, while we wait for that, I think that's exactly what we should be doing. Dr. Mercedes Carnethon: Well that's great. And Xuerong, you really alluded to really, I think what is one of my final questions related to what do you think based on what you have observed in this study, what do you see as the next steps in the research field for your team, your students, or other people who are carrying out this type of work? Dr. Xuerong Wen: Well, that's a great question. We currently have a couple of more manuscripts ongoing in this field, and we will continue conducting the comparative effectiveness and analysis to compare drugs head to head as well as developing and implementing new methodologies to this field. And we hope our study provides real world evidence for clinical decision making, prescribing anticoagulants to patients with atrial fibrillation and chronic liver disease. We also expect the physicians and researchers more and more value the real world data studies, especially when clinical trials are not feasible or ethical. Dr. Mercedes Carnethon: Well, thank you so much. That was such an excellent vision that you provided us with and we're just very grateful that you submitted this fantastic work to the journal Circulation. I know that our readers will enjoy really digging in. The podcast is meant as a teaser to bring you to the journal so that you can read about this wonderful work by Dr. Wen and colleagues. So again, thank you. I'm Mercedes Carnethon, joined with my associate editor partner here, Dr. Sandeep Das. And thank you very much for spending your time with us today, Dr. Wen. Dr. Xuerong Wen: Thanks for this great opportunity to disseminate my study with us, thank you. Dr. Sandeep Das: Thanks Mercedes. Dr. Mercedes Carnethon: Thank you for joining us for this episode of Circulation on the Run. Dr. Greg Hundley: This program is copyright of the American Heart Association 2023. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit ahajournals.org.

Join Dr Carol Wysham and Dr Javed Butler as they discuss the stealth complication of heart failure in patients with type 2 diabetes, including subtle signs and symptoms of heart failure and the importance of early detection and treatment. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/982415). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes https://www.nejm.org/doi/full/10.1056/nejmoa1504720 Framingham Heart Study https://www.framinghamheartstudy.org/ Heart Failure https://emedicine.medscape.com/article/163062-overview Heart Failure: An Underappreciated Complication of Diabetes. A Consensus Report of the American Diabetes Association https://diabetesjournals.org/care/article/45/7/1670/147048/Heart-Failure-An-Underappreciated-Complication-of Brain-Type Natriuretic Peptide (BNP) https://emedicine.medscape.com/article/2087425-overview The Effect of Spironolactone on Morbidity and Mortality in Patients With Severe Heart Failure https://www.nejm.org/doi/full/10.1056/NEJM199909023411001 Eplerenone in Patients With Systolic Heart Failure and Mild Symptoms https://www.nejm.org/doi/full/10.1056/nejmoa1009492 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines https://www.ahajournals.org/doi/10.1161/CIR.0000000000001063

In this episode, we discuss aging and brain health with Dr. Rhoda Au.  Specifically, we cover the Framingham Heart Study and cardiovascular risk factors, the Boston Process Approach, Alzheimer's disease, and digital biomarkers. Show notes are available at www.NavNeuro.com/110 _________________ If you'd like to support the show, here are a few easy ways: 1) Get APA-approved CE credits for listening to select episodes: www.NavNeuro.com/INS  2) Tell your friends and colleagues about it 3) Subscribe (free) and leave an Apple Podcasts rating/review: www.NavNeuro.com/itunes   Thanks for listening, and join us next time as we continue to navigate the brain and behavior! [Note: This podcast and all linked content is intended for general educational purposes only and does not constitute the practice of psychology or any other professional healthcare advice and services. No professional relationship is formed between hosts and listeners. All content is to be used at listeners' own risk. Users should always seek appropriate medical and psychological care from their licensed healthcare provider.]

Listen on Spotify, Apple Podcasts and most other Podcast Platforms. Search "Marc Lobliner Show" Buy Mental Jewels HERE! https://www.tigerfitness.com/products/ambrosia-mental-jewels References: Gordon BR, McDowell CP, Hallgren M, Meyer JD, Lyons M, Herring MP. Association of efficacy of resistance exercise training with depressive symptoms: Meta-analysis and meta-regression analysis of randomized clinical trials. JAMA Psychiatry. 2018;75(6):566. doi:10.1001/jamapsychiatry.2018.0572 Spartano NL, Demissie S, Himali JJ, et al. Accelerometer‐determined physical activity and cognitive function in middle‐aged and older adults from two generations of the Framingham Heart Study. Alzheimer's & Dementia: Translational Research & Clinical Interventions. 2019;5(1):618-626. Salci LE, Martin Ginis KA. Acute effects of exercise on women with pre-existing body image concerns: A test of potential mediators. Psychology of Sport and Exercise. 2017;31:113-122. doi:10.1016/j.psychsport.2017.04.001 Fernández-Bustos JG, Infantes-Paniagua Á, Cuevas R, Contreras OR. Effect of physical activity on self-concept: theoretical model on the mediation of body image and physical self-concept in adolescents. Front Psychol. 2019;10:1537. doi:10.3389/fpsyg.2019.01537 Get my free app: https://www.tigerfitness.com/blogs/training-programs/tiger-fitness-trainer

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Dementia Matters Special Series: The National Strategy for Alzheimer's Disease Data and Research Part 5 Whether it be due to new research findings, innovative approaches and ideas, or technological advancements, Alzheimer's disease research is constantly evolving. Now, dementia research is headed into the digital frontier. Dr. Rhoda Au joins the podcast to discuss digital biomarkers, gamifying cognitive testing, and how the field of Alzheimer's disease research is entering its digital age. Guest: Rhoda Au, PhD, digital technology leader, Boston University Alzheimer's Disease Research Center, co-principal investigator, director of neuropsychology, Framingham Heart Study, professor, Boston University School of Medicine Show Notes Watch Dr. Rhoda Au's presentation from NACC's Spring ADRC Meeting on NACC's YouTube channel. Learn more about Dr. Au at her bio on the Boston University Chobanian & Avedisian School of Medicine website. Learn more about the National Alzheimer's Coordinating Center at 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.

