Podcasts about racial differences

In this episode, we explore the critical role nurses play in advancing health equity within the ICU. Jennifer Adamski, president of the American Association of Critical-Care Nurses, shares insights on how nurses can make a difference at the bedside and the challenges they face. We also discuss strategies for empowering nurses and fostering a culture of equity in critical care.This episode is sponsored by Medtronic.Areia C, King E, Ede J, Young L, Tarassenko L, Watkinson P, Vollam S. Experiences of current vital signs monitoring practices and views of wearable monitoring: A qualitative study in patients and nurses. Journal of advanced nursing. 2022 Mar;78(3):810-22Williams EC, Polito V. Meditation in the Workplace: Does Mindfulness Reduce Bias and Increase Organisational Citizenship Behaviours? Front Psychol. 2022 Apr 11;13:747983. doi: 10.3389/fpsyg.2022.747983. PMID: 35478759; PMCID: PMC9035788.Lewis CL, Yan A, Williams MY, Apen LV, Crawford CL, Morse L, Valdez AM, Alexander GR, Grant E, Valderama-Wallace C, Beatty D. Health equity: A concept analysis. Nurs Outlook. 2023 Sep-Oct;71(5):102032. doi: 10.1016/j.outlook.2023.102032. Epub 2023 Sep 6. PMID: 37683597.Bhavani SV, Wiley Z, Verhoef PA, Coopersmith CM, Ofotokun I. Racial Differences in Detection of Fever Using Temporal vs Oral Temperature Measurements in Hospitalized Patients. JAMA. 2022;328(9):885–886. doi:10.1001/jama.2022.12290P Malhotra, L Shaw, J Barnett, E Hayter, N Hill, P Stockton. St Helens and Knowsley. P179 Patient safety alert: a prospective study on 100 patients highlighting inaccuracy of pulse oximeter finger probes used on ear lobes. Teaching Hospitals NHS Trust, Prescot, UK. 10.1136/thorax-2018-212555.336Torp KD, Modi P, Pollard EJ, Simon LV. Pulse Oximetry. 2023 Jul 30. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 29262014Nitzan M, Romem A, Koppel R. Pulse oximetry: fundamentals and technology update. Med Devices (Auckl). 2014 Jul 8;7:231-9. doi: 10.2147/MDER.S47319. PMID: 25031547; PMCID: PMC4099100Giuliano KK, Bilkovski RN, Beard J, Lamminmäki S. Comparative analysis of signal accuracy of three SpO2 monitors during motion and low perfusion conditions. J Clin Monit Comput. 2023 Dec;37(6):1451-1461. doi: 10.1007/s10877-023-01029-x. Epub 2023 Jun 2. PMID: 37266709; PMCID: PMC10651546Gudelunas MK, Lipnick M, Hendrickson C, et al. Low Perfusion and Missed Diagnosis of Hypoxemia by Pulse Oximetry in Darkly Pigmented Skin: A Prospective Study. Anesth Analg. 2024;138(3):552-561. doi:10.1213/ANE.0000000000006755

When we talk about C-sections, it's often prefaced with “unplanned” or “emergency.” About a third of all the deliveries in the U.S. are cesarean sections, and only about 16% of those are planned. And that leaves a lot of mothers in a position where they're delivering differently than they planned or intended to. And in the U.S., a disproportionate number of those are being performed on black women. So how are we going to get to the root of what's going on? Today on ParentData, we're joined by Molly Schnell, whose paper “Drivers of Racial Differences in C-Sections” explores this phenomenon. Molly is an assistant professor of economics at Northwestern University and her paper found that black mothers with unscheduled deliveries are 25% more likely to deliver by C-section than white mothers. And she argues that implicit racial bias among providers or possibly even a financial incentive in hospitals to fill their operating rooms may play a role in this racial gap.Subscribe to ParentData.org for free access to new articles every week on data-driven pregnancy and parenting.ParentData is generously supported by Honeycomb.

America's Town Meeting of the Air was a public affairs discussion program which began on NBC radio's Blue Network in 1935 and ran for 21 years. It was one of radio's first talk shows, and NBC did not expect it to become a success, but it did, and eventually picked up a sponsor. Each week moderator George Denny Jr presided over an examination of a controversial issue with a large audience present and participating in the discussion. We're going to hear America's Town Meeting of the Air on November 16, 1939. The topic is, Should We ignore Racial Differences? More at KRobCollection.com

His research on police brutality and school incentives won him acclaim, but also enemies. He was suspended for two years by Harvard, during which time he took a hard look at corporate diversity programs. As a follow-up to our recent series on the Rooney Rule, we revisit our 2022 conversation with the controversial economist. SOURCE:Roland Fryer, professor of economics at Harvard University. RESOURCES:"How to Make Up the Covid Learning Loss," by Roland Fryer (Wall Street Journal, 2022)."Roland Fryer on Better Alternatives to Defunding the Police," by Roland Fryer (The Economist, 2020)."Harvard Suspends Roland Fryer, Star Economist, After Sexual Harassment Claims," by Ben Casselman and Jim Tankersley (The New York Times, 2019)."Why Diversity Programs Fail: And What Works Better," by Frank Dobbin and Alexandra Kalev (Harvard Business Review, 2016)."An Empirical Analysis of Racial Differences in Police Use of Force," by Roland G. Fryer, Jr (NBER Working Paper, 2016)."Getting Beneath the Veil of Effective Schools: Evidence from New York City," by Will Dobbie and Roland G. Fryer (American Economics Journal, 2013)."Financial Incentives and Student Achievement: Evidence From Randomized Trials," by Roland G. Fryer (The Quarterly Journal of Economics, 2011)."Toward a Unified Theory of Black America," by Stephen J. Dubner (The New York Times, 2005).Equal Opportunity Ventures.Intus Care.Reconstruction.Sigma Squared. EXTRAS:"Did the N.F.L. Solve Diversity Hiring?" series by Freakonomics Radio (2024)."The True Story of the Gender Pay Gap," by Freakonomics Radio (2016)."Does “Early Education” Come Way Too Late?" by Freakonomics Radio (2015).

Audio Commentary by Dr. Valentin Fuster, Emeritus Editor in Chief

Nathan Cofnas argues that distinct populations have developed specific cognitive abilities due to varying environmental challenges. The conversation explores the definition and validity of racial categorization from a biological perspective, addressing whether certain physical and cognitive differences among races have a genetic basis. Nathan argues that acknowledging these differences does not necessitate negative social implications but rather an honest recognition of human biodiversity. The dialogue delves into the controversy surrounding race realism in academia, including censorship, accusations of racism, and the consequences of denying or accepting biological differences among races. [00:00] Introduction to Race Realism Discussion [00:27] Exploring Human Evolution and Genetic Diversity [02:52] Debating the Reality and Definitions of Race [06:16] The Semantic vs. Metaphysical Nature of Race [12:53] Genetics, Intelligence, and Race [27:26] Addressing Criticisms and Misunderstandings [37:22] Social Implications and Policies on Racial Differences [39:27] The End of Wokeism and the Future of Society [40:14] Quotas and Representation: Navigating the Complexities [41:37] The Role of Environment in Intelligence [46:32] Race, Genetics, and Intelligence: A Controversial Intersection [56:58] The Political and Social Implications of IQ and Race Research [01:06:06] Navigating Academic Freedom and Controversy --- Send in a voice message: https://podcasters.spotify.com/pod/show/braininavat/message

Dr. Bhatt is an integrative veterinarian who received her Doctor of Veterinary Medicine in 2009 from the University of Illinois College of Veterinary Medicine. She became Certified in Acupuncture (CVA) through the Chi Institute of Traditional Chinese Veterinary Medicine. She is also certified in Level II Reiki and Chiropractic / Manipulation. In addition, Dr. Bhatt has served on the Board of Directors for the Chicago Veterinary Medical Association. Dr. Bhatt's medical care philosophy involves finding the appropriate balance between both Western and Eastern therapy options through her house call practice and clinic, Arya Animal Acupuncture. When not involved in veterinary medicine, she engages her artistic side with dance and is playfully referred to as "Dr. Dancer". Topics covered in this episode: Dr. Bhatt's perspectives & experiences with issues of diversity, equity, & inclusion in veterinary medicine  Honoring our religious, ethnic, cultural, & racial differences  Curiosity, connection, & respect over righteousness  Collaboration & support between mobile vets Links and Resources: Visit the Arya Animal Acupuncture - Specialty Integrative Veterinary Medicine website to learn more about Dr. Bhatt Find Arya Animal Acupuncture on Facebook Find Arya Animal Acupuncture on Instagram The House Call Vet Academy links: Find out about The House Call Vet Academy online CE course  Learn more about Dr. Eve Harrison  Learn more about 1-to-1 coaching for current & prospective house call, mobile, & concierge vets Get House Call Vet swag! Find out about the next House Call & Mobile Vet Virtual Conference Music: In loving memory of Dr. Steve Weinberg. Intro and outro guitar music was written, performed, and recorded by house call veterinarian Dr. Steve Weinberg. Thank you to our sponsors! Chronos O3 Vets Rekindling w/ Julie Squires This podcast is also available in video on our House Call Vet Cafe YouTube channel  

Do you want to live to 100? Dietary patterns, community, environment, and stress management play pivotal roles in longevity. From Sardinia's matriarchal villages to Okinawa's garden-rich diets, this episode takes us on a tour of insights. It's not just about living longer, it's about thriving.In today's episode, Jonathan is joined by Dan Buettner and Prof. Tim Spector to discuss the secrets of a longer, healthier life. Together, they journey through the world's blue zones, rare global hotspots where celebrating your 100th birthday is common. The guests also address the threats to these longevity havens and the decline of traditional diets.Dan Buettner is an American National Geographic fellow and New York Times bestselling author. He's also an explorer, educator, and creator of the Netflix series “Live to 100,” which discovers five unique communities where people live extraordinarily long and vibrant lives.Tim Spector is a professor of genetic epidemiology at King's College London, director of the Twins UK study, scientific co-founder of ZOE, and one of the world's leading researchers. He's also the author of Food for Life, his latest book on nutrition and health.If you want to uncover the right foods for your body, head to zoe.com/podcast, and get 10% off your personalized nutrition program.Gut health tips from ZOE Science & Nutrition: Download our FREE gut guide.Follow ZOE on Instagram.Timecodes:00:00 Introduction01:09 Quickfire questions02:33 What are Blue Zones?04:43 Why do people in Blue Zones live longer?06:48 What is a Centenarian?09:00 What are Blue Zone diets?11:49 Foods for longevity15:03 Why are these foods good for us?19:15 Why Blue Zone diets are seasonal and inexpensive 22:30 Is eating meat 5 times a month healthy for us?27:42 Why are the Blue Zones disappearing?31:25 Blue Zone tactics to reduce stress36:02 Can stress reduce life expectancy?40:36 Why unconscious physical activity is best45:07 How can we make our lives more ‘Blue Zone' like?47:23 The number one thing you can do to add years to your life is…48:53 Dan's stress reduction techniques51:39 What is Dan's daily diet?53:16 SummaryMentioned in today's episode:Telomere shortening and the transition to family caregiving in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study from PLOS OneBooks and series from Dan Buettner:The Blue Zones Challenge: A 4-Week Plan for a Longer, Better LifeThe Blue Zones Secrets for Living Longer: Lessons From the Healthiest Places on Earth

In the second installment of this interview, Fae and I discuss racial differences in the kink and fetish communities. We also talk about the judgement that those in various kink and fetish communities can receive. Fae Thin Links: https://www.fae-thin.com/⁠ ⁠https://www.tiktok.com/@mynameis_fae⁠ ⁠https://www.instagram.com/fae.thin --- Support this podcast: https://podcasters.spotify.com/pod/show/1morethingwsologreen/support

Jim talks with Yascha Mounk about the ideas in his new book The Identity Trap: A Story of Ideas and Power. They discuss tribalism among progressives, universalism, the story of Kila Posey, how over-emphasizing ethnic identity fosters zero-sum racial conflicts, how identitarianism led to excess Covid deaths, Foucault's rejection of grand narratives, Edward Said's post-colonialism, Gayatri Spivak's strategic essentialism, being blind to race vs being blind to racism, critical race theory, Derrick Bell's idea of the permanence of racism, how the rejection of universalism escaped college campuses, why progressive organizations are tearing themselves apart, the logic of collective action, how progressive activists have passed off their ideas as those of all non-white people, statistics on police violence, Frederick Douglass's 4th of July speech, cultural appropriation, retaining trust in persuasion, fighting for liberalism, personal & political aspects of the identity trap, and much more. Episode Transcript The Identity Trap: A Story of Ideas and Power, by Yascha Mounk "Why the Latest Campus Cancellation Is Different," by Yascha Mounk JRS EP197 - Susan Neiman on Why Left Is Not Woke "A Political Analysis of Racial Differences in Police Use of Force," by Roland Fryer, Jr. Yascha Mounk is a writer and academic known for his work on the rise of populism and the crisis of liberal democracy. Born in Germany to Polish parents, Mounk received his BA in history from Trinity College Cambridge, and his PhD in government from Harvard University. He is a professor of the practice of international affairs at Johns Hopkins University, the founder of the digital magazine Persuasion, a contributing editor at The Atlantic, host of the podcast “The Good Fight,” a senior fellow at the Council on Foreign Relations, and the author of The Great Experiment and The Identity Trap.

To be a Christian is not only to trust Christ and treasure Christ, but to be indwelt by Christ. And that new identity transforms all our relationships.This show is part of the Spreaker Prime Network, if you are interested in advertising on this podcast, contact us at https://www.spreaker.com/show/3279340/advertisement

To be a Christian is not only to trust Christ and treasure Christ, but to be indwelt by Christ. And that new identity transforms all our relationships.This show is part of the Spreaker Prime Network, if you are interested in advertising on this podcast, contact us at https://www.spreaker.com/show/3279343/advertisement

To be a Christian is not only to trust Christ and treasure Christ, but to be indwelt by Christ. And that new identity transforms all our relationships.This show is part of the Spreaker Prime Network, if you are interested in advertising on this podcast, contact us at https://www.spreaker.com/show/4231678/advertisement

To be a Christian is not only to trust Christ and treasure Christ, but to be indwelt by Christ. And that new identity transforms all our relationships.This show is part of the Spreaker Prime Network, if you are interested in advertising on this podcast, contact us at https://www.spreaker.com/show/3485657/advertisement

https://youtu.be/2nLWCLsmpJ4 On the most extreme use of force – officer-involved shootings – we find no racial differences in either the raw data or when contextual factors are taken into account. We argue that the patterns in the data are consistent with a model in which police officers are utility maximizers, a fraction of which have a preference for discrimination, who incur relatively high expected costs of officer-involved shootings. - Roland G. Fryer J. An Empirical Analysis of Racial Differences in Police Use of Force. Journal of Political Economy. Forthcoming. Watch on Odysee

Justin Holz talks about peer effects in police use of force. “Peer Effects in Police Use of Force” by Justin E. Holz, Roman G. Rivera, and Bocar A. Ba. *** Probable Causation is part of Doleac Initiatives, a 501(c)(3) nonprofit. If you enjoy the show, please consider making a tax-deductible contribution. Thank you for supporting our work! *** OTHER RESEARCH WE DISCUSS IN THIS EPISODE: “The Effect of Field Training Officers on Police Use of Force” by Chandon Adger, Mathew Ross, and CarlyWill Sloan. Probable Causation Episode 90: Matthew Ross. “Does Race Matter for Police Use of Force? Evidence from 911 Calls” by Mark Hoekstra and CarlyWill Sloan. Probable Causation Episode 38: CarlyWill Sloan. “An Empirical Analysis of Racial Differences in Police Use of Force” by Roland G. Fryer Jr. “An Empirical Analysis of Racial Differences in Police Use of Force: A Comment” by Steven N. Durlauf and James J. Heckman. “Wearing Body Cameras Increases Assaults Against Officers and Does Not Reduce Police Use of Force: Results from a Global Multi-site Experiment” By Barak Ariel, Alex Sutherland, Darren Penstock, Josh Young, Paul Drove, Jayne Sykes, Simon Megicks, and Ryan Henderson. “The “Less-Than-Lethal Weapons Effect”- Introducing TASERs to Routine Operations in England and Wales: A Randomized Controlled Trial” by Barak Ariel, David Lawes, Cristobal Weinborn, Ron Henry, Kevin Chen, and Hagit Brants Sabo. “American Policing and the Danger Imperative” by Michael Sierra-Arevalo. “Racial Profiling and Use of Force in Police Stops: How Local Events Trigger Periods of Increased Discrimination” by Joscha Legewie. “Violence and Risk Preference: Experimental Evidence from Afghanistan” by Michael Callen, Mohammad Isaqzadeh, James D. Long, and Charles Sprenger. “Exposure to Violence Predicts Impulsivity in Time Preferences: Evidence from The Democratic Republic of Congo” by Alex Imas, Michael Kuhn, and Vera Mironova. [Working Paper]. “Violence, Psychological Trauma, and Risk Attitudes: Evidence from Victims of Violence in Colombia” by Andrés Moya. “Impact of Violent Crime on Risk Aversion: Evidence from the Mexican Drug War” by Ryan Brown, Verónica Montalva, Duncan Thomas, and Andrea Velásquez. Probable Causation Episode 42: Andrea Velásquez. “Family Violence and Football: The Effect of Unexpected Emotional Cues on Violence Behavior” by David Card and Gordon B. Dahl. “Frustration, Euphoria, and Violent Crime” by Ignacio Munyo and Martin A. Rossi. “Emotional Judges and Unlucky Juveniles” by Ozkan Eren and Naci Mocan. “Nonfatal Injuries to Law Enforcement Officers: A Rise in Assaults” by Hope M. Tiesman, Melody Gwilliam, Srinivas Konda, Jeff Rojek, and Suzanne Marsh. “Emotional Reactivity and Police Expertise in Use-of-Force Decision-Making” by Vivian Ta, Brian Lande, and Joel Suss. “Do Police Make Too Many Arrests?: The Effect of Enforcement Pullbacks on Crime” by Sungwoo Cho, Felipe Conclaves, and Emily Weisburst. “The Effect of Minority Peers on Future Arrests Quantity and Quality” by Roman Rivera. “Police Officer Assignment and Neighborhood Crime” by Bocar Ba, Patrick Bayer, Nayoung Rim, Roman Rivera, and Modibo Sidibé. “Strengthening Police Oversight: Impacts of Misconduct Investigators on Police Officer Behavior” by Andrew Jordan and Taeho Kim. “Does Black and Blue Matter? An Experimental Investigation of Race and Perceptions of Police, and Legal Compliance” by Mackenzie Alston and Emily Owens. “High-Frequency Location Data Shows that Race Affects the Likelihood of Being Stopped and Fined for Speeding” by Pradhi Aggarwal, Alec Brandon, Ariel Goldszmidt, Justin Holz, John A. List, Ian Muir, Greg Sun, and Thomas Yu.

New research finds minorities are 24-33% more likely to be stopped for speeding and will pay 23-34% more in fines, relative to a white driver traveling the exact same speed. UChicago economists John List and Justin Holz join The Pie to discuss how they designed research drawing on high-frequency Lyft data, and its broader implications for future research and policy.

Ep. 91 ✨ “Being Insatiable, Foster Parenting, & RIP Takeoff” Topics: -1 RIP Takeoff- Was It Karma? 00:00-3:35 2 Cutting Family Members Off 3:38-12:12 3 Racial Differences in College and Marrying Young 12:13-18:12 4 Pressure of finding a partner as you get older 18:14-21:02 5 Foster Parenting 21:07-27:17 6 Educational Leadership 27-18-39:35 7 Doubt from employers 39:37-42:30 8 Jasmine wrote a book! 42:31-50:25 9 Being Insatiable in life and love 50:26-59:36 10 supporting your friends 59:37-1:03!^ Listen

Hypertension (elevated blood pressure) is a condition that significantly increases the risk of several diseases and is a major cause of premature death worldwide. In the US, recent estimates suggest that about half of the adult population has hypertension. At a population level, high sodium intake is one of the main dietary risk factors. All population health guidelines recommend keeping sodium intake below certain levels. While, on average, blood pressure correlates with sodium intake, there is a wide range of responses on an individual level. People who see increasing sodium intake lead to increased blood pressure are termed “salt sensitive”. Others, however, don't see much change in blood pressure with increased dietary sodium. Such individuals are classed as “salt resistant”. In this episode, Assistant Professor at Auburn University, Dr. Austin Robinson, is on to discuss whether people who are salt resistant need to keep their sodium intake low or not. And other individual and group differences that exist for hypertension risk and sodium physiology? Links: Subscribe to Premium Episode overview Live event in Berlin Recommended Resources

The Caribbean Radio Show the Chat Reel will be interviewing Patrick Dix on the racial makeup of African Americans (Blacks) and Hispanics (Mexicans) The differences in culture and race. This is a cultural and Archelogical topic . Patrick Dix offers a wealth of information on the cultural exchange.  If you would like to be a supporter of  The Black Jewish Queen Live Chat or the Chat Reel with Billy and Friends you can send your monetary donations through: paypal.me/psychotherapycheckou To support the shoe donations. Contact givebackjamaica@gmail.com or go to webpage www.givebackjamaica.org

Today's ID the Future spotlights Darwinian racism, past and present. In this first half of a panel discussion at the 2022 Center for Science and Culture Insider's Briefing, Darwin Day in America author John West introduces the other panel members, teases an upcoming book, Darwin Comes to Africa, and discusses his experience visiting the Museum of Criminal Anthropology in Turin, Italy, where the work of infamous Darwinian criminologist Cesare Lombroso's racist ideas about evolution and race are on dramatic display. Then historian Richard Weikart, author of Darwinian Racism, debunks the popular media claim that white nationalist racism in America is a Southern evangelical phenomenon. Weikart shows that the most prominent white nationalists show little if any interest in promoting Christianity, Read More › Source

