Podcasts about naveed

Join us for the third event in a 4-part series by the Center for Constitutional Rights and Haymarket Books marking the 20th anniversary of 9/11. In “Stories of Survival: Surviving the post-9/11 human rights crisis and reclaiming rights for all,” we are honored to hear from survivors of the U.S. government's so-called “War on Terror,” who have resisted the U.S.' campaign of human rights abuses, from endless wars in Iraq and Afghanistan, to the global export of the nebulous and discriminatory “terrorism framework”, and the proliferation of domestic policies of surveillance and detention that reinforced existing systems of oppression. From Kabul and Mombasa to Omaha--panelists will share the impact of the harms and together demand accountability and imagine a world repaired. Panelists: Marie Ramtu holds a master's degree in Peace Studies and International Relations from Hekima University College. She's a lobbyist with grassroots, regional, and international niches. Her experience in humanitarian, the human rights and social justice sectors spans at least 14 years. Marie has operated to safeguard the rights of the marginalized refugees and asylum seekers. She has also had a specific focus in influencing a shift in attitude, policies, and practices in the specific protection on the rights of sexual and gender minorities. Before joining Muslims for Human Rights (MUHURI) as the Executive Director, Marie worked with regional and international non-governmental organizations that include the Coalition for the Independence of the African Commission (CIAC), the Network of African National Human Rights Institutions (NANHRI), and Church World Service. Born in Kabul, Afghanistan and raised in rural Washington state, Gazelle Samizay's work often reflects the complexities and contradictions of culture, nationality and gender through the lens of her bicultural identity. Her work in photography, video and mixed media has been exhibited across the US and internationally, including at Whitechapel Gallery, London; Los Angeles Municipal Art Gallery; the California Museum of Photography, Riverside; the de Young Museum, San Francisco; and the Slamdance Film Festival, Park City, UT. In addition to her studio practice, her writing has been published in One Story, Thirty Stories: An Anthology of Contemporary Afghan American Literature and she is a founding member of the Afghan American Artists and Writers Association. Samizay has received numerous awards and residencies, including from the Princess Grace Foundation, NY; Craft Contemporary, Los Angeles; the Arizona Community Foundation, Phoenix; Level Ground, Los Angeles, the Torrance Art Museum, and Side Street Projects, Los Angeles. She received her MFA in photography at the University of Arizona and currently lives in San Francisco. www.gazellesamizay.com. @gsamizay. Naveed Shinwari is a plaintiff in Tanvir v. Tanzin, a case brought in 2013 on behalf of American Muslims who were placed or kept on the No-Fly List by the FBI for refusing to spy on their Muslim communities. He was repeatedly questioned and harassed by the FBI as they attempted to recruit him to spy on others. As retaliation for his refusal to do so, Naveed was placed on the No-Fly List and unable to travel to Afghanistan to visit his wife and daughters for two years. His fight to hold government officials accountable for their abuse of power continues. Moderator: Samah Mcgona Sisay is a Bertha Justice Fellow at the Center for Constitutional Rights, where she specializes in international human rights and challenging inhumane immigration policies and abusive police practices. Prior to coming to the Center for Constitutional Rights, Samah worked as an Equal Justice Works Fellow at African Services Committee. Watch the live event recording: https://youtu.be/1bClT5GmLJk Buy books from Haymarket: www.haymarketbooks.org Follow us on Soundcloud: soundcloud.com/haymarketbooks

Miranda Cosgrove, one of Hollywood's biggest and busiest stars, stat down with Naveed Jamali on the Daily Break to talk about using her voice to empower girls around the country to address the climate change crisis.Find out more here: https://solve.mit.edu/events/solveathon-workshop-with-hp-s-girls-save-the-worldSee Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Naveed gives his short but sweet holiday greetings!See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Naveed takes a look at Section 287(g) of the U.S. Immigration and Nationality Act, which authorizes the Department of Homeland Security to deputize local law enforcement officers to enforce federal immigration law.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Engagement, transparency, trust, and communication. Do these values sound familiar to you? Many businesses claim them as part of their culture, but not many follow them. And at the end, they wonder why people leave. Attracting and retaining talent has become more than a simple technical process. To get the best, you need to go beyond the common. How to do that? Our guest today reveals some valuable insights. Naveed Tejany is the CFO at OJO Labs. As CFO, Naveed oversees financial reporting, financial planning, corporate development, and business operations. Over the years, he has recruited top talent and established critical financial and human resource systems. Under his leadership, the company has raised over 130 million dollars in venture capital from top-tier mission-aligned investors. They have also successfully acquired and integrated four companies. When looking for investment partners, Naveed understands that raising capital from the right partner is critical. In this episode, we discuss: - OJO's distinctive business model - How to hire the best talent for each role - Insights on how to retain talent - The contribution of engagement and transparency in retaining talent For more interviews from the CFO Weekly podcast, check us out on Apple, Spotify, or your favorite podcast player! Presented by Personiv https://insights.personiv.com/cfo-weekly

Known best for his 11 day run as the White House director of communications, Anthony Scaramucci talks with Naveed Jamali about what it's like working with Donald Trump and people in his inner circle.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Naveed sits down with Lincoln Project senior advisor Fred Wellman to explain the reasoning behind the court marshaling viral "accountability" marine, Lt. Col. Stuart Scheller after his sentencing. Plus a nod to Colin Powell after his passing.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Naveed's conversation with former Congressman and CIA officer Will Hurd (R-TX) continues with part 2. Here, the two dive into motivation behind espionage, a new cold war, and how Taiwan plays into China and the US's future.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Former Congressman and CIA officer Will Hurd (R-TX) joins Naveed Jamali in a 2 part interview. In part 1, Naveed and Will talk about the political divide in America, and what can be done to bridge the gap.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

In this episode of Dastaangoi Podcast we get to sit down with adventurer @hunzaonfoot. We discuss a wide range of topics from his journey walking across Pakistan to the current state of tourism.

Naveed breaks down a DHS assessment that warns of violence at the "Justice for J6" rally in Washington DC on September 18th. What should we expect to see?See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

In episode 133 of Today's News Tonight, we're joined once again by Naveed Mohebbi to talk about gaming's latest! And there's some wild bits today such as Platinum being open to a Star Fox Zero Switch port, Nintendo lowering the price of the Switch in Europe, Square Enix's TGS 2021 line-up, a potentially huge leak stemming from GeForce Now...if it's real. Let's discuss all this and more in our latest episode! Check out more from Naveed! Twitter: https://twitter.com/Naveed_Mohebbi YouTube: https://www.youtube.com/c/NaveedMohebbi Twitch: https://www.twitch.tv/naveedmohebbi --- Support this podcast: https://anchor.fm/gvg/support

Naveed Rahman, institutional portfolio manager, shares his outlook on the global markets, and discusses fund positioning of Fidelity Global Intrinsic Value Class. The fund is managed by legendary investor Joel Tillinghast, and Naveed shares they've added more traditional banks, financials, and some consumer credit names to the fund. Naveed also discusses the Jack Hole Symposium, tapering, inflation, and the potential implications on the markets as concerns of the Delta variant spread. Naveed notes employment numbers are strong. Reports month-after-month show a tick up in consumer prices, which all indicate that the U.S. will reduce monetary support at some point. Recorded on August 26, 2021.

Sara Naveed is a Canadian writer, chronic illness advocate, and founder of the blog Fabulous and Fatigued. 14 years ago, she was diagnosed with fibromyalgia following a hit-and-run. Inspired by her experience, she started the blog with the aim of creating awareness and ending the stigma of life with chronic illnesses. Her work has been published in various media outlets and platforms including Yahoo, MSN, The Mighty, The Tired Girl Society and DPC Education Center. Tune in as Sara shares: details of the hit-and-run that eventually triggered her diagnosis what the diagnosis and acceptance processes were like for her, as a teenager how chronic pain has changed her life how fibromyalgia manifests in the body how discovering accessibility services supported her in college that taking holistic approaches to her symptom management has been very supportive for her where she has encountered “toxic positivity” in the reactions of family and friends how her diagnosis has impacted her relationships how she has worked on her mindset to cultivate balance in her life her experiences of acceptance and bias within the medical system, as a Muslim woman of South Asian heritage why she uses CBD to manage symptoms from insomnia and anxiety to chronic pain how the immigrant experience — from a language perspective — impacts healthcare access how the Canadian healthcare system needs improvement in order to better serve patients a reflection on her early experience of chronic illness, and how it inspires her current work the importance of community in ongoing healing and acceptance

S03-E16 Naveed e Fikr Prometheus - نوید فکر - سبط حسن پرومیتھیوس ، پہلا باغی https://youtube.com/playlist?list=PL3GEqwP6dqmj0NW83479uKbP5q0erS0Uz #Urdu #Hindi #Audiobooks

In this episodes we talked with Naveed Ahmed about his evolution from metalcore to pop/hip-hop and his life with In Loving Memory and how his time in that band has shaped his career now! Checkout Naveed here! https://www.instagram.com/naveedahmedny/ Follow Us Here: https://linktr.ee/soundslikenyc

S03-E15 وادی سندھ کا سوشلسٹ صوفی نوید فکر - سبط حسن Naveed e Fikr Sibte Hasan part4 Wadi Sindh ka Socialist Sufi Urdu/Hindi Audiobook You can listen to many other full audiobooks via our Youtube Channel: https://youtube.com/playlist?list=PL3GEqwP6dqmj0NW83479uKbP5q0erS0Uz Abaseen Podcast.

Welcome to an ANI Throwback Episode! In these episodes, we reintroduce you to some of our most popular episodes.Request a Custom Workshop For Your CompanyGet Free Access to Over 15 Negotiation GuidesFollow Kwame on LinkedInIf you've been a listener of the show and you've gotten a lot out of our programming, you can click here to Support Negotiate Anything. Support this show http://supporter.acast.com/negotiate-anything. See acast.com/privacy for privacy and opt-out information.

All eyes are on central banks as investors eagerly await their policy response to different types of inflation. Institutional Portfolio Manager, Naveed Rahman, shares his thoughts on inflation and discusses some potential opportunities in the market. Naveed works alongside portfolio managers Joel Tillinghast and Salim Hart on Fidelity Global Intrinsic Value Class. Naveed believes that on the one hand, if inflation were to come to pass, cheaper companies' value stocks would all benefit disproportionately because large companies can pass through rising input costs. On the other hand, he is unsure if inflation is real as we may simply be seeing a year-over-year comparison that is very flattering for inflation. Naveed also shares his thoughts on wage inflation, noting that employees have a little more bargaining power as the pandemic has made them more flexible to work for different employees. Additionally, Naveed shares that he and his team are overweight financials, consumer credit stocks, and bank stocks as they are inexpensive relative to the market. Recorded on July 28, 2021

S03-E10 سیکولرزم نوید فکر - سبط حسن Naveed e Fikr Sibte Hasan part3 Secularism Urdu/Hindi You can listen to many other full audiobooks via our Youtube Channel: https://youtube.com/playlist?list=PL3GEqwP6dqmj0NW83479uKbP5q0erS0Uz Abaseen Podcast.

Salim Hart, portfolio manager, and Naveed Rahman, institutional portfolio manager, and share their perspectives on the growth of value stocks and provide an update on the Fidelity Global Intrinsic Value Class which Salim manages with Joel Tillinghast. Naveed explains that they expect to see an increase in inflation rates and higher interest rates; this will benefit value stocks. Naveed notes that there has been much mispricing in the last 9-12 months. Attractive pricing is interesting to Naveed but is not always a reason to buy the stocks. They discuss an interesting anomaly the Fidelity research team uncovered in the market and how it reacted to this anomaly. Salim discusses what is attractive within international exposure and notes that the team embraces ESG, with governance being a big focus. They also discuss commodities and REITs (Real Estate Investment Trust). Recorded on May 6, 2021.

Dr. Naveed Sherwani is a serial entrepreneur and technical leader in the world of semiconductors. As a professor at Western Michigan University, he wrote several books and hundreds of articles about chip design and manufacturing. He was the founder of Open Silicon, PeerNova, and was the CEO of SiFive. Currently he’s the Chairman of the Silicon Federation, which aims to democratize chip design.Dr. Sherwani’s Linkedin - https://www.linkedin.com/in/naveed-sherwani-2a789/Timestamps:2:11 - An explanation of the semiconductor shortage5:37 - Roadmap of chip design to final product9:25 - Semiconductors are a human right11:41 - Semiconductors are the new oil17:10 - How do we get semiconductors into the poorest countries?20:08 - Silicon Federation (https://www.linkedin.com/company/siliconfederation/about/)21:59 - How do you incentivize corporations to open source semiconductor technology?24:49 - Will a new era of hardware lead to a Cambrian explosion in startups?27:12 - The next two decades of chip development30:25 - Getting young people excited about hardware38:27 - Is China ahead of the US in artificial intelligence?43:11 - To what extent is ML a hardware problem?45:13 - Building a global education infrastructure 50:00 - How do you democratize education opportunities for the world?53:19 - In your opinion, what is the best piece of software ever built?