video: Dr. Guy Mcpherson Predicts Human Extinction by 2030  Neil Oliver: ‘By taking back control of the money we can begin regaining control of our world' Unpayable Debt & Deadly Vax Causing Hell on Earth – Ed Dowd 2 Testimonials  Trailer For : Science For Hire   Regeneration of brain stem cells boosted by turmeric compound Institute of Neuroscience and Medicine (Germany)  September 28, 2022  A bioactive compound found in turmeric promotes stem cell proliferation and differentiation in the brain, reveals new research published in the open access journal Stem Cell Research & Therapy. The findings suggest aromatic turmerone could be a future drug candidate for treating neurological disorders, such as stroke and Alzheimer's disease. The study looked at the effects of aromatic (ar-) turmerone on endogenous neutral stem cells (NSC), which are stem cells found within adult brains. NSC differentiate into neurons, and play an important role in self-repair and recovery of brain function in neurodegenerative diseases. Previous studies of ar-turmerone have shown that the compound can block activation of microglia cells. When activated, these cells cause neuroinflammation, which is associated with different neurological disorders. However, ar-turmerone's impact on the brain's capacity to self-repair was unknown.  Researchers from the Institute of Neuroscience and Medicine in Jülich, Germany, studied the effects of ar-turmerone on NSC proliferation and differentiation both in vitro and in vivo. Rat fetal NSC were cultured and grown in six different concentrations of ar-turmerone over a 72 hour period. At certain concentrations, ar-turmerone was shown to increase NSC proliferation by up to 80%, without having any impact on cell death. The cell differentiation process also accelerated in ar-turmerone-treated cells compared to untreated control cells.  Lead author of the study, Adele Rueger, said: “While several substances have been described to promote stem cell proliferation in the brain, fewer drugs additionally promote the differentiation of stem cells into neurons, which constitutes a major goal in regenerative medicine. Our findings on aromatic turmerone take us one step closer to achieving this goal.”  Ar-turmerone is the lesser-studied of two major bioactive compounds found in turmeric. The other compound is curcumin, which is well known for its anti-inflammatory and neuroprotective properties.  Study finds mind-body practices lower blood sugar levels in people with type 2 diabetes University of Southern California School of Medicine, September 30, 2022 Mind-body practices such as yoga and meditation are increasingly popular tools for promoting health and combating diseases, including type 2 diabetes. Approximately 66% of Americans with type 2 diabetes use mind-body practices and many do so because they believe it helps control their blood sugar. Until now, however, whether mind-practices can reduce blood glucose levels has never been rigorously quantified. According to new research conducted by a team from the Keck School of Medicine of USC, published in the Journal of Integrative and Complementary Medicine, some mind-body practices can be nearly as effective as commonly prescribed drugs at reducing blood glucose levels in people with type 2 diabetes.  The team analyzed data from randomized controlled trials conducted across the globe between 1993 and 2022. They found 28 trials in which people with type 2 diabetes began a mind-body practice in addition to receiving medication and compared their results with people who only received medication to reduce their blood sugar levels. This study, the first to analyze a range of mind-body practices including meditation, qigong, yoga and mindfulness-based stress reduction and their effect on blood glucose levels, revealed that all mind-body practices led to significant reductions in blood sugar levels.  Taken as a whole, the mind-body practices averaged a .84% reduction in hemoglobin A1c, a measure of the average blood glucose level for the past 3 months. Yoga, the most-studied modality, provided the largest benefit, about a 1% reduction in hemoglobin A1c. The authors noted that a 1% reduction is particularly notable because metformin, the most prescribed diabetes drug, reduces hemoglobin A1c in people with type 2 diabetes by 1.1% on average.  The research suggests that mind-body practices could be used as a both as a complementary nonpharmacological treatment for people with type 2 diabetes and possibly as a preventive measure as well.   Compound in Celery Found to Destroy 86% of Lung Cancer CellsGuangdong Pharmaceutical University (China),   September 28th, 2022 Celery ihas been found to be extremely effective at killing ovarian, pancreatic, prostate, breast, liver, and lung cancer cells. In fact, in a recent study, celery killed up to 86% of cancer cells in the lungs (in vitro). In addition to calming your nervous system, aiding digestion, reducing inflammation, and lowering blood pressure, celery also contains an anti-cancer compound called apigenin, which has been effective at causing apoptosis (cell suicide) in numerous types of cancer cells. Researchers in China have found that by eating just two medium stalks of celery 2 to 3 times a week can reduce the risk of getting lung cancer by 60%. It is still not definitive through the scientists research, however, if the apigenin alone does the work of killing cancerous cells or if they work in cooperation with other compounds found in celery Furthering the link, other research found: “Apigenin widely inhibits cell proliferation of various lung cancer cell lines in a dose-dependent manner and the combination treatment of apigenin and antitumor drugs is very effective in human lung cancer cells, and Nrf2-ARE pathway may contribute to the mechanism.” And another study's abstract focusing on the broader impact of fruit and vegetable intake on cancer concluded: “In particular, high intake of Chinese cabbage (OR = 0.53), chives (OR = 0 .54), carrots (OR = 0.51) and celery (OR = 0.40) was inversely associated with lung cancer. The OR was more than six-fold elevated for smokers reporting low intake of vegetables, and more than four-fold elevated for smokers reporting low intake of fruit, as compared with never smokers reporting high intake of these items.  Moderate alcohol use linked to heart chamber damage, atrial fibrillation in new studyUniversity of California, San Francisco September 28, 2022  A study by UC San Francisco researchers found that even moderate alcohol consumption may change the structure of the heart in ways that increase the risk of atrial fibrillation. “There's growing evidence that moderate alcohol intake may be a risk factor for atrial fibrillation, the most common heart rhythm disturbance in the world, but the mechanism by which alcohol may lead to atrial fibrillation is unknown,” said Gregory Marcus, MD, endowed professor of atrial fibrillation research at UCSF and senior author of the study published in the Journal of the American Heart Association. Marcus and colleagues looked at damage to the left atrium of the heart as a possible pathway between alcohol and atrial fibrillation. Atrial fibrillation is a known risk factor for stroke. The irregular pumping of blood can lead to blood clots, which may travel to the brain and cause stroke. The researchers evaluated data from more than 5,000 adults collected over several years in the Framingham Heart Study, including echocardiograms, medical history and self-reported alcohol intake. The study participants, mostly white and in their 40s to 60s, reported on average just over one drink per day. The overall rate of atrial fibrillation in the group was 8.4 cases per 1,000 people per year – meaning over a 10-year period, eight out of 100 people were likely to develop atrial fibrillation. Every additional drink per day was associated with a 5 percent increase in the yearly risk. Every additional drink per day also was associated with a statistically significant 0.16 millimeter enlargement of the left atrium, highlighting a possible site of physical damage caused by drinking   Ginger effective for muscle pain relief University of Georgia,  Sep 29, 2022 A new study has suggested that daily doses of raw or heat-treated ginger are effective for relieving muscle pain following strenuous exercise.  Some research has shown that ginger may have anti-inflammatory and analgesic properties similar to nonsteroidal anti-inflammatory drugs.  In one study, four to 36 weeks of daily ginger doses (30 to 500 mg.) achieved reductions in knee pain from osteoarthritis.  Researchers from the University of Georgia examined the efficacy of multiple days of ginger doses for relieving experimentally induced muscle pain from 18 eccentric muscle exercises.  For the study, student volunteers were tested on 11 consecutive days while taking ginger supplements. Seventy-four students were divided in three groups given either raw ginger, heated ginger or placebo.  The authors hypothesized that pain ratings after exercise would be lower in the ginger group compared to placebo subjects.  Results from the subjects' responses data showed that both raw and heat-treated ginger lowered muscle pain intensity after eccentric exercise by 25 and 23 per cent, respectively.  Heat treating ginger, therefore, did not increase the analgesic benefit.   Whether ground, instant or decaffeinated, coffee drinking associated with longer life Baker Heart and Diabetes Research Institute (Australia), September 28 2022.  Regardless of the type of coffee consumed, people who drink coffee may live longer, as indicated by research findings reported in the European Journal of Preventive Cardiology. “In this large, observational study, ground, instant and decaffeinated coffee were associated with equivalent reductions in the incidence of cardiovascular disease and death from cardiovascular disease or any cause,” senior author Peter Kistler, PhD, stated.  The study included 449,563 men and women enrolled in the UK Biobank, which recruited UK residents from 2006 to 2010 and collected data concerning dietary intake, including coffee consumed, and other factors. Individuals included in the current investigation did not have cardiovascular disease or heart arrhythmias at the beginning of the study.  During an average follow-up of 12.5 years, 27,809 deaths occurred. Compared with non-coffee drinkers, people who reported drinking ground, instant or decaffeinated coffee had a significantly lower risk of dying from all causes during follow-up. The greatest risk reduction was associated with drinking 2 to 3 cups coffee per day, with ground coffee associated with 27% lower risk compared with no coffee drinking. Drinking any type of coffee was also associated with a reduced chance of developing cardiovascular disease, and 2 to 3 cups was again associated with the most protection. The development of arrhythmias was less among people who consumed ground or instant coffee, but not decaffeinated coffee.  “The beverage contains more than 100 biologically active components,” Dr Kistler remarked. “It is likely that the non-caffeinated compounds were responsible for the positive relationships observed between coffee drinking, cardiovascular disease and survival. Our findings indicate that drinking modest amounts of coffee of all types should not be discouraged but can be enjoyed as a heart healthy behavior.”