This month on Episode 40 of Discover CircRes, host Cynthia St. Hilaire highlights four original research articles featured in the September 2 and September 16 issues of the journal. This episode also features an interview with Dr Jun Yoshioka, and Dr Yoshinobu Nakayama, from the City University of New York, about their study, Interaction of ARRDC-4 with GLUT1 Mediates Metabolic Stress in the Ischemic Heart.   Article highlights:   Jin, et al. Gut Dysbiosis Promotes Preeclampsia   Mengozzi, et al. SIRT1 in Human Microvascular Dysfunction   Hu, et al. Racial Differences in Metabolomic Profiles and CHD   Garcia-Gonzales, et al. IRF7 Mediates Autoinflammation in Absence of ADAR1   Cindy St. Hilaire:        Hi, and welcome to Discover CircRes, the podcast of the American Heart Association's journal, Circulation Research. I'm your host, Dr Cindy St. Hilaire from the Vascular Medicine Institute at the University of Pittsburgh. And today I'm going to be highlighting some articles from September 2nd, and September 16th issues of CircRes. And I'm also going to have a conversation with Dr Jun Yoshioka, and Dr Yoshinobu Nakayama, from the City University of New York, about their study, Interaction of ARRDC-4 with GLUT1 Mediates Metabolic Stress in the Ischemic Heart. But, before I get to the interview, I'm going to highlight a few articles.                                       The first article is from our September 2nd issue, and it's titled, Gut Dysbiosis Promotes Preeclampsia by Regulating Macrophages, and Trophoblasts. The first author is Jiajia Jin, and the corresponding author is Qunye Zhang from the Chinese National Health Commission.                                       Preeclampsia is a late-stage pregnancy complication that can be fatal to the mother, and the baby. It's characterized by high blood pressure, and protein in the urine. The cause is unknown, but evidence suggests the involvement of inflammation, and impaired placental blood supply. Because gut dysbiosis can influence blood pressure, and inflammation has been observed in preeclamptic patients, Jin and colleagues examined this link more closely. They found that women with preeclampsia had altered gut microbiome. Specifically, a reduction in a species of bacteria that produced short-chain fatty acids, and lower short-chain fatty acid levels in their feces, in their serum, and in their placentas. And preeclamptic women had lower short-chain fatty acid levels in their feces, in their serum, and in their placentas compared with women without preeclampsia.                                       They found that fecal transfers from the preeclampsia women to rats with a form of the condition exacerbated the animals' preeclampsia symptoms, while fecal transfers from control humans alleviated the symptoms. Furthermore, giving rats an oral dose of short-chain fatty acids or short-chain fatty acid producing bacteria decreased the animals' blood pressure, reduced placental inflammation, and improved placental function. This work suggests that short-chain fatty acids, and gut microbiomes could be a diagnostic marker for preeclampsia. And microbial manipulations may even alleviate the condition.                                       The second article I want to share is also from our September 2nd issue, and it's titled, Targeting SIRT1 Rescues Age and Obesity-Induced Microvascular Dysfunction in Ex Vivo Human Vessels. And this study was led by Alessandro Mengozzi from University of Pisa.                                       With age, the endothelial lining of blood vessels can lose its ability to control vasodilation, causing the vessel to narrow and reduce blood flow. This decline in endothelial function has been associated with age related decrease in the levels of the enzyme, SIRT1. And artificially elevating SIRT1 in old mice improves animals' endothelial function. Obesity, which accelerates endothelial dysfunction, is also linked to low SIRT1 levels.                                       In light of these SIRT1 findings, Mengozzi, and colleagues examined whether increasing the enzyme's activity could improve the function of human blood vessels. The team collected subcutaneous microvessels from 27 young, and 28 old donors. And both age groups included obese, and non-obese individuals. SIRT1 levels in the tissue were, as expected, negatively correlated with age and obesity, and positively correlated with baseline endothelium dependent vasodilatory function. Importantly, incubating tissue samples from older, and obese individuals with a SIRT1 agonist, restored the vessel's vasodilatory functions. This restoration involved a SIRT1 induced boost to mitochondrial function, suggesting that maintaining SIRT1 or its metabolic effect might be a strategy for preserving vascular health in aging, and in obesity.                                       The third article I want to share is from our September 16th issue. And this one is titled, Differences in Metabolomic Profiles Between Black And White Women and Risk of Coronary Heart Disease. The first author is Jie Hu, and the corresponding author is Kathryn Rexrode, and they're from Brigham and Women's Hospital, and Harvard University.                                       In the US, coronary heart disease, and coronary heart disease-related morbidity, and mortality is more prevalent among black women than white women. While racial differences in coronary heart disease risk factors, and socioeconomic status have been blamed, this group argues that these differences alone cannot fully explain the disparity. Metabolomic variation, independent of race, has been linked to coronary heart disease risk. Furthermore, because a person's metabolome is influenced by genetics, diet, lifestyle, environment and more, the authors say that it reflects accumulation of many cultural, and biological factors that may differ by race.                                       This group posited that if racial metabolomic differences are found to exist, then they might partially account for differences in coronary heart disease risk. This study utilized plasma samples from nearly 2000 black women, and more than 4500 white women from several different cohorts. The team identified a racial difference metabolomic pattern, or RDMP, consisting of 52 metabolites that were significantly different between black, and white women. This RDMP was strongly linked to coronary heart disease risk, independent of race, and known coronary heart disease risk factors. Thus, in addition to socioeconomic factors, such as access to healthcare, this study shows that racial metabolomic differences may underlie the coronary heart disease risk disparity.                                       The last article I want to share is also from our September 16th issue, and it is titled, ADAR1 Prevents Autoinflammatory Processes in The Heart Mediated by IRF7. The first author is Claudia Garcia-Gonzalez, and the corresponding author is Thomas Braun, and they are from Max Planck University.                                       It's essential for a cell to distinguish their own RNA from the RNA of an invading virus to avoid triggering immune responses inappropriately. To that end, each cell makes modifications, and edits its own RNA to mark it as self. One type of edit made to certain RNAs is the conversion of adenosines to inosines. And this is carried out by adenosine deaminase acting on RNA1 or ADAR1 protein. Complete loss of this enzyme causes strong innate immune auto reactivity, and is lethal to mice before birth. Interestingly, the effects of ADAR1 loss in specific tissues is thought to vary. And the effect in heart cells in particular has not been examined.                                     This study, which focused on the heart, discovered that mice lacking ADAR1 activity specifically in cardiomyocytes, exhibit autoinflammatory myocarditis that led to cardiomyopathy. However, the immune reaction was not as potent as in other cells lacking ADAR1. Cardiomyocytes did not exhibit the sort of upsurge in inflammatory cytokines, and apoptotic factors seen in other cells lacking ADAR1. And the animals themselves did not succumb to heart failure until 30 weeks of age. The author suggests that this milder reaction may ensure the heart resists apoptosis, and inflammatory damage because, unlike some other organs, it cannot readily replace cells.   Cindy St. Hilaire:        Today I have with me, Dr Jun Yoshioka, and Dr Yoshinobu Nakayama, and they're from City University of New York. And today we're going to talk about their paper, Interaction of ARRDC4 With GLUT1 Mediates Metabolic Stress in The Ischemic Heart. And this is in our September 2nd issue of Circulation Research. So, thank you both so much for joining me today.   Jun Yoshioka:             Thank you for having us. We are very excited to be here.   Cindy St. Hilaire:        It's a great publication, and also had some really great pictures in it. So, I'm really excited to discuss it. So, this paper really kind of focuses on ischemia, and the remodeling in the heart that happens after an ischemic event. And for anyone who's not familiar, ischemia is a condition where blood flow, and thus oxygen, is restricted to a particular part of the body. And in the heart, this restriction often occurs after myocardial infarctions, also called heart attacks. And so, cardiomyocytes, they require a lot of energy for contraction, and kind of their basic functions. And in response to this lack of oxygen, cardiomyocytes switch their energy production substrate. And so, I'm wondering if before we start talking about your paper, you can just talk about the metabolic switch that happens in a cardiac myocyte in the healthy state versus in the ischemic state.   Jun Yoshioka:             Sure. As you just said, that the heart never stops beating throughout the life. And it's one of the most energy demanding organs in the body. So, under normal conditions, cardiac ATP is mainly derived from fatty acid oxidation, and glucose metabolism contributes a little bit less in adult cardiomyocytes. However, under stress conditions such as ischemia, glucose uptake will become more critical when oxidative metabolism is interrupted by a lack of oxygen. That is because glycolysis is a primary anaerobic source of energy. We believe this metabolic adaptation is essential to preserve high energy phosphates and protect cardiomyocytes from lethal injuries. The concept of shifting the energy type of stress preference toward glucose, as you just said, has been actually long proposed as an effective therapy against MI. For example, GIK glucose insulin petition is classic.                                       Now, let me explain how glucose uptake is regulated. Glucose uptake is facilitated by multiple isophones of glucose transporters in cardiomyocytes. Mainly group one and group four, and the minor, with a minor contribution of more recently characterized STLT1. In this study, we were particularly interested in group one because group one is a basal glucose transporter.                                       Dr Ronglih Liao, and Dr Rong Tian's groups reported nearly two decades ago that the cardiac over-expression of group one prevents development of heart failure, and ischemic damage in mice. Since they are remarkable discoveries, the precise mechanism has not yet been investigated enough, at least to me. Especially how acute ischemic stress regulates group one function in cardiomyocytes. We felt that this mechanism is important because there is a potential to identify new strategies around group one, to reduce myocardiac ischemic damage. That is why we started this project hoping to review a new mechanism by which a protein family, called alpha-arrestins, controls cardiac metabolism under both normal, and diseased conditions.   Cindy St. Hilaire:        That is a perfect segue for my next question, actually, which is, you were focusing on this arrestin-fold protein, arrestin domain-containing protein four or ARRDC4. So, what is this family of proteins? What are arrestin-fold proteins? And before your study, what was known about a ARCCD4, and its relationship to metabolism, and I guess specifically cardiomyocyte metabolism?   Jun Yoshioka:             So, the arrestin mediated regulation of steroid signaling is actually common in cardiomyocytes. Especially beta, not the alpha, beta-arrestins have been well characterized as an adapter protein for beta-adrenergic receptors. Beta-arrestins combine to activate beta-adrenergic receptors on the plasma membrane, promote their endosomal recycling, and cause desensitization of beta-adrenergic signaling. Over the past decade, however, this family, the arrestin family, has been extended to include a new class of alpha-arrestins. But unlike beta-arrestins, the physiological functions of alpha-arrestins remain largely unclear based in mammalian cells. Humans, and mice have six members of alpha-arrestins including Txnip, thioredoxin interacting protein called Txnip, and five others named alpha domain-containing protein ARRDC1 2, 3, 4 and 5. Among them Txnip is the best studied alpha-arrestin. And Txnip is pretty much the only one shown to play a role in cardiac physiology.                                       Txnip was initially thought to connect alternative stress and metabolism. However, it is now known that the Txnip serves as an adapter protein for the endocytosis of group one, and group four to mediate acute suppression of glucose influx to cells. In fact, our group has previously shown that the Txnip knockout mice have an enhanced glucose uptake into the peripheral tissues, as well as into the heart. Now, in this study, our leading player is ARRDC4. The arrestin-domains of ARRDC4 have 42% amino acid sequence similarities to Txnip. This means that the structurally speaking ARRDC4 is a brother to Txnip. So, usually the functions of arrestins are expected to be related to their conserved arrestin-domains. So, we were wondering whether two brothers, Txnip, and ARRDC4, may share the same ability to inhibit the glucose transport. That was a starting point where we initiated this project.   Cindy St. Hilaire:        That's great. And so, this link between ARRDC4, and the cardiac expression of gluten one and gluten four, I guess, mostly gluten one related to your paper, that really wasn't known. You went about this question kind of based on protein homology. Is that correct?   Jun Yoshioka:             That is right.   Cindy St. Hilaire:        And so, ARRDC4 can modulate glucose levels in the cell by binding, and if I understand it right, kind of helping that internalization process of glute one. Which makes sense. You know, when you have glucose come into the cell, you don't want too much. So, the kind of endogenous mechanism is to shut it off, and this ARRDC4 helps do that. But you also found that this adapter protein impacts cellular stress, and the cellular stress response. So, I was wondering if you could share a little bit more about that because I thought that was quite interesting. It's not just the metabolic impact of regulating glucose. There's also this cellular stress response.   Jun Yoshioka:             Right? So, Txnip is known to induce oxidative stress. But about the ARRDC4, we found that ARRDC4 actually does not induce oxidative stress. Instead, we found that it reproducibly causes ER, stress rather than oxidative stress. So, let Yoshinobu talk about the ER stress part. Yoshinobu, can you talk about how you found the ER stress story?   Yoshinobu Nakayama: So, then let's talk about the, yeah, ER stress caused by ARRDC4. The ER stress caused by ARRDC4, year one was the biggest challenge in this study, because it's a little bit difficult to how we found a link of the glucose metabolism to the effect of the ARRDC4, only our stress. And at the other point of the project, we noticed that a ARRDC4 causes ER stress reproducibly, but we did not know how. So, both group one, and ARRDC4 are membrane proteins mainly localized near the plasma membrane. Then how does ARRDC4 regulate the biological process inside in the plasma radical? So, we then hypothesize that ARRDC4 induces intercellular glucose depravation by blocking cellular glucose uptake, and then interferes with protein glycosylation, thereby disturbing the ER apparatus. That makes sense because inhibition of group one trafficking by ARRDC4 was involved in the unfolded protein response in ischemic cardiomyocytes.   Cindy St. Hilaire:        So how difficult was that to figure out? How long did that take you?   Yoshinobu Nakayama: How long? Yeah. Is this the question?   Cindy St. Hilaire:        It's always a hard question.   Yoshinobu Nakayama: I think it's not several weeks. Maybe the monthly, months project. Yeah.   Cindy St. Hilaire:        Okay. It's always fun when, you know, you're focusing on one angle, and then all of a sudden you realize, oh, there's this whole other thing going on. So, I thought it was a really elegant tie-in between the metabolism, but also just the cellular stress levels. It was really nice.                                       So, you created a full body knockout of ARRDC4 in the mouse, and you did all the proper kind of phenotyping. And at baseline everything's normal, except there's a little bit of changes in the blood glucose levels. But I also noticed when you looked at the expression of ARRDC4 in different tissues, it was very high in the lungs, and also in the intestines. And so, I know your study didn't focus on those tissues, but I was wondering if you could possibly speculate what ARRDC4 is doing in those tissues? Is it something similar? Do those cells under stress have any particular metabolic switching that's similar?   Jun Yoshioka:             Well, actually we don't have any complete answer for that question, because like you said, we didn't focus on lung, and other tissues. But I could say that actually the brother of ARRDC4, Txnip, is also highly expressed in lung, and bronchus, and in those organs. So, it's interesting because, which means that, the molecule is very oxygen sensitive, I will say. Both brothers. But that's all we know for now. But that's a very great point. And then we are excited to, you know.   Cindy St. Hilaire.        Yeah.   Jun Yoshioka:             Move on to the other tissues.   Cindy St. Hilaire:        I was thinking about it just because I've actually recently reviewed some papers on pulmonary hypertension. So, when I saw that expression, that was the first thing I thought of was, oh, they should put these mice in a sugen/hypoxia model, and see what happens.   Jun Yoshioka:             Right?   Cindy St. Hilaire:        So, there's an idea for you, Yoshinobu. A K-99 grant or something. And also, because it's a full body knockout, even when you're looking at the heart, obviously the cardiomyocytes are really the most metabolically active cell, but cardiac fibroblasts are also a major component of the heart tissue. And so, do you know, is the, I guess, effects or the protectiveness of the ARRDC4 knockout heart, is it mostly because of the role in the cardiomyocytes or is there a role for it also in the fibroblast?   Yoshinobu Nakayama: Yeah, that's a very great question. Yeah. So, although we use the systemic knockout mice in the study, we believe that the beneficial effect of ARRDC4 deficiency is cardiac, autonomous. But this is because cardioprotection was demonstrated in the isolated heart experiments. But, you know, root is still uniformly expressing all cell types within the heart.                                       To address this, we have tested the specific effects of ARRDC4 on cardiac fibroblasts, and inflammatory cells. ARRDC4 knockout hearts had a twofold increase in myocardial glucose uptake over wild-type hearts during insulin-free perfusion. However, an increase in glucose uptake in isolated cardiac fibroblast or inflammatory cells was relatively mild, with about 1.2 fold increase over wild-type cells.                                       Thus we conclude that cardiomyocytes are the measure contributed to the cardiac metabolic shift. And then the mechanism within cardiomyocytes should play the major role in cardioprotection.   Jun Yoshioka:             I might, at one point, because, you know, the fibroblasts, they don't need to beat, right?   Cindy St. Hilaire:        Right.   Jun Yoshioka:             The inflammasome cells. They don't need to beat neither. So, they don't need that much energy. So, the cardiomyocytes energy metabolism is very important. So, that's why this mechanism is kind of more important in cardiomyocytes than other cell types.   Cindy St. Hilaire:        Yeah. And I think, you know, your phenotyping of the mice at baseline show that there's really no effect in a cell that's not under stress. So, it's really, really nice finding. Yeah.                                       This article, I should say, is featured on the cover of the September 2nd Circulation Research issue. And it's got this really nice 3D modeling of the binding of ARRDC4 to glute one. And I was reading the paper, and the methods said, you use some AI for that. So, I'm sure other people have heard, too, AI in protein modeling is important. But AI in art, right? There's that new DALL-E 2 program. So how are you able to do this? How did that work?   Jun Yoshioka:             So, our study used is called AlphaFold, which applies the artificial intelligence-based deep learning method. AlphaFold, nowadays, everybody really is interested in AlphaFold. AlphaFold uses structural, and genetic data to come up with a model of what the protein of interest should look like. So, that is also how we got the protein structure, ARRDC4. We think that the ability of AlphaFold to precisely predict the protein structure from amino acid sequence would be a huge benefit to life sciences, including of course, cardiovascular science research, because of high cost, and technical difficulties in experimental methods.                                       It's very useful if you can computationally predict the complex from individual structures of ARRDC4. And group one, which is actually structure of group one, is available in a protein data bank. But ARRDC4, it was not available. That's why we used AlphaFold.                                       And then we use the docking algorithm called Hdoc. So, based on these AI analysis, we could successfully identify specific residues in a C terminal arrestin domain as an international interface, that regulates group one function. So, we believe this AI method will pretty much accelerate efforts to understand the protein, protein interactions. And we believe that will enable more advanced drug discovery, for example, in very near future.   Cindy St. Hilaire:        Yeah, it's really great. I started thinking about it in terms of some of the things I'm studying. So yeah, it was really nice. Jun Yoshioka:             Try next time.   Cindy St. Hilaire:        Yeah, I will, I will. Actually, I went to the website, and was playing with it before I got on the call with you. So, how do you think your findings can be leveraged towards informing clinical decision making or even developing therapeutics?   Jun Yoshioka:             So, let me talk about what needs to be done. There are more things we must do.   Cindy St. Hilaire:        Always. Yeah.   Jun Yoshioka:             One of the most clinically relevant questions is whether ARRDC4 inhibition actually can mitigate development of post MI heart failure, and reduce mortality in the chronic phase, not the acute phase. Because in this paper we just did the seven day post MI, which is kind of like acute to subacute phase. But you never know what's going to happen in the chronic phase, right? And that is actually not so simple to answer because there are so many issues that you should consider. For example, Dr E. Dale Abel's lab has reported previously that cardiomyacites, specific group one, knockout in mice does not really accelerate the transition from compensated hypotrophy to heart failure. Also, the same group has shown that the overexpression group one does not actually prevent LV dysfunction in the mouse model of pressure overload. So, it is possible that ARRDC knockout can be, do much, or even harmful to LV remodeling in a chronic phase because chronic phase, it's not, it's getting hypoxy conditions, right?   Cindy St. Hilaire:        Yeah. So, it really might be something, I guess, personalized medicine is not the phrase I'm looking for. But I guess temporarily modulated, it would be something maybe we can figure out in an acute phase versus.   Jun Yoshioka:             Chronic phase.   Cindy St. Hilaire:        Yeah. Yeah.   Jun Yoshioka:             This makes sense. Because, you know, high capacity of ATP synthesis, by oxidating metabolism, could be important for chronic heart failure. So, it's selecting substrates. Energy substrates is no longer, you know, that issue. So, I'm not sure I'm answering your question, but this is the point that we consider to move on to the next.   Cindy St. Hilaire:        Well, that's great. And I think that was my next question, really. What is next? Are you really going to try to pinpoint where you could possibly target?   Jun Yoshioka:             Right. So, the first point we have to figure out about chronic phase, and another point we are interested in, is what's going on at the level of mitochondria. Does ARRDC4 knockout hearts have a different activity of electron transport chain or glycolytic enzymes within mitochondria?   Cindy St. Hilaire:        Or even mitochondrial fission infusion because it's, you know, it's a machinery.   Jun Yoshioka:             Yeah. And how about the other essential pathways in glucose metabolism such as mTOR, AMPK and HEF1, and so on. So, all these must be determined to help understand the more precise role of ARRDC4 in cardiac metabolism, we believe. Cindy St. Hilaire:        It's a wonderful study, and now we have even more questions to ask using your great model. Congratulations again.   Yoshinobu Nakayama: Thank you so much.   Cindy St. Hilaire:        Dr Yoshioka, and Dr Nakayama.   Jun Yoshioka:             Thank you.   Cindy St. Hilaire:        A wonderful paper, and congrats on getting the cover, and thank you so much for joining me today.   Jun Yoshioka:             Thanks well so much for having us.   Yoshinobu Nakayama: Thank you.   Cindy St. Hilaire:        That's it for the highlights from our September 2nd, and our September 16th issues of Circulation Research. Thank you so much for listening. Please check out our CircRes Facebook page, and follow us on Twitter, and Instagram with the handle @circres, and hashtag discovercircres. Thank you to our guests, Dr Jun Yoshioka, and Dr Yoshinobu Nakayama.                                     This podcast is produced by Ishara Ratnayaka, edited by Melissa Stonerm, and supported by the editorial team of Circulation Research. Some of the copy text for 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 2022. The opinions expressed by speakers in this podcast are their own, and not necessarily those of the editors or of the American Heart Association. For more information, please visit ahajournals.org.

On this ID the Future from the vault, catch the first half of a public talk by political scientist John West on how Darwinism has poisoned Western culture. In the lecture, delivered at the Dallas Conference on Science & Faith, West explores how Darwin's purely materialistic theory of evolution drained meaning from nature, undercut the idea of inherent human dignity, and fueled the rise of scientific racism in the twentieth century. West is author of Darwin Day in America: How Our Politics and Culture Have Been Dehumanized in the Name of Science. Source

Transfusion's monthly podcast - read the associated article here: onlinelibrary.wiley.com/doi/10.1111/trf.16935

Host: Dr. Gita S. Pensa, MD We discuss this paper with first author Dr. Joyce Li, MD, MPH. They sought to evaluate racial and ethnic differences in pediatric patients across a broad range of low-value imaging studies in the general ED setting.

We discuss this paper with first author Dr Joyce Li. They sought to evaluate racial and ethnic differences in pediatric patients across a broad range of low-value imaging studies in the general ED setting.

In this episode, we have another special guest on our podcast, Dorn! Dorn is a friend and also Rickey's fitness coach and in this episode, he comes on and shares his story about growing up in the United States as a minority after his parents entered the country as war refugees. We talk about how hard we tried to blend in and fit into society and how he's realized now that he should be doing the complete opposite to honor the Tai Dam culture he comes from

This podcast covers the JBJS June 1, 2022 issue. Featured are articles covering Racial Differences in Care and Outcomes After Total Hip and Knee Arthroplasties; recorded commentary by Dr. Bernstein; Symptoms of Depression and Suicidality in Orthopaedic Surgeons.

In this episode, Antonia and Andrew discuss a selection of articles from the June 1, 2022 issue of JBJS, along with an added dose of entertainment and pop culture. Listen at the gym, on your commute, or whenever your case is on hold!   Articles Discussed: Long-Term Health-Related Quality of Life After Harrington Instrumentation and Fusion for Adolescent Idiopathic Scoliosis. A Minimum 40-Year Follow-up, by Lander et al. Objects in Mirror Are Closer Than They Appear: Symptoms of Depression and Suicidality in Orthopaedic Surgeons, by Stein et al. The Association of Immediate-Use Steam Sterilization with the Incidence of Orthopaedic Surgical Site Infections. A Propensity Score-Matched Cohort Study, by Tantillo et al. Racial Differences in Care and Outcomes After Total Hip and Knee Arthroplasties. Did the Comprehensive Care for Joint Replacement Program Make a Difference?, by Okewunmi et al. Distracted Driving Among Patients with Trauma Attending Fracture Clinics in Canada. The Canadian Multicenter DRIVSAFE Study, by Ristevski et al. Minimal Clinically Important Changes in HOOS-12 and KOOS-12 Scores Following Joint Replacement, by Soh et al. Comparison of Simulated Low-Dose and Conventional-Dose CT for Preoperative Planning in Shoulder Arthroplasty, by Lorenzana et al. Capsular Mechanics After Periacetabular Osteotomy for Hip Dysplasia, by Ng et al.   Link: JBJS website: https://jbjs.org/issue.php   Sponsor: This episode is brought to you by JBJS Clinical Classroom.   Subspecialties: Pediatrics Spine Shoulder Basic Science Hip Knee Trauma Orthopaedic Essentials Infection

In this rebroadcast of a show that first aired in March 2022, host Connor Cyrus talks with white Vermonters who adopted Black children, and hears from a Black woman about being raised by her adopted white family.

In this episode, I discuss ways in which I've combined current event topics from the Iowa Hawkeyes sports teams with my data analysis and process improvement background. I explain a summary of 4 articles I have written, and invite you to read the ones that are of interest to you. Links True or False? Iowa Football Struggles in Games on the West Coast Will Jordan Bohannon Tie or Break the Big Ten 3-Point FG's Made Record? Did Iowa Women Suffer from Lack of Fouls in Loss to Creighton? Racial Differences in Football Player Retention at the University of Iowa Need help in your organization? Let's talk! Schedule a free support call BIZ-PI.com LeanSixSigmaDefinition.com Have a question? Submit a voice message at Anchor.fm --- Send in a voice message: https://anchor.fm/leansixsigmabursts/message

To be a Christian is not only to trust Christ and treasure Christ, but to be indwelt by Christ. And that new identity transforms all our relationships.

Host Connor Cyrus talks with some white Vermonters who have adopted Black children about the challenges and joys that come with transracial adoptions.

A look into how The Western world and Asia has handled the pandemic thru a philosophical lens and what that should mean for African Descendants --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app

Briana Contreras, editor of Managed healthcare Executive, spoke with Dr. Ian Tong, chief medical officer of Included Health in today's episode. The two discussed telehealth use vs. in person care, and more specifically, the racial and ethnic differences in this use of care. They concluded the conversation with how telehealth use has continued to expose more benefits for all patients and for the industry through examples like improvements in reimbursement policies and in addressing health equity issues.