Key plot: Jack reunites with Heller and Audrey An arrested Jack is taken to Heller and asks to go back into the field to help stop Margot While there Audrey goes to see him and they have a heart-to-heart CIA follow a lead on Margot’s video demands which Naveed planted, but it’s a trap and the CIA team are ambushed by an explosive Undercover with Rask Heller agrees to let Jack go undercover and see Karl Rask, an arms dealer Jack has been working for to sabotage his operations, and he’s also a contact of Margot The play: Jack killed Nils, another of Rask’s men, for being a CIA contact and has captured Kate, who was Nils’ contact. Jack needs Rask to complete a bank login so Chloe can access his system Kate opts to inject herself with a drug to knock her out, shocking Jack Prime Minister Davies tracks Jack’s operation after hearing of Heller’s condition and sends in MI5, who interrupt the mission Jack manages to get Chloe access and Kate survives her torturee Simone betrays Margot Naveed is killed after trying to lead the CIA to their location, in front of Simone Naveed’s sister has heard of plans to leave London and Simone is sent to find out what she and her daughter know, which is nothing, but is told to kill them anyway She tries warning them but accidentally stabs Farah and while chasing Yasmin is hit by a bus Jack questions her as Margot sends a drone to kill her, which they narrowly escape Heller sacrifices himself Heller offers Margot a trade: give himself up for the destruction of the drones He reveals to Jack his Alzheimer’s diagnosis and enlists him and Mark to help make the exchange go through Jack gets Heller to Wembley Stadium where he’s asked to go, and Margot fires a missile at him But actually Chloe cloned the feed with Heller in the middle of the pitch and Jack saved Heller - she told him she didn’t know if it would work  Jordan uncovers the truth Jordan finds that files related to Adam Morgan were deleted but Navarro tells him not to pursue it until after the crisis has passed He doesn’t give in and so Navarro, who framed Adam, on the direction of Adrian Cross, has Jordan go to what he says is a dead-drop that will help lead to Margot It’s actually a set-up for an assassination, which Jordan initially survives He figures out Navarro sent the hitter but having gained the upper hand, is stabbed and dies Contact: @The24Podcast 24faithful.com 405-771-0567