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.27.509283v1?rss=1 Authors: Fongang, B., Satizabal, C. L., Kautz, T. F., Ngouongo, Y. W., SherraeMuhammad, J. A., Vasquez, E., Mathews, J., Goss, M., Saklad, A. R., Himali, J., Beiser, A., Cavazos, J. E., Mahaney, M. C., Maestre, G., DeCarli, C., Shipp, E. L., Vasan, R. S., Seshadri, S. Abstract: A bidirectional communication exists between the brain and the gut, in which the gut microbiota influences cognitive function and vice-versa. Gut dysbiosis has been linked to several diseases, including Alzheimer's disease and related dementias (ADRD). However, the relationship between gut dysbiosis and markers of cerebral small vessel disease (cSVD), a major contributor to ADRD, is unknown. In this cross-sectional study, we examined the connection between the gut microbiome, cognitive, and neuroimaging markers of cSVD in the Framingham Heart Study (FHS). Markers of cSVD included white matter hyperintensities (WMH), peak width of skeletonized mean diffusivity (PSMD), and executive function (EF), estimated as the difference between the trail-making tests B and A. We included 972 FHS participants with MRI scans, neurocognitive measures, and stool samples and quantified the gut microbiota composition using 16S rRNA sequencing. We used multivariable association and differential abundance analyses adjusting for age, sex, BMI, and education level to estimate the association between gut microbiota and WMH, PSMD, and EF measures. Our results suggest an increased abundance of Pseudobutyrivibrio and Ruminococcus genera was associated with lower WMH and PSMD (p-values less than 0.001), as well as better executive function (p-values less than 0.01). In addition, in both differential and multivariable analyses, we found that the gram-negative bacterium Barnesiella intestinihominis was strongly associated with markers indicating a higher cSVD burden. Finally, functional analyses using PICRUSt implicated various KEGG pathways, including microbial quorum sensing, AMP/GMP-activated protein kinase, phenylpyruvate, and {beta}-hydroxybutyrate production previously associated with cognitive performance and dementia. Our study provides important insights into the association between the gut microbiome and cSVD, but further studies are needed to replicate the findings. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

A new research paper was published in Aging (listed as "Aging (Albany NY)" by Medline/PubMed and "Aging-US" by Web of Science) Volume 14, Issue 17, entitled, “Aging, prevalence and risk factors of MRI-visible enlarged perivascular spaces.” Cerebral small vessel disease (CSVD) increases with age and is associated with stroke and cognitive decline. Enlarged Perivascular Spaces (ePVS) is an emerging marker of CSVD, but its prevalence over the life span remains unclear. In a new study, researchers Frances Rodriguez Lara, Ashlea Lynn Scruton, Adlin Pinheiro, Serkalem Demissie, Pedram Parva, Andreas Charidimou, Michael Francis, Jayandra J. Himali, Charles DeCarli, Alexa Beiser, Sudha Seshadri, and Jose R. Romero from Boston University School of Medicine, Boston University School of Public Health, NHLBI's Framingham Heart Study, Veterans Affairs Boston Health System, University of Texas Health Sciences Center, and University of California at Davis characterized the age and sex-specific prevalence of ePVS and its relation to age-specific risk factors in a large community-based sample. “In this report we aim to describe 1) the age and sex specific prevalence of ePVS in a large sample of asymptomatic, community dwelling individuals, and contrast ePVS prevalence with the prevalence of vascular risk factors in the same age groups, and 2) study the association of vascular risk factors with burden of ePVS by brain region. This knowledge will help support the increasing number of studies of ePVS as a biomarker of aging and age related adverse neurological outcomes.” Full Press Release - https://aging-us.net/2022/09/22/aging-aging-prevalence-and-risk-factors-of-mri-visible-enlarged-perivascular-spaces/ DOI: https://doi.org/10.18632/aging.204181 Corresponding Author: Jose R. Romero - Email: joromero@bu.edu Keywords: neurological markers, aging, disease marker, perivascular spaces Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204181 About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/agingus​ LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Daily Inspiration from Rabbi Moshe Scheiner - September 13, 2022For more information on Rabbi Scheiner and Palm Beach Synagogue, please visit www.palmbeachsynagogue.org

This week, please join author Ambarish Pandey and Editorialist Linda Peterson as they discuss the article "Frailty Status Modifies the Efficacy of Exercise Training Among Patients with Chronic Heart Failure and Reduced Ejection Fraction: An Analysis from the HF-ACTION Trial" and the editorial "Heart Failure With Reduced Ejection Fraction (HFrEF): ‘The Importance of Being Frail.'" Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast, summary, and backstage pass to the journal and its editors. We're your co-hosts. I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, associate editor director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Well, Carolyn, this week's feature article, Heart Failure Reduced Ejection Fraction in Evaluating the Efficacy of Exercise Training. But guess what? It appears it may be more efficacious in those that have high Frailty Index scores, as opposed to those that may not. But before we get to our feature discussion, let's grab a cup of coffee and go through some of the other articles in the issue. Would you like to go first? Dr. Carolyn Lam: I would love to, and this first paper is one that defines epigenetic biomarkers of lifelong cardiovascular health exposure and really contributes to our understanding of their roles in cardiovascular disease development. First though, a little quiz for Greg. So, Greg, what does DNA methylation mean to you? Dr. Greg Hundley: Well, Carolyn, DNA methylation. So, what I understand is these methyl groups get involved with our DNA and actually affect change over time that leads to phenotypic expression of, maybe, new traits. But I don't know. Maybe I'm not quite up to date. Dr. Carolyn Lam: Oh, you're perfect. Indeed, DNA methylation is a widely characterized epigenetic modification, which means exactly as you said. It's a regulatory modification to our DNA induced by environmental exposures and can affect gene expression. And this is the topic of today's paper by Doctors Zheng, Hou, and Lloyd-Jones from Northwestern University Feinberg School of Medicine and their colleagues. So, what they did is they studied blood DNA methylation at over 840,000 methylation markers measured twice over five years in participants of the CARDIA study. Epigenome-wide association analyses on a clinical cumulative cardiovascular health score were then performed in both CARDIA and compared in the Framingham Heart Study. Dr. Carolyn Lam: The authors identified 45 midlife DNA methylation markers associated with clinical cardiovascular health metrics, such as body mass index, blood pressure, blood glucose, and total cholesterol longitudinally measured since young adulthood. The methylation markers were located in genes involved in lipid metabolism, insulin secretion, and cytokine production, which could not be fully attributed to genetic factors. So, they proposed and validated in summary a methylation-based risk score to promote a personalized cardiovascular disease risk evaluation beyond traditional cardiovascular risk factors. Dr. Greg Hundley: Oh, wow, Carolyn. Interesting, a methylation-based risk score to promote personalized cardiovascular disease risk evaluation. Wow! That's really exciting. Dr. Greg Hundley: Well, I'm going to go to the world of preclinical science, and just like last week where we had a really nice article on myocardial regeneration, this week, we've got another. And so, Carolyn, early neonates of both large and small mammals are able to regenerate the myocardium through cardiomyocyte proliferation for only a very short period after birth. This myocardial regenerative capacity declines in parallel with withdrawal of cardiomyocytes from the cell cycle in the first few postnatal days. No mammalian species examined to date has been found capable of a meaningful regenerative response to myocardial injury later than one week after birth. Dr. Carolyn