On Episode 11 of the Stroke Alert Podcast, host Dr. Negar Asdaghi highlights two articles from the December 2021 issue of Stroke: “Baseline Cognitive Impairment in Patients With Asymptomatic Carotid Stenosis in the CREST-2 Trial” and “Serious Adverse Events and Their Impact on Functional Outcome in Acute Ischemic Stroke in the WAKE-UP Trial.” She also interviews Dr. Mark Parsons about his article “Stroke Patients With Faster Core Growth Have Greater Benefit From Endovascular Therapy.” Dr. Negar Asdaghi:         1) Can the presence of a high-grade asymptomatic carotid stenosis result in development of early dementia? 2) Have you ever wondered if a random poststroke urinary tract infection or hospital-acquired pneumonia can impact the 90-day poststroke outcome? 3) When it comes to the beneficial effect of endovascular thrombectomy, what is the concept of late window paradox, and why do we need to know about this and its relation with the speed of infarct growth? These are the questions that we will tackle in our December podcast. We're covering the best in Stroke. Stay with us. Dr. Negar Asdaghi:         Welcome back to the Stroke Alert Podcast. My name is Negar Asdaghi. I'm an Associate Professor of Neurology at the University of Miami Miller School of Medicine and your host for the monthly Stroke Alert Podcast. For the December 2021 issue of Stroke, we have a large selection of topics, from whether adjusting antiplatelet therapies after stenting for intercranial aneurysms can potentially reduce ischemic events, to studying the outcomes of patients with reversible cerebral vasoconstriction syndrome and analysis from a nationwide study in the United States, which I encourage you to review in addition to listening to our podcast today. Later in the podcast, I have the pleasure of interviewing Dr. Mark Parsons, from the University of New South Wales in Sydney, Australia, on his work suggesting that the beneficial effect of endovascular thrombectomy may be modified based on the speed of infarct growth, from the time of symptom onset to the time when the patient is being considered for reperfusion therapies. But first with these two articles. Dr. Negar Asdaghi:         It has been suggested that the presence of chronic high-grade carotid stenosis can result in early cognitive decline, even in the absence of ischemic stroke secondary to the carotid disease. Multiple mechanisms for this decline have been proposed, including an alteration of cerebrovascular reactivity and ipsilateral hemispheric hypoperfusion. Now, if this is true, then asymptomatic patients harboring a high-grade carotid stenosis would have a lower cognitive status than their age and risk factor in matched counterparts. And this is the exact topic that Dr. Ronald Lazar from the Department of Neurology at the University of Alabama and colleagues studied in this issue of the journal, in their article titled “Baseline Cognitive Impairment in Patients With Asymptomatic Carotid Stenosis in the CREST-2 Trial.” Dr. Negar Asdaghi:         Now, a very quick recap of the CREST-2 Trial. You will recall that CREST-2 is an ongoing randomized trial of patients over 35 years of age with asymptomatic carotid disease of equal or greater than 70%. Asymptomatic is defined as absence of ipsilateral stroke or TIA symptoms within 180 days prior to randomization. Also, a reminder, that to be able to be enrolled in the CREST-2 Trial, patients had to be independent, with no diagnosis of dementia, and they were then randomized to either intensive medical management versus carotid artery stenting, or intensive medical management alone versus carotid endarterectomy. It's important to keep in mind that a secondary outcome of CREST-2 is to see whether carotid intervention over intensive medical management is better in reducing cognitive decline over time in this patient population. Dr. Negar Asdaghi:         Obviously, we'll have these results after the completion of the CREST-2 trial and its follow-up completion, but in the current study, the authors were interested to compare the baseline cognitive function of the CREST-2 candidates, and they were able to compare this baseline cognitive status to participants of the REGARDS population-based study. Now, the acronym for REGARDS stands for "Reasons for Geographic and Racial Differences in Stroke." This was a population-based study in the United States that included over 30,000 community-dwelling White and Black adults over the age of 45. So, think about the REGARDS cohort as the stroke-free participants without the high-grade carotid stenosis. Dr. Negar Asdaghi:         So, to match the two populations, the authors included only CREST-2 participants that were older than 45 years of age and did not have any prior strokes. So, that gave them a sample size of 786 patients for the current analysis with a complete neurocognitive battery of four tests administered over the phone, in the same order in both studies. So, let's go over these cognitive tests. The test included the Word List Learning Sum, assessing the cognitive domain of learning; the Word List Recall, which is a test of memory; and the two tests for executive function, Word Fluency for animal names and fluency for the single letter 'F'; and a brief screen for depression. Dr. Negar Asdaghi:         So, simply put, we have four cognitive tests assessing the three cognitive domains of learning, memory, and executive function. And depending on how the person did on each test, it gave the investigators Z scores for each participant in each category and then they compiled the Z scores in a percentile tabulation for the CREST-2 population and compared these percentiles to the normative data obtained for the REGARDS population. Dr. Negar Asdaghi:         So, what they found was that, well, not surprisingly, the population of CREST-2 had a higher prevalence of cardiovascular risk factors, things like hypertension, elevated lipids, smoking and diabetes. Slightly more than half, exactly 52% of the CREST-2 patients, had a target carotid stenosis vessel on the right side. And then they did some complex statistical models, adjusting for age, race and educational level, and then further adjusting for some vascular risk factors, such as hypertension, diabetes, dyslipidemia, and smoking, for each cognitive test, and they found that the overall Z score for patients in CREST-2 was significantly below expected for higher percentiles and marginally below expected for the 25th percentile for all four cognitive tests, as compared to the normative population. Dr. Negar Asdaghi:         For example, if they were expecting that 90% of the CREST-2 population would score in the 75th percentile for a particular test, or at 95th percentile on a different test, these percentages were significantly lower in the CREST-2 candidates. The greatest cognitive differences were detected for Word List Delay, which is a test of memory, followed with the Word List Learning, which is a test for learning. And the results really did not change when they adjusted for the vascular risk factors, and importantly, unchanged when they adjusted for right- or left-sided stenosis of the carotid, which is important, as language plays an important role in assessment of memory function. Dr. Negar Asdaghi:         So, what did we learn from this study? Well, number one, poor cognition is associated with harboring high-grade asymptomatic carotid occlusive disease, an effect that was only modestly attenuated by further adjustment for other risk factors. Number two, patients with high-grade carotid stenosis showed a significantly lower cognitive performance in the learning and memory domains. This profile of cognitive decline is different than what was typically expected to be seen in the case of vascular dementia, where abnormalities are predominately seen in the test of executive function. Number three, though we don't know the precise mechanism for cognitive impairment in the setting of carotid stenosis, cerebral hypoperfusion seemed to be the leading plausible cause as hippocampus and amygdala are known to be susceptible to hypoperfusion, and the findings of the current study show that the predominant impairment seen in patients with carotid disease seemed to be involving memory and learning. So, really important findings, and lots to still learn on this topic. Dr. Negar Asdaghi:         The occurrence of adverse events during acute treatment and within the first few weeks of acute ischemic stroke are common and can negatively influence the course and clinical outcomes of stroke patients. Serious adverse events, or SAEs, are defined as life-threatening events resulting in death or requiring hospitalization, prolongation of hospitalization, or resulting in significant disability, and they can be either neurological, such as recurrent ischemic events, hemorrhagic complications, seizure disorders, but also can include a myriad of systemic complications, including, but not limited to, occurrence of deep vein thrombosis, pulmonary emboli, cardiac arrhythmias, various infections, GI bleeds, to name a few. Dr. Negar Asdaghi:         In a setting of a clinical trial, patients are regularly and systematically monitored for SAEs, and from these studies we know that, indeed, both adverse events, or AEs, and SAEs are quite common poststroke and are reported in up to 95% of participants of prior randomized trials. Intravenous thrombolysis increased the risk of symptomatic intracerebral hemorrhage, but in general, the rate of SAEs are similar in thrombolyzed and non-thrombolyzed patients. Which clinical characteristics prone stroke patients to what type of side effects is, of course, an intriguing subject for a stroke neurologist. Similarly, it's important to know how, for example, a seemingly indirect complication of ischemic stroke, such as a hospital-acquired urinary tract infection, can potentially affect the stroke outcomes. Dr. Negar Asdaghi:         So, in this issue of the journal, Dr. Iris Lettow from University Medical Center in Hamburg, Germany, and colleagues looked at the subject in the paper titled “Serious Adverse Events and Their Impact on Functional Outcome in Acute Ischemic Stroke in the WAKE-UP Trial.” This was a post-hoc analysis of the WAKE-UP Trial, which was a multicenter randomized trial of MR-guided intravenous thrombolysis with alteplase in ischemic stroke patients with unknown time of onset. The WAKE-UP Trial included 503 patients, and they had 199 SAEs reported for 110 patients, meaning that one in five patients had at least one serious adverse event in the trial. Of those patients who did suffer an SAE, 20 patients, which was 10%, had a fatal outcome. Dr. Negar Asdaghi:         The rate of SAEs were not different between thrombolyzed and non-thrombolyzed patients. But, when they categorized the patients based on who did and who did not experience an SAE, they found that those who experienced an SAE were older, presented with more severe strokes, and were more likely to have a large vessel occlusion. But only higher age and male sex were independent predictors of development of an SAE poststroke. So, let's pause and think about these findings. This was in contrast to the previous studies, where traditionally, the severity of stroke was a predictor of complications, and importantly, the first study to identify male sex as an independent predictor of SAE, whereas, traditionally, female sex had been identified as a risk factor for development of adverse events poststroke. Dr. Negar Asdaghi:         Perhaps what we're seeing with a paradigm shift in improvement in poststroke quality of care. Now, another important finding of this study was that the presence of any SAE, whether neurological or non-neurological, resulted in reduction of favorable outcome by half and almost quadrupled the odds of poor outcome, defined as modified Rankin Scale of four to six at 90 days, even after accounting for all the known confounders. Now, the authors also looked at some interesting details. The organ most effected by serious adverse events poststroke was indeed the nervous system. Almost 50% of all SAEs were neurological in nature. This was then followed by cardiac events. Some examples would include an acute coronary syndrome, MI, various arrhythmias. And the surgical and medical procedures were the third most common category of serious adverse events in this study. Dr. Negar Asdaghi:         And what they found was that SAEs by organ of involvement had a significant association with 90-day outcomes, where any neurological serious adverse events significantly affected 90-day functional outcome poststroke. When adjusting and accounting for important variables, such as age, sex, LVO, this still remained true in terms of a predictor of outcome. In contrast, cardiac serious adverse events, infectious serious adverse events, did not have any effect on the 90-day functional outcome. Dr. Negar Asdaghi:         So, what are the top takeaway messages from this study? Number one, SAEs occur commonly poststroke, and in this particular study, occurred in one in five ischemic stroke patients. Number two, 10% of those who suffer from an SAE had a fatal outcome. Number three, nervous system disorders and cardiac disorders were the most frequent classes of side effects poststroke. And finally, patients suffering from at least one serious adverse event had a lower odds of reaching favorable outcome at 90 days. These findings emphasize the importance of dedicated stroke care, neurointensive care units, and all poststroke efforts to reduce preventable adverse events poststroke. Dr. Negar Asdaghi:         Time is an exceedingly important concept in treatment of patients with acute ischemic stroke. As an example, in a typical stroke related to a proximal large vessel occlusion, the ischemic brain loses an average of two million neurons per minute. Now, endovascular therapy is the standard reperfusion treatment for patients with acute ischemic stroke secondary to a large vessel occlusion. It is an effective treatment to restore blood flow and reperfusion to the brain and had been shown to improve outcomes in stroke patients. Dr. Negar Asdaghi:         Therefore, one would naturally anticipate that the benefits of endovascular therapy would be dramatically reduced with treatment so late. If this is true, then why is it that the beneficial treatment effect from endovascular therapy was even larger in patients treated in the late time window trials, and you will recall that these were patients included from 6 to 16 hours, or 6 to 24 hours, from their symptom onset time. This compared to treatment effects noted in patients enrolled in the early time window trials. This concept is known as the "late window paradox" and does not mean that we have to wait to provide reperfusion therapies to patients. It actually refers to those fortunate few that have robust collaterals and, as a result, have slow infarct growth, which will afford them that extra precious time to remain eligible to receive this life-saving treatment. Dr. Negar Asdaghi:         Joining me now on the podcast is Dr. Mark Parsons from the University of New South Wales in Sydney, Australia, to talk to us about the concept of infarct growth. Dr. Parsons is one of the senior authors of the study published in the current issue of the journal titled “Stroke Patients With Faster Core Growth Have Greater Benefit From Endovascular Therapy,” and will discuss how the beneficial effect of endovascular treatment may be modified by the speed of infarct growth in the early time window after symptom onset. As in every podcast, when I have the pleasure of interviewing a pioneer in the field of stroke, that my guest needs no introduction, but truly Dr. Parsons needs no introduction to our listeners. He's a Professor of Neurology at the University of New South Wales in southwestern Sydney. He's an internationally recognized leader in the field of stroke, stroke clinical trials, and brain imaging whose research has helped improve patient selection for acute stroke reperfusion therapies. It's truly an honor to have him on the podcast today. Welcome, Mark. Thank you so much for joining us all the way in Sydney on a Saturday morning. Dr. Mark Parsons:           Yes, thank you, Negar. It's OK, I have been up for a little while. So, yes, lovely to chat with you, and we haven't chatted in person for quite a long time, and I think I actually remember the last time was in Hamburg, in Germany, at a big stroke conference. I remember it quite well. We had a very pleasant evening with a group of Canadians and Australians, and I had to present a major tenecteplase study finding the next day, and I was a little bit off my game, some of my friends said, and I think that's probably your fault, Negar. Dr. Negar Asdaghi:         Mark, you did really great, and we really, truly, look forward to getting back to in-person meetings. So, let's start with the study here. Can you please tell us about the INSPIRE registry? Dr. Mark Parsons:           So, the INSPIRE registry, that's an acronym. So, it's best to spell out this acronym, so that stands for the "International Stroke Perfusion Imaging Registry." So, that was something we set up quite a while ago when perfusion CT was quite considered advanced or novel. We set that up, I think, in about 2010, and because that was obviously one of my areas of interest, perfusion imaging, we started collecting perfusion CT and CT angiography , and noncontract CT, for that matter, from our stroke patients from a number of centers in several countries. And over time, that built up to over 20 centers around the world, so predominantly Australia and China, because of the close connections that we've got there, but also one site in Canada, actually two sites now. We have so many sites that I sometimes overlook a few. Dr. Mark Parsons:           So, it is international. And what we do is, we collect prospective data from stroke patients, both clinical and their acute imaging, follow-up imaging, follow-up clinical information, and in the majority of patients, we also get three-month Rankin. So, there's now over 3,000 patients in that database with complete datasets from acute baseline imaging through to three months. And that was the dataset that we used for this current study. Dr. Negar Asdaghi:         So, Mark, this is truly an impressive registry. It is not easy to do large-scale imaging-based registries, and this is really impressive to have so many centers involved. Can you tell us about the current study population? Who did you include in the current study paper? Dr. Mark Parsons:           Firstly, we specifically looked at patients that had a large vessel occlusion, or LVO. Of course, the definition of large vessel occlusion varies a bit from place to place, but essentially, that means a clot in a proximal artery to the brain that's potentially retrievable via endovascular thrombectomy. I guess the beauty of the INSPIRE registry is, we started collecting stroke patient data well before endovascular thrombectomy was a routine treatment. We had quite a large number of large vessel occlusion patients in this study who didn't receive endovascular thrombectomy because it simply wasn't available at the time. And then, of course, with all of those big trials that came out in 2015, as you know, and beyond, with thrombectomy becoming routine at all of our INSPIRE sites and many other places around the world, we then had a, I guess, a historical cohort comparison of large vessel occlusion patients that were not given EVT and then, more recently, a cohort of large vessel occlusion patients who were treated with thrombectomy. Dr. Mark Parsons:           The non-thrombectomy patients, in the vast majority, received intravenous thrombolysis because they were in the 4.5-hour time window. I guess the only other thing, the main other inclusion criteria, was we specified that patients in this particular study needed to have a relatively small infarct core, less than 70 mL, and we can talk more about that later, if you like, and a significant area of tissue that's potentially salvageable with reperfusion, the so-called penumbra. Dr. Negar Asdaghi:         Thank you. Just to recap for our listeners, so your current study population included patients presenting early on, within 4.5 hours from symptom onset, with a large vessel occlusion, and because, as you mentioned, the study had been ongoing even before endovascular therapy became a standard of care, you have a group of patients in whom endovascular therapy was offered and you have the comparison to this group to those patients who had an LVO, large vessel occlusion, but simply received intravenous thrombolysis only. Can you now tell us about these two groups, basically, IV thrombolysis versus endovascular therapy group. What were the differences between the two groups, and what were the main clinical outcomes in your study? Dr. Mark Parsons:           Yes. We had about 400 patients in each arm. And though reasonably well matched, I mean, of course, registry, it's not randomized, so you can't have perfectly matched groups, and indeed, in the more recent era where most patients with large vessel occlusion, particularly with this small core, big penumbra on imaging, would go to thrombectomy because they had the so-called ideal target population. So, in the modern era, if patients don't receive EVT, then there's probably a good reason for that. But, essentially, they are around 70 years of age. Their NIH Stroke score was around 15, or the median score, so that's reasonably consistent with large vessel occlusion. And then if you look at the perfusion imaging, so this was all with perfusion CT in our studies, so the core volume was quite small, 15 mL, but there was quite a large range. And the median penumbra volume was actually a bit bigger in the EVT group; it was 80 versus 65 in the penumbral group. Dr. Mark Parsons:           We probably don't need to go into the details of how those core penumbral volumes are calculated, but that might be a bit over-technical for our audience, but happy to elucidate further if you want. Dr. Negar Asdaghi:         Actually, I think it's important to, just briefly, talk about how those values were measured. Dr. Mark Parsons:           Yes, OK. The other thing I should say is that, interestingly enough, we specified the 4.5-hour time window, but in fact, the median time from stroke onset to imaging was just under two hours in both groups, which is quite short. Dr. Mark Parsons:           And indeed, some of the people that are less enthusiastic about perfusion CT than I am would say, "Well, maybe measures of core are not so reliable in that early time window with perfusion CT." I would probably debate that to some degree. But, if we talked to the technicalities, there's quite a lot of data to suggest that the cerebral blood flow threshold is probably the most robust for identifying core, or at least tissue that's destined to infarct. It may not actually be infarcted at the time we measure it, particularly at two hours, but there's quite a lot of data now showing that with perfusion CT with a cerebral blood flow threshold of 30%, depending on software variations, that's a pretty accurate estimate of the final infarct in people that have rapid reperfusion fairly quickly after the perfusion CT. Dr. Mark Parsons:           So, all of these figures that we use are based on, for example, the core threshold on perfusion CT relates to, we validate that from patients, particularly that have had thrombectomy, so we know when they've reperfused. And the theory should be that if the CT perfusion core is an accurate measure of the final infarct, that there should not be much change from the baseline CT perfusion core to the follow-up infarct because there's been reperfusion not long after the perfusion scan. Now, with the penumbral volume, we use software that measures a delay time. Other software, particularly in North America, you would use a Tmax, but they're both basically direct measures of collateral flow. Dr. Mark Parsons:           So, as you know, when you have a large vessel occlusion, say, of a middle cerebral artery and in one segment, the way that blood gets to the cortex, it's typically supplied from the middle cerebral, is via retrograde flow from the anterior cerebral and the posterior cerebral via leptomeningeal collateral, so you actually get blood coming back retrograde bypassing the occlusion. And these measures on perfusion CT delay time in Tmax, actually, give you a measurement in seconds of how long it takes the blood to travel to that part of the brain. And, obviously, the longer the delay in seconds means the poorer the collateral flow. And then, typically, that means the poorer the collaterals, the less time you've got to salvage the penumbra, and the quicker the infarct core will expand. Dr. Negar Asdaghi:         Right. So, in your study, using these perfusion parameters. First, before even we come to the perfusion parameters, you found that overall, when you adjusted for all confounders, endovascular-treated patients had a better, or higher, odds of achieving good 90-day outcomes. This was not a surprising finding when you compare this population of endovascularly-treated patients to those treated with intravenous thrombolysis alone. But what was interesting was, indeed, those analyses related to infarct growth rate. Can you tell us a little bit about this concept of infarct growth rate, and you already mentioned how you measured infarct growth by perfusion imaging. Dr. Mark Parsons:           Thanks, Negar. I guess that's the novel part in it. I guess it would have been quite surprising if we didn't show that EVT was superior to IVT in the early time window. So, that certainly wasn't unexpected, that finding. But I guess the novel part of this study is this relatively new concept of infarct core growth rate. I'm not saying we're the first that's described it because, as you know, there are a number of papers in the literature and talking about the concept of slow infarct core growers versus fast infarct core growers. And you mentioned the late time window thrombectomy studies, DAWN and DEFUSE 3, which actually showed a dramatic benefit in the later time window, up to 24 hours after stroke, in patients who had evidence of perfusion core mismatch. And the concept then was suggested that the reason that these people benefited so much in that late time window was that they had very slow infarct core growth because they had great collaterals. Dr. Mark Parsons:           The treatment effect was bigger in those late time window studies than it was in the early time window thrombectomy studies, which was hypothesized might have included a lot of patients with fast infarct core growth rate, which wasn't really measured in a number of the thrombectomy studies in the early time window. We wanted to look more at, does the rate of infarct core growth have an influence on the effective treatment, with both IV and endovascular treatment? Dr. Mark Parsons:           So, the way we measured infarct core growth was pretty simple, actually. It's basically, we excluded patients with uncertain time of stroke onset because we had more than double this total number of LVO stroke patients with target mismatch, but we had to exclude the patients with uncertain time of onset, which included wake-up stroke and others. So, in this group, where there was a defined time of onset, basically, the infarct core growth rate was simply measured from the volume of the infarct core measured on perfusion CT divided by the time from stroke onset. So, just simplistically, if you've got a core of 50 mL, and it's two hours after stroke onset, then the infarct core growth rate is 25 mL per hour. That's simple, but that obviously assumes a linear core growth rate. And we based that linear model on previous studies of repeated diffusion MR imaging, which is another measure of core, that showed that the core growth rate was linear. Dr. Mark Parsons:           Now, of course, you could criticize that because I suspect, in some patients, the core growth rate is not linear. This is an estimate of core growth rate. Dr. Negar Asdaghi:         Right. So, your study actually found something quite interesting, which I really want you to go over for us and for our listeners, and that's that the beneficial effect of endovascular therapy is superior in those with a fast infarct growth rate, and was not superior, in fact not any different, in those patients who had a slow infarct growth rate. Can you walk us through that, and also tell us how that does not contradict what we've found as part of DAWN and DEFUSE with the slow infarct growers? Dr. Mark Parsons:           Thanks, Negar. It is slightly complicated, so we'll go one step at a time. So, first of all, the core growth rate varied quite a bit in this population. A number of patients, and this is because you saw that the median core in this group was 15 mL, so there was quite a large population of patients that had a core growth rate of less than 15 mL per hour. So, they're your traditional slow growers, slow core growers, who have really great collateral flow. You probably have a number of hours to save the penumbra. Now, I'm not saying that you should waste time in this group of patients, but it might be particularly relevant, for example, if you're transferring from a primary stroke center to a comprehensive stroke center. You know that you're going to have time to save that penumbra because the infarct core is going to grow slowly. Dr. Mark Parsons:           In, for example, in Australia, at least half of our thrombectomy patients come from regional or out of metro centers, where there is a significant transfer time from the primary stroke center to the comprehensive center. So, that may be a particularly important finding to look at in the future for longer transfer times from primary to comprehensive stroke centers. So, then, at the other end of the scale, we had a proportion of patients who had what we call a fast core growth rate of more than 25 mL per hour. And then there were people in the middle between 15 and 25 who we called sort of moderate core growth. So greater than 25 mL per hour was a fast core growth. Dr. Mark Parsons:           We categorized it into those sort of three categories. Again, that's a bit arbitrary, but the reason we did that was that if you look at the IVT group alone, those who had slow core growth rate, less than 15 mL per hour, their rates of good outcome, so a Rankin 0 to 2, so getting back to close to normal function at three months, their rates of a good outcome were almost 60% in the slow core growth rate with IVT. Then, if you go to the other end of the scale with fast core growth with intravenous therapy, the rates of good outcome in that group were only 30%. So, there was a clear decline in terms of three-month good outcomes with intravenous thrombolysis versus core growth rate. So, as the core growth rate increased, the chances of good outcome with intravenous thrombolysis decreased. Dr. Mark Parsons:           Then, if you looked at the EVT group, it was quite interesting that this core growth rate effect had minimal impact on the outcome of the EVT patients. So, in the EVT patients with slow core growth rate, less than 15 mL, the rates of good outcome at three months were, again, close to 60% and identical to the IV therapy group. But, at the other end of the scale, with fast core growth rate above 25 mL with the EVT group, they had a much higher rate of good outcome compared to the IVT group. Their rates of good outcome were around 45%. So, they are a little bit lower than the slow core growers with EVT, but there wasn't much drop-off with core growth rate, and there was a significant increase in good outcomes in the EVT group who had fast core growth compared to the IVT group. Dr. Negar Asdaghi:         So, I just want to summarize this so that I understand it and, of course, want to make sure that it's simplified also for our listeners. So, you found that those people, and it should be noted these are all within the first 4.5 hours. Dr. Mark Parsons:           Yes. Dr. Negar Asdaghi:         So, we understood in that time frame. Those people who had a fast growth rate, they had the greatest benefit from endovascular therapy in this time frame. And those people who had the slow growth rate, that is defined in your study as less than 15 cc per hour, they actually had a similar benefit from endovascular therapy as they did with intravenous thrombolysis. Did I summarize that? Dr. Mark Parsons:           Yes. That's correct. Dr. Negar Asdaghi:         So, Mark, how do you explain this from a pathophysiological standpoint? Dr. Mark Parsons:           Fortunately, there's a relatively simple explanation. So, because of the way that we set up INSPIRE, we collected follow-up infarct volumes as well. From the time window for follow-up infarct measurement was a little bit variable, but it was around 48 hours after stroke onset. In this group of patients, we actually were able to measure final infarct volume and essentially, in the slow core group, so less than 15 cc growth per hour, in that group, with both IVT and EVT, there was minimal infarct growth by the time we measured it at 48 hours. So, both therapies basically led to minimal infarct growth after the treatment, whereas in the fast core growth group, more than 25 cc per hour, the IVT group had much greater infarct growth by 48 hours, about 40 or 50 mL more, on average, than the EVT group. Dr. Mark Parsons:           I guess also, to explain that a touch more, if you look at the slow core growth EVT group versus the fast core growth EVT group, there was still more infarct growth in the fast core growth rate. And this is because you measure the core at a certain time on the CT or the MR. And then, even with the very best system, you're not going to get reperfusion with EVT for at least 30 minutes after that because you have got to get into the angio lab, you have to puncture the groin, and you have got to get up there, and you have got to pull the clot. So, even if you get complete perfect circumstances, it's still usually at least a 30- to 60-minute delay between the perfusion CT and when you're fully reperfused. Dr. Mark Parsons:           But the theory should be, if there's a minimal delay from the perfusion CT to reperfusion, the core at that time should be identical to the follow-up, final infarct volume. And that's what we actually found in the slow core group. It was almost the same. The interesting thing was, it was the same in both IVT and EVT, which basically, we don't know for sure, because we don't know exactly when the IVT group reperfused, but it probably means that because the core growth is so slow in this group, even if you reperfuse later with IV therapy, which we know is the case, often with IV thrombolysis the recanalization is a bit slower than with EVT, so even if you've got delayed reperfusion, if you've got slow core growth rate, you may not get much infarct expansion at all, whereas if you've got fast core growth rate, getting reperfusion as quickly as possible after your CT is crucial to limit subsequent infarct growth before reperfusion. And that's exactly what we found in the fast core growers, that EVT substantially limited that subsequent infarct growth and led to better clinical outcomes as well. Sorry, again, that was a long explanation. Dr. Negar Asdaghi:         Mark, but these are really important findings, and as you alluded to earlier, I believe that they have major implications in how the systems of care are organized and our transfers are going to be decided upon in the future. We have a few minutes before we end the podcast here, and I want to ask you, do you think it's fair to have a similar concept that's studying the infarct growth rate in the late time window, especially in the sort of past 12 hours time window in the future? Dr. Mark Parsons:           Yeah, it's a fascinating question, Negar. In fact, we do have a paper somewhere under review. I think Stroke might have knocked it back. Anyway, but it's actually looking exactly at this concept, but the fascinating thing is, in the late time window, you see very few true fast growers because they actually present early. This is what the paper under review is talking about. So, in fact, most people that you see with a favorable imaging pattern in the late time window, such as DAWN and DEFUSE 3, the core is relatively small. In patients with fast core growth, by the time you get to six hours, you've got a massive core and no penumbra, so they are typically not offered endovascular therapy because there's no salvageable tissue and there's already lots of damage, even on the non-con CT. Dr. Mark Parsons:           So, it would be actually really interesting to look just at the late time window, and I'm sure others are doing that, too, but I suspect what we'll find is that the distribution of core growth is pretty narrow. It's mostly the slower core growers, and it's very clear that most of the really fast, and we're actually looking at this now in people with large infarct core over 70 mL, in fact, they present, the ones that we've got at least, present very early. So, it'll be a fascinating area to look at, for sure. Dr. Negar Asdaghi:         Mark, it is definitely fascinating. We look forward to covering that paper, hopefully in our future podcast. But I want to leave you, reminding you that I'm a mild stroke person, so I am definitely interested in looking at these slow grow rate infarct patients because there are also, as you know, some studies suggesting that the slow growth infarct actually can happen sub-clinically on only a radiographic basis, and especially important in the mild group patients. But, we are out of time. Professor Mark Parsons, thank you so much for joining us all the way from Sydney, and it's been a pleasure interviewing you. Dr. Mark Parsons:           Thank you, Negar. Lovely to chat and hope to see you very soon in person. Dr. Negar Asdaghi:         Thank you. Dr. Negar Asdaghi:         And with that, we end our podcast for the December 2021 issue and close the first year of the Stroke podcast. A year ago, Dr. Ralph Sacco, the Editor-in-Chief of Stroke, approached me to talk about the importance of starting a podcast for Stroke as an accessible means to highlight the great work published in the journal, and also introduce me to the amazing Stroke editorial staff. Dr. Negar Asdaghi:         One year, hundreds of reviewed papers, and 11 podcasts later, from missed deadlines to late night emails, early morning texts, and weekend recordings, our podcast has become a bit more than just a quick review of the literature. It has truly become our podcast family. Overcoming the time differences and impossible schedules, you made time to interview with us, listen to us, and work with us as we reached out to researchers across the globe who contributed to this journal and to the podcast. Lots of laughter and a few tears. Like every family, ending the year reminds us of some good times and, of course, the difficult times. Dr. Negar Asdaghi:         So, I want to end our final podcast of the year with a topic that we haven't really covered in our journal, but I think may sprinkle some magic on your holiday season, and that's the topic of quantum biology. Wrapped in mysticism with a pseudoscientific flavor, physicists, neurologists, anesthesiologists, and philosophers have been hard at work deciphering whether consciousness may have similar properties to quantum particles. From superposition to entanglement and coherence, is it possible that your mind may have something to do with the epigenetics, up and down regulation of genes and presentation treatment and, importantly, outcome of various medical or neurological disorders? Now, even if this was proved to have a low scientific validity, as a stroke scientist, isn't it amazing to be working in the one field that ensures the brain, which is the home of consciousness, remains healthy? So, let's think about the power of consciousness in altering the outcome of medical conditions with our ever-excitement to stay alert with Stroke Alert. Dr. Negar Asdaghi:         This program is copyright of the American Heart Association, 2021. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, visit AHAjournals.org.

Implicit Bias in Residency Applications (https://jamanetwork.com/journals/jamaophthalmology/article-abstract/2785454) Venture Capital Investments in Ophthalmology (https://www.aaojournal.org/article/S0161-6420(21)00744-2/fulltext) Physician-Industry Relationships and KOLs (https://www.aaojournal.org/article/S0161-6420(21)00752-1/fulltext) Racial Differences in Glaucoma Care (https://www.aaojournal.org/article/S0161-6420(21)00742-9/fulltext)

In this podcast, Sri Banerjee, MD, PhD, MPH, MAS, Anayra Tua-Lopez, PhD, MPH, and David Harvey, PhD, MPH, speak about the racial differences in the association between endocrine disruptors and obesity, including higher BPA levels found in Hispanic Americans compared with the general population in the United States.

Davidson KW et al. Screening for prediabetes and type 2 diabetes: US Preventive Services Task Force recommendation statement. JAMA 2021 Aug 24; 326:736. (https://doi.org/10.1001/jama.2021.12531)  The Task Force found moderate-certainty evidence that screening is beneficial for nonpregnant adults (age range, 35–70) who are overweight (i.e., body-mass index [BMI], ≥25 kg/m2) or obese (BMI, ≥30 kg/m2) and have no symptoms of diabetes. Referring patients for, or directly providing, effective preventive interventions is recommended (B recommendation).  The main change from the 2015 recommendation is the lower age threshold for screening — 35 rather than 40. The decision was made because of the increasingly younger age of onset for diabetes and the known benefits of intervention at a wide range of ages. Notably, the USPSTF found little direct evidence that screening improves clinical outcomes;   Lifestyle modifications and metformin are considered appropriate interventions for preventing or delaying onset of diabetes; however, metformin is not approved for this specific use by the U.S. FDA. ---- NO NO NO NO NO NO NO you cant do that..    Aringer M et al. European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) SLE classification criteria item performance. Ann Rheum Dis 2021 Feb 10; 80:775. (https://doi.org/10.1136/annrheumdis-2020-219373) Diagnosising SLE—its always lupus till its not lupus but new diagnosis criteria In 2019, the European League Against Rheumatism and the American College of Rheumatology published the following classification criteria for systemic lupus erythematosus (SLE; Ann Rheum Dis 2019; 78:1151):·                     Positive antinuclear antibody (ANA) test with titer ≥1:80 is a required “entry criterion.”·                     If the ANA criterion is met, points are assigned from seven clinical categories and three immunologic test categories; a criterion is not counted if another cause is more likely than SLE.  A score ≥10 is considered to be consistent with SLE. When these criteria were validated, sensitivity for SLE was 96%, and specificity was 93%. But ANA what about ANA Sensitivity and specificity of ANA were 99.5% and 19.4%, respectively. NEXT  Gómez-Outes A et al. Meta-analysis of reversal agents for severe bleeding associated with direct oral anticoagulants. J Am Coll Cardiol 2021 Jun 22; 77:2987. (https://doi.org/10.1016/j.jacc.2021.04.061)Use of direct oral anticoagulants (DOACs) is associated with about a 3% annual risk for major bleeding, though that varies by age, comorbidity profile, and concomitant therapies.  investigators examined clinical outcomes associated with the use of 4-factor prothrombin complex concentrate (4PCC), idarucizumab, or andexanet for severe DOAC-associated bleeding.These drugs are greatBut if you do bleed then about 20% of the time we cant get hemostasis with mortality around 18% DESPITE getting reversal agents.. This is good to talk to your patients about— The risk of bleeding in 1 and 33 per year..Out of every 3300 people treated about 20 people will have a bleed that isn't controlled and 18 of those people will die.It sounds like a lot but remember without these drugs the risk of stroke is much much higher, of course depending on your comorbid conditions. NEXT  Cardiovascular risk prediction in type 2 diabetes before and after widespread screening: a derivation and validation study - ClinicalKeyLancet, The, 2021-06-12, Volume 397, Issue 10291, Pages 2264-2274, Copyright © 2021 Elsevier Ltd Formulas for cardiovascular (CV) risk calculations are based on population studies and generally include diabetes as a major risk factor. Do formulas that were derived when diabetes usually was diagnosed at later stages overestimate CV risk for people in whom diabetes is diagnosed early?? Basically long ago we diagnosed in DM at a1c of 12 not we diagnosis it at a1c of 6-6.5-7—even prediabetes at a1c of 5.5……Those are not the same population so now are we over diagnosing CV risk??? The answer for this new zeeland study was yes--In this modern diabetic population, the median 5-year risk for an adverse CV event, as estimated by the new formula, was 4.0% in women and 7.1% in men. The older formula overestimated median risk in women (14.7%) and in men (17.1%).This is has to do with new Zealand not the the more recent and commonly used American pooled cohort equation but even that I would love to see put through the ringer as many of the studies were done back in the 90s, over thirty years ago, when we were quite as sharp about diagnosing diabetes yet…either way you have to remember the ascvd risk score is for discussion it is not evidence based gold it is a conversation starter   Next DVT – I am always confused when people say airline travel is a risk factor. I have sat on my couch for 6 hours without moving and I never got a dvt so why would being on a plane for 3 hours. Well maybe it is something I don't understand about air travel because as this paper Munger JA et al. Television viewing, physical activity and venous thromboembolism risk: The REasons for Geographic and Racial Differences in Stroke (REGARDS) study. J Thromb Haemost 2021 Jun 2; [e-pub]. They looked to see if tv watching was associated with DVT and it was not – it didn't matter if you just watched a little bit of tv per day or over 4 hours of tv per day, there was no association with increase DVT and TV hours per day once accounting for total activity.. yes those that are watching TV move less and are more obese but is it he TV watching or just all the risk factors…. This article says it is the risk factors. Last articleKelly CR et al. Prevention, diagnosis, and treatment of Clostridioides difficile infections. Am J Gastroenterol 2021 Jun; 116:1124. (https://doi.org/10.14309/ajg.0000000000001278)    Oral vancomycin or fidaxomicin generally is favored for treating patients with nonsevere CDI, but metronidazole is acceptable for low-risk patients — especially when cost is a factor. Patients with severe CDI should be treated with either oral vancomycin or fidaxomicin (but not metronidazole). Severe disease is defined as having a leukocytosis >15,000 white blood cells/mm3 or a creatinine level of >1.5 mg/dL. Fecal microbiota transplantation (FMT) should be considered for refractory or severe CDI. *******A first recurrence should be treated with tapering/pulsed-dose vancomycin or fidaxomicin if it was not the initial therapy. ********A patient experiencing a second or further recurrence of CDI should be treated with FMT, delivered via a colonoscope or capsules, with enemas used when colonoscopy or capsules are not available. Repeat FMT can be used to treat a recurrence within 8 weeks of initial FMT. *****Patients with recurrent CDI who are not FMT candidates or have relapsed after FMT can be given long-term oral vancomycin prophylaxis to prevent recurrences. Oral vancomycin prophylaxis also can be considered when patients with recurrent CDI are given systemic antibiotics.