Dr Carolyn Lam: Welcome to Circulation on the Run! Your weekly podcast summary and backstage pass to the journal and its editors. We're your co-hosts, I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: I'm Greg Hundley, Associate Editor, Director of the Pauley Heart Center, VCU Health in Richmond, Virginia. Dr Carolyn Lam: Greg, we got double features today. Now, the first one's all about fruit and vegetables. Now, before you switch off, this is a very important one, okay? So, listen on. And the second is on the EMBRACE heart failure trial. Now, this was a late breaker, very important, more data on empagliflozin, that SGLT2 inhibitor. So really, really fun discussions coming right up. But first, can I dig into one of the papers that I'm really dying to tell you about? Dr. Greg Hundley: Absolutely. Dr Carolyn Lam: Okay. This is all about the diagnostic performance of high-sensitivity cardiac troponin T strategies, that super hot topic. We know that European data support the use of low high sensitivity troponin measurements or a 0/1 hour algorithm for myocardial infarction or to exclude MACE among emergency department patients with possible acute coronary syndrome. However, there's really very modest U.S. data to validate these strategies. This study today from Dr. Allen and colleagues from University of Florida, really evaluated the diagnostic performance of an initial high sensitivity cardiac troponin T measure below the limit of quantification. And that is six nanograms per liter, a 0/1 hour algorithm, and their combination with heart scores for excluding MACE in a multi-site U.S. cohort. And this is the largest prospective multi-site U.S. study of high sensitivity troponin T strategies to date. Dr. Greg Hundley: Wow, Carolyn you've really piqued my interest. So what did they find? Dr Carolyn Lam: Okay. And initial high sensitivity, cardiac troponin T below that level of quantification of six nanograms per liter was associated with a negative predictive value of 98.3% for 30-day MACE. Okay. That was that value itself. Now the 0/1 hour algorithm rolled out 57.8% of patients with a negative predictive value of 97.2% for 30-day MACE. The addition of a low-risk heart score to that initial high sensitivity troponin T level below that six nanogram per liter and the 0/1 hour algorithm improved the negative predictive value for 30-day MACE to 99% and 98.4% respectively. Dr. Greg Hundley: Wow. Carolyn, it looks like a really comprehensive analysis of the high sensitivity troponin. So tell us what are the clinical implications of this study? Dr Carolyn Lam: So these data seem to imply that when used without a risk score and initial high sensitivity troponin T below six nanograms per liter, or a 0/1 one hour algorithm, may not have sufficient sensitivity or negative predictive value to exclude 30-day MACE in the U.S emergency department patients. But the addition of that low-risk heart score to those measures improves the negative predictive value, but rolls out fewer patients. And so in totality, these results suggest that in the U.S. Emergency departments, adding a risk score to either of these strategies really increases their safety. Dr. Greg Hundley: Boy, great new information in our journal. Well, Carolyn, I'm going to switch to the world of basic science and start to evaluate in this next paper, the regulation of cellular signatures in children with dilated cardiomyopathy, and the work comes to us from Dr. Stephanie Dimmeler from Goethe University in Frankfurt. So Carolyn, Stephanie's team performed single nuclei RNA sequencing with heart tissues from six children with dilated cardiomyopathy. One was age 0.5, 1.75 and another at 5, 6, 12, and then 13 years of age. And they did this to gain insight into age and disease-related pathophysiology, pathology, and molecular fingerprints. And the goal was to gain further insight into dilated cardiomyopathy, which is a leading cause of death in children with heart failure. Dr Carolyn Lam: Cool. So what did they find Greg? Dr. Greg Hundley: Right, Carolyn. So, the number of nuclei in fibroblast clusters increased with age in dilated cardiomyopathy patients, a finding that was consistent with an age-related increase in cardiac fibrosis quantified by cardiovascular magnetic resonance imaging. Dr. Greg Hundley: Now Carolyn, fibroblast of the dilated cardiomyopathy patients over six years of age showed a profoundly altered gene expression pattern with enrichment of genes encoding fibrillary collagens, modulation of proteoglycans and a switch in thrombospondin isoforms and signatures for fibroblast activation. Additionally, Carolyn, a population of cardiomyocytes with a high pro-regenerative profile was identified in infant dilated cardiomyopathy patients, but was absent in those children that were greater than six years old. And this cluster in these infants showed high expression of cell cycle activators, such cyclin D family members increased glycolytic metabolism and any oxidative genes and alterations in beta adrenergic signaling genes. Dr Carolyn Lam: Wow. That sounds like a magnificent and elegant study. Could you boil it down to the take home messages? Dr. Greg Hundley: You bet. Carolyn. Great question. So two points first, infants with a predominantly regenerative cardiomyocyte profile, may preferentially receive treatment strategies to support cardiac regeneration while patients with a pattern associable with cardiac fibrosis may benefit from an early anti-fibrotic therapy to avoid diastolic dysfunction. And second, despite the impracticality of performing these large cohort studies in children with dilated cardiomyopathies, tailored pharmacological treatment is possibly realistic. For example, based on the expression of beta adrenergic signaling genes. Dr Carolyn Lam: Oh wow. That is super cool. That's Circulation for you, publishing these amazing basic science papers with very big clinical implications. Well, I've got another basic science paper for you and this time I've learned a new word actually. It's called O-GlcNAcylation. I should get you to say it after me. I had to get our editor-in-chief Joe Hill to teach me to say that, O-GlcNAcylation. So, cardiomyopathy from diverse causes is marked by increased O-GlcNAcylation. Now, in this paper, co-corresponding authors, Dr. Anderson and Umapathi from Johns Hopkins University provide a new genetic mouse model to control myocardial O-GlcNAcylation independent of pathological stress. Their data actually provided evidence that excessive O-GlcNAcylation caused cardiomyopathy, at least in part due to defective energetics. Enhanced O-GlcNAcase activity was well-tolerated. And conversely, attenuation of O-GlcNAcylation was beneficial against pressure overload induced pathological remodeling in heart failure. Dr. Greg Hundley: Interesting, Carolyn. So what are the clinical implications of these findings? Dr Carolyn Lam: Well, the data really provide new proof of concept that excessive O-GlcNAcylation is sufficient to cause cardiomyopathy, and they also suggest that attenuation of this excessive O-GlcNAcylation may represent a novel therapeutic approach for cardiomyopathy. Dr Carolyn Lam: Shall we go on and sort of wrap up on what else is in this issue? Because I'd like to talk about highlights from the Circulation family of journals that Sarah O’Brien really beautifully summarizes, talking about everything from Circulation: Arrhythmia & Electrophysiology, to [Circulation:] Cardiovascular Quality & Outcomes. It's just a beautiful piece where we get all the highlights. Must read. There's also a Perspective piece by Dr. Gillis on Rhythm Control in Atrial Fibrillation: Is Earlier the Better?, and that discusses the EAST-AFNET 4 and early AF trials. Dr. Greg Hundley: Very good, Carolyn. Well, from the mailbox, professors Pan and Liu exchange letters regarding a prior response to a letter regarding the article Genetic Architecture of Abdominal Aortic Aneurysm in the Million Veteran Program. Also, Dr. Arbus-Redondo has an EKG challenge entitled, Dual Chamber Pacemaker after Sinus Node Dysfunction and an Enlarged Right Atrium. Is it what it seems? Dr. Greg Hundley: And then finally, Dr. Corrado has a very nice Research Letter, entitled, Serial versus Single Cardiovascular Screening of Adolescent Athletes. Dr. Greg Hundley: Well, Carolyn, I'm dying to hear about fruits and vegetables. How about we get onto those featured discussions? Dr Carolyn Lam: Cheeky, cheeky, Greg. Here we go. Dr Carolyn Lam: Oh, I'm so excited about today's featured discussion because it's about my favorite thing, fruits and vegetables. Okay, wait a minute, everybody. Before you start rolling your eyes, this is a really important one. Have you ever asked yourself, what is the optimal intake levels of fruit and vegetables for maintaining long-term health? Well, guess what? We're about to find out and I'm so pleased to have the first author of today's feature paper, Dr. Wang Dong, and he's from Harvard medical school and Brigham Women's Hospital. We also have our Associate Editor, Dr. Mercedes Carnethon from Northwestern University and our Associate Editor who is also the editorialist to this paper, Dr. Naveed Sattar from University of Glasgow. So welcome, everyone. Dr. Wang, please tell us what you did in this study and what were your main results? Dr. Wang Dong: Thank you, Carolyn. So, basically, in this study, we analyzed the data from two long running cohort study. That is the Nurses' Health Study and Health Professional Follow-Up Study. So these two study includes more than 100,000 participants who had been followed for up to 30 years. And we also include a meta-analysis that includes in total 26 studies and about two million participant from 29 countries, and had countries around the world. So, basically, the major finding from this study is, of course, the intake of fruits, vegetable is inversely associated with the risk of death from all cause and the different kinds of cause-specific mortality. And we have a very interesting finding that is intake of about five servings per day, that can be translated into two serving of fruits and three servings of vegetables per day, was associated with the lowest risk of total mortality. So that's an optimal intake level for fruits and vegetable. Dr. Wang Dong: And another important finding from this study is, not all foods that some people consider to be fruits and vegetables can offer the same health benefits. For example, in this study, we found that starch vegetables such as peas and corn, and some fruits juice and potatoes are actually not associated with any benefit in terms of longevity. On the other hand, if you look at green living vegetables such as spinach, kale, and fruits that's orange color fruits and vegetables, that's rich in beta-carotene and vitamin C such as citrus fruits and berries, carrots they're associated with a substantial reduction in the risk of total mortality. That's a major finding from this paper. Dr Carolyn Lam: Oh, I just love it. I mean, just like such wholesome, beautiful findings from a wonderful study. Now, if I could ask you, cause I think the first thing everyone's going to say is, okay, these are associations. I mean, what'd you do about the residual risks? Could you maybe describe how you try to address some of these things like, is taking in fruits and vegetables just a surrogate for people who, I don't know, exercise more, for example? Dr. Wang Dong: Yeah. So in original data analysis, we actually have extensive data collection of all kinds of foods, lifestyle, risk factors, medication use, any health-related variables. So we carefully adjust for a large number of confounding factors. So actually another thing I want to point out, most all of these health-related lifestyle factors actually are inverse confounding factors in this kind of analysis. So when you adjust for other confounding factors, it's tend to attenuated your inverse association. So the review from confounding actually wouldn't be a major explanation for this association. Dr Carolyn Lam: Oh, that's great. And by the way, I think I misspoke. I'm not sure if I said residual confounding or residual risk just now, but you absolutely read me right, that I meant residual confounding. So thanks. Now that we've got that out of the way, if I could ask Mercedes, please. I mean, ah, another fruits and vegetables paper, I mean, what made this one different that we said we have to have it at Circulation. Dr Mercedes Carnethon: Well, thanks so much, Carolyn. And thank you Dong, for your team's outstanding work. I know what excited me about it was the demonstration of something that we have adopted into our lexicon, that one needs five fruits and vegetables. So I was excited to see you quantify it. In particular, the question I have for you is, did you see that these patterns of association of fresh fruit and vegetable intake were consistent across the age range and in both sexes? Dr. Wang Dong: Yes, of course. In total, this acts as a stratification variable. So basically, in our original data analysis, we did the analysis in the Nurses' Health Study, which all the participants are women, and in the Health Professional Follow-Up study, in which all the participants are men, would be analyzed separately and we found very consistent results in both cohorts. Then will be the meta-analysis to meta-analyze the results from these two cohorts. It comes out age, actually if you look at the paper, I think in one of the supplemental table, with the age stratified analysis, to look at the a better association if it still holds in different age group. And we did found that the results is pretty consistent in different age groups. And also, I would point out this meta-analysis provides further support to show that this results is generalizable in different people with different social economic status, demographics status also from different background. Dr Mercedes Carnethon: Thank you so much, Dong. it brings me to what Naveed wrote about in his editorial, that food is medicine and I just really loved that and loved the implications of that. So, I don't know, Naveed, if you've got some comments to make? Questions? Dr Naveed Sattar: Yeah, thanks Mercedes. No, I really love this as well because clearly the cardiovascular community, we do lots of trials. Lots of us are nihilists and just look at trials, but actually it's hard to do trials in the food and the dietary area, but these data are very consistent. I think there are multiple potential mechanisms that may explain this. We all have to eat every day, so it's a big part of our lives. Increase fiber intake, increase potassium, micronutrients, food displacement, the more fruit and veggies you eat, the less you'll eat of other things that perhaps are not as protective. And actually, part of the motivation to write an editorial was to put all that into context in terms of mechanisms. And particularly fiber, I think we underestimate the importance of fiber, but then it was also to discuss, well, if this is true, how do we help people make the changes? Dr Naveed Sattar: And at the level of policy, at the level of high risk groups, and my own particular favorite is really communicating dietary change in the clinic. And one of the things I often try, and we put this in a kind of headline figure in the editorial, was actually getting people to try to undergo the palate test or the retraining their palates. I have lots of patients, who, would you believe, in the west of Scotland, never really eat fruit and veg, and I really pushed them to say, "Look, would you please try? And it might take a few weeks for you to retrain your palate". And lots of people come back saying, "Ah, you're correct. And my God, now I like banana and I now like salad." Dr Naveed Sattar: So actually, there's lots of tips that we can do to help people increase from their average of two to three intake, which is the vast majority of population, to four to five, but it's a gradual process and it requires good communication with our patients and to compel them that these changes might take time, but that if they make these changes, they can get to a point where they really enjoy eating fruit and veg and all the multiple health benefits that come, which this paper has now showed, Mercedes. Dr Naveed Sattar: I think for me, that was the real nub of this. Dr Carolyn Lam: Naveed, I just love the way you express it. And indeed, everyone take up that editorial and look at that beautiful figure. I love the colorful fruits and vegetables on top because it also reminds us, and this paper shows, we are not talking about potato chips, and was it those, corn and peas. But, you know, we're talking about nutrition and fiber and the good stuff. Oh, this is just amazing. I wish we could go on forever, but we have a double feature this issue. And I just want to end by saying, thank you, thank you all of you, for being on the show today. It was such an important topic and I really loved the discussion as I'm sure the audience did. Thank you. Dr Mercedes Carnethon: Thank You. Dr Naveed Sattar: Thanks very much. Dr. Wang Dong: Thank you so much. Dr Carolyn Lam: I am so pleased to have with us today, a friend, a deeply admired colleague and the corresponding author of today's feature discussion, Dr. Mikhail Kosiborod from Saint Luke's Mid America Heart Institute. Dr Carolyn Lam: Welcome, Mikhail. And thank you for publishing this beautiful paper on EMBRACE heart failure with us. I know that this was presented as a late-breaking trial at the Heart Failure Society of America meeting, and it's a very much anticipated paper, but maybe I could start with it's all about SGLT2 inhibitors these days. So please tell us how does EMBRACE add to this accumulating knowledge that we have on SGLT2 inhibitors and heart failure? Dr. Mikhail Kosiborod: Well, first of all, Carolyn, thanks so much for publishing our trial in Circulation. And you're right, SGLT2 inhibitors have been taking the world of cardiometabolic medicine and heart failure by storm over the past few years. EMBRACE is a very unique trial because it really, took this world of rapidly developing technology in heart failure and heart failure monitoring, and coupled it with one of the hottest topics in heart failure today in terms of drug management, which is the advent of SGLT2 inhibitors and the emergence SGLT2 inhibitors as a efficacious therapy, not just for prevention of heart failure, but also treatment of heart failure. Because as you know, pulmonary artery pressure and hemodynamic status are one of the strongest predictors of patient outcomes, both in terms of symptoms, hospitalizations, and deaths in heart failure. And we know actually that monitoring and intervening on elevated pulmonary pressure in this patient population may lead to hospitalizations and possibly even death. Dr. Mikhail Kosiborod: But up until recently, it's been very difficult to monitor pulmonary pressures and to use them as an outcome in heart failure trials, because you will have to use invasive monitoring, essentially a right heart catheterization to get that data. Well, now we can actually have this implanted sensors like CardioMEMS, which are the sensors that we use in EMBRACE-HF trial. So, the question we wanted to ask is, we know SGLT2 inhibitors in DAPA-HF and EMPEROR-Reduced trials, clearly reduce the risk of cardiovascular death and hospitalization for heart failure, worsening heart failure, but the mechanisms have been hotly debated. Is there a possibility these agents can actually have an impact on hemodynamic status and pulmonary pressures? And that's the key central question that we tried to address and EMBRACE-HF trial by using this novel technology at the time, now it's been around for a few years, to noninvasively measure pulmonary pressures and use it as a primary outcome in our trial. Dr Carolyn Lam: Mikhail, first of all, hats off, it was a very, very clever idea to look at these patient populations who already have CardioMEMS right, and then perform this randomized trial. I mean, when I saw this, I was like, "Aw, man, how come I didn't think of that? That's just like so clever, but it's just so Mikhail to be ahead of the curve." But I'd like to remind the audience, this was a prospective randomized trial, the pre-specified outcomes, right? So maybe you could describe that in a greater detail and then the results. Yeah. Dr. Mikhail Kosiborod: Absolutely. Well, Carolyn, first of all, once again, thank you very much. You're being very kind. We do think it was a very novel clever idea and that you're absolutely correct, as this was very rigorously designed, randomized, double blind placebo controlled investigating trial within this study and 10 sites in United States. And the patients had to have heart failure, either with reduced or preserved ejection fraction, about half-and-half actually, as it turned out to be once it's all said and done with the trial. Because they had to have implanted CardioMEMS for clinical indication previously, they were quite advanced in terms of their heart failure. So more than half of the patients were in NYHA class III or IV, they had elevated brain natriuretic peptide levels, they had hybrid symptoms as you would expect. And essentially the patients were screened, and if they were eligible, randomized to use a empagliflozin-placebo in a double-blind fashion. Dr. Mikhail Kosiborod: And they were monitored actually for a couple of weeks prior to randomization to get a baseline pulmonary artery diastolic pressure. They were then treated for 12 weeks with empagliflozin, 10 milligrams a day, or a matching placebo. And we were measuring pulmonary pressure twice a day, every day for the 12 week treatment period, and then at the end of the treatment period, the treatment was stopped, but we actually continued to measure pulmonary pressure for one additional week again, twice a day, every day. So we actually saw what happened for one week after the treatment was stopped. And, as I mentioned before, the patient population was quite advanced from a heart failure standpoint. These were patients that were adequately managed with guideline-directed medical therapy for heart failure. Of course, about half of those patients have, have HFpEF. Did I mention before was the standard of care is not a thoroughly defined? Dr. Mikhail Kosiborod: And essentially what we observed was quite remarkable, which is average pulmonary artery diastolic pressure at baseline was about 22 millimeters of mercury across the patient population, and in patients treated with empagliflozin, there was quite a rapid reduction in pulmonary artery diastolic pressure that we saw almost immediately within one week as compared with placebo. And that divergence of curves in terms of pulmonary artery diastolic pressure continued over the entire 12-week treatment period. And by the end of the treatment period, there was nearly two millimeter of mercury difference in favor of empagliflozin, with lower pulmonary artery diastolic pressure in patients with empagliflozin compared with placebo. And also interestingly, even after the treatment was stopped for an additional week, those curves continued to diverge, with even greater lowering of pulmonary artery diastolic pressure in patients that received empagliflozin. So, I think to our knowledge, this is the first evidence from a randomized clinical trial, randomized double blind placebo controlled clinical trial, that SGLT2 inhibitors, in this case, empagliflozin, have essentially direct the congestion effect towards a lower pulmonary artery pressure rapidly and with effect amplified over time. Dr Carolyn Lam: Yes. Congratulations and beautifully present it there. Now, if I could ask a few more questions now, because the things will come up there. What happened to the diuretic dose? Is this depend on diuretic dose? Are there any subgroups that appeared to benefit more? Dr. Mikhail Kosiborod: No, excellent question, Carolyn. So first of all, we monitored average daily furosemide equivalent dose continuously throughout the trial, and what we observed was that there was no difference in diuretic dose, essentially, between the two groups from a loop diuretic management standpoint. Now, remember this patients are getting frequent pulmonary pressures with diuretics being adjusted all the time. But if you look at what happens over time, that's one of the figures in the paper you see essentially the flat lines in both groups. And coupling that with the fact that pulmonary pressures continue to diverge for another week after the treatment was stopped, at least in my mind, suggests that this hemodynamic benefits as we observed with empagliflozin as compared with placebo was lowering of pulmonary pressures is likely not simply due to diuretic effect. It just cannot be explained only by diuretic effect. I think these findings are very much in line with the analysis that we had in DAPA-HF trial with the analysis that recently were published from EMPEROR-Reduced, showing that you just can't explain what you see with heart failure benefits with SGLT2 inhibitors simply by diuresis. Dr Carolyn Lam: Fascinating. Well, how about the question of diabetes? Dr. Mikhail Kosiborod: Yes. So in terms of subgroups, that you mentioned, we did do subgroup analysis. Now I will say that the subgroup analysis have to be interpreted with a great deal of caution in this trial, because the entire trial had about 65 patients, so it's a small trial. It was really powered to look at the entire patient population and look at the primary end point of the diastolic pressure. Nevertheless, as I mentioned before, we had half-and-half reduced and preserved EF and we did not see a statistically significant heterogeneity in the treatment effect when we look at patients with reduced to preserved EF, so that hopefully both for outcome trials in preserved EF heart failure, we'll see, of course, what happens with that. And in terms of diabetes we saw a bit greater effect in patients with diabetes as compared to patients without diabetes, in terms of pulmonary artery pressure reduction. Dr. Mikhail Kosiborod: But again, I would just strongly caution interpretation of those subgroups because certainly when we look at clinical outcomes in those DAPA-HF and EMPEROR-Reduced, we see no such difference. We see that the benefits, right, the hard clinical outcomes, benefits, are quite consistent regardless of diabetes status. I will say one other thing, which I think is really important. If you look at the pulmonary artery pressure trajectory in patients treated with placebo in EMBRACE-HF, you see that they actually go up over time. And this is in patients that have frequent monitoring of blood pressures, our own guideline-directed medical therapy are closely watched by predominantly heart failure cardiologists and their teams to make sure that they're well-managed. And despite that, you see this increase in pulmonary pressure over time, and that's just another reminder to us that heart failure is a progressive disease despite best available therapy. Dr. Mikhail Kosiborod: These patients deteriorate over time, which is why treatment, novel advancements, treatments like SGLT2 inhibitors and their effective implementation is just so important because we know the benefits occur very early. We saw one week here, when we start seeing separation of curves, certainly see a significant difference by 12 weeks with pulmonary pressure. But of course we know with clinical outcomes, we see within a few weeks of randomization, already a significant benefit in reducing CV death and hospitalization for heart failure, both in DAPA-HF and EMPEROR-Reduced trials. So I think that's a critical point for clinicians to keep in mind at the time of the death. Dr Carolyn Lam: Mikhail, those are just such important and practical take-home messages. Thank you again. In the last minute though, I just really, really have to go back to that very clever method. Could I just pick your brain? I mean, it's like a very clever population. This CardioMEMS population that maybe what's in the future plans? Give us a sneak peek! Dr. Mikhail Kosiborod: Well, Carolyn, very insightful as always. I really think of it as a novel platform for drug development and heart failure. I think this is the proof of concept. This is really the first time we did something in the heart failure space was with monitoring of pulmonary pressures that shows that drugs that work for hard clinical outcomes actually do something meaningful on hemodynamics. We've struggled for such a long time in heart failure to have a good surrogate endpoints that would be reflective of clinical outcomes. This may be it. It may be one of them. And I think EMBRACE-HF is a good concept proving study that can say, if you have a compound and you think that compound may be effective for heart failure. So of course the congestion is so important that we know correlates so well with clinical outcomes Dr. Mikhail Kosiborod: When we started to trial all the way back to late 2015, very few patients had this device. It's not lots of patients have this device. And testing novel treatments to try to understand will there promise in heart failure, and even making go-no-go decisions, in terms of drug development, I think is starting to become a potential future development, which we should at least seriously consider in the heart failure space. Dr Carolyn Lam: Wow, Bravo. And Mikhail, I mean. Okay, audience, listen, you heard it right here. This is amazing. Thank you once again for publishing with us and congratulations on the beautiful paper. Dr Carolyn Lam: And from Greg and I, thank you audience for joining us again today, you've been listening to Circulation on the run. Tune in again next week. Dr. Greg Hundley: This program is copyright of the American Heart Association 2021.  