Lam: Interesting. Now, I see that these investigators worked with possums. Could you tell me why they did that, and what did they find, Greg? Dr. Greg Hundley: Right, Carolyn. So, this work was led by Dr. Wataru Kimura from the RIKEN Center for Biosystems Dynamic Research and their colleagues. The reason they studied possums, so the marsupial possum maintains cardiomyocyte proliferation and a capacity for myocardial regeneration for at least two weeks after birth. Remember we stated before, all the other mammalian species, it's only one week after birth. So, this appears to be the longest postnatal duration of such a capacity among mammals examined to date, and AMP kinase signaling was implicated as an evolutionary conserved regulator of mammalian postnatal cardiomyocyte proliferation. Dr. Greg Hundley: And they additionally found that in a separate mouse experiment, the authors noted that the pharmacological inhibition of AMP kinase signaling was sufficient to extend the postnatal window of cardiomyocyte proliferation in neonatal mice, so really exciting work in the area of cardiomyocyte regeneration. Dr. Carolyn Lam: Wow, indeed! And I've learned now about possums. Thank you, Greg. Dr. Carolyn Lam: So, Greg, have you ever asked yourself, what is the frequency, penetrance, and variable expressivity of dilated cardiomyopathy-associated gene variants in the general population? Well, guess what? This next paper addresses just that in more than 18,600 UK Biobank participants who had undergone whole-genome sequencing, ECG, and cardiovascular magnetic resonance imaging. Dr. Greg Hundley: Wow, Carolyn, another really interesting study from the UK Biobank. So, what did they find? Dr. Carolyn Lam: So, this study is from Dr. Chahal from the Center for Inherited Cardiovascular Diseases Wellspan Health in Lancaster, Pennsylvania and colleagues, and they found that approximately one in six of adults with putative pathogenic variants in dilated cardiomyopathy genes exhibited early dilated cardiomyopathy features potentially associated with the genotype. And it's most commonly manifesting with arrhythmias in the absence of substantial ventricular dilation or dysfunction. Dr. Carolyn Lam: Among individuals with putative pathogenic dilated cardiomyopathy gene variants, ECG or CMR-detected early features were nearly four times more common than clinically manifest dilated cardiomyopathy or early features. Over 90% of subjects with these gene variants in dilated cardiomyopathy-associated genes did not have a prior history of dilated cardiomyopathy, and the overall clinical or subclinical penetrance of dilated cardiomyopathy-associated single pathogenic variants was highly variable between genes ranging from zero to 67%. And so, in conclusion, a genotype-first screening approach for dilated cardiomyopathy using a large genetic panel is currently not suitable in the general population due to incomplete understanding of the genetic architecture and reduced penetrance of the associated genes. Dr. Greg Hundley: Very nicely said, Carolyn. Wow! Well, let's take a look and see what's in the mailbag. And first, there's a Research Letter from Professor Huguenard entitled, “Frequency of Screening Detected Intracranial Aneurysms in Patients With Loeys-Dietz Syndrome.” And our own Bridget Kuehn has a really nice piece on Cardiology News. Dr. Carolyn Lam: Nice. There's also an On My Mind paper by Dr. Sattar, McGuire, and Gill entitled, “High-Circulating Triglycerides Are Most Commonly a Marker of Ectopic Fat Accumulation: Connecting the Clues to Advanced Lifestyle Interventions,” and an exchange of letters between Dr. Groothof and myself, Dr. Lam, regarding my article on “Efpeglenatide and Clinical Outcomes With and Without Concomitant SGLT-2 Inhibition in Type 2 Diabetes: An Exploratory Analysis of the AMPLITUDE-O Trial.” Dr. Carolyn Lam: Ah, that was awesome. Well, thanks, Greg. I am so excited to get to the future discussion that you queued us on so well, frailty in heart failure with reduced ejection fraction. Here we go. Dr. Greg Hundley: You bet. Dr. Greg Hundley: Welcome, listeners, to this July 12th, 2022 feature discussion. And we have with us today, Dr. Ambarish Pandey from University of Texas Southwestern Medical Center in Dallas, Texas, and Dr. Linda Peterson, an editorialist for this article from Washington University in St. Louis. Welcome to you both. Well, Ambarish, We're going to start with you. Could you describe for us basically the background information that went into the preparation of your study, and what was the hypothesis that you wanted to address? Dr. Ambarish Pandey: Thanks, Greg, for having me on this, and thanks to Circulation for publishing our article. Yeah, I think the premise for this study stems from the longstanding known benefit of exercise training in patients with heart failure with reduced ejection fraction. Now, that was shown in the HF-ACTION trial, where individuals with chronic stable heart failure with reduced ejection fraction underwent exercise training, and there was demonstrated benefit in quality of life and adjusted analyses. There was a protocol-specified adjusted analysis that did demonstrate improvement in some of the key primary endpoint. Dr. Ambarish Pandey: Based on these results, CMS has approved exercise training and cardiac rehabilitation in patients with chronic stable heart failure with reduced ejection fraction. However, despite this mandate from CMS and generally well-accepted benefits of exercise training in heart failure with reduced ejection fraction, the uptake of exercise training has been pretty low, and there's a lot of heterogeneity in the improvement in outcomes that is associated with exercise training. Dr. Ambarish Pandey: So, we wanted to see whether frailty, which is a well-characterized syndrome of reduced physiologic reserve and impaired homeostatic tolerance to stressors and is common in patients with HFrEF, we wanted to see how frailty modifies the beneficial effects of exercise training in HFrEF. And based on the existing literature and some of the prior works we have done, we hypothesized that individuals who are frail and who have more functional impairments are going to have more targets for improvement in their functional status and thus would be more likely to benefit from exercise training. And we looked at this in the HF-ACTION trial itself and using the Rockwood Frailty Index and the difference in primary outcome and treatment effect of exercise among frail and non-frail individuals. Dr. Greg Hundley: Very interesting, so really sort of a look back in HF-ACTION data. Describe a little bit more for us that study design, and then specifically, what was the study population that you used to test your hypothesis? Dr. Ambarish Pandey: Right. So HF-ACTION was a randomized control trial multi-centered that was sponsored by NHLBI and was conducted in the early 2000s and basically focused on chronic stable patients with heart failure with reduced ejection fraction who have not had a hospitalization in the past six weeks and have ejection fraction less than 35% and class II to IV. And these participants were randomized in one-to-one fashion to getting aerobic exercise training followed by some home-based exercise versus the usual care. Dr. Ambarish Pandey: And in our study, what we looked at was we looked at the effect modification by baseline frailty status on the treatment effect of exercise training. So, we calculated the frailty index, which is a well-established measure of frailty using a Rockwood Index Model, and we stratified patients by frail versus non-frail status based on a Frailty Index cut-off of 0.21, such that higher index identifies more frail participants. And then, we looked at how the treatment benefit of exercise training on different outcomes was differential across the frail and non-frail strata. We looked at qualitative interaction, and we also looked at the Frailty Index, so the continuous variable to assess the benefits of exercise across the spectrum of frailty in the study population. Dr. Greg Hundley: And so, before we get to your study results, how many patients were in your study? Give us an idea of what was the range in age, and then also the composition of sex? How many men? How many women? Dr. Ambarish Pandey: Right, so this is really important because that's addressed to the generalizability of the study. So, the study included around a little over 2,100 participants. The mean age was 59 years. 