Both sucrose and high fructose corn syrup linked to increased health risks University of California at Davis, August 31, 2021 Consuming sucrose, the more "natural form of sugar," may be as bad for your health as consuming high fructose corn syrup, according to a University of California, Davis, study published in the Journal of Clinical Endocrinology and Metabolism. "This is the first dietary intervention study to show that consumption of both sucrose- and high fructose corn-sweetened beverages increase liver fat and decrease insulin sensitivity," said Kimber Stanhope, a research nutrition biologist with the UC Davis School of Veterinary Medicine. "People often have a skewed perspective of aspartame and give sucrose a pass, but this study suggests that consumers should be equally concerned about both major added sugars in our food supply." Participants (18 to 40 years old) were assigned to beverage groups matched for sex, body mass index, fasting triglyceride, lipoprotein and insulin concentrations. They drank three servings a day of either a sucrose-sweetened beverage, a high fructose corn-sweetened beverage, or an aspartame-sweetened beverage for 16 days. The double-blind study was unique in that the 187 subjects lived in a clinical unit for 3.5 days before beverage consumption and during the final days of beverage consumption. Thus, their diet and activity levels were controlled prior to the assessments of risk factors that occurred before and after beverage consumption. This control helped the researchers document how quickly the study subjects, even those who were very lean or normal weight, showed changes in liver fat, insulin sensitivity, and circulating lipids, lipoproteins and uric acid when they drank the added sugars. There were no significant differences between the effects of sucrose and those of high fructose corn syrup, and both the sugar-sweetened beverages increased risk factors compared with aspartame-sweetened beverages. "Within the span of two weeks, we observed a significant change in liver fat and insulin sensitivity in the two groups consuming sucrose- or high fructose corn syrup-sweetened beverages," Stanhope said. "That's concerning because the prevalence of fatty liver [nonalcoholic fatty liver disease] and Type 2 diabetes continues to increase globally." Decreased insulin sensitivity is an important risk factor for Type 2 diabetes, and seeing a clinically significant change within two weeks highlights the need for consumers to read labels carefully and be aware of the source of added sugars, she said. Sucrose may be labeled as sugar, cane sugar or evaporated cane juice among other names, but they're all sugar. Consumer misconception Stanhope said the study is important because many consumers consider high fructose corn syrup to be more detrimental to health than sucrose. Many consumers also believe consuming sucrose is safer than consuming aspartame. Previous human and animal studies have shown that sugar-sweetened beverages are associated with increased fat in the liver. This study further substantiates that those beverages can promote fat accumulation in the liver and lead to metabolic syndrome. "It's all physiologically connected, although we're not sure [in what] direction it goes," Stanhope said. "It's very likely that the mechanism by which we develop metabolic syndrome goes through liver fat and insulin resistance. An increase in liver fat can be benign for a certain amount of time and for certain people. But it can also progress to associated inflammation in liver cells that causes fibrosis and negatively impacts liver function, which can make an individual more prone to liver cancer."   Consuming a Mediterranean diet associated with lower risk of sudden cardiac death during 9.8-year period University of Alabama, August 31, 2021 The July issue of the Journal of the American Heart Association reported the finding of a trend toward a lower risk of sudden cardiac death in association with greater adherence to a Mediterranean diet during an average of 9.8 years of follow-up.* The study also uncovered a trend toward a higher risk of sudden cardiac death associated with greater intake of a Southern dietary pattern. Sudden cardiac death, as defined by the National Heart, Lung, and Blood Institute-sponsored expert panel is “an unexpected death without obvious extracardiac cause, occurring with a rapid witnessed collapse, or if unwitnessed, occurring within one hour after the onset of symptoms.” The current investigation included 21,069 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, which included men and women aged 45 years and older, among whom 42% were black. A high proportion of study participants resided in a region of the U.S. often referred to as the “stroke belt”. In previous research, five dietary patterns were derived from responses to dietary questionnaires administered upon enrollment in REGARDS. These included a pattern observed in the Southeastern United States that is characterized by added fats, fried food, eggs, organ meat, processed meat and sugar‐sweetened beverages. All subjects' diets were subsequently scored for adherence to a Mediterranean diet, which included a high intake of vegetables, fruit, legumes, cereals and fish; a lower intake of meat and dairy products; a high ratio of monounsaturated fat to saturated fat consumption, and moderate alcohol intake. In-home examinations obtained physical measurements, information concerning medication use, a physical health summary, electrocardiographic evaluation, and blood and urine sample collection. Cardiovascular events and deaths were tracked via twice-yearly calls to participants or next of kin, and other methods.  During follow-up, 401 sudden cardiac deaths occurred. After adjustment for a number of factors, subjects whose Mediterranean diet scores placed them among the top one-third of participants had a risk of sudden cardiac death that was 26% lower than subjects whose scores were among the lowest third. The protective effect of the diet was limited to participants with no history of coronary heart disease at the beginning of the study. Among men and women whose adherence to the Southern dietary pattern was among the top quarter of participants, the risk of sudden cardiac death was 46% higher than those among the lowest quarter. “We know of no published studies investigating the possible associations of dietary patterns with risk of sudden cardiac death,” wrote authors James M. Shikany, DrPH, of the University of Alabama at Birmingham, and colleagues. However, they remarked that protective effects against the condition have been revealed in association with nuts and fish, which are Mediterranean diet components. They added that the omega 3 fatty acids in fatty fish have been proposed as responsible for the benefit observed in association with greater fish intake and may help protect against sudden cardiac death via their effects on resting heart rate, blood pressure, vascular endothelial function, triglyceride concentrations, inflammatory pathways and other factors. Furthermore, laboratory studies have revealed antiarrhythmic effects for omega 3s.  “Although observational in nature, these data suggest that diet may be a modifiable risk factor for sudden cardiac death and should be discussed with patients,” they wrote.         Aging-US: Dietary supplementation with green tea catechins and cocoa flavanols Cocoa, but not GTE, reduced aging-associated microgliosis and increased the proportion of neuroprotective microglial phenotypes Universitat de Lleida and Institut de Recerca Biomèdica de Lleida (Spain), September 1, 2021 Aging-US published "Beneficial effects of dietary supplementation with green tea catechins and cocoa flavanols on aging-related regressive changes in the mouse neuromuscular system" which reported that green tea extract (GTE) and cocoa-supplemented diets significantly improved survival rate of mice. GTE increased density of VAChT and VGluT2 afferent synapses on neuromuscular junctions. Cocoa, but not GTE, reduced aging-associated microgliosis and increased the proportion of neuroprotective microglial phenotypes. Dr. Jordi Calderó from IRBLleida said, "Sarcopenia, the progressive loss of skeletal muscle mass and function with age, is considered the main causative factor of the physical performance decline in the elderly." Sarcopenia, the progressive loss of skeletal muscle mass and function with age, is considered the main causative factor of the physical performance decline in the elderly. The compromised muscular function associated to sarcopenia has a negative impact on the life quality of older adults and increases the risk for disability, fall-associated injuries, morbidity, and mortality. The authors have recently reported a marked increase in the microglial and astroglial pro-inflammatory phenotypes (M1 and A1, respectively) in the spinal cord of aged mice. This may be due to the presence of anti-inflammatory and neuroprotective (M2 and A2) glial subpopulations. Caloric restriction, based on a diet low in calories, has been shown to attenuate aging sarcopenia in various species by acting at different levels of the skeletal muscle. Caloric restriction has also been reported to ameliorate age-related changes in rodent NMJs and to prevent MN and motor axon degeneration found to occur with aging [11, 21]. In a similar way, some dietary supplements have been shown to counteract age related changes that contribute to neuromuscular dysfunction (reviewed by [12) Plant flavonoids have gained particular attention as dietary compounds for keeping good health and preventing a number of diseases, particularly cardiac disorders and cancer. The Calderó Research Team concluded in their Aging-US Research Output that, green tea and cocoa flavonoids from GTE and cocoa significantly increased survival rate of aged mice. Both diets preserved NMJ innervation and maturity, delayed the senescence process of the skeletal muscle, and enhanced its regenerative capacity. Future research is needed to investigate whether higher doses of flavonoid are needed and/or longer-term interventions can help restore proper motor function.   How the mind sharpens the senses Ruhr University Bochum (Germany), August 27, 2021 A study conducted with experienced scholars of Zen-Meditation shows that mental focussing can induce learning mechanisms, similar to physical training. Researchers at the Ruhr-University Bochum and the Ludwig-Maximilians-University München discovered this phenomenon during a scientifically monitored meditation retreat. The journal Scientific Reports, from the makers of Nature, has now published their new findings on the plasticity of the brain. Participants of the study use a special meditation technique The participants were all Zen-scholars with many years of meditation practice. They were scientifically escorted during a four-day Zen-retreat in the spiritual center "Benediktushof", Germany. The retreat was held in complete silence, with at least eight hours of meditation per day. All participants practiced their familiar meditation, which is characterized by a non-specific monitoring of thoughts and surroundings. Additionally, some participants applied a special finger-meditation for two hours per day, during which they were asked to specifically focus on their right index finger and become aware of spontaneously arising sensory percepts in this finger. Subsequent assessment of the group that practiced finger-meditation showed a significant improvement in the tactile acuity of the right index and middle finger. A control group that had maintained their familiar meditation practice for the whole time, showed no changes in tactile acuity. Data show significant improvement of the sense of touch In order to assess the sense of touch quantitatively, researchers measured the so-called "two-point discrimination threshold". This marker indicates how far apart two stimuli need to be, in order to be discriminated as two separate sensations. After the finger meditation, the performance improved on average by 17 percent. By comparison, tactile acuity of the visually impaired is 15 to 25 percent above that of typical sighted individuals, because their sense of touch is used so intensively to make up for the reduced visual information. Hence, the changes induced by meditation are comparable to those achieved by intense long-term training. Meditation induces plasticity and learning processes as active training or physical stimulation It is known for long that extensive training induces neuroplasticity, which denotes the ability of the brain to adapt and restructure itself, thereby improving perception and behavior. Recently, the group of neuroscientists of the Neural Plasticity Lab headed by Hubert Dinse has shown that these processes can be initiated even without training by mere exposure to passive stimulation, which was translated only recently into a stimulating glove, which is used as therapeutical intervention in stroke patients. The fact that merely mental states without any physical stimulation can improve perception has now been shown for the first time. "The results of our study challenge what we know about learning mechanisms in the brain. Our concept of neuroplasticity must be extended, because mental activity seems to induce learning effects similar to active stimulation and physical training," Dinse suggests.      Antibiotics increase the risk of colon cancer Umea University (Sweden), September 1, 2021 There is a clear link between taking antibiotics and an increased risk of developing colon cancer within the next five to ten years. This has been confirmed by researchers at Umeå University, Sweden, after a study of 40,000 cancer cases. The impact of antibiotics on the intestinal microbiome is thought to lie behind the increased risk of cancer. “The results underline the fact that there are many reasons to be restrictive with antibiotics. While in many cases antibiotic therapy is necessary and saves lives, in the event of less serious ailments that can be expected to heal anyway, caution should be exercised. Above all to prevent bacteria from developing resistance but, as this study shows, also because antibiotics may increase the risk of future colon cancer,” explains Sophia Harlid, cancer researcher at Umeå University. Researchers found that both women and men who took antibiotics for over six months ran a 17 per cent greater risk of developing cancer in the ascending colon, the first part of the colon to be reached by food after the small intestine, than those who were not prescribed any antibiotics. However, no increased risk was found for cancer in the descending colon. Nor was there an increased risk of rectal cancer in men taking antibiotics, while women taking antibiotics had a slightly reduced incidence of rectal cancer. The increased risk of colon cancer was visible already five to ten years after taking antibiotics. Although the increase in risk was greatest for those taking most antibiotics, it was also possible to observe an admittedly small, but statistically significant, increase in the risk of cancer after a single course of antibiotics. The present study uses data on 40,000 patients from the Swedish Colorectal Cancer Registry from the period 2010–2016. These have been compared to a matched control group of 200,000 cancer-free individuals drawn from the Swedish population at large. Data on the individuals' antibiotic use was collected from the Swedish Prescribed Drug Register for the period 2005–2016. The Swedish study broadly confirms the results of an earlier, somewhat smaller British study. In order to understand how antibiotics increase the risk, the researchers also studied a non-antibiotic bactericidal drug used against urinary infections that does not affect the microbiome. There was no difference in the frequency of colon cancer in those who used this drug, suggesting that it is the impact of antibiotics on the microbiome that increases the risk of cancer. While the study only covers orally administered antibiotics, even intravenous antibiotics may affect the gut microbiota in the intestinal system. “There is absolutely no cause for alarm simply because you have taken antibiotics. The increase in risk is moderate and the affect on the absolute risk to the individual is fairly small. Sweden is also in the process of introducing routine screening for colorectal cancer. Like any other screening programme, it is important to take part so that any cancer can be detected early or even prevented, as cancer precursors can sometimes be removed,” says Sophia Harlid.      High dose vitamin C may stop the progression of leukemia, study reveals Perlmutter Cancer Center at New York University August 28, 2021 Exciting new research shows that a six-month regimen of high-dose intravenous vitamin C slowed the progression of leukemia by stopping leukemic cells from multiplying. The study builds upon other research that demonstrates vitamin C's potential to inhibit and even kill cancer cells – without harming healthy tissue. Let's take a closer look at how vitamin C is demonstrating its amazing potential to fight cancer. Vitamin C stimulates a vital cancer-fighting enzyme In leukemia, white blood cells fail to mature, so they regenerate themselves and multiply uncontrollably – a process that stops the body from producing the mature white blood cells needed by the immune system to fight infections. Researchers have discovered that a gene mutation plays a major role in the development of many cases of leukemia. 50 percent of patients with chronic myelomonocytic leukemia, 30 percent of patients with pre-leukemia and 10 percent of acute myeloid leukemia patients have a genetic disorder that decreases amounts of TET2 – a vital enzyme that helps undifferentiated cells mature into normal blood cells. This TET2 gene mutation accounts for 42,500 cancers yearly in the United States. The new study, conducted at Perlmutter Cancer Center at New York University Langone Health and published in the peer-reviewed scientific journal Cell, examined vitamin C's potential to stimulate TET2 – and the results were encouraging. Genetically restoring TET2 blocks replication of cancer cells and safely kills them The researchers found that intravenous high-dose vitamin C helps restore TET2 function, causing “faulty” stem cells in bone marrow to die off. Vitamin C produced results when it was used on human leukemia cells carrying the TET2 mutation – and it also stopped the growth of transplanted leukemia cancer stem cells in mice that had been genetically engineered to lack TET2. The vitamin achieved this effect by promoting DNA demethylation in the cancerous cells. Researchers also found that combining vitamin C with PARP inhibitors – drugs which cause cancer cell death – improved its effectiveness even more. In fact, vitamin C seemed to have a potentiating effect, making the leukemic cells more vulnerable to the PARP inhibitors. Study author Benjamin Neel, Ph.D., noted that the team was excited by the prospect that high-dose vitamin C might become a “safe treatment for blood diseases caused by TET2-deficient leukemia stem cells, most likely in combination with other targeted therapies.” Neel called for preclinical and clinical trials to test high-dose intravenous vitamin C in human patients – and for further research to identify other substances that might help to potentiate the vitamin C treatment. Researchers are particularly hopeful that using vitamin C with cancer drugs could provide an alternative to toxic chemotherapy – which can be dangerous and even fatal to patients with acute myeloid leukemia. Note: The researchers used extremely high dosages of intravenous vitamin C in the study – amounts that would be impossible to obtain by oral ingestion alone. Amazing NEWS: Vitamin C has outperformed approved clinical and experimental drugs Other recent, peer-reviewed research is blazing exciting new inroads into the area of potential uses of this powerful vitamin to stop cancer. In a study newly published in Oncotarget, researcher found that high-dose vitamin C stopped tumors cold by impairing cancer stem cell metabolism and interfering with their ability to grow and spread. Researchers noted that the nutrient worked as a pro-oxidant in cancer cells – stripping them of the antioxidant glutathione and producing oxidative stress and apoptosis, or cell death. In addition, vitamin C interfered with glycolysis, the process that creates energy in cell mitochondria. And, while lethal to cancer cells, it left healthy cells unaffected. The researchers concluded that vitamin C was a “promising new agent,” and called for more study to explore its use in preventing and slowing tumors. The team also reported that vitamin C outperformed seven different substances, including stiripinol – an FDA-approved clinical drug – and various experimental medications. Researchers noted that vitamin C was 1,000 times – that's right, 1,000 times – more effective in combating cancer stem cells than 2-DG, an experimental pharmaceutical drug. (It is hard to understand why these eye-opening results have received so little attention from mainstream medicine. Especially in light of the fact that – unlike toxic chemotherapy drugs – this essential vitamin has caused few side effects in clinical studies.) But, I think we can quickly see how this news might be threatening to the profits of the pharmaceutical industry. The fact is: conventional medicine has long downplayed or ignored promising vitamin C research. But, as forward-thinking, innovative researchers continue to examine vitamin C's many benefits, its potential to combat cancer may yet be recognized.

In this episode, Imani and Reginald discuss with Dr. Backhus and Dr. Goodney the historical implications of the longstanding poor relationship between the Black community and the medical community, and its effect on current practices and patient care in vascular surgery. They also explore the role of research in creating demonstrable changes in practice to aid in ameliorating this relationship. Leah Backhus, MD, MPH, FACS (@leahbackhusmd) practices at Stanford Hospital and is Chief of Thoracic Surgery at the VA Palo Alto, where she focuses on thoracic oncology and minimally invasive surgical techniques. She is also Co-Director of the Thoracic Surgery Clinical Research Program and has grant funding through the Veterans Affairs Administration and NIH. Her current research interests are in imaging surveillance following treatment for lung cancer and cancer survivorship. She is a member of the National Lung Cancer Roundtable of the American Cancer Society serving as Chair of the Task Group on Lung Cancer in Women. She also serves on the Board of Directors of the Society of Thoracic Surgeons. As an educator, Dr. Backhus is the Associate Program Director for the Thoracic Track Residency and is the Chair of the ACGME Residency Review Committee for Thoracic Surgery.  Phillip Goodney MD, MS (@DartmthSrgHSR) is a vascular surgeon, health services researcher, Vice-Chair of Research in the Department of Surgery, Director of the Center for the Evaluation of Surgical Care at Dartmouth (CESC), and Co-Director of the VA Outcomes Group at Veterans Affairs Medical Center in White River Junction, Vermont. His research interests include outcomes assessment using both quantitative and qualitative methods, clinical trials, patient preferences, and shared decision making. He received a Career Development Award from the National Heart, Lung, and Blood Institute in 2010, the Lifeline Research Award from the Society for Vascular Surgery (SVS), and research funding from VA HSR&D, PCORI, FDA, and others. He was elected to the American Surgical Association in 2016 and serves on multiple editorial boards of surgical, cardiovascular, and health services journals.  Background The U.S. Public Health Service Syphilis Study at Tuskegee American Eugenics and Forced Sterilization The Story of Henrietta Lacks Johns Hopkins NP Colonoscopy Training Additional Resources:  Warren et al. (2020) “Trustworthiness before Trust — Covid-19 Vaccine Trials and the Black Community.” NEJM, 383(22) Blanchard et al.(2020)  “A Sense of Belonging.” NEJM, 383(15): 1409–1411 Armstrong et al. (2007) “Racial/Ethnic Differences in Physician Distrust in the United States.” AJPH. 97(7): 1283–1289. DeShazo, Richard D. (2020) The Racial Divide in American Medicine: Black Physicians and the Struggle for Justice in Health Care. University Press of Mississippi.  Jacobs et al. (2006) “Understanding African Americans' Views of the Trustworthiness of Physicians.” JGIM. 21(6): 642–647 Frakt, Austin. (2020) “Bad Medicine: The Harm That Comes From Racism.” The New York Times. Tweedy, Damon. (2016) Black Man in a White Coat: a Doctor's Reflections on Race and Medicine. Picador, Armstrong et al. (2013) “Prior Experiences of Racial Discrimination and Racial Differences in Health Care System Distrust.” Medical Care. 51(2): 144–150 Greenwood et al. (2018) “Patient–physician gender concordance and increased mortality among female heart attack patients” PNAS. 115(34): 8569-8574. SVS Foundation VISTA Program Host Introductions Imani McElroy, MD, MPH (@IEMcElroy) is a general surgery resident at the Massachusetts General Hospital in Boston, MA. Reginald Nkansah, MD (@NkansahReginald) is a first-year vascular surgery resident at the University of Wahington in Seattle, WA. What other topics would you like to hear about? Let us know more about you and what you think of our podcast through our Listener Survey or email us at AudibleBleeding@vascularsociety.org. Follow us on Twitter @audiblebleeding Learn more about us at https://www.audiblebleeding.com/about-1/ and #jointheconversation.