On today's show I speak with navi, an Artistic Lead at Flying V theater in Washington DC.  We discuss their background in music and how that lead them to theater through the Capital Fringe Festival, what the DC theater scene is like, the definition of "nerdcore" in terms of music, and what it means to be the Artistic Lead of the R&D department for a theater. For a full transcript of this episode visit beyondthelightspodcast.com.Mentioned in this Episode[00:02:53] Capital Fringe Festival[00:04:19] Pointless Theater Company[00:04:24] Flying V[00:14:34] Synetic Theater Company[00:25:02] Doom Remix[00:27:26] Nerdcore Music Competition [00:27:42] Naveed 19[00:37:38] Paperless Pulp[00:45:34] Gallaudet University Follow naviFacebookInstagramBand CampFollow Flying VWebsiteFacebookTwitterInstagramFollow Beyond the LightsWebsiteFacebookTwitterInstagram

The journey to product-market fit is just that — a journey. Many companies think they have it, when in fact they don't. Others struggle to really break through. Naveed Iqbal's startup Dolr helps people to get $0 student loan debt faster. They operate as both a B2C and B2B model, targeting organizations to offer Dolr as an employee benefit. With multiple target audiences they've had to make sure they have PM-fit at both the end user and the economic buyer levels. And on their path towards owning it at this stage, they've learned a lot of tough lessons around looking at the data, recognizing confirmation bias, and making hard decisions related to growth. Naveed steps to the mic in our season premiere to share these lessons and advice for scaling up.Find Naveed online:https://www.linkedin.com/in/naveed-h-iqbal/Find Dolr online:https://www.getdolr.com/https://www.instagram.com/getdolrhttps://www.linkedin.com/company/dolr/Plus: Hear the elevator pitch of Startup Hypeman portfolio client Swish House, using the Que PASA Elevator Pitch(TM) Formula! See acast.com/privacy for privacy and opt-out information.

Tune into our episode with Naveed Hussain. He is a nurse and teacher from Montreal, Quebec. He was featured in the New York Times, The Globe & Mail, The Montreal Gazette, CBC's The National, The Current and As It Happens for his work fighting COVID-19 and his petition to honor legendary jazz musician Oscar Peterson. We touch on so many important topics during this episode including all of his work to bring justice to minority communities within Montreal.    Follow us on instagram @2avgbrowngirlsContact: 2avgbrowngirls@gmail.comLeave us a review on apple podcast Positive Holiday by WinnieTheMoogLink: https://filmmusic.io/song/6041-positive-holidayLicense: http://creativecommons.org/licenses/by-sa/4.0/

Naveed Wagle, MD, has specialized training and research experience in the treatment of cancer of the central and peripheral nervous system. Dr. Wagle treats patients with primary and metastatic brain tumors as well as neurologic complications of cancer at Providence Saint John’s Health Center. As an expert resource to Pacific Neuroscience Institute and the community, Dr. Wagle brings a wealth of knowledge and experience in neuro-oncology clinical trials design and implementation. For more information: https://www.pacificneuroscienceinstitute.org/about-us/our-team/ | (310) 582-7640

This week, join author Chintan Dave and Associate Editor Naveed Sattar as they discuss the risk of cardiovascular outcomes in Type 2 Diabetes patients following the addition of SGLT2 inhibitors versus sulfonylureas to baseline GLP-IRA therapy. 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 Dr. Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, Associate Editor, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Carolyn Lam: Greg, I love today's featured paper. It's a question everybody's asking. It's about cardiovascular outcomes, potential benefits, following the addition of SGLT2T2 inhibitors versus sulfonylureas to baseline GLP-1 receptor agonist therapy. Now, okay, I'm going to keep you waiting because that was just a hook. We got to get to us summaries first. And I'm going to start. The first original paper I want to describe is an analysis of myocardial infarction from the ischemia trial. And it looks at the impact of different definitions on the incidents, prognosis and treatment comparisons. Dr. Carolyn Lam: Because I know you're going to ask, I'm going to tell us a little bit about ischemia. So in an ischemia and initial invasive strategy did not significantly reduce rates of cardiovascular events or all-cause mortality compared with a conservative strategy in patients with stable ischemic, heart disease, and moderate to severe myocardial ischemia. The most frequent component of the composite cardiovascular end points was myocardial infarction. So in the current report from Dr. Chaitman and colleagues from St. Louis University school of medicine, the aim was to compare treatment effects on the primary and major secondary competent end points in the ischemia trial using the pre-specified primary and secondary MI definitions. Dr. Greg Hundley: So Carolyn, what were those two EBI definitions, the primary and secondary? Dr. Carolyn Lam: Right. Now, I'm going to try to simplify this. So, for procedural MI, the primary MI definition use CK-MB as the preferred biomarker, whereas the secondary definition used cardiac troponin. Dr. Greg Hundley: Great, Carolyn. So what did they find? Dr. Carolyn Lam: So procedural MI definition had an important impact on event frequency and subsequent prognosis. When the pre-specified secondary MI definition was applied, the conservative strategy had a significantly lower composite event rate for the primary and major secondary trial end points, due to an increased number of procedural MIs in the invasive strategy. Furthermore, spontaneous Type One MI events associated with increased risk of cardiovascular death were reduced with an invasive strategy, which is either PCI or CABG. Dr. Greg Hundley: Nice, Carolyn. Well, my first paper actually is a favorite topic of yours, HFpEF. And it really involves the central command and the regulation of exercise rate response. It comes to us from Dr. Ben Levine and colleagues at the University of Texas Southwestern Medical Center in Dallas. Dr. Carolyn Lam: Yay. Dr. Greg Hundley: All right, Carolyn. So chronotropic incompetence is common in HFpEF. And it's linked to impaired aerobic capacity. Whether upstream, autonomic signaling pathways are responsible for raising exercise heart rate are impaired in patients with HFpEF, That's really unknown. Dr. Carolyn Lam: Yep. It is something that we wonder. And so what did Dr. Levine find? Dr. Greg Hundley: Thanks Carolyn. So the central command, so vaguely mediated and the metabo-barrow receptor function, which is sympathetically mediated in patients with HFpEF, We're not different from healthy senior controls, despite significantly lower peak whole body exercise, heart rates. So these results, Carolyn, demonstrate key reflex autonomic pathways, regulating exercise, heart rate responsiveness are actually intact in patients with HFpEF. Great new work from Dr. Ben Levine. Dr. Carolyn Lam: And I love the way you summarized that. Thank you, Greg. Well, my next paper is the first report implicating the cross priming function of dendritic cells in immunopathology after Type Two MI. And that includes inflammation, fibrosis and functional decline. Dr. Greg Hundley: So tell us a little bit more Carolyn about these dendritic cells? Dr. Carolyn Lam: Ah-ha so I was ready for that question. So after ischemic injury to the myocardium, dendritic cells respond to cardiomyocyte necrosis present the cardiac antigen to T-cells and potentially initiate a persistent auto-immune response against the heart. So cross priming dendritic cells may have the ability to activate both CD4-positive helper and CD8-positive cytotoxic T-cells in response to necrotic cells. And may thus be crucial players in exacerbating auto-immunity targeting the heart. Dr. Carolyn Lam: So, in this study, authors led by Dr. Sattler from Imperial College, London, performed some elegant mouse experiments and showed that cross-priming dendritic cells were present in the heart and activate it after ischemic injury. Depletion of these dendritic cell cross priming function, inhibited accumulation, and activation of cytotoxic T-cells and stopped myocardial immunopathology and functional decline. So with cross-priming, these authors provided a targetable pathway to prevent activation of T-cells cyto-toxicity and persistent post Mia immunopathology exacerbating heart failure risk. Dr. Greg Hundley: Oh, beautiful. Carolyn, what a great description there. So my next paper comes to us from Dr. David Park from the New York University school of medicine. So Carolyn elevated intracardiac pressure due to heart failure, induces electrical and structural remodeling of the left atrium that begets atrial myopathy and arrhythmias. At present the underlying molecular pathways that drive atrial remodeling during cardiac pressure overload are poorly defined. So the purpose of this study for these investigators was to characterize the response of the ETV1 signaling axis in the left atrium during cardiac pressure overload in humans, as well as mouse models. And explore the role of ETV1 in atrial electrical and structural remodeling. Dr. Carolyn Lam: Ah, another study involving both animal and human models. Very important subject too. So what were the results? Dr. Greg Hundley: Well, Carolyn, evidence from both the Cleveland Clinic, Biobank Human Subjects Repository and the animal science experiments revealed that ETV1 is downregulated in the left atrium during cardiac pressure overload. Thereby contributing to both the electrical and the structural remodeling that we observe in the left atrium during cardiac pressure overload. Dr. Carolyn Lam: Nice. Well, let's quickly finish up with what's in the mailbag. We've got a research letter by Dr. Randi on the lack of evidence of AEs to expression and replicative infection by SARS-CoV-2 in human endothelial cells. There's another by Dr. Stokes on the association of cigarette and electronic cigarette use patterns with levels of inflammatory and oxidative stress biomarkers among US adults. And another research letter by Dr. Hemelsoet on screening for Fabry disease in male patients with arrhythmia requiring pacemaker or ICD. Dr. Greg Hundley: Thanks Carolyn. So I've got a paper it's a cardiovascular case series from Dr. Workman that involves a case of presyncope after transcatheter aortic valve replacement. Dr. Özeke has an ECG challenge reminding us that common things occur commonly. Dr. Zaha has a Perspective entitled, "Mending Broken Hearts, a New Treatment Paradigm for Immune Checkpoint Inhibitor Induced Myocarditis." And then finally, Dr. David Goff, the director of the NHLBI has a wonderful perspective piece (Special Report). And it really addresses some results from the Bethesda conference at the National Heart Lung and Blood Institute and the American Heart Association. And it was co-sponsored the bending curve of cardiovascular disease mortality, the Bethesda plus 40 years Symposium. Dr. Greg Hundley: The report, Carolyn, summarizes the relevant research, policy, and practice opportunities discussed at the symposium, including participant led discussion that explored the challenges and barriers in promoting cardiovascular health, across lifespan. And established a potential framework for observational research interventions that would begin in early childhood. Well, Carolyn, how about now we jump forward to that feature discussion. Dr. Carolyn Lam: All right, now we can go. Dr. Greg Hundley: Well, listeners, we are to the feature discussion today. And we have with us Dr. Chintan Dave from Rutgers University in New Jersey, and our own associate editor, Dr. Naveed Sattar from Glasgow, Scotland. Welcome gentlemen. Chintan, could you explain to us some of the background information that went into the construct of your study and then what hypothesis did you want to test? Dr. Chintan Dave: So just for background, so we know that artheriscraotic cardiovascular events in heart failure typically occur in higher prevalence in patients with type two diabetes. What's been really exciting in recent years is that certain second-line therapies, namely SGLT2 inhibitors and GLP-1 receptor agonist in these large cardiovascular outcome trials have shown to reduce the incidents of cardiovascular events. So from these trials, we can infer that SGLT2 inhibitors typically reduce heart failure hospitalizations, and also have an impact on 3P-MACE, which is just the composite of cardiovascular death, non-fatal MI and non-fatal stroke hospitalizations. While GLP-1 receptor agonist tend to reduce, also have an impact on 3P-MACE, but they also have some modest benefits in heart failure hospitalizations as well. Dr. Chintan Dave: So now that we know that these agents reduce cardiovascular risk, what's not known is, whether or not, if we can use these agents together to further maximize a reduction in cardiovascular events. So in the cardiovascular outcome trials the dual use of SGLT2 two inhibitors and GLP-1 receptor agonists was rare and ranged from between 0% to 5.3%. So as a starting point, we said, "Okay, let's look at observational data to see what happens when you add SGLT2 inhibitors to patients who are already using GLP-1 receptor agonist." And we hypothesized that, given the orthogonal pharmacodynamic effects on cardiovascular risk, adding SGLT2 inhibitors to existing GLP-1 receptor therapy should further reduce cardiovascular events. Dr. Greg Hundley: Very good. And can you describe for us your study population and study design? Dr. Chintan Dave: Sure. So we used three databases in the US. Two of these databases were commercial claims data, which is typically your employer based insurance plans, which have patients between the ages of 18 and 64. And we supplemented that data with Medicare fee for service claims, which have patients over the age of 65. So within these three databases, we identified patients who have a diagnosis of type two diabetes and are already a GLP-1 receptor therapy or GLP-1RAs and initiating either SGLT2 inhibitors or sulfonylureas. Dr. Chintan Dave: And after we identified this patient population, we controlled for several pertinent variables that could be considered confounders, including socio-demographic variables, diabetes complications, and cardiovascular conditions. And we had two primary endpoints. The first primary end point of interest was a composite cardiovascular endpoint, which is defined as the composite of non-fatal MI or nonfatal stroke hospitalizations in all cause mortality. The reason we used all cause mortality instead of cost specific mortality is basically because we didn't have information on cause of death. So we have to resort to a more generic definition of mortality in the composite cardiovascular endpoint. The second primary endpoint that we used was heart failure hospitalizations. So we then in this population, estimated hazard ratios using basically a time to event framework. Dr. Greg Hundley: Okay. And what were your results? Dr. Chintan Dave: So after applying the eligibility criteria in all three databases and after doing a one-to-one propensity score matching, we had 12,500 patients who initiated SGLT2 inhibitors and 12,500 patients in the sulfonylurea groups. For the true primary end points the addition of SGLT2 inhibitors to baseline GLP-1RA therapy was associated with a 22% decrease in the incidents of composite cardiovascular end point or an adjusted hazard ratio of 0.78. And the caught 95% confidence intervals were statistically significant. For the endpoint of heart failure hospitalizations, we noted a 36% decrease in the risk of heart failure hospitalizations with the adjusted hazard ratio being 0.64. And again, that was statistically significant as well. Dr. Chintan Dave: The CCE or the Composite Cardiovascular Endpoints was driven primarily by non-statistical decreases in the risk of MI by about 25%, in all cause mortality by about 32%. But we also found no effect on stroke, which is also in line with what others have reported. The other thing we looked at was also to look at any evidence for heterogeneity in treatment effects by presence of cardiovascular diseases. And we found no statistical significant difference in that aspect. The last thing we looked at also was to look at any evidence of heterogeneity by baseline cardiovascular disease in the patient groups. And we found no evidence to that effect. Dr. Greg Hundley: Very nice. Well, Naveed help us put this study in perspective with some of the other research that I know you're familiar with related to the use of SGLT2 inhibitors and GLP-1 receptor agonists. Dr. Naveed Sattar: Yeah. Thanks Greg. So as we all know, the biggest gains in diabetes in the last few years is these two costs of the trucks SGLT2 inhibitors and GLP-1. We believe and the evidence suggests that SGLT2s, are more cardiorenal in its benefits, and GLP-1 more atherothrombotic. So the hope is that if you combine these drugs, you get additional benefits, but there are no trials that have actually tested this. So this particular paper being kind of first observational, look at adding an SGLT2 versus another drug on top of a GLP-1, tries to get at that particular question. And it provides an early hint that yes, if you add an SGLT2 on top of the GLP-1, you get additional benefits. Giving us some insight that yes, you combine these two classes of drugs, you might get additional benefit in one drug on its own. Dr. Naveed Sattar: Of course, this is not trial. Some of our readers are going to be nihilist and will not believe the data because it's not a trial, but that's fine. But it's done as well as it possibly can. This observational propensity analysis is well matched. The data have some kind of external validity in the sense that the greatest benefits or risks reductions, but for heart failure post-acquisition, which is what we would believe ratio to inhibitors. So there is some sense of validity here, but clearly colleagues, they want to know, and I actually had a patient in the clinic on Tuesday who was on a GLP-1 and actually was an SGLT2. And I wanted to add the GLP-1. And this kind of evidence provides me some evidence of confidence that yes, by adding both drugs, I might get additional benefits in that one drug on its own. Dr. Naveed Sattar: So what you're going to ask next, Craig, and I'll give my answer first. What we really need to do now is actually do the trials. And I think the trials will predominantly work, adding GLP-1 on people who are on SGLT2, because I think more people will be initially an SGLT2 because it's a oral therapy. Then we'll add GLP-1. Although we do have a new oral GLP-1 in play as well. So, that's the kind of paradigm we're in. Some hints, the combination gives you more than the single drug and I think that's really quite promising for people. Dr. Greg Hundley: Very nice. So Naveed suggesting a clinical trial to confirm some of these results. Chintan, do you have anything to add? What study do you think or what area of investigation in this field do you feel is next in line? Dr. Chintan Dave: Yeah, I mean, I would just start by saying that I agree with everything that Naveed said in the sense that this is a starting point. And that I think the key take home from this study that sort of is going to be published is basically that not only do SGLT2 inhibitors reduce the cardiovascular events in patients using GLP-1 therapy, but the fact that the magnitude of this reduction is very similar. What was noted in cardiovascular outcome trials of SGLT2 inhibitors for GLP use was very minimal. In other words, you can super impose the cardiovascular benefit profile of the SGLT2 inhibitors, which were seen in trials two patients using GLP-1 therapy. Dr. Chintan Dave: Now the converse is what needs to be done next, basically, where we need to look at what happens when you add GLP-1 receptor agonist, to SGLT2 inhibitors, as Naveed just said. And he raised a really good point in that more patients are going to be on SGLT2 inhibitors, because they want to avoid GLP-1 receptor agonist because they don't want to use injectable therapies. Of course we have oral semaglatites maybe that may mitigate these issues. But the fact that that aspect is still unknown, could potentially be really good idea for future studies. So that potentially would be a nice, good step. Dr. Greg Hundley: Excellent. Dr. Naveed Sattar: Can I see one last thing, Greg? There is a trial coming this year called AMPLITUDE‐O, which is a GLP-1 trial, which does have a fair number of people on base than SGLT2s. We might be able to get a curly hint at that ongoing trial in the next six months to a year. Dr. Greg Hundley: Excellent. Well, we want to thank both Chintan Dave from Rutgers and our own associate editor, Dr. Naveed Sattar from Glasgow, Scotland. And really presenting information from US Claims databases highlighting the addition of SGLT2 inhibitors to GLP-1 receptor agonists and finding there was an association with a further reduction of cardiovascular risk relative to the use of GLP-1 agonists alone. On behalf of both Carolyn and myself, we want to wish you a great week. And catch you next week On the Run. This program is copyright of the American Heart Association, 2021.  