28% were women, and 32% were self-reported black individuals with chronic stable heart failure. That was the demographic distribution. The age was slightly younger than what you've commonly see in observational studies with heart failure, and that is largely because the study recruited patients who were able to do exercise training and were able to do exercise tests with peak VO2 and peak VO2 peak excess capacity assessment at baseline and follow-up. So, that kind of selected for a slightly younger population. Dr. Greg Hundley: Very nice. And so, what were your study results? Dr. Ambarish Pandey: So our study results are, indeed, pretty interesting. We identified that around 60% of patients with chronic stable heart failure with reduced ejection fraction who were in the trial were actually frail based on the Rockwood Frailty Index Model. And we observed that among the study participants, the exercise training was associated with significant improvement in the primary composite endpoint of all-cause hospitalization or death in frail participants, but not in the non-frail or less fail participants. And there was a significant treatment interaction, such that baseline frailty modified the treatment effect of exercise training for the primary composite endpoint. Dr. Ambarish Pandey: Now, this was largely driven by a significant reduction in all-cause hospitalization among frail individuals who underwent exercise training, and not so much by an effect on mortality. And we did not see a significant difference in the mortality component of the primary composite endpoint across frail versus non-frail status participants. So, in a nutshell, baseline frailty did modify the treatment effect, largely driven by substantial reduction in the risk of all-cause hospitalization among frail participants more than non-frail participants. Dr. Greg Hundley: And before we get to Linda in her interpretation of your study, Ambarish, did you see the same effects in frail men, in frail women? And also, what about in individuals that might be a little older versus those that were perhaps younger? Dr. Ambarish Pandey: That's a really important question, and we were a little bit limited to do further subgroups because we are dealing with around, I think, 2,000 participants and we had frail, non-frail, and we did not do a further subgroup stratification by sex or by age. The age range was rather narrow. It's 58 years plus/minus 13 years, so we didn't really have a lot of older individuals above 75, something like what REHAB-HF Trial has shown in the news, a recent trial. Dr. Ambarish Pandey: We couldn't address the question of whether the effect modification was further modified by sex or age, so I think that's the two-level interaction. But I think that is something that would be interesting to test perhaps in a pool analysis of multiple exercise training studies, which is something we are considering. Dr. Greg Hundley: Thank you. Well, listeners, now we're going to turn to our editorialist, Dr. Linda Peterson, from Washington University in St. Louis, and, Linda, very provocative results here, heart failure reduced ejection fraction. And certainly, we like to go to things like cardiac rehab, but we're hearing this it seemed to make a difference if you were frail versus not frail. Dr. Linda Peterson: Right, I think that's an important distinction here in this article as Ambarish has so eloquently put forth, and it's especially important because other articles have shown in looking at the PARADIGM-HF Study and ATMOSPHERE it appears that one out of two patients with HFrEF are actually frail. And so, the magnitude of these findings and the importance of these findings is highlighted by that study. And this frequency of frailty is roughly double that of community-dwelling adults who are over age 90, so we're thinking of frailty usually as much older adults, but in HF-ACTION, actually, the patients' average age was 60 in the patients with HFrEF. Dr. Linda Peterson: So, there's almost an accelerated aging phenotype we're seeing here in a large proportion of the patients who have HFrEF. I think this has an enormous impact on a lot of the patients that we're seeing with HFrEF, and we should be alerted to looking for frailty and potentially screening for frailty. And I think another highlight of this study is that it points out the importance of frailty because frail patients have a 50% higher risk of hospitalization and death, according to some other studies, particularly one by Faray and their group and also by Yang and their group. Dr. Linda Peterson: And so, it highlights the importance of getting patients who are frail with HFrEF into cardiac rehab or getting them some sort of aerobic exercise training. But paradoxically, frailty is also associated with a lower likelihood of those particular patients on getting into cardiac rehab and also getting on goal-directed medical therapy. And that was shown by Phil Ades and his group. So, I think the importance of these findings by Ambarish and his group are to be commended, and they're very important for a large proportion of our patients with HFrEF. Dr. Greg Hundley: Very nice. Well, let's turn back to Ambarish, and then follow up with Linda. Ambarish, what do you see as the next study that should be performed in follow-up to your study? Dr. Ambarish Pandey: I think that's a great question. And I think we are just beginning to realize the magnitude of impact that frailty has in the care of patients with heart failure. And this goes across the spectrum of ejection fraction, both HFpEF or heart failure with preserved ejection fraction and heart failure with reduced ejection fraction. Indeed, the burden of frailty is higher in patients with heart failure with preserved ejection fraction, and they are more of the accelerated aging phenotype. Dr. Ambarish Pandey: And I think the next study basically should look at a targeted approach to exercise training or category of intervention among patients who are most likely to benefit from it, which would be patients who have a high frailty burden or patients who have HFpEF. I think they go hand in hand when it comes to frailty and HFpEF. So, I think that's the next study to do is to see to what extent we can actually identify and target exercise training in the highest risk individuals who are most likely to benefit from it because that subset of highest modifiable risk is indeed identified by frailty and when you look at other subtypes by HFpEF which has a lot of high frailty burden. Dr. Greg Hundley: And, Linda, from your perspective, what do you see as the next study to be performed in this sphere of research? Dr. Linda Peterson: Yeah, I think this study really provides a springboard for future studies in HFrEF, in particular. One, what hospital interventions can be done in patients to get them moving more, and really assess is there a possibility of different types of exercises to get patients less frail even while they're in the hospital when they're enroute to going home? And then also, how do we have different mechanisms by which we can get more patients into cardiac rehab? Clearly, our national average of getting patients who qualify for cardiac rehab, which is a class I indication is 20% at best, and the aim from the AHA is 70%. Dr. Linda Peterson: There's a big gap there, so interventions looking at implementation and getting patients to cardiac rehab or looking at other types of aerobic exercise training, such as home-based cardiac rehab for patients who don't have a cardiac rehab center next to them, I think the field is wide open for different studies to springboard off of these findings. Dr. Greg Hundley: Very nice. Well, listeners, we want to thank Dr. Ambarish Pandey from University of Texas Southwestern Medical Center in Dallas, Texas, and our editorialist, Dr. Linda Peterson, from Washington University in St. Louis, for bringing us this research study, highlighting that among patients with chronic stable heart failure and reduced ejection fraction, that baseline frailty modified the treatment effect of aerobic exercise training with a greater reduction in the risk of all-cause hospitalization. Dr. Greg Hundley: Well, on behalf of Carolyn and myself, we want to wish you a great week, and we will catch you next week on the run. Speaker 5: This program is copyright of the American Heart Association 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit ahajournals.org.