Saw palmetto boosts testosterone synthesis Kyung Hee University (South Korea), June 30 2021.   The June 2021 issue of the Journal of Medicinal Food reported the finding of a beneficial effect for saw palmetto against symptoms of andropause in rats.  "Andropause, the male equivalent of menopause, is the set of symptoms caused by the age-related deficiency in male hormones that begins to occur in men in their late 40s to early 50s," Jeong Moon Yun and colleagues explained. "The symptoms of andropause include physical, psychological, and sexual problems, such as fatigue, increased body fat, decreased muscle strength and sexual function, depression, and memory loss." Dr Yun and associates evaluated the effects of an extract of saw palmetto in Leydig cells (in which testosterone biosynthesis occurs) subjected to oxidative stress and in aged rats. In Leydig cells, the administration of testosterone lowered 5 alpha-reductase (which converts testosterone to dihydrotestosterone) and increased total testosterone.  In rats, one of three doses of saw palmetto extract was administered for four weeks. A control group of animals received no treatment. At the end of the treatment period, saw palmetto supplemented rats had significantly less fat tissue weight gain and total weight gain compared to the controls, without a gain in other tissue weight. Serum triglycerides, total cholesterol and the LDL to VLDL cholesterol ratio were also lower in the supplemented groups. Serum total and free testosterone and sperm counts were higher, and sex hormone binding globulin (SHBG) and 5 alpha-reductase levels were lower in all supplemented groups in comparison with the controls. In tests of muscle endurance, rats that received saw palmetto had longer swimming times compared to the control group.  "We suggest that supplementation of saw palmetto may relieve the symptoms of andropause syndrome, including decreased spermatogenesis and muscle endurance and metabolic syndrome by increasing testosterone biosynthesis and bioavailability," the authors concluded.         Diet rich in omega 3 fatty acids may help reduce headaches Trial provides 'grounds for optimism' for many people with persistent headaches and those who care for them University of North Carolina, July 1, 2021 Eating a diet rich in omega 3 (n-3) fatty acids reduces the frequency of headaches compared with a diet with normal intake of omega 3 and omega 6 (n-6) fatty acids, finds a study published by The BMJ today. Modern industrialised diets tend to be low in omega 3 fatty acids and high in omega 6 fatty acids. These fatty acids are precursors to oxylipins - molecules involved in regulating pain and inflammation. Oxylipins derived from omega 3 fatty acids are associated with pain-reducing effects, while oxylipins derived from omega 6 fatty acids worsen pain and can provoke migraine. But previous studies evaluating omega 3 fatty acid supplements for migraine have been inconclusive. So a team of US researchers wanted to find out whether diets rich in omega 3 fatty acids would increase levels of the pain-reducing 17-hydroxydocosahexaenoic acid (17-HDHA) and reduce the frequency and severity of headaches. Their results are based on 182 patients at the University of North Carolina, USA (88% female; average age 38 years) with migraine headaches on 5-20 days per month who were randomly assigned to one of three diets for 16 weeks.  The control diet included typical levels of omega 3 and omega 6 fatty acids. Both interventional diets raised omega 3 fatty acid intake. One kept omega 6 acid intake the same as the control diet, and the other concurrently lowered omega 6 acid intake. During the trial, participants received regular dietary counseling and access to online support information. They also completed the headache impact test (HIT-6) - a questionnaire assessing headache impact on quality of life. Headache frequency was assessed daily with an electronic diary. Over the 16 weeks, both interventional diets increased 17-HDHA levels compared with the control diet, and while HIT-6 scores improved in both interventional groups, they were not statistically significantly different from the control group.  However, headache frequency was statistically significantly decreased in both intervention groups.  The high omega 3 diet was associated with a reduction of 1.3 headache hours per day and two headache days per month. The high omega 3 plus low omega 6 diet group saw a reduction of 1.7 headache hours per day and four headache days per month, suggesting additional benefit from lowering dietary omega-6 fatty acid.  Participants in the intervention groups also reported shorter and less severe headaches compared with those in the control group. This was a high quality, well designed trial, but the researchers do point to some limitations, such as the difficulty for patients to stick to a strict diet and the fact that most participants were relatively young women so results may not apply to children, older adults, men, or other populations.  "While the diets did not significantly improve quality of life, they produced large, robust reductions in frequency and severity of headaches relative to the control diet," they write.  "This study provides a biologically plausible demonstration that pain can be treated through targeted dietary alterations in humans. Collective findings suggest causal mechanisms linking n-3 and n-6 fatty acids to [pain regulation], and open the door to new approaches for managing chronic pain in humans," they conclude. These results support recommending a high omega 3 diet to patients in clinical practice, says Rebecca Burch at the Brigham and Women's Hospital, in a linked editorial. She acknowledges that interpretation of this study's findings is complex, but points out that trials of recently approved drugs for migraine prevention reported reductions of around 2-2.5 headache days per month compared with placebo, suggesting that a dietary intervention can be comparable or better.  What's more, many people with migraine are highly motivated and interested in dietary changes, she adds. These findings "take us one step closer to a goal long sought by headache patients and those who care for them: a migraine diet backed up by robust clinical trial results."     The Southern diet - fried foods and sugary drinks - may raise risk of sudden cardiac death University of Alabama, June 30, 2021  Regularly eating a Southern-style diet may increase the risk of sudden cardiac death, while routinely consuming a Mediterranean diet may reduce that risk, according to new research published today in the Journal of the American Heart Association, an open access journal of the American Heart Association. The Southern diet is characterized by added fats, fried foods, eggs, organ meats (such as liver or giblets), processed meats (such as deli meat, bacon and hotdogs) and sugar-sweetened beverages. The Mediterranean diet is high in fruits, vegetables, fish, whole grains and legumes and low in meat and dairy. "While this study was observational in nature, the results suggest that diet may be a modifiable risk factor for sudden cardiac death, and, therefore, diet is a risk factor that we have some control over," said James M. Shikany, Dr.P.H., F.A.H.A., the study's lead author and professor of medicine and associate director for research in the Division of Preventive Medicine at the University of Alabama at Birmingham. "Improving one's diet - by eating a diet abundant in fruits, vegetables, whole grains and fish such as the Mediterranean diet and low in fried foods, organ meats and processed meats, characteristics of the Southern-style dietary pattern, may decrease one's risk for sudden cardiac death," he said. The study examined data from more than 21,000 people ages 45 and older enrolled in an ongoing national research project called REasons for Geographic and Racial Differences in Stroke (REGARDS), which is examining geographic and racial differences in stroke. Participants were recruited between 2003 and 2007. Of the participants in this analysis, 56% were women; 33% were Black adults; and 56% lived in the southeastern U.S., which is noteworthy as a region recognized as the Stroke Belt because of its higher stroke death rate. The Stroke Belt states included in this study were North Carolina, South Carolina, Georgia, Tennessee, Alabama, Mississippi, Arkansas and Louisiana. This study is the latest research to investigate the association between cardiovascular disease and diet - which foods have a positive vs. negative impact on cardiovascular disease risk. It may be the only study to-date to examine the association between dietary patterns with the risk of sudden cardiac death, which is the abrupt loss of heart function that leads to death within an hour of symptom onset. Sudden cardiac death is a common cause of death and accounted for 1 in every 7.5 deaths in the United States in 2016, or nearly 367,000 deaths, according to 2019 American Heart Association statistics. Researchers included participants with and without a history of coronary heart disease at the beginning of the study and assessed diets through a food frequency questionnaire completed at the beginning of the study. Participants were asked how often and in what quantities they had consumed 110 different food items in the previous year. Researchers calculated a Mediterranean diet score based on specific food groups considered beneficial or detrimental to health. They also derived five dietary patterns. Along with the Southern-style eating pattern, the analysis included a "sweets" dietary pattern, which features foods with added sugars, such as desserts, chocolate, candy and sweetened breakfast foods; a "convenience" eating pattern which relied on easy-to-make foods like mixed dishes, pasta dishes, or items likely to be ordered as take-out such as pizza, Mexican food and Chinese food; a "plant-based" dietary pattern was classified as being high in vegetables, fruits, fruit juices, cereal, bean, fish, poultry and yogurt; and an "alcohol and salad" dietary pattern, which was highly reliant on beer, wine, liquor along with green leafy vegetables, tomatoes and salad dressing. Shikany noted that the patterns are not mutually exclusive. "All participants had some level of adherence to each pattern, but usually adhered more to some patterns and less to others," he explained. "For example, it would not be unusual for an individual who adheres highly to the Southern pattern to also adhere to the plant-based pattern, but to a much lower degree." After an average of nearly 10 years of follow-up every six months to check for cardiovascular disease events, more than 400 sudden cardiac deaths had occurred among the 21,000 study participants. The study found: Overall, participants who ate a Southern-style diet most regularly had a 46% higher risk of sudden cardiac death than people who had the least adherence to this dietary pattern. Also, participants who most closely followed the traditional Mediterranean diet had a 26% lower risk of sudden cardiac death than those with the least adherence to this eating style. The American Heart Association's Diet and Lifestyle recommendations emphasize eating vegetables, fruits, whole grains, lean protein, fish, beans, legumes, nuts and non-tropical vegetable cooking oils such as olive and canola oil. Limiting saturated fats, sodium, added sugar and processed meat are also recommended. Sugary drinks are the number one source of added sugar in the U.S. diet, according to the Centers for Disease Control and Prevention, and the American Heart Association supports sugary drink taxes to drive down consumption of these products. "These findings support the notion that a healthier diet would prevent fatal cardiovascular disease and should encourage all of us to adopt a healthier diet as part of our lifestyles," said Stephen Juraschek, M.D., Ph.D., a member of the American Heart Association's Nutrition Committee of the Lifestyle and Cardiometabolic Health Council. "To the extent that they can, people should evaluate the number of servings of fruit and vegetables they consume each day and try to increase the number to at least 5-6 servings per day, as recommended by the American Heart Association. Optimal would be 8-9 servings per day. "This study also raises important points about health equity, food security and social determinants of health," he continued. "The authors describe the "Southern Diet" based on the U.S. geography associated with this dietary pattern, yet it would be a mistake for us to assume that this is a diet of choice. I think American society needs to look more broadly at why this type of diet is more common in the South and clusters among some racial, ethnic or socioeconomic groups to devise interventions that can improve diet quality. The gap in healthy eating between people with means and those without continues to grow in the U.S., and there is an incredible need to understand the complex societal factors that have led and continue to perpetuate these disparities." This current research expands on earlier studies on participants from the same national stroke project, REGARDS. In a 2018 analysis, Shikany and colleagues reported that adults ages 45 and older with heart disease who had an affinity for the Southern diet had a higher risk of death from any cause, while greater adherence to the Mediterranean diet was associated with a lower risk of death from any cause. And in a 2015 study, the Southern diet was linked to a greater risk of coronary heart disease in the same population. The large population sample and regional diversity, including a significant number of Black participants, are considered strengths of the REGARDS research project. However, potential limitations of this study include that that dietary intake was based on one-time, self-reported questionnaires, thus, it relied on the participants' memory. Self-reported diet can include inaccuracies leading to bias that could reduce the strength of the associations observed. One usual association that remains unexplained is that among individuals with a history of heart disease, those who most adhered to the sweets dietary pattern had a 51% lower risk of sudden cardiac death than participants who followed that pattern the least. Researchers note that they found "no viable explanation for the inverse association of the sweets dietary pattern with risk of sudden cardiac death in those with a history of coronary heart disease."     5-minute workout lowers blood pressure as much as exercise, drugs 'Strength training for breathing muscles' holds promise for host of health benefits University of Colorado, July 2, 2021 Working out just five minutes daily via a practice described as "strength training for your breathing muscles" lowers blood pressure and improves some measures of vascular health as well as, or even more than, aerobic exercise or medication, new CU Boulder research shows. The study, published June 29 in the Journal of the American Heart Association, provides the strongest evidence yet that the ultra-time-efficient maneuver known as High-Resistance Inspiratory Muscle Strength Training (IMST) could play a key role in helping aging adults fend off cardiovascular disease - the nation's leading killer.  In the United States alone, 65% of adults over age 50 have above-normal blood pressure - putting them at greater risk of heart attack or stroke. Yet fewer than 40% meet recommended aerobic exercise guidelines. "There are a lot of lifestyle strategies that we know can help people maintain cardiovascular health as they age. But the reality is, they take a lot of time and effort and can be expensive and hard for some people to access," said lead author Daniel Craighead, an assistant research professor in the Department of Integrative Physiology. "IMST can be done in five minutes in your own home while you watch TV." Developed in the 1980s as a way to help critically ill respiratory disease patients strengthen their diaphragm and other inspiratory (breathing) muscles, IMST involves inhaling vigorously through a hand-held device which provides resistance. Imagine sucking hard through a tube that sucks back.  Initially, when prescribing it for breathing disorders, doctors recommended a 30-minute-per-day regimen at low resistance. But in recent years, Craighead and colleagues have been testing whether a more time-efficient protocol--30 inhalations per day at high resistance, six days per week--could also reap cardiovascular, cognitive and sports performance improvements. For the new study, they recruited 36 otherwise healthy adults ages 50 to 79 with above normal systolic blood pressure (120 millimeters of mercury or higher). Half did High-Resistance IMST for six weeks and half did a placebo protocol in which the resistance was much lower.  After six weeks, the IMST group saw their systolic blood pressure (the top number) dip nine points on average, a reduction which generally exceeds that achieved by walking 30 minutes a day five days a week. That decline is also equal to the effects of some blood pressure-lowering drug regimens.  Even six weeks after they quit doing IMST, the IMST group maintained most of that improvement. "We found that not only is it more time-efficient than traditional exercise programs, the benefits may be longer lasting," Craighead said. The treatment group also saw a 45% improvement in vascular endothelial function, or the ability for arteries to expand upon stimulation, and a significant increase in levels of nitric oxide, a molecule key for dilating arteries and preventing plaque buildup. Nitric oxide levels naturally decline with age.  Markers of inflammation and oxidative stress, which can also boost heart attack risk, were significantly lower after people did IMST. And, remarkably, those in the IMST group completed 95% of the sessions. "We have identified a novel form of therapy that lowers blood pressure without giving people pharmacological compounds and with much higher adherence than aerobic exercise," said senior author Doug Seals, a Distinguished Professor of Integrative Physiology. "That's noteworthy." The practice may be particularly helpful for postmenopausal women. In previous research, Seals' lab showed that postmenopausal women who are not taking supplemental estrogen don't reap as much benefit from aerobic exercise programs as men do when it comes to vascular endothelial function. IMST, the new study showed, improved it just as much in these women as in men.  "If aerobic exercise won't improve this key measure of cardiovascular health for postmenopausal women, they need another lifestyle intervention that will," said Craighead. "This could be it." Preliminary results suggest MST also improved some measures of brain function and physical fitness. And previous studies from other researchers have shown it can be useful for improving sports performance. "If you're running a marathon, your respiratory muscles get tired and begin to steal blood from your skeletal muscles," said Craighead, who uses IMST in his own marathon training. "The idea is that if you build up endurance of those respiratory muscles, that won't happen and your legs won't get as fatigued." Seals said they're uncertain exactly how a maneuver to strengthen breathing muscles ends up lowering blood pressure, but they suspect it prompts the cells lining blood vessels to produce more nitric oxide, enabling them to relax. The National Institutes of Health recently awarded Seals $4 million to launch a larger follow-up study of about 100 people, comparing a 12-week IMST protocol head-to-head with an aerobic exercise program. Meanwhile, the research group is developing a smartphone app to enable people to do the protocol at home using already commercially available devices. Those considering IMST should consult with their doctor first. But thus far, IMST has proven remarkably safe, they said. "It's easy to do, it doesn't take long, and we think it has a lot of potential to help a lot of people," said Craighead.   Research suggests atheroprotective role for chrysin Fu Jen Catholic University (Taiwan), July 1, 2021 According to news reporting originating from New Taipei, Taiwan, research stated, “Atherosclerosis and its related clinical complications are the leading cause of death. MicroRNA (miR)-92a in the inflammatory endothelial dysfunction leads to atherosclerosis.” Our news editors obtained a quote from the research from Fu Jen Catholic University, “Kruppel-like factor 2 (KLF2) is required for vascular integrity and endothelial function maintenance. Flavonoids possess many biological properties. This study investigated the vascular protective effects of chrysin in balloon-injured carotid arteries. Exosomes were extracted from human coronary artery endothelial cell (HCAEC) culture media. Herb flavonoids and chrysin (found in mint, passionflower, honey and propolis) were the treatments in these atheroprotective models. Western blotting and real-time PCRs were performed. In situ hybridization, immunohistochemistry, and immunofluorescence analyses were employed. MiR-92a increased after balloon injury and was present in HCAEC culture media. Chrysin was treated, and significantly attenuated the miR-92a levels after balloon injury, and similar results were obtained in HCAEC cultures in vitro. Balloon injury-induced miR-92a expression, and attenuated KLF2 expression. Chrysin increased the KLF2 but reduced exosomal miR-92a secretion. The addition of chrysin and antagomir-92a, neointimal formation was reduced by 44.8 and 49.0% compared with balloon injury after 14 days, respectively. Chrysin upregulated KLF2 expression in atheroprotection and attenuated endothelial cell-derived miR-92a-containing exosomes.” According to the news editors, the research concluded: “The suppressive effect of miR-92a suggests that chrysin plays an atheroprotective role.” This research has been peer-reviewed.     False-positive mammogram results linked to spike in anxiety prescriptions Penn State University, July 2, 2021 Women who experience a false-positive mammogram result are more likely to begin medication for anxiety or depression than women who received an immediate negative result, according to a study led by Penn State researcher Joel Segel. The finding highlights the importance of swift and accurate follow-up testing to rule out a breast cancer diagnosis. The study found that patients who receive a false-positive mammogram result are also prescribed anxiety or depression medication at a rate 10 to 20 percent higher than patients who receive an immediate negative result. These prescriptions are new and not continuations of previously prescribed medicines. A false-positive result is one where a suspicious finding on the screening mammogram leads to additional testing that does not end up leading to a breast cancer diagnosis. Additionally, within that group of patients who required more than one test to resolve the false-positive there was a 20 to 30 percent increase in those beginning to take anxiety or depression medications. The increase was particularly noticeable among women with commercial insurance who required multiple tests to rule out a breast cancer diagnosis. "The results suggest that efforts to quickly resolve initially positive findings including same-day follow-up tests may help reduce anxiety and even prevent initiation of anxiety or depression medication," said Segel, assistant professor of health policy and administration at Penn State. This study demonstrates that some women who experience a false-positive mammogram may need additional follow-up care to effectively handle the increased anxiety that may accompany the experience, Segel said. More importantly, from a practitioner standpoint, the study identifies sub-populations who may be most at risk of increased anxiety following a false-positive mammogram, Segel said. Specifically, women whose false-positive result requires more than one follow-up test to resolve, women with commercial insurance who undergo a biopsy, women who wait longer than one week to receive a negative result, and women who are under age 50 may all be at higher risk of experiencing clinically significant anxiety or depression. "Regular breast cancer screening is critical to early detection," Segel said. "Patients should continue to work with their providers to ensure they are receiving guideline-appropriate screening and should follow up with their providers if they experience either anxiety or depression following screening or any type of care." Researchers studied commercial- and Medicaid-claims databases to identify women ages 40 to 64 who underwent screening mammography with no prior claims for anxiety or depression medications. The findings recently appeared in Medical Care.     Thymoquinone in Black Seed oil increases the expression of neuroprotective proteins while decreasing expression of pro-inflammatory cytokines Florida A&M University, June 29, 2021    According to news originating from Tallahassee, Florida, research stated, "Neuroinflammation and microglial activation are pathological markers of a number of central nervous system (CNS) diseases. Chronic activation of microglia induces the release of excessive amounts of reactive oxygen species (ROS) and pro-inflammatory cytokines." Our news journalists obtained a quote from the research from Florida A&M University, "Additionally, chronic microglial activation has been implicated in several neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Thymoquinone (TQ) has been identified as one of the major active components of the natural product Nigella sativa seed oil. TQ has been shown to exhibit anti-inflammatory, anti-oxidative, and neuroprotective effects. In this study, lipopolysaccharide (LPS) and interferon gamma (IFN gamma) activated BV-2 microglial cells were treated with TQ (12.5 mu M for 24 h). We performed quantitative proteomic analysis using Orbitrap/Q-Exactive Proteomic LC-MS/MS (Liquid chromatography-mass spectrometry) to globally assess changes in protein expression between the treatment groups. Furthermore, we evaluated the ability of TQ to suppress the inflammatory response using ELISArray ™ for Inflammatory Cytokines. We also assessed TQ's effect on the gene expression of NFKB signaling targets by profiling 84 key genes via real-time reverse transcription (RT2) PCR array. Our results indicated that TQ treatment of LPS/IFN gamma-activated microglial cells significantly increased the expression of 4 antioxidant, neuroprotective proteins: glutaredoxin-3 (21 fold; p< 0.001), biliverdin reductase A (15 fold; p< 0.0001), 3-mercaptopyruvate sulfurtransferase (11 fold; p< 0.01), and mitochondria] Ion protease (> 8 fold; p< 0.001) compared to the untreated, activated cells. Furthermore, TQ treatment significantly (P < 0.0001) reduced the expression of inflammatory cytokines, IL-2 = 38%, IL-4 = 19%, IL-6 = 83%, IL-10 = 237%, and IL-17a = 29%, in the activated microglia compared to the untreated, activated which expression levels were significantly elevated compared to the control microglia: IL-2 = 127%, IL-4 = 151%, IL-6 = 670%, IL-10 = 133%, IL-17a = 127%. Upon assessing the gene expression of NFKB signaling targets, this study also demonstrated that TQ treatment of activated microglia resulted in > 7 fold down-regulation of several NFKB signaling targets genes, including interleukin 6 (IL6), complement factor B (CFB), chemokine (C-C motif) ligand 3 (CXCL3), chemokine (C-C) motif ligand 5 (CCL5) compared to the untreated, activated microglia. This modulation in gene expression counteracts the > 10-fold upregulation of these same genes observed in the activated microglia compared to the controls. Our results show that TQ treatment of LPS/IFN gamma-activated BV-2 microglial cells induce a significant increase in expression of neuroprotective proteins, a significant decrease in expression inflammatory cytokines, and a decrease in the expression of signaling target genes of the NF kappa B pathway. Our findings are the first to show that TQ treatment increased the expression of these neuroprotective proteins (biliverdin reductase-A, 3-mercaptopyruvate sulfurtransferase, glutaredoxin-3, and mitochondrial Ion protease) in the activated BV-2 microglial cells. Additionally, our results indicate that TQ treatment decreased the activation of the NF kappa B signaling pathway, which plays a key role in neuroinflammation." According to the news editors, the research concluded: "Our results demonstrate that TQ treatment reduces the inflammatory response and modulates the expression of specific proteins and genes and hence potentially reduce neuroinflammation and neurodegeneration driven by microglial activation."

#25 Do parents parent differently across races? Are there considerations for Black parents that other parents don't have? What's with whuppins? The Souljah's discuss parenting styles, differences in parenting between races, and cross-racial adoption. Plus, Andres can't seem to stop laughing!*** Correction *** In the episode, Andres mentioned John Legend was the first African American to get EGOT status. That was incorrect. He is the first African American male to get the honors. Whoopi Goldberg was the first African American to win all four awards. She won two of those awards in the same year.Helpful LinksParenting styles Pew Research https://www.pewresearch.org/social-trends/2015/12/17/3-parenting-approaches-and-concerns/Racial Differences and academic achievement https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930341/Racial Differences in Parenting Styles https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4362953/ and https://etd.ohiolink.edu/apexprod/rws_etd/send_file/send?accession=bgsu1320162825&disposition=inlineInfluence off Race on Parent Judgements https://www.irp.wisc.edu/publications/focus/pdfs/foc242e.pdfRacial and Ethnic Differences in Parenting Stress https://link.springer.com/article/10.1007/s10826-013-9833-zParenting differences across cultures https://theconversation.com/parenting-practices-around-the-world-are-diverse-and-not-all-about-attachment-111281Corporal Punishment https://www.apa.org/pi/families/resources/newsletter/2017/04/racial-traumahttps://www.verywellfamily.com/types-of-parenting-styles-1Parenting Styles, Economics, and Extracurricular activities https://journals.sagepub.com/doi/pdf/10.1177/0192513X10386305095045Rita Moreno - In Praise Of the Only Living EGOT Who's Won All 4 Awards as a Performer [Billboard]MacKenzie Thomas album https://open.spotify.com/album/7v6ZSabXARDkpTRmNRzFeR?si=86XtP00KS6GPU97_iarSJA————————————Plenty of options to connect with us:Email: hello@christiansouljah.com Hit us up on social media:Facebook: http://facebook.com/groups/christiansouljahInstagram: https://www.instagram.com/christiansouljah/Abdullah's Instagram and Twitter: @Dat_Dude_DullahJustine's Facebook: https://www.facebook.com/tina.akinyi.7Andres' Twitter @Andres_Amador

In this soundbite, William Schaffner, MD, speaks about the differences in COVID-19 vaccination intent and factors that affect COVID-19 vaccination acceptance, including what is being done to bridge gaps and encourage uptake in the Black population. This topic was presented at the 2021 virtual Annual Conference on Vaccinology Research sponsored by the National Foundation for Infectious Diseases.

Misusing the term "racial differences" when we really mean "cultural differences". This is National Military Appreciation Month. Mike speaks with the founder of Warrior Foundation Freedom Station, Sandy Lehmkuhler, about a very special even happening on Memorial Day.

In this episode we interview historian of science Iris Clever about her research untangling the early 20th century entanglements of the biometricians, physical anthropology, and race. She pursues this topic through the exploration of work by the statistician and Galton protégé, Karl Pearson, and one of Pearson’s favorite students, Geoffrey Morant. Morant, who publicly opposed Nazi racism in the 1930s and 40s maintained the biological reality of race and the possibility of racial differences in mental characteristics. Resources: Clever, I., & Ruberg, W. (2014). Beyond Cultural History? The Material Turn, Praxiography, and Body History. Humanities, 3(4), 546-566. https://www.mdpi.com/2076-0787/3/4/546/htm Morant, G. M. (1934). 126. A Biometrician's View of Race in Man. Man, 99-105. https://www.jstor.org/stable/2790912 Morant, G. M. (1939). The races of central Europe: A footnote to history: G. Allen & Unwin Limited. Morant, G. M. (1952). The Significance of Racial Differences. Paris: UNESCO. Wagenmakers, E.-J. (2018, 5/3/2018). Karl Pearson’s Worst Quotation? [Racist quotes from Karl Pearson's writings]. Retrieved from https://www.bayesianspectacles.org/karl-pearsons-worst-quotation/

In this episode, we learn how the incorrect choices we make in the food we eat can affect our brains long term.   This episode is sponsored by WYSK Spark Radio, https://live365.com/station/Spark-Radio-a82219. To keep this podcast going please feel free to donate at https://paypal.me/yopistudio?locale.x=en_US If you would like to read more on this topic or any other previous topics, you can do so by checking out our blog at https://yopistudio.blogspot.com/ Feel free to see what we are up to by following us at:  https://twitter.com/Dauricee https://www.facebook.com/yopistudio/ https://www.facebook.com/LouisianaEntertainmentAssociation/ To listen to the podcast, watch creative videos and skits go to https://www.youtube.com/channel/UCvn6tns6wKUwz9xZw11_vAQ/videos Interested in projects Daurice has worked on in the movie industry you can check it out at www.IMDb.com under Daurice Cummings. For comments or questions, you can reach us at yopi@post.com To read more about today’s topic check out the references below. Previous Episodes of Interest: https://yopistudio.podbean.com/e/can-you-guess-the-worst-ingredient-for-your-body-70/ https://yopistudio.podbean.com/e/the-effects-of-soda-in-your-body-68/ https://yopistudio.podbean.com/e/ep-38-nutty-for-brain-power/ References: Widya RL, Kroft LJM, Altmann-Schneider I, et al. Visceral adipose tissue is associated with microstructural brain tissue damage. Obesity. 2015;23(5):1092-1096. doi:10.1002/ oby.21048 Rippe JM, Angelopoulos TJ. Sucrose, High-Fructose Corn Syrup, and Fructose, Their Metabolism and Potential Health Effects: What Do We Really Know?12. Adv Nutr. 2013;4(2):236-245. doi:10.3945/an.112.002824 Berti V, Murray J, Davies M, et al. Nutrient patterns, and brain biomarkers of Alzheimer’s disease in cognitively normal individuals. J Nutr Health Aging. 2015;19(4):413-423. doi:10.1007/s12603-014-0534-0 Gu Y, Scarmeas N. Dietary Patterns in Alzheimer’s Disease and Cognitive Aging. Curr Alzheimer Res. 2011;8(5):510-519. Molteni R, Barnard RJ, Ying Z, Roberts CK, Gómez-Pinilla F. A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning. Neuroscience. 2002;112(4):803-814. doi:10.1016/s0306-4522(02)00123-9 Lennerz BS, Alsop DC, Holsen LM, et al. Effects of dietary glycemic index on brain regions related to reward and craving in men. Am J Clin Nutr. 2013;98(3):641-647. doi:10.3945/ajcn.113.064113 Qiu Q, Lin X, Sun L, et al. Cognitive decline is related to high blood glucose levels in older Chinese adults with the ApoE ε3/ε3 genotype. Transl Neurodegener. 2019;8. doi:10.1186/ s40035-019-0151-2 Beilharz JE, Maniam J, Morris MJ. Short-term exposure to a diet high in fat and sugar, or liquid sugar, selectively impairs hippocampal-dependent memory, with differential impacts on inflammation. Behav Brain Res. 2016;306:1-7. doi:10.1016/j.bbr.2016.03.018 Akiyama H, Barger S, Barnum S, et al. Inflammation and Alzheimer’s disease. Neurobiol Aging. 2000;21(3):383-421 Kiage JN, Merrill PD, Robinson CJ, et al. Intake of trans fat and all-cause mortality in the Reasons for Geographical and Racial Differences in Stroke (REGARDS) cohort. Am J Clin Nutr. 2013;97(5):1121-1128. doi:10.3945/ajcn.112.049064 Ginter E, Simko V. New data on harmful effects of trans-fatty acids. Bratisl Lek Listy. 2016;117(5):251-253. doi:10.4149/bll_2016_048 Patterson E, Wall R, Fitzgerald GF, Ross RP, Stanton C. Health Implications of High Dietary Omega-6 Polyunsaturated Fatty Acids. J Nutr Metab. 2012;2012. doi:10.1155/2012/539426 Sánchez-Villegas A, Verberne L, Irala JD, et al. Dietary Fat Intake and the Risk of Depression: The SUN Project. PLOS ONE. 2011;6(1):e16268. doi:10.1371/journal. pone.0016268 Bühler M, Mann K. Alcohol and the Human Brain: A Systematic Review of Different Neuroimaging Methods. Alcohol Clin Exp Res. 2011;35(10):1771-1793. doi:10.1111/j.1530- 0277.2011.01540.x Ebrahim IO, Shapiro CM, Williams AJ, Fenwick PB. Alcohol and sleep I: effects on normal sleep. Alcohol Clin Exp Res. 2013;37(4):539-549. doi:10.1111/acer.12006 Zahr NM, Kaufman KL, Harper CG. Clinical and pathological features of alcohol-related brain damage. Nat Rev Neurol. 2011;7(5):284-294. doi:10.1038/nrneurol.2011.42 Bertelli AAA, Das DK. Grapes, wines, resveratrol, and heart health. J Cardiovasc Pharmacol. 2009;54(6):468-476. doi:10.1097/FJC.0b013e3181bfaff3 Beilharz JE, Maniam J, Morris MJ. Diet-Induced Cognitive Deficits: The Role of Fat and Sugar, Potential Mechanisms and Nutritional Interventions. Nutrients. 2015;7(8):6719- 6738. doi:10.3390/nu7085307 Henderson ST. High carbohydrate diets and Alzheimer’s disease. Med Hypotheses. 2004;62(5):689-700. doi:10.1016/j.mehy.2003.11.028 Oddy WH, Allen KL, Trapp GSA, et al. Dietary patterns, body mass index and inflammation: Pathways to depression and mental health problems in adolescents. Brain Behav Immun. 2018;69:428-439. doi:10.1016/j.bbi.2018.01.002 Lenoir M, Serre F, Cantin L, Ahmed SH. Intense Sweetness Surpasses Cocaine Reward. PLoS ONE. 2007;2(8). doi:10.1371/journal.pone.0000698 Humphries P, Pretorius E, Naudé H. Direct and indirect cellular effects of aspartame on the brain. Eur J Clin Nutr. 2008;62(4):451-462. doi:10.1038/sj.ejcn.1602866 Lindseth GN, Coolahan SE, Petros TV, Lindseth PD. Neurobehavioral effects of aspartame consumption. Res Nurs Health. 2014;37(3):185-193. doi:10.1002/nur.21595 Pase MP, Himali JJ, Beiser AS, et al. Sugar- and artificially sweetened beverages and the risks of incident stroke and dementia: A prospective cohort study. Stroke. 2017;48(5):1139-1146. doi:10.1161/STROKEAHA.116.016027 de la Monte SM, Neusner A, Chu J, Lawton M. Epidemiological Trends Strongly Suggest Exposures as Etiologic Agents in the Pathogenesis of Sporadic Alzheimer’s Disease, Diabetes Mellitus, and Non-Alcoholic Steatohepatitis. J Alzheimers Dis JAD. 2009;17(3):519-529. doi:10.3233/JAD-2009-1070 Khambadkone SG, Cordner ZA, Dickerson F, et al. Nitrated meat products are associated with mania in humans and altered behavior and brain gene expression in rats. Mol Psychiatry. 2020;25(3):560-571. doi:10.1038/s41380-018-0105-6 Tong M, Neusner A, Longato L, Lawton M, Wands JR, de la Monte SM. Nitrosamine Exposure Causes Insulin Resistance Diseases: Relevance to Type 2 Diabetes Mellitus, NonAlcoholic Steatohepatitis, and Alzheimer’s Disease. J Alzheimers Dis JAD. 2009;17(4):827- 844. Presley TD, Morgan AR, Bechtold E, et al. Acute effect of a high nitrate diet on brain perfusion in older adults. Nitric Oxide. 2011;24(1):34-42. doi:10.1016/j.niox.2010.10.002    

This week on the pod Tiff and Autumn celebrate Selena Sloan Butler and discuss parent involvement in K-12 education. Racial Differences in Parent Involvement in K-12 School Activities