Take our survey here: https://forms.gle/fzHSg3oLqFfhGF6C6In this episode, Naveed Iqbal, CEO at Dolr, discusses navigating difficult conversations with cofounders, vendors, and partners of a business or start up. Request a Custom Workshop For Your CompanyGet Free Access to Over 15 Negotiation GuidesDolr WebsiteFollow Naveed on LinkedInFollow Kwame on LinkedInIf you've been a listener of the show and you've gotten a lot out of our programming, you can click here to Support Negotiate Anything.Kwame Christian with Naveed Iqbal, PhD Support this show http://supporter.acast.com/negotiate-anything. See acast.com/privacy for privacy and opt-out information.

This week features Two Feature Discussions. In our first discussion, author Thomas Metkus and Guest Editor Allan Jaffe discuss the article "Myocardial Injury in Severe COVID-19 Compared to Non-COVID Acute Respiratory Distress Syndrome." Then in our second discussion, author Naveed Sattar and Guest Editor Ileana Piña discuss the article "Effect of Empagliflozin on Left Ventricular Volumes in Patients with Type 2 Diabetes, or Prediabetes, and Heart Failure with Reduced Ejection Fraction (SUGAR-DM-HF)." 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 Dr. Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: I'm Dr. Greg Hundley, Associate Editor, Director of the Pauly Heart Center at VCU Health in Richmond, Virginia. Dr. Carolyn Lam: Guess what? Double feature again, this episode with the first talking about empagliflozin and its effect on left ventricular volumes in patients with type two diabetes, pre-diabetes, and HFrEF, and this is the sugar DM heart failure study. Dr. Greg Hundley: Carolyn, the second of our double feature Tuesday is a paper that involves myocardial injury in severe COVID-19 compared to non-COVID acute ARDS. Well, let's grab a cup of coffee and Carolyn this week, I'm going to jump into my first paper, which comes to us from Dr. Are Kalstad from the University of Oslo at the Oslo University Hospital. Carolyn, this study tested the hypothesis that the daily addition of 1.8 grams of N-3 PUFA to standard of care, secondary prophylaxis in elderly patients who have survived a acute MI would reduce the risk of subsequent cardiovascular events during two years of follow-up. Dr. Carolyn Lam: Interesting, Greg and a clinically important question. So what did they find? Dr. Greg Hundley: Yes, Carolyn. They enrolled 1,027 subjects who were randomized in this investigator initiated, multi-center randomized clinical trial of adding that 1.8 grams of n-3 PUFA, 930 milligrams of EPA, and 660 milligrams of DHA versus placebo, which was a corn oil supplement, daily to the standard of care in 70 to 82 year old patients with recent, so within two to eight weeks, acute myocardial infarction. The authors found that they could not detect reduction in clinical events in these elderly patients with the recent acute EMI treated with the 1.8 grams of n-3 PUFAs daily for two years. So, a negative study, Carolyn. Dr. Carolyn Lam: Surely, we'll add to that debate that's just so interesting surrounding the PUFAs. But let's go onto another paper I want to tell you about, it provides novel insights into the complex crosstalk between the cardiac endothelial cells and cardiomyocytes during cardiac repair after myocardial infarction. This paper is from Dr. Taleb and colleagues from Park Inserm in France. Their study suggested a deleterious role for endothelial indoleamine 2,30-dioxygenase-1, which I'm now going to abbreviate as IDO, which is an enzyme involved in tryptophan catabolism. They found that the specific deletion of IDO in endothelial cells enhanced cardiomyocytes survival and contractility leading to cardiac function improvement. The IDO dependent effects were mediated by endothelial cell production of kynurenine. The study in essence found that therapeutic strategies targeting cardiac IDO could, in fact, constitute an innovative approach to curb cardiac dysfunction following MI. This was followed by an editorial by Drs. Ma and Wang from Thomas Jefferson University. Dr. Greg Hundley: Very nice, Carolyn. Great studies again from the world of basic science. Well, my next paper comes to us from Professor Gerasimos Filippatos from the University of Athens Hospital. Carolyn, this was a sub-study of the FIDELO-DKD trial that evaluated the effect of the nonsteroidal selective mineralocorticoid receptor antagonists finerenone on kidney and cardiovascular outcomes in patients with chronic kidney disease and type two diabetes with optimized renin angiotensin system blockade. Compared with placebo, finerenone reduced the composite kidney and cardiovascular outcomes. Here the authors report the effect of the finerenone on individual cardiovascular outcomes and in patients with and without a history of atherosclerotic cardiovascular disease. Dr. Carolyn Lam: This is a much anticipated paper. Very excited for you to describe the findings, Greg. Dr. Greg Hundley: Thanks, Carolyn. Among patients with chronic kidney disease and type two diabetes, finerenone reduced the incidents of the composite cardiovascular outcome, that included time to cardiovascular death, myocardial infarction stroke, or hospitalization for heart failure. Additionally, there was no evidence of differences in treatment effect based on pre-existing cardiovascular disease status. Dr. Carolyn Lam: Emerging therapies. Isn't that awesome? Well, some other papers in this issue, there's a White Paper (Frontiers) about the therapy in patients with atrial fibrillation treated with oral anticoagulation undergoing PCI, a North American perspective, 2021 update by Dr. Angiolillo. There's a Research Letter on the gradient of risk and associations with cardiovascular efficacy of ertugliflozin by measures of kidney function, and these are observations from VERTIS-CV trial by Dr. Cherney. There's also a sub-study analysis from Explorer HCM, and that is entitled “Mavacamten Favorably Impacts Cardiac Structure in Obstructive Hypertrophic Cardiomyopathy.” This is by Dr. Saberi. There's another Research Letter on COVID-19 myocardial pathology evaluation in athletes with by CMR and that's by Dr. Clark. Dr. Greg Hundley: Very nice, Carolyn. I have an exchange of letters from Dr. Alkhalil and Kuzemczak, as well as Dr. Navarese regarding the article, “Comparative Efficacy and Safety of Oral P2Y12 Inhibitors in Acute Coronary Syndrome: A Network Meta-Analysis of 52,816 Patients From 12 Randomized Trials.” Next, there's another exchange of letters from Dr. Kastrati and Ferracane regarding the article, “Comparative Efficacy and Safety of the Same Oral P2Y12 Inhibitors in Acute Coronary Syndromes.” Dr. Karabinos has a nice ECG challenge. It's a bizarre down sloping ST segment elevation challenge. Finally, Carolyn, there's a Perspective piece from Dr. Okorodudu entitled, “Exposure to Cardiology as a Strategy to Increase Black Men Involvement in Medicine.” Well, Carolyn, how about we get on to those two feature discussions? Dr. Carolyn Lam: Oh, yes. Exciting. Let's go. Dr. Greg Hundley: Well, listeners, we are here for our first feature discussion today on this February 9th. We have with us Dr. Tom Metkus from Johns Hopkins and Dr. Allan Jaffe from Rochester. Tom, can you tell us what was the background that really framed this study and what hypothesis did you want to address? Dr. Thomas Metkus: This study really arose out of a time and a place in the COVID pandemic. If you can all turn your clocks back to late last spring, we were all enmeshed in the clinical care of many patients with COVID here in the United States, depending on your geography, and also reading an increasing number of reports from other centers that had been enmeshed in the pandemic for some time about myocardial injury, elevated troponin, different aspects of cardiac disease in patients with COVID-19. My background is as a cardiac intensivist, dual boarded in cardiology and critical care, and so this was of particular interest to me, specifically so in that my clinical practice at the time was in a COVID ICU. I spent much of the day every day taking care of these patients, so conceptualizing what myocardial injury meant, what's the pathogenesis, and what does it mean, was an open-ended question at the time. There are certainly many reasons to think that COVID-19 is particularly cardiotoxic. There's obviously the pro-thrombogenic nature of the illness. There's the inflammatory nature of the illness. Dr. Thomas Metkus: Yet, we also found that clinically, there was certainly many patients with COVID-19 who acted like they had myocardial injury from ARDS and pneumonia and we had investigated this in some prior studies prior to the pandemic. Really, the aim of the study was to clarify to the extent that we could and contribute to the growing body of knowledge about what is the prevalence and prognostic significance of myocardial injury in COVID-19. We felt that we had a unique lens on this because we also had a cohort of patients with generic ARDS who had cardiac biomarkers assessed, gave us a nice opportunity to do that. Dr. Thomas Metkus: Our hypothesis, that was really based on our clinical gestalt at the time from being in the ICU every day with COVID-19 patients, was that there are assuredly COVID-19 patients who have unique features of myocardial injury, myocarditis or malignant arrhythmias, or requiring mechanical support. But perhaps more, or at least a majority have myocardial injury that looks and acts an awful lot like it would in a sepsis patient, in an ARDS patient. We hypothesized that myocardial injury in COVID-19 would be more similar than different to the generic ARDS population. As such, we drew a population of patients with COVID-19 from our health system here across several hospitals, and did a bit of a comparison with our historical cohort of ARDS patients. Dr. Greg Hundley: Great description, Tom. Tell us a little more about that study population. You said there was going to be a comparison. What were some of the outcomes that you wanted to evaluate? Dr. Thomas Metkus: Right. This question alludes to an important point as we try to delve and do inference around the COVID literature in general, which is to say the pandemic is heterogeneous across geography and across time. In looking at this study, or indeed any study, and understanding of the study population where these ambulatory patients or intubated patients or patients on the ward, for example, as well as any comparison group are these sepsis patients, pneumonia patients, influenza patients, it's just imperative to do inference and to place the study in context. This study, we sought to look at only intubated patients, and that was partially driven by clinical interest, partially driven by the ability then to provide a comparison to our ARDS cohort. So, intubated patients with COVID-19. Dr. Thomas Metkus: The comparison group is from a study of acute respiratory distress syndrome patients. Primary lung injury patients that were drawn in turn from NHLBI sponsored areas, network clinical trials. That was a study that was a secondary analysis that we did where we checked troponin levels in everybody. A true cross sectional assessment. That's important in that there's a selection bias, isn't there, when you just look at patients who had troponin drawn in the context of clinical care? So, I think for this study in particular, it's important to note that the comparison group of ARDS patients was truly cross-sectional and that it was a population defined who had biomarkers assessed in the entirety; whereas our COVID-19 population was intubated patients who had troponin checked at the point of clinical care. Dr. Thomas Metkus: Now, to address some of the potential biases that are inherent in that assessment of exposure, we purposefully looked at only patients who had troponin assessed within 24 hours of intubation, really to sync up time zero in a sense. It's also important to note the time course of the pandemic. These patients were all in the late spring and very early summer. This was really before steroids, before the recovery trial, before steroids became standard of care. And really, health systems wonder a fair bit of duress at that time and indeed, as many of the listeners will know, the outcomes for hospitalized patients have improved since then for many reasons. But it's only to point out that this study was a place in geography and a place in time, and there are certainly implications about that that I'm sure we'll focus on subsequently. Dr. Greg Hundley: How many subjects did you enroll and what were your study results? Dr. Thomas Metkus: Our COVID-19 patient population here in the Johns Hopkins Hospital included 243 patients. All of them were intubated with COVID-19, so severe disease. Of those, we reported that just over half had clinical troponin levels greater than the upper limit of normal. We assessed the main clinical factors associated with elevated troponin in that patient population, which are largely similar to other reports and they include chronic kidney disease, lactate levels of the marker of malperfusion, ferritin fibrinogen levels as markers of systemic inflammation. We showed as have others that there's a graded increase in mortality with increasing amounts of myocardial injury. Then, probably what I would found the most interesting component of the study is that when we did covariate adjustment for features of critical illness, renal failure, lactate, how severe your hypoxemia was, vasopressor use, age, and sex. Age, sex, and multi-organ dysfunction in a sense. Dr. Thomas Metkus: The association of troponin with mortality attenuated quite significantly. That's similar to what we found in a general ARDS population and consistent with a paradigm of myocardial injury in the non-cardiac critically ill. I think the final finding that we would emphasize is that after you adjust for those mediating factors, the incidence of myocardial injury in COVID-19 was at least comparable to that in the general area's population. It gives an idea to place myocardial injury in context, in my view, as a function of critical illness in most COVID-19 patients. Surely, not all. There are patients with unique syndromes, but in many or most. Dr. Greg Hundley: Well, Alan, let's turn to you. Help us put these results that Tom has described for us really in the context of what we're learning about the heart and in patients with COVID-19. Dr. Allan Jaffe: Well, let me start by saying that as a cardiologist, too, at the Mayo Clinic in Rochester, Minnesota, we've studied previously patients with acute respiratory failure. In point of fact, although most of you are not quite as old and may not remember, when we first started seeing ARDS patients, many of the same issues that are here today for COVID, came up. For example, and people may not remember this, we actually did a randomized trial of anti-platelet therapy in patients with ARDS because we were convinced that thrombosis was ubiquitous and was a frequent contributor to the illness that we saw. So that if one thinks about it in another sense and says, "If you'll correct for modern day technology that gives us some additional insights, how different really is COVID ARDS from standard ARDS." I think what this paper has substantiated is that there are lots and lots of similarities that exist. I think that's important because it keeps us from chasing around and looking for some additional issues for us to try and take care of or treat additionally. Dr. Allan Jaffe: That said, I think the way to conceptualize it is some of the troponin elevations are because patients who have chronic heart disease get COVID and they may have those elevations right at admission. There's an acute component