Tom Osborn was born and raised in Kenya, where he currently works to create community solutions for mental health challenges. He graduated from Harvard College with High Honors and went on to co-found GreenChar, an organization that provides homes and institutions in rural areas of Kenya. Tom was the youngest recipient of the Echoing Green Fellowship and has been on the Forbes' 30 under 30 list in Social Entrepreneurship. He created the Shamiri Institute in order to shift the stigma around mental health in the younger population.    Today, Shay Beider speaks with Tom Osborn about his work in Africa. He describes the shortage of clinical experts, the stigma around mental health in Kenya, and why he decided to create an institution for young people that is run by young people. The program trains high school graduates in character strengths interventions and these techniques are implemented in after school programs. By creating involvement and excitement within the community, great strides can be made to improve the mental health of the youth. Tom also touches on the effect of systematic racism in the delivery of healthcare and his unique approach to meeting this challenge. By shifting to community based solutions, great advances can be made in people's capacity to flourish.    Transcripts for this episode are available at: https://www.integrativetouch.org/conversations-on-healing    Show Notes: Check out Tom Osborn's TedTalk, “A New Way to Help Young People With Their Mental Health” Asset Framing is a narrative model defining people by their assets and aspirations before noting the challenges and deficits. To find out more, click here Read more about the Framingham Heart Study to discover the dynamic spread of happiness across social networks    This podcast was created by Integrative Touch, which is working to change the way people experience healthcare. A leader in the field of pediatric integrative medicine, the organization supports families whose children have any type of special health or medical need. This includes kids with cancers, genetic conditions, autism, cerebral palsy, traumatic stress, and other serious health issues. The founder, Shay Beider, pioneered a new therapy called Integrative Touch™Therapy that supports healing from trauma and serious illness. The organization reaches thousands of people each year in hospitals and communities and offers unique Telehealth programs to families and healthcare providers during this challenging time. Thanks to the incredible support of volunteers and contributors, individuals are able to receive wellness education and integrative medical services at little or no cost

It’s a study that laid the foundation of many more studies. The now famous Framingham Heart Study asked a simple question: Who is at risk for heart disease? Answers poured in over the years. Dr. Castelli was its third director and shares what’s been learned.

This week, please join author Vasan Ramachandran and Associate Editor Mercedes Carnethon as they discuss the article "Temporal Trends in the Remaining Lifetime Risk of Cardiovascular Disease Among Middle-Aged Adults Across 6 Decades: The Framingham Study." Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast, summary and backstage pass to the journal and its editors. We're your co-hosts. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center in Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, Associate Editor, Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Carolyn Lam: Greg, I'm so excited about today's feature paper. You see, I trained at the Framingham Heart Study and today's feature paper talks about the temporal trends in the remaining lifetime risk of cardiovascular disease among middle aged adults across six decades in the Framingham Heart Study. Truly a landmark study and a discussion nobody wants to miss. But first, let's talk about the other papers in today's issue, and I understand that you've got one ready. Dr. Greg Hundley: You bet Carolyn. I'll get started first. Thank you. So my first paper comes from Dr. Daniel Mark from Duke University and it refers to the ISCHEMIA trial. Dr. Carolyn Lam: Ooh, could you please first remind us what is the ISCHEMIA trial and are you presenting a substudy, is that correct? Dr. Greg Hundley: Right, Carolyn. So the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches, or ISCHEMIA, compared an initial invasive strategy with an initial conservative strategy in 5,179 participants with chronic coronary disease and moderate or severe ischemia. And this sub study of the ischemia research program included a comprehensive quality of life analysis. Dr. Carolyn Lam: So very interesting. What did they find Greg? Dr. Greg Hundley: Right, Carolyn. So this study included 1,819 participants. 907 in the invasive, 912 in the conservative. And collected a battery of disease specific and generic quality of life instruments by structured interviews at baseline. And then at three, 12, 24 and 36 months post randomization, and then finally at study closeout. Now Carolyn, these assessments included an angina related quality of life assessment from the 19 item Seattle Angina Questionnaire, a generic health status assessment, an assessment of depressive symptoms, and for North American patients, cardiac functional status from the Duke Activity Status Index, or DASI. In this study, Carolyn, in terms of results, the median age was 67 years and about 20% were women and about 16% were nonwhite. So Carolyn, getting to the results. The estimated mean difference for the SAQ 19 summary score favored invasive therapy. And remember the SAQ 19 was the Seattle Angina Questionnaire. Dr. Greg Hundley: Next, no differences were observed in patients with rare or absent baseline angina. Next, among patients with more frequent angina baseline, those randomized to invasive had a mean point higher score on the SAQ 19 summary score than the conservative approach, with consistent effects across all of the SAQ subscales including physical limitations, angina frequency and quality of life health perceptions. For the DASI, and remember DASI refers to the Duke Activity Status Index, no difference was estimated overall by treatment. But in patients with baseline marked angina, DASI scores were higher for the interventional arm. Whereas patients with rare or absent baseline angina showed really no treatment related differences. Dr. Carolyn Lam: Oh, okay. So a lot of results. What's the take-home message, Greg? Dr. Greg Hundley: Right, Carolyn. Glad you asked. So in the ISCHEMIA comprehensive quality of life substudy, patients with more frequent baseline angina reported greater improvements in the symptom physical functioning and psychological wellbeing dimensions of quality of life when treated with an invasive strategy. Whereas patients who had rare or absent angina baseline reported no consistent treatment related quality of life differences. Dr. Carolyn Lam: Wow. Thank you, Greg. Very interesting indeed. Now from angina to now cholesterol. Now, cholesterol guidelines typically prioritize primary prevention statin therapy based on 10 year risk of cardiovascular disease. Now the advent of generic pricing may in fact justify expansion of statin eligibility. Moreover, 10 year risk may not be the optimal approach for statin prioritization. So these issues were looked at in this next paper by authors led by Dr. Kohli Lynch from Northwestern University and colleagues who estimated the cost effectiveness of expanding preventive statin eligibility, and evaluated novel approaches to prioritization from a Scottish health sector perspective. A computer simulation model predicted long term health and cost outcomes in Scottish adults, age 40 years or more. Dr. Greg Hundley: So Carolyn, what did they find? Dr. Carolyn Lam: The advent of generic pricing has rendered preventive statin therapy cost effective for many adults. Absolute risk reduction guided statin therapy, which is based on 10 year cardiovascular disease risk and non HDL cholesterol levels, is cost effective and would improve population health. Whereas age stratified risk thresholds were more expensive and less effective than alternative approaches to statin prioritization. So guidelines committees may need to expand statin eligibility and consider new ways to allocate statins based on absolute risk reduction rather than 10 year risk thresholds. Dr. Greg Hundley: Very nice Carolyn. Always important, new information regarding statin therapy. Well Carolyn, my next paper comes to us from the world of preclinical science. And Carolyn, as you know, the regenerative capacity of the heart after myocardial infarction is limited. And these authors led by Dr. Tamer Mohamed from University of Louisville previously showed that ectopic introduction of Cdk1, CyclinB1 and Cdk4, CyclinD1 complexes and we'll refer to