In this issue, author Monika Safford and Associate Editor discuss the article “Number of Social Determinants of Health and Fatal and Nonfatal Incident Coronary Heart Disease in the REGARDS Study (Reasons for Geographic and Racial Differences in Stroke).” Then authors Jennifer Ho and Timothy Churchill discuss their Research Letter “Evaluation of 2 Existing Diagnostic Scores for Heart Failure With Preserved Ejection Fraction Against a Comprehensively Phenotyped Cohort.”   TRANSCRIPT BELOW: 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 Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, director of the Pauley Heart Center at VCU health in Richmond, Virginia. Dr. Carolyn Lam: Guess what, Greg? We're going to talk to a lovely friend and wonderful colleague Dr. Jennifer Ho soon regarding her research letter on the HFpEF diagnostic scoring criteria. Dr. Greg Hundley: Very nice, Carolyn. Well, I've also got another feature discussion in this issue involving the reasons for geographic and racial differences in stroke. It's from the REGARDS study. But first, how about we grab a cup of coffee and jump into the next articles in the issue. Dr. Carolyn Lam: I've got my coffee, Greg and I'm ready to tell you about acute infection and endotoxinemia. We know that infections are a well-established risk factor for cardiovascular inflammation, increasing the risk for a cardiovascular complication within the first weeks after that infection. However, what is the mechanism underlying such an association? Well here, Dr. Soehnlein from Germany and colleagues utilized a model of endotoxinemia to link acute infection and subsequent neutrophil activation with acceleration of vascular inflammation. Acute infection was mimicked by injection of a single dose of lipopolysaccharide into hypercholesterolemic mice. Dr. Greg Hundley: So, Carolyn, what did they find? Dr. Carolyn Lam: Well they found that neutrophils and specifically neutrophil extracellular traps controlled accelerated atherosclerosis during endotoxinemia. These neutrophil extracellular traps or NET-resident histone H2a, heightened arterial monocyte recruitment in endotoxinemia in a mechanism involving electrostatic charge interaction. The clinical implications are that therapeutic neutralization of NET-resident cationic molecules, including histone H2a by use of antibodies or peptides may protect patients at cardiovascular risk during an acute infection from secondary events. Dr. Greg Hundley: Wow, Carolyn. Really interesting. Well, my paper comes from Dr. David Park from New York University School of Medicine. Carolyn, elevated intracardiac pressure due to heart failure, induces electrical and structural remodeling in the left atrium that begets atrial myopathy and arrhythmias. The underlying molecular pathways that drive atrial remodeling during cardiac pressure overload are poorly defined. The authors sought in this study to characterize the response of the ETV1 signaling axis in the left atrium during cardiac pressure overload in humans and mouse models and explore the role of ETV1 in atrial electrical and structural remodeling. Dr. Carolyn Lam: Nice. And so what did they find, Greg? Dr. Greg Hundley: Well Carolyn, using the Cleveland Clinic Biobank of human left atrial specimens and their mouse models, these authors found that ETV1 is down regulated in the left atrium during cardiac pressure overload, thereby contributing to both electrical and structural remodeling of the left atrium. Dr. Carolyn Lam: Nice. Well Greg, let's talk about what else is in today's issue. There's a Perspective piece from Dr. Delgado on “Changing the Paradigm in the Management of Valvular Heart Disease: In Addition to Left Ventricular Ejection Fraction, Focus on the Myocardium. There's a Research Letter from Dr. Lurz on closure of iatrogenic atrial septal defect following transcatheter mitral valve repair, the randomized MITHRAS trial. There's an exchange of letters between Dr. McAvoy and Dr. Kim regarding the article, Cardiovascular Risk of Isolated Systolic or Diastolic Hypertension in Young Adults. And an ECG challenge by Dr. Avila on complete AV block cured by atrial pacing. Dr. Greg Hundley: Very nice, Carolyn. Dr. David Saadoun has an In Depth review on medium and large vessel vasculitis and Dr. Christy Avery has a Research Letter reporting on the trends in US cancer and heart disease mortality from the period of 1999 through 2018. Well, Carolyn, how about now we jump into those feature discussions? Dr. Carolyn Lam: Yep, double features. Here we go. Dr. Greg Hundley: Well listeners, this is the first of our double feature on this January 19th and we're so fortunate today to have Monika Safford from Weill Cornell in New York and our own associate editor, Mercedes Carnethon from Northwestern University in Chicago. Monika, we'll start with you. Could you tell us a little of the background information pertaining to this study and what hypothesis did you want to address? Dr. Monika Safford: Sure. Well, thank you first of all, for the opportunity. We've been studying social determinants of health. I think there's a lot of attention that has come on social determinants of health from health system perspectives in recent years but I think there's less of a recognition of individual practicing physicians of what they can do. What's happened is that there are population managers at most health systems and it seems like it's a fairly distant undertaking compared to day to day clinical care. We wondered whether there was a way to begin to integrate social determinants of health more in the day to day management of patients. And that was really the major motivation here was to take this fairly late recognition, I think, compared to the sociology world of the importance and the relative importance of social determinants to see if we could help clinicians actually use this information to inform their clinical management.   Dr. Greg Hundley: Very nice. And so what was the study population that you worked with? And what was your study design? Dr. Monika Safford: Sure. The REGARDS study, REGARDS stands for reasons for geographic and racial differences in stroke, is a large national cohort, more than 30,000 people who live all over the 48 contiguous United States. About 44% of them are African-Americans and the rest are whites. Everybody was 45 and older at the time of their recruitment between 2003 and 2007. And we're now following them longitudinally for outcomes and among the outcomes are coronary heart disease and a causes of death. It's a terrific cohort to study racial disparities, if you're interested in differences between African-Americans and whites. Dr. Greg Hundley: And what did you find? Dr. Monika Safford: We did find, which was our initial hypothesis, that the greater the burden of social determinants that an individual is exposed to, the greater the independent risk. There's a definite graded risk. If you just simply count up social determinants, that should really be part of the social history that we're all taught to take in medical school. The greater the number, the higher the risk. And what was really quite concerning was that once you adjusted for all of the things that are available in a typical cohort study, physiologic measures, past medical history, health behaviors. There still was this massive, independent effect, 50% greater after accounting for all of those wonderful phenotypic markers that we have available in a cohort study. Dr. Greg Hundley: And what were some examples of these social determinants that we should all be thinking about? Dr. Monika Safford: Sure. Educational level. We all ask our patients, what was their educational attainment? Income has come a little bit under scrutiny. We don't typically ask our patients what's your annual household income? But there are lots of proxy markers so we are aware of what our patients can afford and can't afford when we prescribe medications. We have to know whether or not this is something that is within the realm of possible for individual patients. We should get a very good sense of what their financial situation is. Their social circumstances. Are they isolated? Do they live alone? Are we living in a state that is one of those states that doesn't really have a robust public health infrastructure? Are we living in a rural area? Are we in a health professional shortage area? Most physicians are aware of these types of variables. Dr. Greg Hundley: Very nice. Well, Mercy, let's turn to you. Can you help us put these findings that Monika is sharing with us today in the context with other studies that have performed really related to this topic?   Dr. Mercedes Carnethon: Certainly. I'd love to summarize that as well as ask the question. We've known for some time that social determinants of health are associated with many different health outcomes, primarily cardiovascular diseases. We know that the access that individuals have to resources to promote their health and protect themselves really do influence what happens to them in the long run. I was extremely pleased to read this paper prepared by Monika and her group in the REGARDS study because it had many strengths that exceed those of prior studies, namely the large sample size, the significant representation of both Blacks and whites, as well as the ability to study both fatal and non-fatal outcomes. And I think that the summary provided by Monika was excellent and I would love to follow with a few questions if I might. Namely, were the social determinants similarly associated with outcomes in Blacks and whites? We know certainly in this country that the two are correlated. And I just wondered whether or not you saw similar patterns of association whereby those who had adverse social determinants of health also had higher rates of mortality in both Blacks and whites? Dr. Monika Safford: Yeah. Wow, what a great question. There's only so much that you can cover in one paper. In this paper, we were really focused on this concept of the burden and a simple count of social determinants of health. And we actually did not stratify by race. We didn't examine this separately by race, but that is exactly what we're doing in another similar study right now. That is a really, really important question because some of these determinants may not be similarly associated for Blacks and whites. Dr. Mercedes Carnethon: I'd like to follow as well, so what surprised you about the findings in this study? Dr. Monika Safford: Probably the biggest surprise was the difference in the association or the strength of the association between incident fatal CHD. This is primarily sudden death and this is what we all want to try to avoid because this is people who we don't yet recognize having coronary disease. And then when they die at their presentation, it's very frustrating. We sure would love to be able to intervene. We have gotten very good at intervening after people survive a myocardial infarction but the surprising thing was that the strength of this association was really much more pronounced for incident fatal CHD than it was for non-fatal MI. We don't understand the reason for that. That's a puzzling finding that we're definitely diving into as we speak. Dr. Greg Hundley: Monika, what do you see is the next study to be performed in this space? Dr. Monika Safford: What we're doing right now is we are demonstrating that this is a robust finding across a number of different endpoints. We have a very similar study on stroke, showing large magnitude of exactly the same finding. And we have one that's about to come out on diabetes, hypertension. We are really looking to demonstrate that this approach, this very simple approach of just counting up the number of social determinants, really is a cross cutting observation across a number of different cardio-metabolic outcomes, which would then lend credence to the possibility that physicians could really integrate this into their clinical care management. There's a whole host of studies that need to be done to better understand nuances such as those that Mercedes mentioned. We are really taking a deep dive into how to integrate social determinants of health on the ground into clinical care management, not just for larger health system population managers, but for individual clinicians. Dr. Greg Hundley: Mercedes, would you like to add anything? Dr. Mercedes Carnethon: I'm very pleased to see this work and I think that I really like the practical nature of it and with the counting of the social determinants of health. I think you're right that we often can go very deep in cohort studies and look at things in very nuanced way. However, I like that this presents an opportunity for clinicians interfacing with patients to have a quick and easy tool to recognize some of the background risks that they face. Thank you for this important work. Dr. Greg Hundley: Yes. Well listeners, we really appreciate the opportunity to speak today with Monika Safford from Weill Cornell in New York and our own associate editor, Mercedes Carnethon from Northwestern in Chicago and helping us to understand how social determinants can be used clinically to help identify those at increased risk of adverse cardiovascular events. Dr. Greg Hundley: Well, now we're going to turn to our second in our double feature and we'll get to that in just a moment. Dr. Greg Hundley: Well listeners, we're now on to our second feature discussion. It's a double feature on this January 19th. And we have with us Dr. Tim Churchill and Dr. Jennifer Ho, both from Massachusetts General Hospital in Boston, Massachusetts. Well Tim, we're going to start with you. Could you describe for us a little bit of the background related to your study? And what hypothesis did you want to address? Dr. Timothy Churchill: Absolutely. The background behind this study that we wanted to look at was the recent emergence of the H2PEF score and the HFA-PEFF diagnostic algorithm coming out of the European Society just about a year ago. And we wanted to look at how these two diagnostic tools perform in terms of diagnosis of HFpEF, which as we all know, is a really challenging and complicated, varied and challenging to diagnose condition. And so our specific question, as more than a hypothesis per se, was really to investigate the diagnostic performance of both of these tools against what we consider really a gold standard hemodynamic definition of HFpEF using the patients who were undergoing comprehensive level three cardiopulmonary exercise testing with invasive hemodynamics. Dr. Greg Hundley: Very nice. Tell us a little bit, how did you configure your study population? And what was your study design? Dr. Timothy Churchill: At our institution, we have a large cardiopulmonary exercise testing program and we took patients coming in from there and who had a preserved ejection fraction, which we defined in line with guidelines as 50% or above and then available transthoracic echocardiography that we could review. And we performed a detailed research over read on the clinical transthoracic echo that had been performed. And we coupled that with the lab data that was drawn on the day of the exercise test, coupled that with the medical history that was previously collated and we tried to look at a population that had all of the necessary score components to assess each of these two scores. Dr. Timothy Churchill: And then what we did was we calculated each of the two scores and compared their outputs against, again, as I said, what we consider our gold standard definition of HFpEF, which is a invasively defined definition that accounts for both filling pressures, as well as the relationship of the pulmonary capillary wedge pressure to cardiac output with exercise. Trying to account for the changes in the wedge with increases in flow, increases in cardiac output with exercise. Dr. Greg Hundley: Very nice. And just quickly, how many patients did you include in this study? And did you have an equal representation of men and women? Dr. Timothy Churchill: We ended up including a 156 patients and there was a female predominant in line with the overarching with both our overarching exercise testing cohort, but also in line with, I would say, the overarching prevalence of HFpEF in many other studies. We ended up with 67% women with an average age of 59 years old. Dr. Greg Hundley: Very nice. What did you find? Dr. Timothy Churchill: I would say our biggest message, our biggest takeaway was that we found that both of these scores performED quite well overall and performed in a broadly similar fashion. We did note however, that there was a significant under ascertainment of HFpEF at some of the lower scores, which we highlighted as a potential weakness in terms of using these scores for the diagnosis of community HFpEF in that there was a certain number of patients with low scores who would be classified as either not having HFpEF or a low probability HFpEF, who we found to fit our hemodynamic definition. And so we highlighted that as a potential weakness or potential consideration of these. That's one area where these scores might potentially miss people. Dr. Greg Hundley: Very nice. Well, let's turn to Jennifer. Jennifer you are spending much of your career helping the world understand more or bringing to light more information really in this field of heart failure and specifically focusing on patients with preserved ejection fractions. How do you put your findings here in the context with some of the other world's literature relative to patients with heart failure preserved ejection fraction? Dr. Jennifer Ho: Thank you, Greg. First off, I just want to say that we greatly appreciate the opportunity to participate in this podcast and on behalf of all of our coauthors, we're just thrilled to be here. I guess there are a couple of points that I would take away to try to place our study within the clinical context of HFpEF in general. Number one, we know that HFpEF diagnosis is challenging, which I think is something so fundamental to our field and needs a lot further work. But a lot of other groups have really struggled with trying to define HFpEF and really figuring out who these patients are. There's a lot of work going on there. Dr. Jennifer Ho: I would say that our findings really show that these non-invasive tools developed by other groups do help enrich for individuals with HFpEF and that they perform quite well with some potential of misclassification in these lower risk individuals. I'll also say that what's new in our study is that we were able to show a direct relationship of these scores and functional implications that really affect how our patients feel. And so we were able to show that these noninvasive scores really enrich for patients with lower exercise capacity as measured by peak VO2, two worse chronotropic response to exercise, and also worse hemodynamic responses to exercise. And so I think that that's really powerful in taking these noninvasive scores that have been developed by other groups and really showing that there are direct functional consequences for our patients depending on where you're scoring. Dr. Greg Hundley: Very nice. Jennifer, where do you think we take these scoring systems next? What do you think is the next research that needs to be performed in this particular space? Dr. Jennifer Ho: That's a great question, Greg. I think we do recognize that our sample may be subject to referral bias. These are all patients who were referred for clinical indications for a cardiopulmonary exercise test with invasive hemodynamic monitoring. And so I do think that validation of these scores is necessary across wider samples so we can really affirm generalizability overall. I think on a more fundamental level, so much more work is needed in the HFpEF space in general to better understand disease pathogenesis. We recognize that there's heterogeneity with respect to clinical presentation, with respect to cardiac and extra cardiac organ involvement, with respect to how we even define the disease in the first place. I think a lot of work needs to really focus on potential deep phenotyping approaches and other approaches to tease apart potential subgroups of individuals that have HFpEF that might be more uniform so we can understand all the contributors that really lead to this disease. Dr. Greg Hundley: Very nice. Tim, would you like to add anything? Dr. Timothy Churchill: I would really echo. I think the biggest immediate question in my mind would be replicating this model and or similar approaches to really using invasive validation in other contexts that may or may not have the same referral population. One of the biggest things that drove this original study originally was that many of the other validation efforts that have formed so far have been based on consensus. And so we think there's a lot of value added by the invasive hemodynamics. And so I think extending that approach, I think can offer a lot of additional value as well in different contexts. Dr. Greg Hundley: Very nice. Well listeners, we really want to thank both Dr. Jennifer Ho and Dr. Tim Churchill for bringing us this very informative study and helping us evaluate these new noninvasive scoring methods and comparing them with really well done invasive measures to best characterize patients with HFpEF. And then as Dr. Ho said, perhaps identify groups that further phenotyping may be indicated in other research studies to identify those that are best suited for specific therapies to improve their overall condition. 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. Dr. Greg Hundley: This program is copyright of the American Heart Association, 2021.

We *almost* dismantle the patriarchy, talk about times when Multi-Level Marketing acolytes tried to proselytize us, and discuss how shows like Atlanta use horror as a vehicle to teach us empathy for those in different racial or political groups than us.

Coffee & Electrolytes, Cancer Diet Recommendation?, Lipids in Black People, Should I Increase My Carb Intake?, Water Before Bed Make your health an act of rebellion. Join The Healthy Rebellion Please Subscribe and Review: Apple Podcasts | RSS Submit your questions for the podcast here   Show Notes: News topic du jour: Over 100 Scientists, Doctors, & Leading Authorities Call For Increased Vitamin D Use To Combat COVID-19 Scientific evidence indicates vitamin D reduces infections & deaths 1. Coffee & Electrolytes  [15:26] Valerie says: Hey Robb & Nikki! I’ve read on the web that coffee depletes (or can deplete) electrolytes. Is this accurate? And if so, is it because it’s a diuretic? Thanks for all that you do! Been following you since 2013 when I first read the Paleo Solution and it “cured” my Crohn’s disease. Have a good one :) 2. Cancer Diet Recommendation?  [17:05] Levi says: Good day dream-team, Robb and Nicki, I was recently informed through several CT scans, PET scans, and MRI scans my cancer has returned, spreading into my brain and into my lungs. In 2015, I was diagnosed with a stage-3 melanoma cancer, reaching into my lymph nodes in my neck. The tissue site and the lymph nodes were removed and I was cancer-free ever. However, last week, after days of excruciating headaches, I was led to the ER by my better-half, my wife. I am about to embark on several biopsies of my lungs, more scans to view my bone marrow, the beginning of radiation and immunotherapy, and a ton of prescriptions (narcotics, steroids, anti-seizure, etc.). Though I am going to take the advice and opinions of the team of doctors on my case, I have already become overwhelmed with the amount of information presented by them and other friends and family. My question is really centered on general recommendations for diet and pain management. I hear to take CBD and turmeric and DHA, to eat no sugar, to try juicing, etc. I am skeptical of any friend advice, but also do not want to blindly walk into radiation and immunotherapy with only Norco and steroids to get by. I am usually very active, working out five days per week, keeping a largely animal-based diet, staying low-carb. However, since this has begun, I am lethargic, easily off-balance, and sedentary, thus my movement has been limited to couch surfing. Also, I am 31 and plan to have a long life, so any recommendations that you can provide that are short-term and long-term will be appreciated and implemented. Sorry for the rambling, but I think you get the gist. You two are rockstars and I will keep being one the six listeners every week. Levi https://peterattiamd.com/fasting-and-cancer/ 3. Lipids in Black People  [28:39] Phillipa says: Can you talk a bit about the differences in interpretation of lipid panels for black people? I understand that triglycerides are normally lower than white people and so the trig/HDL ratio is not a good estimate of insulin resistance. Is the LPIR score still as valid as a health measure in the black population? What are the most useful markers on a standard lipid panel if you cannot get a LPIR? Thank you for all your wisdom.... Are There Clinical Implications of Racial Differences in HbA1c? Yes, to Not Consider Can Do Great Harm! "Studies that have compared HbA1c levels by race have consistently demonstrated higher HbA1c levels in African Americans than in whites. These racial differences in HbA1c have not been explained by measured differences in glycemia, sociodemographic factors, clinical factors, access to care, or quality of care. Recently, a number of nonglycemic factors and several genetic polymorphisms that operate through nonglycemic mechanisms have been associated with HbA1c. Their distributions across racial groups and their impact on hemoglobin glycation need to be systematically explored. Thus, on the basis of evidence for racial differences in HbA1c, current clinical guidelines from the American Diabetes Association state: “It is important to take…race/ethnicity…into consideration when using the A1C to diagnose diabetes.” However, it is not clear from the guidelines how this recommendation might be actualized. So, the critical question is not whether racial differences in HbA1c exist between African Americans and whites; the important question is whether the observed differences in HbA1c level are clinically meaningful." 4. Should I Increase My Carb Intake?  [39:16] Aidan says: Hey Robb just read wired to eat and loved it I’m pretty active and been doing a ketogenic diet for the past six months and felt great at first then fell into some electrolytes issues I then started to implement a target approach with 50 g of carbs round my workouts with a mix of glucose and fructose however I still feel low in energy I have recently upped my carbs to 150-200g of carbs and feel a little better, I listened to chris Masterjohn recently and he said that even a sedentary person needs 200g of carbs to fuel the brain so I am a bit confused how I should tackle this and whether I should change to high carb as you have said in previous videos where people go wrong is where there in the middle not high carb or high fat and if It would be beneficial to specialise in one fuel source however I know how important fats are for health thanks Aidan 5. Water Before Bed  [44:08] Katie says: Hi Robb and Nicki! Thank you so much for all you do and for your relentless quest to uncover the truth, stay on top of science, and deliver it in an easily digestible way! Here’s what I’m pondering: I’ve read that it’s ideal to stop drinking water after dinner and late into the evening in order to allow the kidneys to rest during sleep, as well as to avoid middle of the night bathroom breaks, which obviously disrupt sleep. (I’ve also read that needing to pee in the middle of the night can mean that the kidneys are being overly stimulated by their neighbors, the adrenal glands, but that might be another topic altogether). Anyways, in trying to make sure that I’m getting adequate sodium, I salt my food with a pretty heavy hand, but I find it makes me really thirsty in the late evening. I drink 1-2 LMNTs earlier in the day, and wondering, should I dial back on the salt at dinner? Or drink more before bed? Or just deal with a little thirst? As a side note, if I get thirsty in the evening and go to bed without water, I wake up without feeling thirsty. Overall, I feel like my hydration levels are pretty good. Thanks again for all you do! Sponsor: The Healthy Rebellion Radio is sponsored by our electrolyte company, LMNT. Have you tried LMNT electrolytes yet? If not, this is the time to do it. Until January 31st, 2021 you can get a FREE 8 count sample pack (just pay shipping!). You’ll get: 2 sticks each of citrus salt, raspberry, orange, and RAW unflavored. Click here to get your free LMNT sample pack Transcript: Download a copy of this transcript here (PDF)

Dr. Raghav Tripathi interviewed by Karen Kagha, MD, FAAD

Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. 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 from VCU Health, the Pauley Heart Center in Richmond, Virginia. Dr Carolyn Lam: Our feature paper today is very important and pertinent to the times, talking about the multi-system inflammatory syndrome in children in our current global SARS coronavirus 2 pandemic. Really, really important stuff, but you have to hold on, listen with us to this summary which is full of really exciting papers. You know what, Greg? I'm going to start. So what do you know about the rostral medial prefrontal cortex of our brains? Dr Greg Hundley: Well, let's see. I wonder if it has anything to do with emotion or stress maybe? Dr Carolyn Lam: Oh, you're too smart. Either that or that coffee is loaded. Very good answer. The rostral medial prefrontal cortex is an important brain region that processes stress and regulates immune and autonomic functions. Now, since psychological stress is a risk factor for major adverse cardiovascular events in individuals with coronary artery disease, our authors today, Dr Shah and colleagues from Rollins School of Public Health, Emory University, hypothesize that changes in the rostral medial prefrontal cortex activity with emotional stress may be informative for future risk of MACE or major adverse cardiovascular events. They examined 148 participants with stable coronary artery disease who underwent acute mental stress testing using a series of standardized speech or arithmetic stressors and simultaneous brain imaging with high resolution positron emission tomography brain imaging. They defined high rostral medial prefrontal cortex activation as a difference between stress and control scans greater than the median value for the entire cohort. They also measured interleukin-6 levels 90 minutes post stress and high frequency heart rate variability during stress. Dr Greg Hundley: Wow, Carolyn, what an intriguing article correlating the imaging findings with stress and systemic inflammation. What did they find? Dr Carolyn Lam: So they found that higher roster medial prefrontal cortex activity with mental stress was independently associated with higher risk of major adverse cardiovascular events. Immune and autonomic responses to mental stress contributed to the increased of adverse events among those with the higher stress reactivity. Stress-induced activation may therefore represent a new method of risk stratification of individuals with coronary artery disease. Dr Greg Hundley: Very nice. That really ties a lot together. Makes a lot of sense, Carolyn. Well, my first paper is from Dr Patrick Ellinor from Massachusetts General Hospital and the Harvard Medical School, but first Carolyn a quiz. So here's the background to the quiz. I'm going to talk about the heart myocytes versus the fibroblast versus the microcirculatory cells. So within each of those groups, Carolyn, this is a way or no way, are all the cell types the same? Dr Carolyn Lam: Well, at embryonic stage maybe? All right, I'll be superficial about it. No way, they're different. Dr Greg Hundley: Very good, Carolyn. These authors applied recent advances in low input RNA sequencing that allowed definitions of cellular transcriptome to assess the cellular and transcriptional diversity of the non-failing human heart. Dr Carolyn Lam: Wow. What did they find? Dr Greg Hundley: Carolyn, the author sequences the transcriptomes of 287,269 single cardiac nuclei, revealing a total of nine major cell types and 20 subclusters of cell types within the human heart. Cellular subclasses included two distinct groups of resident macrophages, four endothelial subtypes, and two fibroblast subsets. Comparisons of cellular transcriptomes by cardiac chamber or sex reveal diversity not only in cardiomyocyte transcriptional programs, but also in subtypes involved in the extracellular matrix remodeling and vascularization. Using genetic association data, the authors identified strong enrichment for the role of cell subtypes in cardiac traits and diseases. Therefore, Carolyn, the authors' identification of discrete cell subtypes and differentially expressed genes within the heart will ultimately facilitate the development of new therapeutics for cardiovascular diseases. Dr Carolyn Lam: Okay, I have to admit that's a lot more diversity than I anticipated. Very cool, Greg. Ha, I got a question for you. What do you think of abdominal aortic aneurysms and Niemann-Pick disease have in common? Dr Greg Hundley: I definitely need phone a friend. Dr Carolyn Lam: Here, let me tell you about it. The link is in transcription factor EB. Now what is transcription factor EB? It's a master regulator of lysosome biogenesis that has beneficial effects on lysosomal storage diseases. Now, Dr Fan from University of Cincinnati College of Medicine and Dr Chen from University of Michigan Medical Center are co-corresponding authors of this paper and they and their coauthors found that transcription factor EB expression was reduced in human aneurysms. Vascular smooth muscle cells selective knockout promoted abdominal aortic aneurysm development via induction of vascular smooth muscle cell apoptosis in mice. In addition, they found that 2-hydroxypropyl beta cyclodextrin, which is an FDA approved cyclodextrin derivative currently used to increase the solubility of drugs and under phase two clinical trial to treat Niemann-Pick disease type C1. So they found that this compound activates transcription factor EB and inhibits abdominal aortic aneurysm in multiple mouse models. So these findings intriguingly demonstrate the potential use of transcription factor EB activators to treat abdominal aortic aneurysms. Dr Greg Hundley: I don't think I would've gotten that quiz right for sure. My next paper is from Professor Marco Valgimigli from the University of Bern. It's entitled "Cangrelor Tirofiban and Chewed or Standard Prasugrel Regimens in Patients with ST Segment Elevation Myocardial Infarction". These are the primary results of the Fabulous Faster trial. Since the standard administration of newer oral P2Y12 inhibitors, including Prasugrel or Ticagrelor provides suboptimal early inhibition of platelet aggregation in ST segment elevation myocardial infarction patients undergoing primary PCI. These authors sought to investigate the effects of Cangrelor, Tirofiban, and Prasugrel administered as chewed or integral loading dose on inhibition of platelet aggregation in patients undergoing primary PCI. Dr Carolyn Lam: Ah. So what was the design of this study and who did they enroll, Greg? Dr Greg Hundley: Carolyn, a total of 122 P2Y12 naive ST elevation myocardial infarction patients were randomly allocated one to one to one to Cangrelor, 40 subjects, Tirofiban, 40 subjects, both administered as bolus and two hour infusion followed by 60 milligrams of Prasugrel or 60 milligram loading dose of Prasugrel, 42. The latter group underwent an immediate one-to-one some randomization to chewed, so 21 subjects there, or integral, 21 subjects there, tablets administration. The trial was powered to test three hypotheses: non-inferiority of Cangrelor compared with Tirofiban using a noninferiority margin of 9%. Second, superiority of both Tirofiban and Cangrelor compared with chewed Prasugrel. And finally, superiority of chewed Prasugrel as compared with integral Prasugrel, each with an alpha of 0.016 for the primary end point that was 30 minute inhibition of platelet aggregation at light transmittance aggregometry in response to 20 micromoles per liter of adenosine diphosphate. Dr Carolyn Lam: Wow. A comprehensive study. Okay, so what did they find? Dr Greg Hundley: Well, Carolyn. Cangrelor proved inferior on inhibition of platelet aggregation compared with Tirofiban. Next, both treatments yielded greater on inhibition of platelet aggregation compared with chewed Prasugrel which led to higher active metabolite concentration, but not greater inhibition of platelet aggregation compared with integral Prasugrel. Therefore, Carolyn, Tirofiban by exerting more potent and consistent innovation of platelet aggregation may be more effective than Cangrelor in reducing the risk of acute ischemic complications. Now, all of these results need to be further ascertain in the context of studies powered for clinical end points. Dr Carolyn Lam: Thanks, Greg. All right, well, let's sum up what else is in this issue. I've got few papers really related to COVID-19. First as a perspective by Dr Oudit on ACE2: A Double-Edged Sword. Then we have an On My Mind paper by Dr Kevin Shah titled Tissue is the Issue, Even During a Pandemic. We have a research letter by Dr Adusumalli on Telemedicine Outpatient Cardiovascular Care During the COVID-19 Pandemic, is this bridging or opening the digital divide? And finally, another research letter by Dr Priori on the association of hydroxychloroquine with QT interval in patients with COVID-19. Dr Greg Hundley: Very good, Carolyn. Well, I've got a couple extra papers as well. The first is an exchange of letters between Dr Ji-jin Zhu and our own Dr James de Lemos regarding the article Racial Differences in Malignant Left Ventricular Hypertrophy and Incidence of Heart Failure: A Multicohort Study. Also, Dr Daniel Schimmel has a case series entitled Not for the Faint of Heart: A Rapidly Evolving Case of Syncope During Pregnancy. And then finally, Dr Michael Sayre has a research letter focusing on the prevalence of COVID-19 in out of hospital cardiac arrest, implications for bystander CPR. Dr Carolyn Lam: Nice Greg. Well, let's hop on to the feature discussion, shall we? Dr Greg Hundley: You bet. Dr Carolyn Lam: We've been hearing a lot about the COVID-19 pandemic and its effects in adults, but today's feature paper deals with the so important and topical issue of the multi-system inflammatory syndrome in children in the context of this COVID-19 pandemic. I am so pleased to have with us the corresponding author of today's feature paper, Dr Damien Bonnet from the Necker Sick Children's, University of Paris, as well as our associate editor, Dr Gerald Greil from UT Southwestern. Damien, thank you so much for this very, very important study. Everyone's been looking for data, and I truly think yours are just the definitive ones that we have now, but please tell us a bit about the study and what you found. Dr Damien Bonnet: In Paris, we have been alerted by an increase of admission of children with acute heart failure in context of long-lasting fever with different organ involvement. So we started in mid-April to signal to our health authorities that there was an emerging entity. Since then we have seen these rare entity about 100 of times in various areas. So it's so rare entity because there are 3 million children living in my area. And this syndrome is composed of different signs. The first one is a high fever lasting for more than three days, gastrointestinal or digestive symptoms, sometimes skin anomalies, heart arrhythmia, and of course heart failure with sometimes shock. So this syndrome has some similarities with a known other syndrome that is Kawasaki disease that we all know in pediatric cardiology. And we will discuss that later, I think. It's certainly a different entity. So we started to treat them as if they were Kawasaki-like disease with immune blood splints and the majority of them improved rapidly with this type of treatment. And while some of them were on ECMO at baseline or in severe condition, they all improved. And fortunately in my institution did not have any dead. So that's the summary of what we have submitted to circulation. Dr Carolyn Lam: Thank you so much, Gerald, could you help frame for us once again how important this study is, and this condition is to recognize? And then I know you've got some questions for Damien too. Dr Gerald Greil: Thank you so much, Damien, for submitting your work to circulation and the reason why we all thought it's particularly important because you guys in Europe got the first rife. In the United States, North America, South America, kind of getting confronted with all these patients. And we are all very keen to learn from you. And obviously one of the first things when we get confronted with these patients now is how are we going to treat them? You mentioned IVIG as a possibility, I'm sure you have other options or experiences. Can you explain what is your evidence and how did you choose current treatment strategies? Dr Damien Bonnet: I think that at baseline, we used the IVIG because these patients resemble those with Kawasaki disease shock. Certainly today there has been different reports and the spectrum of clinical signs and biological anomalies in this syndrome differ from that of Kawasaki. But still the treatment with anti-inflammatory agents, IVIG, or other agents has the objective to accelerate recovery and potentially to prevent cardiac injury in Kawasaki disease. We have not demonstrated that in the present entity. So there is today, I think no evidence to say that IVIG should be given to all patients with this disease. But certainly treating the severe inflammation as an impact in cardiac function. Dr Gerald Greil: We were kind of reminded when you saw these patients of Kawasaki disease, which is probably every pediatrician, pediatric cardiologist has a similar idea when you see these patients. Is it Kawasaki disease? Is it not? Dr Damien Bonnet: I think that we have to balance the answer. There are some clinical signs that are shared between the multisystem inflammatory syndrome and Kawasaki disease. The continuous signs, the lymphadenopathies with fever, but the inflammation is much more intense in this entity and the other aspect is Kawasaki disease mainly involves arteries, as in arthritis. And this syndrome is mainly affecting the mitochondria. That's what, at least what we see today. What we don't have is the late outcome. But today, at least in the patient that we have seen in Paris, we have not seen a high prevalence of coronary artery involvement, both at initial phase and later on. I think that the mechanism, the exaggerated inflammation, and the deleterious effect on myocardium of this inflammatory storm, has similarities with that of Kawasaki disease. Dr Gerald Greil: So since you've got a lot of experience, can you just summarize for us, how do you treat these patients once they come into your hospital? So we have a little bit of a guideline, but the current state of the arts. Dr Damien Bonnet: The paper that we are discussing today does not include all categories of patients with this syndrome. We included in this paper only patients who were admitted for acute heart failure, but today we have seen children with less severe disease. So when we admit them in Paris, we systematically dose BNP or anticrobian B depending on the institution. And if it is abnormal, we check the echo. And if the echo is abnormal, we will treat all of them with IVIG. That's the treatment that we do. If they are in shock, we associate IVIG and steroids. Today, I cannot say that it is a precise guideline two fold. It’s just our experience and we have not observed any fatalities. And the older patients recovered quite rapidly, let's say within a week for the majority of them. Dr Gerald Greil: So what do you think are the next steps? I mean, we collected from different institutions around the world their experience with this kind of type of disease. It seems to become more prevalent. What do you think is the next step for us as physicians in the scientific community? Dr Damien Bonnet: And that there are clinical issues. So the first one is to see or to look at potential cardiac residual anomalies, mitochondrial or coronary arteries aneurism, because today we have not precise information of that. The second is probably observational because it will be difficult to randomize young children, is what is the optimal treatment at baseline or what is the optimal strategy? And is it possible to stratify the strategy as I just said, but I don't have evidence for that. And for the long term, I think that trying to identify why only some children have this disease and why the other don't have, if there is any genetic susceptibility, it will be something interesting. And potentially as we discussed already together, it might give us some keys to better understand Kawasaki disease as well. Dr Gerald Greil: Thank you so much for summarizing that. I mean, we are all very much looking forward to working together with you and other groups around the world to get a little bit more and better insight in this kind of type of disease and how to treat them best and how to follow them up best. Dr Carolyn Lam: Thank you so much, Damien and Gerald. I mean, I'm sure I speak behalf of the entire audience that I learned a lot just listening to your very open and honest conversation of what we've seen, what we've experienced, what we don't yet know. Listeners, you have to refer to a beautiful accompanying editorial that Gerald invited, and it is by Dr John Simpson and Dr Jane Newburger from Evalina London Children's Hospital and Harvard Medical School, respectively. Thank you so much for joining us today. And please remember, you've been listening to Circulation on the Run. Tune in again next week. Dr Greg Hundley: This program is copyright the American Heart Association, 2020.  