having to do with critical illness that is nicely described in this manuscript. Then, there are those unique clinical features, whether you think it's myocarditis, I'm not sure how common myocarditis, type 2 MI, ischemia, a variety of things, and maybe a new type of myocarditis that we're finding with some very peculiar cells that we see in interstitium with or without increases in troponin. But I think it puts it into the bucket of saying, treat these patients conventionally and look for the other complications. I think that's a terribly important message that I was attracted to when I read this paper. So, thank you, Tom. Dr. Greg Hundley: Very good. Well, Tom, what do you see as the next study really to be performed in this space? I'll ask you first and then come back and gather some of Allan's thoughts. Dr. Thomas Metkus: Absolutely. I love that framing about kind of COVID in the heart, which is to say that there are some things that are direct pathogenic related to COVID and there are some things that are secondary, and then there are some things related to patients with underlying heart disease coming to care. I think the next set of studies that can help us disentangle this are related to that paradigm in that more multimodal phenotyping, biomarker phenotyping, but also echo phenotyping and MRI phenotyping, we're starting to see those come down the pike to say, here's the biomarker evidence of myocardial injury, but what does that mean, functionally? What does that mean from an imaging perspective? The second important facet for the next series of studies will be the long-term follow-up. We know from the general critical care literature, that there is indeed a powerful and important entity of the post critical illness syndrome, and in COVID that's come to be called long COVID or the long hauling. We've known that even patients with general critical illness get that and to the extent that the heart plays a role in that, it implies one needs to follow these patients prospectively. Dr. Thomas Metkus: I think the other implication of this work for the next set of studies is that there are many biases that can be brought to bear when reviewing the pandemic literature and assuredly an editorial team sees the entire spectrum of them, but they would include, as I alluded to, careful selection of patients assuring meaningful classifications of exposure at a uniform time assuring adequate comparison groups. That's really going to be the key to doing good inference. Then, the final thing I'll add is that the next set of studies should and will integrate clinical research and clinical epidemiology with causal inference principles with using what we're learning from the basic science community, to have conceptual models about how has COVID affecting the heart at the cellular level, et cetera, et cetera, et cetera. In a sense, that community of researchers that you see coming together in this pandemic is why doing this work is very rewarding and I think meaningful. I think those are all features of the next set of studies that should include indeed epidemiologic analysis, randomized trials, and basic science analysis. Dr. Greg Hundley: Allan, do you have anything to add? Dr. Allan Jaffe: Well, I want to endorse the idea that one of the problems in this field is that patients present at different times with different clinical syndromes, because some of them have been at home, some of them have been hospitalized, some of them are recognized de novo late. One of the things that's necessary as a consistent repetitive approach so that we get consistent data, not only on each COVID patient sequentially, but also on the control group that is important. The other point I'll emphasize that Tom mentioned is that individuals who have elevated troponins who are critically ill with ARDS and most likely with COVID as well, have some sort of underlying cardiovascular disease. Often once those patients leave the hospital there, the troponin is out of sight and out of mind. COVID is reminding us by showing us the panoply of additional clinical syndromes that exist post-hospitalization. That as with ARDS, I would argue, that's a mistake. These patients need to have follow-up with cardiology to investigate what that underlying cardiovascular component is. Dr. Greg Hundley: Great. Well listeners, we want to thank Dr. Tom Metkus from Johns Hopkins om Johns Hopkins and Dr. Allan Jaffe from the Mayo Clinic in Rochester, Minnesota for bringing us this study regarding intubated patients with COVID-19, indicating that the myocardial injury shares many similarities to that experienced by patients with ARDS. Now listeners, we will turn to our second feature discussion on this February 9th. Dr. Greg Hundley: Well, listeners, welcome to our second feature discussion today. We have with us, Dr. Naveed Sattar from Glasgow, Scotland, and our guest editor, Dr. Ileana Pina from Detroit Medical Center. Welcome to you both. Naveed, we'll start with you. Could you describe some of the background that helped you formulate this study and what hypothesis did you want to address? Dr. Naveed Sattar: Yeah, thanks Greg. When I was watching the empirical outcomes study, I almost fell off my seat when I saw the results in heart failure, hospitalization. I actually, I sent a text to John McMurray who wasn't actually at the meeting and I sit next door to John McMurray who's obviously preeminent heart failure. I worked also with many of the fantastic heart failure colleagues, Mark Pietri, Cardic Joon and colleagues. At that time I felt, well, actually it wouldn't it be lovely, I was aware of MRI studies they've done on other drugs in heart failure and I thought, well, if this drug effects improves heart failure, well potentially, although we didn't have it amply reduced at the time or have heart failure, they've come subsequently. Perhaps it changes, lead to cardiac remodeling. Dr. Naveed Sattar: So we've designed the randomized placebo control trial of empirical fluorescent versus placebo and 105 patients who had heart failure with ejection fraction below 40%. We wanted big 4th ventricles as Professor McBuddy would tell me, we have lots of debates about these things to really give us adequate power follow-up for at least 36 weeks to see if we can see improvements in left ventricular installment volume or global longitudinal strain, which were our primary outcomes. Dr. Greg Hundley: Very nice. Great overview of the study design. Who did you enroll? I know patients with an ejection fraction less than 40%, but equal numbers of men and women, was this ischemic heart disease? Dr. Naveed Sattar: I think the majority of patients were male about two-thirds average age, 68, pretty much like the empirical reduced to that by half population. About 80% here had type two diabetes, about 20% had pre-diabetes. The other characteristics, the majority had class 2, NYHA Class IV heart failure, minority Class III. About a third were already on arnes. Also, the background theoretically was fantastically well. Dr. Naveed Sattar: The other critical thing we really did, we excluded people with atrial fibrillation because that really affects the quality of the MRI. Our group and it's a brilliant journey to be, I'm not a heart failure expert, but working with all these colleagues, they have brilliant experience in this. They know the mistakes to avoid, and one of them is, do not include people with atrial fibrillation because your MRIs will just not be readily interpretable. Also, it needs to be big enough. It needs to have big enough volumes to begin with to be able to see a change. It needs to be long enough to potentially see the remodeling. All that experience of John, Mark and Pandeep were put together in a really tight protocol. When the results came, I almost, again, fell off my seat because well, it worked. I guess, you're going to ask me about the results and what we find. Dr. Greg Hundley: Absolutely. Tell us about those results. We're waiting to hear. Dr. Naveed Sattar: Two primary outcomes were really what we saw was a reduction in the left ventricular and systolic volume index and by six mils per meter squared, and the diastolic volume index by 8.2 mils per meter squared. We didn't see a change in global longitudinal strain. We did not see changes in KCCQ or six minute walk test, but actually the reality is we now know the size of this chart is underpowered to see changes in six minute walk tests or KCCQ, in lieu of another trial that has some changes in that, but we didn't see them and I think our study was done ... I can tell you, Greg, the amount of work that went in this study, the quality control that people should look at the supplement when it comes out, the degree of attention to imaging protocols and quality control was, I think in my experience, unparalleled. Dr. Naveed Sattar: The team really pulled out all the stops to get this, but so the reductions in the volumes, that's probably the key thing. We think that this may reflect the reverse cardiac remodeling and that we think then fits in what you see with other drugs that benefit patients with heart failure. Because the bigger the volumes, the more people tend to die with heart failure or get readmitted. If you shrink the ventricles, that probably their contractility improves. What the actual mechanism is, I don't know, but I'm sure Ileana probably come in there in terms of discussing potential pathways. The final thing I should say is just for the internal validity or external validity, NT-proBNP did come down, suggesting less left ventricle wall stress. Schematic also went up. All the things that we've seen in the big trials was there so I think we've done a really strong, robust trial. Dr. Greg Hundley: Thank you, Naveed. Well, Ileana, as a guest editor, what attracted you to this paper? Then, how do you put the results from this study in the context with some of the other publications related to SGLT 2 inhibition in patients with heart failure? Dr. Ileana Piña: I think all of you know, that we, the heart failure community is pretty excited about these drugs and what they're doing. I also nearly fell off my chair when I saw the first EMPA-REG and I saw those curves splitting. Then, I further did that when the DAPA data came out and you see these curves split up almost immediately. What was attractive about this paper is that we really don't know how this happens. We think we do, but we really don't. We don't think necessarily that it's the glucose excretion, because that maybe happens in diabetics, but not necessarily in the non-diabetics. Yet the drugs seem to work in both. But remodeling is such a fascinating concept. I personally happen to love the concept of reverse remodeling. It's something that we in the heart failure community really believes that if we can reversely remodel the ventricle, then outcomes will get better.   Dr. Ileana Piña: We really link them. Your proBNPs were elevated but not huge. This wasn't a very sick debilitated population. This was primarily Class II. Pretty well-medicated in background, you didn't necessarily give the doses clearly, but pretty well with percentages of RAS inhibition and everything else. Now you see that the volumes are coming down and you say, "Wow, is that what's it doing?" If it happens that quickly, because remember, we've got to explain why the curves of heart failure, hospitalizations split up almost immediately. You did show in your time of follow-up that these changes occurred during that follow-up. I am actually not at all surprised that you didn't see anything in the KCCQ because we know that first of all, the patients weren't that sick to start with so it's hard to see improvement when you don't have a lot of sickness and a six- minute walk. This group, for a six-minute walk, is going to have a very wide standard deviation. A six-minute walk doesn't really distinguish the people who are doing well. To me, it's more for the sicker. Dr. Ileana Piña: The fact that neither of these things change doesn't bother me at all. But I think that the next step before Greg asked me, is what's the outcome. In other words, can you tie that reverse remodeling directly to an outcome, be it mortality, which is getting argued out there, whether all the drugs are the same? Or just even the heart failure hospitalization, which I think is a very important outcome in this population. You did it well, you did it carefully, you can tell the data's very clean. You did do a little bit better with the women, so I can't scold you for that as I usually do, because you've had about 30 some percent women, which is very similar to what the big EMPEROR trial has had. I'm always fighting to get more women in the trial. Dr. Ileana Piña: At some point you may want to examine the reverse remodeling by gender, by sex, actually and see, even though you have a small number, you have 105 patients, you may not have enough data. But I think in the future, because we do believe that women remodel differently and reversely remodeled differently. That would be very interesting to see if there's any differences. Dr. Greg Hundley: Thank you, Ileana. Naveed, do you have anything to add? Ileana's really laid out on a nice course to follow forward. Do you have anything to add to her comments? Dr. Naveed Sattar: No, I completely agree with all of them. I think the key thing is nice that this came out straight after EMEPEROR-reduced and a year after that, for heart failure with the team that, John and colleagues were led out. I was involved in the EMPEROR-reduced so that the mechanism helps. I think clinicians buy into this concept. It does what they think drugs do to improve heart failure outcomes. I think that helps and it might help prescribing, get people the confidence that these drugs do work in a mechanism that works. Dr. Naveed Sattar: The only thing that I think we would love to have done is if doing the MRIs even sooner, how quickly do these actual volumes change? We think it's reverse remodeling, but maybe we need another trial doing MRIs at one month, three months just to see how quickly these volumes do actually change. Because I still think that's a bit of doubt. But having said all that, I've loved this journey working with my fantastic Hatfield colleagues, a brilliant team in Glasgow. We're now thinking about the next trial. Let's see where we get to in terms of algorithms and trials, but the diabetes, heart failure, kidney disease fraternity coming together is fantastic. I'd loved being part of that journey. So great. Dr. Ileana Piña: There's another interesting observation in your data was a hematocrit. It's really tiny, but the signal is there, which to me has also been fascinating. We see a lot of anemia in this population. A benefit in the hematocrit, I think, is really important. The fact that you did this with MRI, I don't think this is a good echo study, to do this with echo. I think you need the reliability and the precision of an MRI.   Dr. Naveed Sattar: Yeah, I agree. We have other data coming up, Ileana, in terms of renal blood flow, because you've mentioned that as well at the same time, which we haven't yet analyzed. There's a lot more data which needs a good Biobank and pick some of these mechanisms. So, yeah, fantastic. Dr. Greg Hundley: Well listeners, this has been an excellent discussion and we want to thank Dr. Naveed Sattar from Glasgow and our guest editor, Dr. Ileana Pina from Detroit Medical Center, bringing us these results regarding the administration of empagliflozin and favorable changes in left ventricular volumes in patients with heart failure and a reduced ejection fraction. 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. This program is copyright of the American Heart Association, 2021.  