those now as 4F, promoted cardiomyocyte proliferation in 15 to 20% of infected cardiomyocytes in vitro and in vivo and improved cardiac function after MI in mice. So Carolyn, in this study using temporal single cell RNA sequencing, the investigative team aimed to identify the necessary reprogramming stages during the forced cardiomyocyte proliferation with 4F on a single cell basis. And also using rat and pig models of ischemic heart failure, they aim to start the first preclinical testing to introduce 4F gene therapy as a candidate for the treatment of ischemia induced heart failure. Dr. Carolyn Lam: Oh, wow Greg. So what did they find? Dr. Greg Hundley: Several things, Carolyn. First, temporal bulk and single cell RNA sequencing and further biochemical validations of mature HIPS cardiomyocytes treated with either LAcZ or 4F adenoviruses revealed full cell cycle reprogramming in 15% of the cardiomyocyte population at 48 hours post-infection with 4F. Which was mainly associated with sarcomere disassembly and metabolic reprogramming. Second Carolyn, transient overexpression of 4F specifically in cardiomyocytes was achieved using a polycistronic non-integrating lentivirus encoding the 4F with each driven by a TNNT2 promoter entitled TNNT2-4F polycistronic-NIL. Now this TNNT2-4F polycistronic-NIL or control virus was injected intra myocardial one week after MI in rats, so 10 per group, and pigs, six to seven per group. Dr. Greg Hundley: And four weeks post-injection the TNNT2-4F polycistronic-NIL treated animals showed significant improvement in left ventricular injection fraction and scar size compared with the control virus treated animals. And four months after treatment, the rats that received TNNT2-4F polycistronic-NIL still showed a sustained improvement in cardiac function without obvious development of cardiac arrhythmias or systemic tumorigenesis. And so Carolyn this study advances concepts related to myocellular regeneration by providing mechanistic insights into the process of forced cardiomyocyte proliferation and advances the clinical feasibility of this approach by minimizing the oncogenic potential of the cell factors, thanks to the use of a novel transient and cardiomyocyte specific viral construct. Dr. Carolyn Lam: Wow. What a rich study. Thanks so much, Greg. Dr. Greg Hundley: Well, Carolyn, how about if we see what else and what other articles are in this issue. And maybe I'll go first. So there's a research letter from Dr. Wu entitled Modeling Effects of Immunosuppressive Drugs on Human Hearts Using IPSC Derived Cardiac Organoids and Single Cell RNA Sequencing. Carolyn, there's an EKG challenge from Dr. Yarmohammadi, entitled “Fast and Furious, A Case of Group Beating in Cardiomyopathy.” And then finally from Dr. Tulloch, a really nice Perspective entitled “The Social Robots are Coming, Preparing For a New Wave of Virtual Care in Cardiovascular Medicine. Dr. Carolyn Lam: Oh, how interesting. Well, also in the mail back is an exchange of letters of among Drs. Lakkireddy, Dhruva, Natale, and Price regarding Amplatzer Amulet Left Atrial Appendage Occluder versus Watchman Device for stroke prophylaxis, a randomized control trial. All right. Thank you so much, Greg. Shall we go on to our feature discussion now? Dr. Greg Hundley: You bey. Welcome listeners to our feature discussion today. And we're so fortunate we have with us today, Dr. Vasan Ramachandran from Boston University and our own Associate Editor, Dr. Mercedes Carnethon from Northwestern University in Chicago. Welcome to you both. And Vasan, let's start with you. Could you describe for us some of the background information pertaining to your study and what was the hypothesis that you wanted to address? Dr. Vasan Ramachandran: Thank you, Greg, first of all for having me. So we know two facts. One is that heart disease and stroke disease death rates and incidents are declining over the last six decades in the United States. Juxtapose against that is also the observation that there is rising incidence of obesity and overweight, and also a rising burden of diabetes. There are a lot of advances in our ability to treat high blood pressure, high cholesterol, as well as high blood sugar. So we wanted to ask the question, given the historic trends in control awareness of risk factors and their control, interrupted by this escalating burden of obesity, overweight, and diabetes, what is the lived experiences of people over time in terms of the risk of developing heart disease or stroke using a metric we call as the remaining lifetime risk of developing heart disease or stroke. Dr. Greg Hundley: The hypothesis you wanted to address? Dr. Vasan Ramachandran: The hypothesis we wanted to address was that perhaps the decline in the incidence of heart disease and stroke may have decreased over time given the escalating burden of overweight, obesity and diabetes. Dr. Greg Hundley: Very nice. And can you describe for us your study population and your study design? Dr. Vasan Ramachandran: Thank you, Greg. So the Framingham Heart Study is one of the oldest running epidemiological studies in the world. We have multiple cohorts. The study began in 1948 with the original cohort, the offspring cohort enrolled in 1971, third generation cohort in 2002, and two minoritized cohorts in the 1990s and 2002. So we have an observation period of different cohorts over a six decade period. So we asked the question, if you were a participant in the Framingham study between 1960 and 1979 and then 1980 to 1999, and then 2000 to 2018, what was your lifetime risk of experiencing a heart disease or stroke in the three different time periods? Is it going down, is it steady or is it going up? Dr. Greg Hundley: Very nice. And so, Vasan, describe your study results. Dr. Vasan Ramachandran: Look, what we found was if you look at the first, the 20 year period from 1960 to 1979, and compare that with the latest, which is 2000 to 2018, in the initial time period, the lifetime risk of developing heart disease or stroke in a man was pretty high. It was about one in two. And that for a woman was about one in three. So when you come to the latest epoch, what we find that the risk of one in two men had dropped to about one in three men in the latest decade. For women, the risk declined from what was one in three in the earlier epoch to one in four. So approximately there was about a 36% reduction in the lifetime probability of developing heart disease or stroke across the six decade period of observation. Dr. Greg Hundley: Very nice. And so help us a little bit, put the context of your results into what that might mean for us today as we are managing patients with atherosclerotic disease. Dr. Vasan Ramachandran: Yes, Greg. What it means is that the permeation of the advances in science in terms of the screening of risk factors, awareness of risk factors, medications to lower these risk factors effectively, the clinical trials that have given us these new medications, they may have translated into a reduction in risk over time. That the lived experience of people in the later decades is better in terms of having a lower risk of heart disease or stroke as the consequence of multiple advances that have happened in heart disease and stroke. Dr. Greg Hundley: Well, thank you so much Vasan. Well listeners, now we're going to turn to our Associate Editor, Mercy Carnethon. And Mercy, you have many papers come across your desk. What attracted you to this particular paper and how do you put these results really in the context of other science pertaining to risk associated with populations that may have atherosclerotic cardiovascular disease? Dr. Mercedes Carnethon: Thanks so much for that question, Greg. And again, Vasan, I really thank you and your team for bringing forth such outstanding research. You know, as cardiovascular disease epidemiologists, we were all raised and taught that what we know about risk factors for cardiovascular disease are based on the Framingham cohort. And so I was really excited to see this very comprehensive piece of work that characterized what the Framingham study has identified and also leverages the unique characteristics of a study that started in 1948. Dr. Mercedes Carnethon: So, you know, we're almost 75 years in and actually has the ability that cross sectional studies don't have to look over longer periods of time at risk. And you know, when we think about papers that excite us, that we really want to feature in circulation, they are papers that teach us something new. And I will say there were aspects of this work that confirmed what I had heard but had not seen using empirical data. Namely that the remaining lifetime risks for developing cardiovascular disease were going down over time, and they were going down secondary to better management and recognition of the risk factors that the