In early June, as communities across the country organized protests against racism in all its forms, Mathematica released a statement denouncing social injustice and affirming that black lives matter. This episode provides insight behind why Mathematica's CEO wanted to make that statement. It's also about how the events in late May and early June prompted two lifelong friends to talk about race in ways they hadn’t before. The guests for this episode are Paul Decker and Chris Williams. Decker is the president and CEO of Mathematica. Williams is the founder of OnPacePlus and the chief of ophthalmology at Crozer-Chester Medical Center in Delaware County, Pennsylvania. Paul is white. Chris is Black. They grew up together in Jacksonville, Illinois. For this episode, Decker and Williams are interviewing each other.

Doing a crusade for some black churches in Colorado, I asked the Lord why He made some people black and some white. His answer focuses precisely where our nation is undergoing a crisis right now - whose global rule is going to stand. I found myself in a legal battle that depicted how our enemy works to try to stop us.Cornerstone Magazine  Go here for more in depth encouragement.New episodes every Monday, Wednesday & Friday at noon. Don't forget to 'follow' & 'share.'

It's high time for another feedback episode! Listeners chime in on questions, comments, and concerns regarding how to talk with your conservative friends and families, BLM, billionaires, blaxit, and more. Lots of stats, lots of studies, lots of reports to peruse! Links mentioned in this podcast...   On "Moral Licensing" Revisionist History Podcast, "The Lady Vanishes" Journal of Experimental Social Psychology, "Endorsing Obama Licenses Favoring Whites" On police brutality University of Chicago Law School - International Human Rights Clinic, "Deadly Discretion: The Failure of Police Use of Force Policies to Meet Fundamental International Human Rights Law and Standards" NBER Working Paper, "An Empirical Analysis of Racial Differences in Police Use of Force" by Roland G. Fryer, Jr. Wall Street Journal, "What the Data Say About Police", by Roland G. Fryer, Jr. Criticism of Dr. Fryer's paper Snopes, "Harvard Study Doesn't Disprove Racial Bias in Officer-Involved Shootings" Slate, "The Research is Only as Good as the Data" Washington Post, "Why it’s impossible to calculate the percentage of police shootings that are legitimate" On the "School-to-Prison Pipeline" Wikipedia overview ACLU, "School-to-Prison Pipeline" Education Week, "Policing America's Schools" ABC News, "FBI: More than 30,000 children under age 10 have been arrested in the US since 2013" On the "Blaxit" to Africa BBC, "The African American who moved to Ghana 'to escape US racism'"  

For more information on the "REasons for Geographic and Racial Differences in Stroke" (REGARDS) study, click here.  New episodes every Tuesday! Subscribe so you don't miss a beat! Also, join us for our monthly live podcasts on Facebook and Youtube!Join the Conversation! Follow us on social media!3 Black Docsfacebook.com/3blackdocstwitter.com/3blackdocsinstagram.com/3blackdocsYouTubeDr. Karen Winkfieldfacebook.com/drkarenwinkfieldtwitter.com/drwinkfieldinstagram.com/drwinkfieldDr. Zanetta Lamarfacebook.com/drzanettainstagram.com/drzanetta

Dr. Anna Zisman, on behalf of her colleagues, discusses the findings from the study "Racial Differences in Risk Factors for Kidney Stone Formation."

Dr. Anna Zisman, on behalf of her colleagues, discusses the findings from the study "Racial Differences in Risk Factors for Kidney Stone Formation."

A roundup of 10 studies highlighting the health disparities between black and white Americans. The second paragraph of the Declaration of Independence states clearly: “all men are created equal.” But does this hold true for all people in 2020? Yes, Americans can legally vote in elections, go to school or assemble in groups to peacefully protest. However, true equality goes beyond laws and policies. From inadequate access to fresh food and clean water, to screening in early stages of disease or the inability to rent an apartment because of discriminatory housing practices, these long standing systemic inequities for some black Americans can have long lasting effects on health. For more information about this story visit: https://healthblog.uofmhealth.org/lifestyle/health-inequality-actually-a-black-and-white-issue-research-saysResources:Racial Disparities in the Time of COVID-19Study Explores Why Prostate Cancer Mortality is Higher in Black MenMinority Patients Benefit From Having Minority Doctors, But That’s a Hard Match to MakeRacial and Ethnic Disparities in Insurance Access Impact Maternal-Infant HealthYoung African Americans with Colon Cancer Fare WorseWhy Does Dying Cost More for People of Color?Blood Pressure Associated with Racial Differences in Cognitive DeclineStudy Reveals Blind Spot in Coverage of Low Vision DevicesACA Helped Make Health Insurance Access More Equal, But Racial and Ethnic Gaps RemainEven Before COVID-19, Many Adults Lacked Stable Food SupplyVisit Michigan Medicine’s Office for Health Equity and Inclusion for anti-racism support and tools. See acast.com/privacy for privacy and opt-out information.

Harvard Lecturer Laura Schifter explains disproportionality and why so many students of color are placed in special education, often in separate classrooms from their peers. While income status is sometimes accepted as the reason behind this phenomenon, Schifter says that doesn't tell the full story. In this EdCast, Schifter shares recent research into this issue and discusses the challenges facing special education.

Welcome to episode 17 of You Can't Say That! A Soc 119 Podcast about the class, culture & other topics. Today's podcast we cover if noticing racial differences in racist or not, what makes a source credible, and a discussion of black families in the United States today. Check out our Social Media: Class website: https://www.soc119.org, Facebook: https://www.facebook.com/soc119, Twitter: https://twitter.com/soc119, Snapchat: SOC_119, Instagram: https://www.instagram.com/soc_119/ Discord Server: https://discord.gg/CRVnH7P --- Send in a voice message: https://podcasters.spotify.com/pod/show/you-cant-say-that/message

Jean A. Welsh, RN, MPH, PhD joins JAMA Network editors to discuss a cohort study and secondary analysis of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study which looked at the association of sugary beverage consumption with mortality among US adults. Read the article here: https://ja.ma/2XySimk. JNO Live is a weekly broadcast featuring conversations about the latest research being published in JAMA Network Open. Follow us on Facebook, Twitter and YouTube for details on the next broadcast.

We live in a beautifully diverse world. Unfortunately, our world is also plagued by racial and ethnic division. As families, we can bring unity and change by embracing our differences. But it requires that we pass onto our kids what it means to walk in love, not fear—a lesson that's easier said, than done. In this episode, author Trillia Newbell, sits down with us to discuss: How to talk to our kids about families who look different from ours Whether or not we should raise our kids to be "color blind" What it looks like for us as adults to model unity and love in our home How we should talk to our kids about the history of racial tensions And most importantly, how the gospel transcends racial and ethnic differences Show Notes: Trillia Newbell is the author of If God is For Me, a 6-week Bible study on Romans 8 (2019), Enjoy: Finding the Freedom to Delight Daily in God's Good Gifts (2016), Fear and Faith: Finding the Peace Your Heart Craves (2015), United: Captured by God's Vision for Diversity (2014), and a children’s book, God’s Very Good Idea: A True Story of God’s Delightfully Different Family. You can find her at trillianewbell.com and follow her on twitter at @trillianewbell. Bring the 2019 Parent's Summit to your church via simulcast! Click here to learn more. 

Jane Ferguson:                 Hello, welcome to Getting Personal: Omics of the Heart. It is June 2018, and this is podcast episode 17. I'm Jane Ferguson, an assistant professor of medicine at Vanderbilt University Medical Center, and a proponent of precision medicine, genomics, and finding ways to prevent and treat heart disease. Jane Ferguson:                 This podcast is brought to you by Circulation: Genomic and Precision Medicine, and the AHA Council on Genomic and Precision Medicine. Jane Ferguson:                 For our interview this month, early career member, Jennie Lin talked to Beth McNally about science and careers in genomic medicine. We'll have more on that later but first I want to tell you about the cool papers we published in the journal this month. Jane Ferguson:                 First up, Orlando Gutierrez, Marguerite Irvin, Jeffrey Kopp, Cheryl Winkler, and colleagues from the University of Alabama at Birmingham, and the NIH, published an article entitled APOL1 Nephropathy Risk Variants and Incident Cardiovascular Disease Events in Community-Dwelling Black Adults. This study was conducted in over 10 thousand participants of the Reasons for Geographic and Racial Differences in Stroke, or, REGARDS Study. They examined associations between APOL1 variants and incident coronary heart disease, ischemic stroke, or composite CVD outcome. Because there are coding variants in the APOL1 Gene that are only found in individuals of African ancestry, these are hypothesized to contribute to the disparities in cardiovascular and renal disease in African Americans. Jane Ferguson:                 The authors found that carrying the risk variants was associated with increased risk of ischemic stroke, but only in individuals who did not have diabetes, or chronic kidney disease. They hypothesize that because diabetes and kidney disease already increase CVD risk, the variant does not have an additional effect on risk in individuals with existing comorbidities. But, it contributes to small vessel occlusion and stroke in individuals without diabetes. Jane Ferguson:                 They also found that the magnitude and strength of the association became stronger in a model adjusted for African ancestry, suggesting an independent effect of the APOL1 risk variants. Jane Ferguson:                 While future work is needed to study this more, this is an important step in understanding the complex relationship between APOL1 and disease. Jane Ferguson:                 Next up, Daniela Zanetti, Erik Ingelsson, and colleagues from Stanford, published a paper on Birthweight, Type 2 Diabetes, and Cardiovascular Disease: Addressing the Barker Hypothesis with Mendelian Randomization. The Barker Hypothesis considers that low birthweight as a result of intrauterine growth restriction, causes a higher future risk of hypertension, type 2 diabetes, and cardiovascular disease. However, observational studies have been unable to establish causality or mechanisms. Jane Ferguson:                 In this paper, the authors used Mendelian Randomization as a tool to address causality. They used data from the UK Biobank, and included over 237,000 participants who knew their weight at birth. They constructed genetic predictors of birthweight from published genome wide association studies, and then looked for genetic associations with multiple outcomes, including CAD, stroke, hypertension, obesity, dyslipidemia, dysregulated glucose and insulin metabolism, and diabetes. Jane Ferguson:                 The Mendelian randomization analysis indicated that higher birthweight is protective against CAD type 2 diabetes, LDL cholesterol, and high 2 hour glucose from oral tolerance test. But, higher birthweight was associated with higher adult BMI. This suggests that the association between low birthweight and higher disease risk is independent of effects on BMI later in life. While the study was limited to a well nourished population of European ancestry, and would need to be confirmed in other samples, and through non-genetic studies, it suggests that improving prenatal nutrition may be protective against future cardiometabolic disease risk. Jane Ferguson:                 Laura Muino-Mosquera, Julie De Backer, and co-authors from Ghent University Hospital, delved into the complexities of interpreting genetic variants, as published in their manuscript, Tailoring the ACMG and AMP Guidelines for the Interpretation of Sequenced Variants in the FBN1 Gene for Marfan Syndrome: Proposal for a Disease- and Gene-Specific Guideline. Jane Ferguson:                 With a large number of variants being uncovered through widespread sequencing efforts, a crucial challenge arises in their interpretation. The American College of Medical Genetics and Genomics, and the Association for Molecular Pathology put forward variant interpretation guidelines in 2015, but these were not tailored to individual genes. Because some genes have unique characteristics, the guidelines may not always allow for uniform interpretation. Jane Ferguson:                 In their manuscript, the authors focused on variants in fibrillin-1 that cause Marfan Syndrome, and reclassified 713 variants using the guidelines, comparing those classifications to previous in-depth methods which had indicated these variants' causal or uncertain significance. They find 86.4% agreement between the two methods. Jane Ferguson:                 Applying the ACMG, AMP guidelines without considering additional evidence may thus miss causal mutations. And it suggests that adopting gene specific guidelines may be helpful to improve clinical decision making and accurate variant interpretation. Jane Ferguson:                 Delving deeper into FBN1 and Marfan Syndrome, Norifumi Takeda, Ryo Inuzuka, Sonoko Maemura, Issei Komuro, and colleagues from the University of Tokyo examined the Impact of Pathogenic FBN1 Variant Types on the Progression of Aortic Disease in Patients With Marfan Syndrome. They evaluated 248 patients with pathogenic, or likely pathogenic, FBN1 variants, and examined the effect of variant subtype on severe aortopathy, including aortic root replacement, type A dissections, and related death. They found that the cumulative aortic event risk was higher in individuals with haploinsufficient type variants, compared with dominant negative variants. Jane Ferguson:                 Within individuals with dominant negative variants, those that affected Cysteine residues, or caused in-frame deletions, were associated with higher risk compared with other dominant negative mutations, and were comparable to the risk of the haploinsufficient variants. These results highlight the heterogeneity and risk of the FBN1 variants, and suggest that individuals with haploinsufficient variants, and those carrying dominant negative variants affecting Cysteine residues or in-frame Deletions, may need more careful monitoring for development of aortic root aneurysms. Jane Ferguson:                 Lydia Hellwig, William Klein, and colleagues from the NIH, investigated the Ability of Patients to Distinguish Among Cardiac Genomic Variant Subclassifications. In this study, they analyzed whether different subclassifications of variants of uncertain significance were associated with different degrees of concern amongst recipients of genetic test results. 289 subjects were recruited from the NIH ClinSeq Study, and were presented with three categories of variants, including variants of uncertain significance, possibly pathogenic, and likely pathogenic variants. Participants were better able to distinguish between the categories when presented with all three. Whereas, a result of possibly pathogenic given on its own, produced as much worry as a result of likely pathogenic. The authors conclude that multiple categories are helpful for subjects to distinguish pathogenicity subclassification, and that subjects receiving only a single uncertain result, may benefit from interventions to address their worry and to calibrate their risk perceptions.  Jane Ferguson:                 Erik Ingelsson and Mark McCarthy from Stanford, published a really nice review article entitled Human Genetics of Obesity and Type 2 Diabetes: Past, Present, and Future. Over the past decade, we've had a lot of excitement, optimism, and also disappointment in what genome-wide association studies can deliver. Doctors Ingelsson and McCarthy do a great job laying out the history and the successes in the field of genetic interrogation of obesity and diabetes, as well as acknowledging where reality may not live up to the hype, what challenges remain, and what the future may hold. They also have a figure that uses an analogy of a ski resort to emphasize the importance of taking a longitudinal perspective. And I would argue that any paper that manages to connect apres-ski with genomics is worth reading, for that alone. Jane Ferguson:                 Robert Roberts wrote a perspective on the 1986 A.J. Buer program, pivotal to current management and research of heart disease. Highlighting how the decision by the AHA in 1986 to establish centers to train cardiologists and scientists in molecular biology, has led to huge advances in knowledge and treatment of heart disease. Jane Ferguson:                 Finally, rounding out this issue, Kiran Musunuru and colleagues, representing the AHA Council on Genomic and Precision Medicine, Council on Cardiovascular Disease in the Young, Council on Cardiovascular and Stroke Nursing, Council on Cardiovascular Radiology and Intervention, Council on Peripheral Vascular Disease, Council on Quality of Care and Outcomes Research, and the Stroke Council, published a scientific statement on Interdisciplinary Models for Research and Clinical Endeavors in Genomic Medicine. Jane Ferguson:                 This paper lays out the field of cardiovascular research in the post genomic era, highlights current practices in research and treatment, and outlines vision for interdisciplinary, translational research and clinical practice, that could improve how we understand disease, and how we use those understandings to help patients. Jane Ferguson:                 Our guest interviewer today is Dr. Jennie Lin, an Assistant Professor at Northwestern Universities Feinberg School of Medicine, and the incoming Vice Chair of the Early Career Committee of the AHA Council on Genomic and Precision Medicine. As an aside, Jennie is a great person to follow on Twitter for insights into genomics and kidney disease, and as a bonus, she also posts the occasional dog photo. So she's well worth following just for that. You can find her on Twitter @jenniejlin. As you'll hear, Jennie talked to Dr. Beth McNally about her view on genomic medicine, and Beth also shared some really great practical tips for early career investigators building their independent labs. So make sure you listen all the way to the end. Take it away Jennie. Dr. Lin:                                  Thank you for tuning in to this edition of Getting Personal: Omics of the Heart, a podcast by the Genomic and Precision Medicine Council of the American Heart Association, and by Circulation: Genomic and Precision Medicine. Today I am joined by Dr. Elizabeth McNally, the Elizabeth J Ward Professor of Genetic Medicine, and director of the Center for Genetic Medicine at Northwestern University. Beth, thank you for taking time to chat with all of us. Dr. McNally:                       Happy to be here. Dr. Lin:                                  As a successful physician scientist, you have been interviewed in the past about your life, your scientific interests, and advice for budding investigators. I don't want to rehash everything you have already stated beautifully in an interview with Circ Res, for example. But instead wanted to focus more on your views of genetic medicine and genome science today. Dr. Lin:                                  So you mentioned in that prior Circ Res interview that you started your laboratory science training and career during college, when you participated in a project focused on genetic variation among children with muscular diseases. What have you found to be most interesting about the process of identifying functional genetic variants back then, and also that on-going work now. Dr. McNally:                       Well, I think over the years I've been doing this is the tools have gotten so much better, to be able to actually define the variants much more comprehensibly than we ever could in the past. And then also to be able to study them, and very much to be able to study them in context. And so I look at the revolutions in science that will cause people to look back on this era as the era of genetics. It began obviously with PCR, we couldn't have gotten anywhere without that. Dr. Lin:                                  Right. Dr. McNally:                       And then you leap forward to things like next generation sequencing, and IPS cells, and now CRISPR/Cas gene editing. And to realize that the last three happened within a decade of each other, is going to be so meaningful when you think about the next few decades, and what will happen. So being able to take an IPS cell and actually study a mutation or a variant in context of that patient, the rest of their genome, is really important to be able to do. Dr. Lin:                                  Okay, Great. And so, where do you envision ... with taking say for example, this next gen. technology, CRISPR/Cas9, studying variants in an IPS cell, for example. How do you envision this really revolutionizing the study of human genetics for patients? And how far do you think we've come in fulfilling that vision, and what do you think should be our focus going forward? Dr. McNally:                       I think broadly thinking about human genetics we're really very much still at the beginning, which I know is hard to say and hard to hear. But, we've spent a lot of the last 15 years very focused on that fraction of the genome that has high frequency, or common variation, through a lot of the GWA studies. With those common variants, we had a lot of associations, but relatively small effects of a lot of those, causing a lot of people to focus on the missing heritability and where we might find that hiding. And of course, now that we have deep sequencing, and we have deep sequencing where we've really sampled so much more of the genome, and from so many more people, I think we're just at the beginning of really appreciating that rare variation. And beginning again to really appreciate that 80-85% of the variation that's in each of our genomes is really characterized as rare. Dr. McNally:                       And so we really each are quite unique, and that when we understand a variant we do have to understand it in the context of all that other variation. So computationally that's very challenging to do. Obviously requires larger and larger data sets. But even in doing that, you are not going to find exact replicates of the combinations that you see in any one individual. While I know everybody would love that we're going to have the computational answer to all of this, it's still going to come down to a physician and a patient and making what you think is that best decision for the patient, based hopefully on some genetic data that helps inform those decisions. Dr. Lin:                                  Right, right. So it kind of gets into this whole concept of precision medicine, which has gained a lot of popularity and buzz in recent years, and Obama has really brought it to the forefront in the public arena. You mention rare variants in ... finding rare variants in each patient, for example. And moving a little bit away from some of the common variants that we find in GWAs. What does it mean for a patient to have a rare variant and come see you in your cardiomyopathy clinic, is it going to be precision for that patient, or suing rare variants among many different individual patients to try to find function for a gene? Dr. McNally:                       It's a great question. So I think the first way we approach it is, it depends who's asking the question. So if it's somebody who comes to me who has cardiomyopathy, or has a family history of cardiomyopathy and sudden death, that's a very different question to ask what's going on with their rare variants, for example in cardiomyopathy genes. Now if you translate that over to, I have a big population of people, I don't particularly know what their phenotype is, and I see rare variants for cardiomyopathy, those are two fundamentally different questions. So we very much know a lot about how to interpret rare variants for cardiomyopathy in the context of a patient or a family who has disease, and I do emphasize the latter part of that, the family, working with families and seeing how variants segregate within families. We interpret that very differently, and I think it's appropriate to interpret that very differently in that context. And that's completely different than again, going against what is the regular population, notice I'm not calling it normal population- Dr. Lin:                                  Right. Dr. McNally:                       ... but the general population that's out there. The first step in doing that is the list of the ACMG, American College of Medical Genetics, actionable genes. So this is an interesting question in and of itself. It's 59 genes, of course that list is too small, and it should be bigger than that, and ultimately that will happen. But to take a population based approach to those actionable genes, and looking across the population, finding someone who's got variants in, lets say our favorite genes MYH7, MYBPC3. Knowing what that risk means on a population level is very different than knowing what that means in the context of a patient who comes to you, who has that variant, runs in their family, and has clear disease. Those again, really two different questions, and we have to come up with what's the best practices on that, how to answer either of those questions. Dr. McNally:                       I think the first step working with patients and families who have known disease and have clear variants that segregate with disease, I think its very powerful. I think we've probably got close to a good decade of doing that already. It's incredibly useful for those patients and families. It helps us reduce their risk. It helps us treat them early, it helps us manage their arrhythmias. There's no question that that information is incredibly valuable, but we're still learning how to process that across the population, and how to answer that question for people who are coming who don't already have disease. Dr. Lin:                                  Right, right. That makes sense. And I guess that kind of plays into a follow up question about whether or not we need to test, or think about every variant of unknown significance in lab, and ... the- Dr. McNally:                       It's a great ... You know again, you always have to very carefully consider the context in which the question's being asked. So again, if you're talking about a relatively normal population, well, walking, healthy person, and you're seeing variants of uncertain significance, that's a very different question than somebody who's coming in to you with cardiomyopathy and has a highly suspicious variant of uncertain significance that falls right within the head domain of MYH7. We know a lot about that, and we can do a lot of interpretation in that case. Dr. McNally:                       However, I would say that to put too much value on what we do in the research lab ... Just putting a regulatory hat on for a second and thinking about it, there's nothing from a regulatory standpoint that really validates what we do in the research lab, to say that we can really fairly adjudicate a VUS or not. We can't do that, that's over-valuing what we do in research lab. Dr. McNally:                       So I think, how do we consider variants among certain significance? I think it's really important to recognize that it's exactly that, it's a variant of uncertain significance. And so when you're a clinician taking that to a patient, you have to approach it from the standpoint of saying, this is a variant of uncertain significance. Which means we don't know whether it's pathogenic, but we also don't know that its benign. Because I think right now what we've seen, a lot of clinicians, and even researchers, fall into the path of this believing that variant of uncertain significance is the equivalent of benign. That's not true. It is simply ... That is a rare variant, and we don't know whether it's pathogenic or non-pathogenic. And hopefully overtime we will learn more to better assess that, and better provide the interpretation of what that means in the context of that patient. Dr. McNally:                       It's a good conversation to have. It's important to recognize they're not necessarily pathogenic, but they're also not necessarily benign. Dr. Lin:                                  Mm-hmm (affirmative). So do you see a role, for example, when you see this variant of uncertain significance, is there a role to go back into lab, for example, and try to knock that mutation to IPSC's and test to see if its pathogenic? Or is that going a step too far? Dr. McNally:                       In some cases, that is the right thing to do. Because genetics is so powerful, genetics doesn't only give you the association of a gene with an outcome, and GWAs was fabulous at doing that ... giving us a lot of variants, and often nearby genes, sometimes far away genes, but linking genes to phenotypes, and that's very powerful. But specific variants can actually tell you a lot about mechanism, about how a gene and protein actually function, and how it functions when it's broken. And so, particularly where you can gain a lot from the research front in understanding mechanism, then I think it's really powerful to take those things to the laboratory and to use that to learn about mechanism. Dr. McNally:                       Sometimes you can do it to help adjudicate whether something's pathogenic or not, but again, I think we want to be cautious in doing that. Because what we do in the res ... I always like to say, "What we do in the research lab isn't exactly CLIA certified." Dr. Lin:                                  Right. Dr. McNally:                       There isn't anything magical about what we do, but we definitely ... It is so powerful what's available out there in terms of the genetic variants, and teaching us about how genes and proteins interact. And so I think it is such a rich resource of information right now. The things I bring back to the laboratory, and get my students and trainees excited about working on, is usually where I think we can gain something new about mechanism. Dr. Lin:                                  Right, right, right. Since you are a role model physician scientist, and you think about questions in lab that will ultimately benefit your patients, and you are a genetic cardiologist. What are your thoughts on doing genome editing as a possible therapy for your patients? It's a little bit of a loaded question [crosstalk 00:21:51], it's a little bit controversial. Dr. McNally:                       So I think, no doubt CRISPR/Cas9 gene editing is transforming what we do in the research setting. It's a fantastic tool. Is it a perfect tool? No. Anybody who has been using it a lot in the lab knows that it is much better than anything we've had before, but still quite limited in fidelity and efficiency. And so imagining that we are going to do that in patients is still pretty daunting to me. We do enough gene editing in cells to know that you have to select through an awful lot of cells before you get the one that has the exact variant you are trying to make. So that's not something we can tolerate in the human setting. But we're not there yet, we know that. Dr. McNally:                       Many of the disorders I see clinically are things that are autosomal dominant due to very precise single base-pair changes. And so envisioning how we're going to correct only one copy of an allele and do in a very precise manner, we don't have those tools available yet. Now on the other hand, if you look at a disease like one of the diseases I spend a lot of time on, Duchenne muscular dystrophy, where the majority of mutations are deletions. It's X-linked, it's male, so there's only one copy of the gene, and we know a whole lot about the structure and function of the gene. We know that if we take out this other part we can skip around that mutation and make an internally truncated protein. That's actually a very good use of gene editing, because it only requires making deletions. They don't need to be very precise, and there's only one copy of it that you have to do the gene editing on. Dr. McNally:                       So I see that being something in the near term that will happen, simply because the genetics positions it well to be something where that could be successful. The hard part is still how are we going to get the guides, and how are we going to get the Cas9 in safely into all the cells that need to be treated? And ultimately that lands us back at looking at what our delivery vehicles are. Which at this point in time is still viral delivery, and still has a lot of issues around can we make enough of it? Are people immune to it? So all those questions that come with viral delivery. So still lots of hurdles, but you can see some paths where it makes sense to go forward. Dr. Lin:                                  Very interesting. Okay great. Well thank you for providing your thought on human genetics and genome science. We're going to switch gears for the last portion of this podcast, and talk about your thoughts on career development issues for young investigators. At a recent AHA Scientific Sessions meeting, you participated on a panel that was assembled to provide advice to early career scientists. When you were starting out, what were some of the biggest challenges you faced when you were transitioning to independence and building your own lab, and what's your advice to those facing the same challenges today? Dr. McNally:                       Well, even though I did it quite a few years ago, many of the things are still the same. Transitioning to independence, I think is easier if you pick up and move and start in a new place. I think it's much easier to establish your independence when you're not in the same place as your mentor. That said, we have many more people who now stay in the same place as where their mentors were and we have many more approaches towards doing that. So I think people are much more open to both possibilities as being ways of doing that. But at some level it still comes down to starting your own lab, and you hopefully have been given some start-up resources and you have to think about how to wisely spend them, and how to really get things going. I don't think this is changed either. Dr. McNally:                       I usually tell people, don't just start in one area, if you can, start in two areas because things don't work, and sometimes things do work. In reality when you look at people who are successful, they're often working in more than one area. And so the sooner you start getting comfortable working in more than one area, that's a good thing. Now ideally, they should be areas that have some relationship to each other, and then feed each other in terms of information so that they grow off each other. But what does that practically mean? I always say, "Well if you can hire two people and start them on two different paths, that's a really good way to get going." And practical things like look at all different kinds of private foundations and things like that for getting some good pilot start up money to help develop new projects in the lab. And always be looking at how can these projects help me develop a bigger data package, that's going to put me in a good competitive position for example bigger grants and federal funding, and things along those lines. Dr. McNally:                       Very much a stepwise process. People want to shoot for the moon and get the biggest things first, but sometimes just focusing on the smaller steps which are definitely achievable and building your path towards those bigger steps is the smarter way of doing it. Dr. Lin:                                  That's great advice. You also mentioned recently that young investigators should try to have as many mentors as possible. What advice would you have for, in particular, early career genomics investigators, for finding these mentors passed the postdoc phase? Some of us get introduced at the postdoc phase to maybe some other collaborating labs, but those are really collaborations of our mentors per se. Dr. McNally:                       Well I think especially in the field of genetics and genomics, collaboration is key, and I will say one of the things that has changed over since I started doing this is there is a lot more understanding of the need to collaborate. Not so many years ago, it wasn't really an independent investigator went and started a lab, and it would be your trainees and the papers would have only those people on it. Dr. McNally:                       I think these days, the best science is where you've tackled a problem from multiple different directions, one or two of those being genetics, genomics directions. And then sometimes there's other ways that you've approached that scientific problem. And by necessity, that usually involves collaborating with other people. And your role is sometimes to be the coordinator of all those collaborators, and that's where again you might be in a senior author position then doing that. But your role sometimes is to be the good collaborator. And so when I look at people being successful right now, seven, eight years in to running their own lab, I like to see that they've been the organizer of some of those, that they've collaborated with people who are even senior to them, and that they've established those good collaborations, but that they've taken the leading role in doing that. But also that they've had middle author contributions, that they've been a good collaborator as well. Dr. McNally:                       And so, part of that is not being afraid to collaborate, and to recognize the value of doing that. And what's so great about doing that is you can collaborate with people at your same institution where you are, but you can also collaborate with people all over the world, and I think that's what we do. You go to where you need somebody who is using a technique or an approach that really helps answer the question you want to have answered. And so that's reaching out to people and really establishing again that network and good collaborators which you can do by a whole bunch of ways. You can do it by meeting somebody at a meeting, scientific meeting. You can do it through emails, phone calls, Skype, all sorts of different ways that you can reach out and collaborate with people. Dr. McNally:                       It is easier than ever to share data and share ideas, but that negotiation of how to establish the terms of the collaboration and how to make it be successful is a critically important part of being a scientist. And what we now know when we look at the promotion process, is people who do that effectively, that's a really important mark of being a successful scientist, and marks them as somebody who should be promoted through the process. So great. Dr. Lin:                                  Yeah. No I agree. Certainly with the direction science is moving, it's definitely very difficult to work in a siloed manner. Dr. McNally:                       Yeah. Well you won't get very far. You'll be able to have some really good first ideas, and show some proof of principle approaches. But to really, really address an important scientific problem, we know that you have to see those signals using multiple different methods. And once you have five different ways showing you that that's the right answer, then you're much More confident that you've gotten to the right answer. Dr. Lin:                                  Right. Alright, so I think we're going to wrap up. Do you have any other final thoughts for any other young investigators or genomics researchers listening to this podcast? Dr. McNally:                       It's a great time to be doing genetics and genomics, and particularly human genetics, where we now finally have all this information on humans, and we'll have even more of it in the future. So I think humans are coming close to becoming a real experimental system. Dr. Lin:                                  Excellent. Alright well thank you so much for your time. It was a pleasure having you on this podcast. Dr. McNally:                       Great. Thank you for doing this. Jane Ferguson:                 As a reminder, all of our original research articles come with an accompanying editorial, and these are really nice to help give some more background and perspective to each paper. To read all of these papers, and the accompanying commentaries, log on to circgenetics.ahajournals.org. Or, you can access video summaries of all our original articles from the circgen website, or directly from our YouTube channel, Circulation Journal. And lastly, follow us on Twitter @circ_gen, or on Facebook, to get new content directly in your feed. Jane Ferguson:                 Okay, that is it from us for June. Thank you for listening, and come back for more next month.  