#MeetTheYoungKashmir #100Kashmir. Naveed Yousuf, A level qualified Rugby coach and the only national Rugby player from South Kashmir with a silver and gold medal to his tag. He started playing at the age of 15 and has played 15 nationals till now. Presented By: BQE Software

Raine Maida (Our Lady Peace) is my guest this week on the "Life Cast" series! Fronting one of the most successful bands in Canadian rock history is just one of his many jobs.In this episode, we break downBreaking OLP in TorontoWhen did he feel he finally wrote "The Song" and how it changed the band?What was the hardest album to make?How to balance touring and fatherhood?What's next for him and OLP?It's episode 50 and I couldn't be more excited to have Raine along for a chat to celebrate it!https://www.ourladypeace.comBrought to you by https://drinkpartake.comPowered by Blue Microphoneshttps://www.bluemic.com/en-ca/#ourladypeace #bluemic #drinkpartake

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Vanessa Kirby meets Naveed Jamali, an FBI operative who worked his way into the world of espionage. Hoping to impress US Intelligence, Naveed used family connections to set himself up as a double agent, fooling the Russians into revealing their operations on American soil. Armed only with a secret recording device, an encyclopaedic knowledge of spy movies and a high tolerance for fast food, he spent 3 years luring in one of Russia's most senior operatives. Could YOU make it up as you went along? From SPYSCAPE, the home of secrets and skills. A Cup And Nuzzle production. Series producer: Gemma Newby. Produced by Claire Crofton. Music by Nick Ryan.

I talk with Dr. Naveed Nosrati about hands, surgery, transgender, plastic surgery, and before we get started I cover the news for the week  check out my website at www.myshitypodcast.com 

Designing with Pre-Loved FurnitureWelcome, listeners, to Women Emerging Fearlessly, the podcast dedicated to helping women live with fearless confidence, and to know how amazing they truly are. I’m your host, Janelle Anderson, and in Episode 41 I chat with Naveed Jo Hyder about interior design. Listen to this episode to get inspired with ideas on how to use vintage or pre-loved furniture in your décor!Naveed Hyder is the founder and CEO of H5 Interiors Inc., which is driven by her passion for remodeling older homes and designing timeless interiors, and her love for all things organic, original, sustainable, and vintage. Naveed, also known as Jo by many, has a keen eye for remodeling spaces. She can transform any space into an inviting and unique interior with a balance of color and texture that infuses a noticeable harmony for her clients, evoking a positive influence on their mood and well-being for years to come. Her overall goal is to advocate the undervalued impact of well-designed spaces on those living and working there, the simplicity of remodeling versus demolishing older homes, the elements required in designing a space and how a well-designed space affects our mood. She’s passionate about restoring old buildings and embracing vintage furniture for their quality and attention to detail.In this episode, we talk about:How to use YOUR hand-me-down OR inherited furniture in YOUR contemporary space.What to look for in furniture to determine its worthModernizing furniture can be simpleBenefits and the ripple effects on the environment on upcycling and preserving older, high quality furniture.If you’d like to work with Naveed on your own projects, you can find her information below:https://H5Interiors.com; https://www.instagram.com/h5interiors; https://www.facebook.com/h5interiorsDid you enjoy the show? Subscribe to the podcast wherever you listen to podcasts, and please consider leaving a positive review. If you’d like to work with Janelle on becoming fearlessly confident, email her at janelle@emerginglifecoaching.com.Website: www.emerginglifecoaching.comhttps://www.facebook.com/emerginglifecoachinghttps://twitter.com/nellie_53https://www.pinterest.com/emerginglifecoaching/_created/https://www.linkedin.com/in/emerginglifecoaching/Podcast theme music by composer Jared LeDoux; www.jaredledoux.comPodcast produced by: Shana T.; www.shanatphoto.com

Fatphobia has been described as society's last ‘ism'. Whilst our understanding of weight and health has changed over time, there is still a stigma towards people who are overweight or obese, and an assumption that they must be unhealthy, and unhealthy by choice. However, the correlation between weight and health may not be as clear cut as our societal biases would lead us to believe, and, therefore, the challenge for GPs is to make a conscious efforts to overcome our preconceptions so that they may provide the best support for our obese patients. This week, we discuss the need for a zero tolerance towards fat shaming at an organisational level, and how we can make GP practices more accessible for this group of patients. We also talk about retraining the palette in order to sustain weight loss, and our duty to lobby for better community-based weight management services. Our guests: Stephanie deGiorgio is a GP, and the clinical lead in the UTC at Queen Elizabeth The Queen Mother Hospital, Margate. She has a special interest in obesity. Naveed Sattar is a professor of Metabolic Medicine at the University of Glasgow. His main research concerns investigating the prevention, causes and management of diabetes, heart disease and obesity.

Fatphobia has been described as society's last ‘ism'. Whilst our understanding of weight and health has changed over time, there is still a stigma towards people who are overweight or obese, and an assumption that they must be unhealthy, and unhealthy by choice. However, the correlation between weight and health may not be as clear cut as our societal biases would lead us to believe, and, therefore, the challenge for GPs is to make a conscious efforts to overcome our preconceptions so that they may provide the best support for our obese patients. This week, we discuss the need for a zero tolerance towards fat shaming at an organisational level, and how we can make GP practices more accessible for this group of patients. We also talk about retraining the palette in order to sustain weight loss, and our duty to lobby for better community-based weight management services. Our guests: Stephanie deGiorgio is a GP, and the clinical lead in the UTC at Queen Elizabeth The Queen Mother Hospital, Margate. She has a special interest in obesity. Naveed Sattar is a professor of Metabolic Medicine at the University of Glasgow. His main research concerns investigating the prevention, causes and management of diabetes, heart disease and obesity.