Framingham cohort study had really been instrumental in identifying in the first place. Dr. Mercedes Carnethon: There were surprising elements of the paper. The surprising elements being that I think as you brought up earlier, we were concerned that risk factors that were on the rise, such as obesity, were threatening these increases in life expectancy. And it was really nice to see that the findings held, even in the face of rising risk factors. And just to summarize, what I really like about this piece when we situate it within circulation, where we are addressing clinical treatment factors, where we're also featuring clinical trials and even other epidemiologic studies, is that your work identifies for us the overall context in which the clinicians who read the journal are thinking about managing patients and where we're going. It highlights our successes, but it also really brings up what we need to do next. And I look forward to hearing from you about where you think this may be headed. Dr. Greg Hundley: Well, Mercy, you're teeing us up for that next question. Vasan, what do you think is the next study or studies that need to be performed in this space? Dr. Vasan Ramachandran: Thank you, Greg and Mercy, for your kind comments. Like I shared, this is a success story for a predominantly white population in the Northeast. We are very much aware about the heterogeneity and the geographic variation in heart disease burden in our country. So one of the success stories interpretation might be this represents the upper bound. What can happen to a population that is compliant with screening of risk factors, awareness of risk factors, treatment and healthcare access. I think the next set of studies should broaden the study population to bring in additional populations that are more diverse, that are also followed up over a period of time to assess and put the current observations in the appropriate context. Do we see similar findings longitudinally in other cohorts with non-white participants? Is it different, is their lived experience different? If so, why? And that could inform us how we can reach the success story and replicate it across the entirety of our country. Dr. Greg Hundley: And Mercy, do you have anything to add? Dr. Mercedes Carnethon: I do. You know, I really like that focus on broadening to whom these results are applicable. We've undergone a lot of shifts within our country and also around the world. You know, circulation, we have a worldwide readership. I would love to see this sort of work replicated across different countries to the extent that we have the data to do so, recognizing that limitation. But I'd love to see work focus on comparing how these things change in low income countries, middle income and high income countries, so that we can really think about resource allocation and find strategies to try to replicate the successes that we are seeing based on the data from the Framingham heart and offspring studies. Dr. Greg Hundley: Excellent. Well listeners, we really appreciate the opportunity to get together today with Dr. Vasan Ramachandran from Boston University and our own Associate Editor, Dr. Mercedes Carnethon from Northwestern University in Chicago. And really appreciate them for bringing us these epidemiologic data from the Framingham cohort, indicating that over the past decades, mean life expectancy increased and the remaining lifetime risk of atherosclerotic cardiovascular disease decreased across individuals in the cohort, even after accounting for increasing incidences of other cardiovascular risk factors like obesity and smoking. Well on behalf of Carolyn and myself, we want to wish you a great week and we will catch you next week on the run. Dr. Greg Hundley This program is copyright of the American Heart Association, 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit ahajournals.org.

Research shows that dieting is not only ineffective but detrimental to our health. So diet culture has rebranded itself under the guise of a ‘healthy lifestyle'. But the underlying message is still that thinness is best no matter the cost. This has created a culture of demonizing certain foods, elevating others, and making the pursuit of health a matter of moral virtue.In this week's episode, I'll give you a perspective on healthy eating that you may not have considered before. I hope that what I share with you today will help you realize that health is a spectrum, and that it looks different for every person every day.What you'll learn in the episode: You'll learn:The uncommonly known eating disorder, orthorexiaThe negative effects of being health obsessedHow to look at health from a big-picture perspectiveMentioned on the show: “Eating Disorders on the College Campus.” National Eating Disorders Association, Feb. 2013.Arcelus, Jon et al. “Mortality rates in patients with anorexia nervosa and other eating disorders. A meta-analysis of 36 studies.” Archives of general psychiatry 68,7 (2011): 724-31. https://doi.org/10.1001/archgenpsychiatry.2011.74Dulloo AG, Jacquet J, Montani JP, Schutz Y. How dieting makes the lean fatter: from a perspective of body composition autoregulation through adipostats and proteinstats awaiting discovery. Obes Rev. 2015 Feb;16 Suppl 1:25-35. doi: 10.1111/obr.12253. PMID: 25614201.Faidon Magkos, On adaptive thermogenesis: just another weight-loss tale?, The American Journal of Clinical Nutrition, Volume 112, Issue 5, November 2020, Pages 1157–1159, https://doi.org/10.1093/ajcn/nqaa262Chao, Ariana M et al. “Food cravings, binge eating, and eating disorder psychopathology: Exploring the moderating roles of gender and race.” Eating behaviors vol. 21 (2016): 41-7. doi:10.1016/j.eatbeh.2015.12.007Mahmood, S. S., Levy, D., Vasan, R. S., & Wang, T. J. (2014). The Framingham Heart Study and the epidemiology of cardiovascular disease: a historical perspective. Lancet (London, England), 383(9921), 999–1008. https://doi.org/10.1016/S0140-6736(13)61752-3Herbert BM, Blechert J, Hautzinger M, Matthias E, Herbert C. Intuitive eating is associated with interoceptive sensitivity. Effects on body mass index. Appetite. 2013 Nov;70:22-30. doi: 10.1016/j.appet.2013.06.082. Epub 2013 Jun 26. PMID: 23811348.Blomain, E. S., Dirhan, D. A., Valentino, M. A., Kim, G. W., & Waldman, S. A. (2013). Mechanisms of Weight Regain following Weight Loss. ISRN obesity, 2013, 210524. https://doi.org/10.1155/2013/210524Get my free guide 5 Ways to Feel Secure, Confident & Empowered (without obsessing about food & your body)

Friends Shannon, Sophie, and Steven talk about the science behind, well, them. They discuss the data of friendships and how we perceive them, the science of what brings people together, and how seeing your pals could actually help you live longer. Ever wonder why you and your friend love the same song, movie, or fast casual salad? They get into that too. So tell a pal and join your virtual friends as we discuss everything friendship! Follow us on Instagram @thescienceofselfcare, and if you like the show, support us through Patreon at www.patreon.com/scienceofselfcare. Episode citations: You Might Actually Be In Love With Your Best Friend, The Cut Podcast, February 10 2021 Zerubavel, N., Bearman, P. S., Weber, J., & Ochsner, K. N. (2015). Neural mechanisms tracking popularity in real-world social networks. Proceedings of the National Academy of Sciences of the United States of America, 112(49), 15072–15077. https://doi.org/10.1073/pnas.1511477112 Parkinson, C., Kleinbaum, A.M. & Wheatley, T. Similar neural responses predict friendship. Nat Commun 9, 332 (2018). https://doi.org/10.1038/s41467-017-02722-7 The Future Friendship Machine, NPR: https://www.npr.org/2019/12/06/785523942/video-the-future-friendship-machine Ellen Peters, J. Marianne Riksen-Walraven, Antonius H. N. Cillessen, Carolina de Weerth. Peer Rejection and HPA Activity in Middle Childhood: Friendship Makes a Difference. Child Development, 2011; DOI: 10.1111/j.1467-8624.2011.01647.x Trudel-Fitzgerald, C., Zevon, E. S., Kawachi, I., Tucker-Seeley, R. D., Grodstein, F., & Kubzansky, L. D. (2020). The Prospective Association of Social Integration With Life Span and Exceptional Longevity in Women. The journals of gerontology. Series B, Psychological sciences and social sciences, 75(10), 2132–2141. https://doi.org/10.1093/geronb/gbz116 Graham, A. L., Zhao, K., Papandonatos, G. D., Erar, B., Wang, X., Amato, M. S., Cha, S., Cohn, A. M., & Pearson, J. L. (2017). A prospective examination of online social network dynamics and smoking cessation. PloS one, 12(8), e0183655. https://doi.org/10.1371/journal.pone.0183655 Fowler, J. H., & Christakis, N. A. (2008). Dynamic spread of happiness in a large social network: longitudinal analysis over 20 years in the Framingham Heart Study. BMJ (Clinical research ed.), 337, a2338. https://doi.org/10.1136/bmj.a2338