00:15 A rant on so-called ‘for black people’ movements [...]

Interview with Pankaj Arora, MD, author of Racial Differences in Plasma Levels of N-Terminal Pro–B-Type Natriuretic Peptide and Outcomes: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study, and Thomas J. Wang, MD, author of Natriuretic Peptide Deficiency—When There Is Too Little of a Good Thing

This episode builds upon the recent focus a growth around the NFL boycott and #TakeAKnee protests by revisiting the strategic goal of the movement (to decrease police violence against non-threatening black people).  We recap the findings from the July 2016 Harvard produced working paper titled "An Empirical Analysis of Racial Differences in Police Use of Force" as well as a rebuttal Harvard article titled "Roland Fryer is wrong: There is racial bias in shootings by police". We conclude by reinforcing the fact that simply protesting the NFL is not enough. Real change will only come when the black community has the wealth and political clout to demand and win equal treatment under the law.  We are still waiting on that first crucial conviction. Get more episodes, and find links to over 200 VERIFIED & ORGANIZED Resource Links broken into 25 Categories to help you find anything you need for business, job growth, education, professional networks, financing, and of course, Buying from Black-Owned Businesses at buyblackpodcast.com. Contact the Host (Gerald Jones) Email: gerald@buyblackpodcast.com Cell: 501.765.3998 Twitter/FB/IG: @buyblackpodcast

Dr. Carolyn Lam:               Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Our feature paper this week tells us more about aortic wall inflammation, and how this predicts abdominal aortic aneurysm expansion, as well as need for surgical repair. Much more, right after these summaries.                                                 Our first original paper sheds light on a novel mechanism for adult cardiac regeneration. This is a paper from first authors Drs. Wang, and Lee, and corresponding authors Dr. Chen, Houser, and Dr. Jeng from Third Military Medical University from Chongqing, China.                                                 In an elegant series of experiments using mouse models, the authors showed that mature adult cardiomyocytes could re-enter the cell cycle and form new cardiomyocytes though a three-step process: of dedifferentiation, proliferation, and redifferentiation. Intercellular calcium signals from neighboring functioning cardiomyocytes through gap junction induce the redifferentiation process. Furthermore, they showed that this mechanism contributed to new cardiomyocyte formation in post MI hearts in mammals. In summary, this study contributes to our understanding of adult cardiac regeneration and could lead to novel strategies to repair the injured heart.                                                 The next paper provides mechanistic data that may explain why thrombotic complications are more prevalent in patients with diabetes, and why some anti-platelet drugs may have limited efficacy in patients with diabetes. In this paper by first author, Dr. Hu, corresponding author Dr. Ding, and colleagues from Fudan University in Shanghai, China, the authors show that platelets of patients with Type 2 diabetes express high levels of activated P2Y12 receptor.                                                 The P2Y12 inverse agonist inhibited P2Y12 activity of platelets from diabetic patients and rats, more than Cangrelore, leading to a stronger in-vivo antithrombotic effect in thrombosis rat models with diabetes. Increased platelets P2Y12 receptor expression in diabetes was mediated by a high-glucose reactive oxygen species, NF-kappaB pathway. In summary, platelet P2Y12 receptor expression was shown to be significantly increased, and the receptor was constitutively activated in Type 2 diabetic patients, which contributed to platelet hyperactivity, and limited anti-platelet drug efficacy in Type 2 diabetes.                                                  The next paper tells us that the majority of cardiovascular disease events are now occurring amongst adults with a systolic and diastolic blood pressure of less than 140 over 90 millimeters mercury. Prior data have shown us that the majority of incident cardiovascular disease events occurred among U.S. adults with higher systolic and diastolic blood pressures of above 140 over 90. However, over the past several decades, blood pressure has declined and hypertension control has improved. Thus, in the current study, Dr. Tajeu and colleagues from Temple University College of Public Health in Philadelphia estimated the percentage of incident cardiovascular disease events that occur at blood pressures below 140-90 in a pooled analysis of three contemporary U.S. cohorts: the Reasons for Geographic and Racial Differences in Stroke, or, REGARDS study, the Multi-Ethnic Study of Atherosclerosis, or MESA study, and the Jackson Heart study.                                                 In these three U.S. cohorts that enrolled after 2000, more than 60% of incident cardiovascular disease events occurred among participants with blood pressures below 140 over 90 millimeters mercury. In the 2001 to 2008 National Health and Nutritional Examination survey mortality follow-up study, 58% of cardiovascular disease stats occurred in U.S. adults with blood pressures below 140 over 90. Among participants taking anti-hypertensive medication, with blood pressures below 140 over 90, only one-third of those who are eligible for starting treatment were taking one, and approximately 20% met the SPRINT eligibility criteria.                                                 In conclusion, while higher blood pressure levels are associated with increased cardiovascular disease risk, in the modern era the majority of incident cardiovascular disease events occur in U.S. adults with blood pressure below 140 over 90. Although absolute risk and cost effectiveness should still be considered, additional cardiovascular disease risk reduction measures for adults with blood pressure less than 140 over 90, and at high risk for cardiovascular disease, may be warranted.                                                 Well, that brings us to the end of our summaries. Now, for our feature discussion. Dr. Carolyn Lam:               On today's podcast discussion, we will be talking about aortic wall inflammation as a possible functional, or biological, imaging bio-marker that may add to the usual structural measurements of size that we use to predict abdominal aortic aneurysm expansion and rupture. Now, to discuss this very important paper, we have the corresponding author, representing the MA3RS study investigators, Professor David Newby from the Center for Cardiovascular Science in Edinburgh, as well as a familiar voice now, Dr. Joshua Beckman, associate editor from Vanderbilt University. Welcome, gentlemen. Professor David Newby: Hi, there. Dr. Joshua Beckman:      So great to be here again, thanks for having me. Dr. Carolyn Lam:               So great that you're back again, Josh! But David, let's start with you. Could you just summarize what this trial was about and your main findings? Professor David Newby: Sure, so this was a major clinical trial that we undertook in the U.K. and Scotland. We approached patients who were in a surveillance program who had an abdominal aortic aneurysm, and we asked the question, "Is there anything we can do better than just serial ultrasound measurements that currently are stunned to this care?" So, in Edinburgh, we developed a technique using ultrasmall, superparamagnetic particles of iron oxide, which is a bit of a powerful ... so we shortened that to USPIOs; these are really small iron particles that are so small they can cross vascular spaces and they get gobbled up by tissue resident macrophages, and then causes a signal that we can detect on magnetic residents' scanning MRI.                                                 So we were really asking the question, "Can we do better than ultrasound by using what we call USPIO-enhanced MRI?" Dr. Carolyn Lam:               So a biological or functional imaging parameter versus just structural. And so, what were your main findings? Professor David Newby: We recruited around 361 patients and ultimately 341 went into the trial because of various exclusions, et cetera. And we followed these patients up for, on average, around three years. And so we were following it up every six months with ultrasound, with other various assessments, and ultimately what we found was that the USPIO-enhanced magnetic residents' scan was positive in around half of patients, and in those patients that took up the USPIOs in their abdominal aortic aneurysm wall, those patients, their aneurysms expanded quicker. So rate of expansion was higher, and they went on the have the primary event of either elective repair, or rupture. And, don't forget, that the clinicians who were looking after these patients, they didn't know the results of the MRI so it didn't influence their clinical minds, when this was completely independent of the clinical team.                                                 So, for the first time, we demonstrated that imaging or tracking macrophages in the abdominal aortic wall could, indeed, predict both disease progression and clinical outcome. Dr. Carolyn Lam:               And Josh, you know, no one can say it better than you: could you just describe what we discussed as the editors about the significance of such a finding? Dr. Joshua Beckman:      I think there's a few things to take home from these three that are really incredible. First, David, were you surprised at the concordance between the USPIO-enhanced imaging and smoking, or was that something that you expected? Professor David Newby: That was a big surprise. That was, actually, as we discussed in the manuscript, quite an interesting finding, and as always with an interesting find, we dig around in the background, and it actually gets more and more exciting and plausible because of the mechanistic work that we'd seen in the pre-clinical science that preceded our trial. So yes, it was a surprise, but actually the more we got into it, the more it made sense. Dr. Joshua Beckman:      One of the other things that I think is really important to talk about is how you get this study done, and one of the things I found incredibly impressive ... I am unaware of any other multi-sensor MRI study like this. How did you organize this amongst the different institutions? Professor David Newby: It can be a bit of a challenge. So I've done quite a few multi-sensor trials in Scotland, and imaging trials, and the community in Scotland actually is very, very supportive and we got a good network of folks. So the three centers are actually two imaging centers: one in Edinburgh one in Glasgow, a further recruitment center in a city just in the center of Scotland, Sterling. And the patients ... we were able to obviously make sure the scanners did the same protocols; fortunately, they were the same scanner, make and model. So that all obviously helped, but we had a lot of inundation, phantom work, to make sure both centers got things right.                                                 But there was a huge motivation to get this done, and I'm indebted to Charles Riditi and Colin Barrie in Glasgow for doing the, and supporting the, imaging work, and also a medical physicist here in Edinburgh, Scott Semple, who'd done a lot of the work to get this to happen. So there's a teamwork in Scotland and the NHS, where the access to patients are in the screening program as well, which made recruitment really well and very efficient. And we started exactly to target, which is pretty unusual in clinical trials, often takes longer to recruit patients, but it was a great team effort. The imaging quality, we checked, verified, centrally read, and it was really good to see it delivered in that way. Dr. Joshua Beckman:      Do you think that agent, the iron oxide particles, is going to be the contrast agent, I guess, of the future, or do you think because it is now so consistent with smoking, it's gonna be more of an investigational tool? Professor David Newby: So there's a couple of things to say here on ferumoxital, which is the USPIO we used. It's currently licensed in the U.S. for the treatment of anemia and chronic renal failure, but it can also be used as an imaging agent and actually this, I think increasingly, might have a role; not just in aneurysms, but elsewhere. So the first thing you can do is actually do angiography with this agent. [Obviously gadolinium is getting a lot of press at the moment, with problems with warnings coming out, of residual brain deposition, and so on. With the USPIOs, you can use this in renal failure patients, so again, another contraindication for us to concern about: NSF in renal failure patients. So actually, for angiography, I think it's going to have an increasing role.                                                 For imaging of inflammation, we've previously demonstrated that you can track inflammation post-myocardial infarction, so you can see air is lighting up following myocardial infarction. We have some papers out on that, and I think, if you are in the business of looking at cellular inflammation, macrophage trafficking, then this technique really can be helpful.                                                 When we come to aneurysm studies, I think it is less clear because ultimately, doing a quick ultrasound, in fact can give you the information together with all of the clinical risk factors, like smoking, and you get to the same end point without doing the MRI. Then, clearly, it's not going to be that impactful. Having said that, I think sometimes we will have patients who've got all this information and we're not sure which way to go. So I think it could be used as an almost umpire test, if you're not sure whether to proceed with surgery or not. And I think, also, if we discover new agents that are anti-inflammatory that may impact on disease progression, with a normal therapy, then clearly this might be a good buyer market to use in future therapeutic trials. Dr. Joshua Beckman:      Yeah, I actually see a huge potential for the testing of new agents, to see whether or not it reduces the inflammation that's associated. I'm gonna ask you a theoretical question, if that's okay with you. Part of the inflammatory process in the aneurysm is based on oxidative stress, but I've always wondered if you provide more oxygen, which may enhance the oxidative stress reaction, are you actually worsening the reaction at the time you're doing the study? Is that possible, or am I just concerned about nothing and making it up? Professor David Newby: Well, obviously your [inaudible 00:13:19] stressors is important in all of cardiovascular disease, and if you increase oxygen supply, maybe you indeed induce more oxidative stress. In the context of an aneurysm, often there's quite an hypoxic state in the aneurysm wall, because obviously the intraluminal thrombus can buffer the wall itself from it, obviously the vasovasorum come in, but they may not be as efficient in doing that. Some of the areas that we're seeing light up probably are quite hypoxic, so they'll be in an oxygen-deprived state. So I think that needs to be put in the balance, too, and there has been some suggestion that iron particles can increase oxidative stress, and it has been suggested maybe harmful; we've not seen that, we've had absolutely no adverse reactions at all in all of our patients. We had one patient whose blood pressure fell a little bit, but we didn't have to medically intervene at all, so it was just observed and it passed; of course it might be due to many things.                                                 We've also studied this in patients with myocardial infarctions, I've said, also bypass surgery, people who've had bypass surgery. We've also published on using these agents there, and again, we've seen absolutely no adverse reactions. And you would've thought, in the context of those situations, if you were going to see an adverse effect you would've seen it behind. Dr. Carolyn Lam:               David, I've got a question for you. I think you mentioned, a little bit earlier, that end of the day this enhanced MRI did not improve the risk stratification beyond the current predictors of clinical outcome in abdominal aortic aneurysms, but what are the next steps for you? Professor David Newby: There's a couple of things, which we've been thinking through. Firstly, I think the primary end point of the trial was mostly driven by repair, and when we looked at the emergent events, so dying, and rupturing, the signal got stronger and very close to statistical significance. And obviously when you've got a population of patients whose elective surgeries mostly dominated by the ultrasound scan decision, therefore makes it difficult to prove, on top of that, the MRI will have value. So it's quite high, and on a difficult bar to cross, so some of the thoughts we've had are thinking about predicting rupture, rather than repair. And there will also be potential for actually doing a trial, where we actually base decisions on the aneurysm, and if you've got an intermediate category of patient, where you're not sure which way to go, those patients you then do use as an arbiter, and that might have, therefore, proof or value for it.                                                 And the final area that we're probably thinking about exploring is, "Okay, paths for macrophages." Is there other pathophysiological processes that we might want to explore with other agents, that might predict aneurysm growth and rupture even stronger, and macrophage inflammation? So those are some of the thoughts that we've had about where the next steps will be. Dr. Joshua Beckman:      This is an incredible amount of work and I always think it's important to make clear to everybody who's listening to this podcast that, even though we may not all do the same kinds of research, it needs to be made clear that having a multi-sensor study in this topic, with this technique, is incredibly impressive. And the physiology that was brought forth, in addition to the clinical stuff that we just heard about, I think is what makes this worthy of a podcast.                                                 Dr. Newby, thanks so much for participating. Professor David Newby: Thank you so much, that's very kind. And just to reiterate, it has been a long journey and a huge effort, but we're reaping the rewards now, and it's nice to see the data being published in circulation. Dr. Carolyn Lam:               Gentlemen, it has been so wonderful having you here to discuss this. Thank you so much for your time.  

Interview with Saket Girotra, MD, and Lee Joseph, MD, MS, authors of Temporal Changes in the Racial Gap in Survival After In-Hospital Cardiac Arrest, and Myron L. Weisfeldt, MD, author of Racial Differences in In-Hospital Cardiac Arrest: Good News: Cautious Optimism is Welcome

A discussion of the evidence and methodological issues pertaining to explaining the causes of racial differences in intelligence, with a focus on evaluating the hereditarian hypothesis that such differences are largely genetic. Recommended pre-listening is Episode 81: Intelligence Part 2.

Glenn C. Loury is the Merton P. Stoltz Professor of the Social Sciences and Professor of Economics at Brown University. He has taught previously at Boston, Harvard and Northwestern Universities, and the University of Michigan. He holds a B.A. in Mathematics (Northwestern University, 1972) and a Ph.D. in Economics (MIT, 1976). Professor Loury has published mainly in the areas of applied microeconomic theory, game theory, industrial organization, natural resource economics, and the economics of race and inequality. He has been elected Fellow of the American Academy of Arts and Sciences and of the Econometric Society, Member of the American Philosophical Society, Vice President of the American Economics Association, and President of the Eastern Economics Association. He is the recipient of a Guggenheim Fellowship and a Carnegie Scholarship to support his work. As a prominent social critic and public intellectual, writing mainly on the themes of racial inequality and social policy, Professor Loury has published over 200 essays and reviews in journals of public affairs in the U.S. and abroad. He is a member of the Council on Foreign Relations, is a contributing editor at The Boston Review, and was for many years a contributing editor at The New Republic. Professor Loury’s books include One by One, From the Inside Out: Essays and Reviews on Race and Responsibility in America (The Free Press, 1995 – winner of the American Book Award and the Christianity Today Book Award); The Anatomy of Racial Inequality (Harvard University Press, 2002); Ethnicity, Social Mobility and Public Policy: Comparing the US and the UK (ed., Cambridge University Press, 2005); and, Race, Incarceration and American Values (M.I.T. Press, 2008). Glenn Loury hosts The Glenn Show on Bloggingheads.tv, and he can be reached on Twitter at @GlennLoury. Books and articles discussed in this podcast: Ta-Nehisi Coates. “The Case for Reparations.” The Atlantic. June, 2014. Thomas Chatterton Williams. “Loaded Dice.” The London Review of Books. December, 2015. Benjamin Wallace-Wells. “The Hard Truths of Ta-Nehisi Coates.” New York Magazine. July, 2015. Jill Leovy. Ghettoside. Spiegel & Grau. 2015. Roland G. Fryer, Jr. “An Empirical Analysis of Racial Differences in Police Use of Force.” National Bureau of Economic Research working paper. July, 2016. Glenn C. Loury. “Ferguson Won’t Change Anything. What Will?” The Boston Review. January, 2015.

The concept of race is a complex matter, and often it is difficult to have a real conversation about race and ethnicity without tensions rising and offenses being launched. Deborah has a dialogue about the definition of race and more with Dr. Candis Watts Smith of UNC-Chapel Hill, Dr. Mark Anthony Neal of Duke University, and Samone Oates-Bullock, a student at UNC-CH.

The concept of race is a complex matter, and often it is difficult to have a real conversation about race and ethnicity without tensions rising and offenses being launched. Deborah has a dialogue about the definition of race and more with Dr. Candis Watts Smith of UNC-Chapel Hill, Dr. Mark Anthony Neal of Duke University, and Samone Oates-Bullock, a student at UNC-CH.

Tune in when Patricia interviews Debbie Irving, a white, Boton-based racial justice educator and author of Waking Up White: And Finding Myself in the Story of Race. She has written the book she wishes someone had handed her years ago: a story-based Racism 101 for white people. Its narrative memoir format provides a mainstream read that gives white readers the basics needed to access complex understandings about racism. Similarly, many people of color yearn for authentic, informed dialogue about racism with white friends,family and colleagues. Debby will discuss the touch point she provides in her book for examining differences and paints a clear picture of why the first step in addressing cross-cultural issues of an y kind is understanding one's own culture.

Tune in when Patricia interviews Debbie Irving, a white, Boton-based racial justice educator and author of Waking Up White: And Finding Myself in the Story of Race. She has written the book she wishes someone had handed her years ago: a story-based Racism 101 for white people. Its narrative memoir format provides a mainstream read that gives white readers the basics needed to access complex understandings about racism. Similarly, many people of color yearn for authentic, informed dialogue about racism with white friends,family and colleagues. Debby will discuss the touch point she provides in her book for examining differences and paints a clear picture of why the first step in addressing cross-cultural issues of an y kind is understanding one's own culture.

A more poignant version of the, "Black people are different from white people" discussion. Bryson lives in Bed Stuy and acknowledges how his whiteness is inherently ruining it.

A conversation with two leading experts on race and community–police partnerships: Baltimore’s Lieutenant Colonel Melvin Russell and national scholar Dr. Phillip Goff. Speakers: Phillip Atiba Goff, Joe Jones, Diana Morris, Melvin Russell. (Recorded: Jun 17, 2013)

Join us for a conversation with two leading experts on race and community-police partnerships. Baltimore's own Lieutenant Colonel Melvin Russell and national scholar Dr. Phillip Goff will address some provocative issues: What are the underlying causes of racial differences in arrests? What role does implicit bias play? Is it possible for communities and police to work together in a meaningful way?Joe Jones, executive director of the Center for Urban Families and OSI-Baltimore board member, will serve as moderator.Lt. Col. Melvin Russell, a 30-year veteran of the Baltimore Police Department, serves as the chief of its Community Partnerships Division. He previously served as the commanding officer of Baltimore's Eastern District.Dr. Phillip A. Goff is the executive director of research for the Consortium for Police Leadership in Equity and assistant professor of social psychology at the University of California, Los Angeles. He is a leader in psychological research on race, gender, and policing.  Recorded On: Monday, June 17, 2013

Author Toya Z. Like podcast discusses her process in writing the article and its relationship to her work at large.

How to handle kids who point out racial differences. Like what you hear? Help us out by writing a review at iTunes!