This week’s episode includes author Charlotte Andersson and Associate Editor Naveed Sattar as they discuss familial clustering of aortic size, aneurysms, and dissections in the community. TRANSCRIPT: 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 Greg Hundley, director of the Pauley Heart Center at VCU health in Richmond, Virginia. Well, Carolyn, our feature this week has to do with aortic size, aneurysms, and predilection to dissection. But before we get to that, how about if we grab a cup of coffee and go through some of the other articles in the issue? Dr Carolyn Lam: I got my coffee, Greg, and you know what? I'm going to start with quiz for you. Dr Greg Hundley: All right. Dr Carolyn Lam:  True or false, in the setting of obesity and/or diabetes, cardiac substrate metabolism shifts towards increased fatty acid oxidation, while lipid accumulates in the heart? True or false? Of course, you're right. Oh, but there's a part two. Can you guess, by increasing fatty acid oxidation, will we induce or prevent obesity-induced lipotoxic cardiomyopathy? Dr Greg Hundley: I'm going to say, because you asked it in the way you asked it, prevent. Dr Carolyn Lam: Wow. All right. Well, the truth is we didn't really know before today's paper. The specific link between cardiac metabolism and lipotoxic cardiomyopathy was elusive and there was no specific therapy available for this condition. And these authors, Dr Rong Tian from University of Washington and colleagues, hypothesized that cardiac pathology-associated obesity would be attributable to the imbalance of fatty acid supply and oxidation. So using a diet-induced obesity model in the current study, they demonstrated that enhancing fatty acid oxidation through deletion of acetyl-CoA carboxylase 2, was sufficient to prevent obesity-induced cardiomyopathy. So, increasing cardiac fatty acid oxidation alone does not cause cardiac dysfunction, but instead protects against cardiomyopathy in chronically obese mice. The cardiac-protective effect of increasing fatty acid oxidation and obese mice is through maintenance of Parkin-mediated mitophagy, and thus preventing mitochondrial dysfunction. These findings indicate that impaired mitophagy contributes to mitochondrial dysfunction in obese mice, and that targeting the Parkin-dependent pathway is a viable therapeutic intervention for obesity-induced cardiomyopathy. Dr Greg Hundley: Very nice. Carolyn. Dr Carolyn Lam: I'm going to be greedy and go on to my next paper. So Greg, do you think cardiac regeneration is possible? Dr Greg Hundley: Well, Carolyn, I would have said, several years ago, no, but that trip that we took to China with Joe Hill and Hesham Sadek, our Associate Editor and our Chief Editor, convinced me otherwise. So I'm going to definitely answer yes on this one. Dr Carolyn Lam: Oh, Greg, you're just too smart. And speaking of China, this next paper is from there, from co-corresponding authors, Dr Nie and Hu, from Fuwai Hospital National Center for Cardiovascular Disease and Chinese Academy of Medical Sciences and Peking Union Medical College. So, using seven genetic mouse lines, they identify that Oncostatin M is the top upregulated cytokine during neonatal heart regeneration. Oncostatin M is a pleiotropic secretory protein that belongs to the interleukin 6 family, and associates with the pathological process of dilated cardiomyopathy. And these authors found that macrophages promote heart regeneration by secreting Oncostatin M, which promotes cardiomyocyte proliferation via a co-receptor, gp130. Employing RNA-seq and functional screening, they further found that Src-mediated gp130 triggered cardiomyocyte proliferation by activating the downstream signaling pathway involving Yap, with Y357 phosphorylation independent of the Hippo pathway. So the last thing that they did was show that gene therapy with adenovirus-associated virus and coding this activated gp130 improved heart regeneration and pumping function, thus serving as a potential therapeutic target. An amazing paper. Dr Greg Hundley: Very nice, Carolyn. What a great summary and so much detail. Well, Carolyn, I'm going to turn our attention to catecholaminergic polymorphic ventricular tachycardia. And this article comes to us from Dr Jason Roberts, from the Western University. Carolyn, genetic variants in calsequestrin 2 can cause an autosomal recessive form of catecholaminergic polymorphic ventricular tachycardia, though isolated reports have identified arrhythmogenic phenotypes among heterozygotes. So in this study, a total of 112 individuals, including 36 catecholaminergic polymorphic ventricular tachycardia probands, 24 were homozygotes for compound heterozygotes, and 12 were pure heterozygotes, against 76 family members possessing at least one presumed pathogenic calsequestrin 2 variant. These were all identified. Dr Carolyn Lam: Wow, a very precious cohort. So what did they find, Greg? Dr Greg Hundley: This international multicenter study of calsequestrin 2 catecholaminergic polymorphic ventricular tachycardia really redefined its heritability and confirmed that pathogenic heterozygous calsequestrin 2 variants may manifest with a catecholaminergic polymorphic ventricular tachycardia phenotype, indicating a need to clinically screen these individuals. Among individuals heterozygous for a pathogenic calsequestrin 2 rare variant, medical therapy and exercise restriction are likely not necessary in the absence of the catecholaminergic polymorphic ventricular tachycardia phenotype. Though, you have to be certain over time, an intermittent clinical screening to ensure they remain phenotype-negative should be obtained. Dr Carolyn Lam: Wow, Greg, clinically important study there. Well, I'm going to go back to the basic science world and talk about calcineurin. Now, calcineurin has long been implicated in the induction of pathological cardiac remodeling but has not been therapeutically targetable for the prevention of heart failure because of its pleiotropy and our lack of understanding of its specific protein-protein interactions and compartmentation within the cardiomyocyte. Dr Greg Hundley: Okay. Carolyn, do you want me to give background on calcineurin? Dr Carolyn Lam: No, Greg, you're off the hook. I'm going to give you some background on calcineurin. So, calcineurin is the calcium-calmodulin-dependent phosphatase that exists as a heterodimer, consisting of a catalytic subunit and a regulatory subunit. Now, of the three catalytic subunit isoforms, alpha, beta, gamma, it's the beta isoform that appears to be the most important for the development of cardiac hypertrophy. Binding of calcium to the calcineurin regulatory subunit enables binding of the calcium-calmodulin complex, thereby releasing auto-inhibition and freeing the enzyme to dephosphorylate downstream substrates. That's the background. Now, in today's issue, we have this great paper from co-corresponding authors, Dr Kapiloff from Stanford University, and Dr Nikolaev from University Medical Center Hamburg. And, with their colleagues, they described the discovery of a calcineurin catalytic subunit beta binding protein Cdc42-interacting proteins 4, and I'm going to call that CIP4, which functions as a scaffold to sequester the pool of calcineurin near the sarcolemma of cardiomyocytes, where it regulates pro-hypertrophic signaling. These findings have really important implications for understanding how cardiac calcineurin is selectively activated by stress signals, as opposed to the pleiotropic second messenger, calcium, that really floods the cardiomyocytes during each contractile cycle. Furthermore, the data provide proof of concept for an innovative therapeutic approach, whereby CIP4-anchoring activity is selectively inhibited to block the action of a small pathogenic pool of calcineurin as a means of treating heart failure. How about that? This is really discussed in an elegant editorial by doctors, Woulfe, Travers, and McKinsey. Dr Greg Hundley: Very interesting, Carolyn. Sounds like another possibility for treating and managing heart failure. Well, let me share with you some of the other findings in our mailbag this week. First, I've got, from Professor Lang Li and Stephen Wiviott, they swap research correspondence regarding the prior publication entitled, Effect of Dapagliflozin on Atrial Fibrillation in Patients with Type 2 Diabetes Mellitus, Insights from the DECLARE-TIMI 58 Trial. And then Professor Laszlo Littmann has a nice ECG challenge for us related to a high-risk ECG that exposed some downstream worrisome vital signs. Dr Carolyn Lam: In addition, there's a perspective piece by Dr Nambi discussing the fact that a zero-calcium score is desirable, but isn't enough to defer therapy, given that up to one-third of events will occur in this group. There's also an In Depth paper by Dr Borlaug, entitled, “Altered Hemodynamics and End Organ Damage in Heart Failure, The Impact on the Lung and Kidney,” and oh boy, this one is so beautifully illustrated. Just a must read for the understanding of the hemodynamics in the lung and kidney and heart failure. Next is a research letter by Dr Loeys on enrichment of rare variants in the Loeys-Dietz syndrome genes in spontaneous coronary artery dissection, and not in severe fibromuscular dysplasia. And finally, another research letter by Dr Arora on racial differences in serial NT-proBNP levels in heart failure management with insights from the GUIDE-IT Trial. What a rich issue, but let's move on to our future discussion, shall we? Dr Greg Hundley: You bet, Carolyn. Well, listeners, we're now getting to our feature discussion and it's very interesting this week where we're going to evaluate aortic aneurysms. And we have with us one of the lead authors of this paper, Dr Charlotte Andersson from Boston Medical Center, and our own Associate Editor, Naveed Sattar from Glasgow, Scotland. Charlotte, welcome to our feature discussion. Could you tell us a little bit about the background and the hypothesis that you put forward with this study? Dr Charlotte Andersson: The background for this study was based on clinical work and what we observed in clinic. We had a few patients where we had been stricken by the fact that they came in with an acute aortic syndrome and they had a first-degree relative themself with the condition, but they did not look syndromic at all. And we started to wonder, what is the actual risk in the community, in people without obvious syndromic features of suffering from an aortic event itself. And although there are quite a few studies out there that have, to some degree, focused on the familial clustering of aortopathies, there is not a lot of information based on communities and whole entire populations. So we wanted to, frankly, estimate what is the incidence rates of aortic dissections and aortic aneurism in the community if you have a first-degree relative that has suffered from the disease themselves. Dr Greg Hundley: How you organize your study and what was your population and what was your design? Dr Charlotte Andersson: This study was actually based on two independent samples. First, we used the Framingham Heart study population that is very densely phenotypes over many years of spanning three generations of participants, where we looked at people who had at least one parent who had an aortic size in the upper quartile index to body-surface area and adjusted for age and sex. And we saw what's the risk of you, as a child, having an aortic size in the same upper quartile. And second, we looked in the general Danish population, the Danish healthcare system is, as you probably know, governmental funded and we have very good registries of all hospitalizations, all outpatient visits, and so we were able to link more hard clinical events in people with and without a first-degree relative. What we did was we started time when people had an aortic dissection, we identified all the first-degree relatives in these people, and we matched them with up to 10 sex and age match controls from the general population without a first-degree relative with the disease. Dr Greg Hundley: What did you find? Dr Charlotte Andersson: We found that in the Framingham sample, if you had at least one parent who belongs into the upper quartile of aortic size, you had an odds ratio of two to three, adjusted for various clinical risk factors, such as hypertension and smoking yourself. And in Danish population, we found that if you had a first-degree relative with an aortopathy, the hazard rates for you developing the disease yourself was almost a tenfold-increase compared to age and sex match controls. And importantly, seemed like hazard ratios use were, more or less, unchanged when we start adjusting various known risk factors, such as bicuspid aortic valve, Marfan syndrome, and Ehlers-Danlos syndrome, normally those kinds of things. And we also found that the younger your proband were at the time of an acute event, the higher was your relative risk yourself. So among people who were below the age of 50 when they suffered an event, the hazard ratios were up to a 50-fold increase. Dr Greg Hundley: Very nice. Naveed, what attracted you to this article as it was coming through the editorial process? And then second, how do we take the information that Charlotte's just conveyed and will be published here today, how do we take this in the context of what we already know about aortic aneurysms? Dr Naveed Sattar: I think it's a beautiful study, so well done, Charlotte. I think it's a beautiful fusion. As Charlotte said, an in-depth cohort study, which has got very well-measured parameters of systematic points and a fantastic population-based data set from Denmark, which Sweden shares and Scotland shares and relatively small countries like us share. So small countries like Denmark punch above their weight in these kinds of studies, which is fantastic. But there's a rich seam of research that comes from these, and this is one of them. So I think that fusion of two data sets with different strengths and limitations combined giving off same signals is good. I think, as Charlotte said, this is the first major population study to look at this question. So there's been people around the world who have got this sense that the aortic aneurism may well be familial, this provides, probably, some of the best data to suggest, yes, it definitely is. Now the questions going forward is, okay, at what point do you screen everybody's got a family history with a proband, or do you screen those who've got a family history of younger probands? And I think what Charlotte and the team and other people around the world thar are going to look at this say, "Okay, we now think, in addition to screening, for example, in the UK and the US we probably screen just men above 65, where most of the disease is, do we also then implement screening in younger people with family histories? And who do we screen, and when and how? And do we need to develop some kind of risk score?" And then when we do that screening, what do we do about it? Is going to be the questions and I'm sure Charlotte and her colleagues have thought about these things and it'd be interesting to see what her view is on those things. But I think it was a beautiful study in every sense. Dr Greg Hundley: So Charlotte, he's really set you up nicely, what study do we need to perform next in this area? What are you and your group thinking about? Dr Charlotte Andersson: Yeah, I think there are two implications of this study. First, clinical, as Naveed says. They already had a sense that aortic diseases were heritable, and I think these data definitely support that we should probably screen first-degree relatives. And I think, at some extent, this is what the guidelines already encourage us to do. So I'm not sure it would be feasible to randomize people or do a clinical trial where we screen some but not others. I'm not sure that would be ethical. I think the evidence is too strong for familial clustering and that we should probably screen these people. But I think also, our estimates, they are so strong that I suspect that there are likely more genetic variants associated with non-syndromic aortopathies that we are not aware of just yet. So I think the next step would be to try to disentangle the genetics a little bit more. I have seen some preliminary analysis based on the UK Biobank, for instance, and I think there are more genetic variants to come up with also, more common genetic variants, at least, that we are not aware of just yet. So that would be the next step as I see it. Dr Naveed Sattar: And that might particularity in younger probands. Dr Charlotte Andersson: Right. Dr Naveed Sattar: Those with the younger probands, because it looks like, as you said, the hazard ratio, the risks, are so high, it could also potentially be monogenic, but anyway. Dr Charlotte Andersson: I agree. Dr Greg Hundley: Well, Charlotte, Naveed, we really appreciate your time and taking this opportunity to discuss these really interesting findings and helping us understand that, truly, there may be a familial component to understanding this disease process, particularly in patients with aortic aneurysms that may go on to develop aortic dissections. Well listeners, we hope you have a great week and on behalf of Carolyn and myself, catch you on The Run next week. This program is copyright, the American Heart Association, 2020.  

In episode 1, we invited Naveed Ahmad, CEO and Founder from Muscat Livestock, the leading distributor of red meat in Oman. Listen to how Naveed navigated his business during the COVID-19 pandemic and shifted strategy to expand into online retail and target new consumer segments, as well as benefitting from digital receivable finance and online banking. See acast.com/privacy for privacy and opt-out information.

Lewis Maleh talks with Professor Naveed Sattar, Professor of metabolic medicine and an expert in the prevention and management of diabetes, obesity and heart disease, from the University of Glasgow. Professor Naveed Sattar was one of the key contributors to Public Health England’s (PHE) recent report on COVID-19 and obesity. In this episode they discuss how being obese or overweight puts you at greater risk of serious illness or death from Covid-19. They also talk about the importance of a healthy lifestyle a giving your immune system the best chance of fighting off infections. *This episode was recorded live on google hangouts. Show notes: Professor Naveed Sattar LinkedIn: https://bit.ly/3hioOjp -------------------------------------------------------------------------------­----------------- This episode is supported by Audible: Start your 30 day free trail today! using the following link: bit.ly/2YVdZJU - Auto-renews at £7.99/month after 30 days - 1 book monthly membership - Cancel anytime Take your pick from the world’s largest selection of audiobooks including best sellers, latest releases, sci-fi, fantasy and more. Disclaimer: If you sign up using our link, we make a small percentage and you help to support our podcast for which we are truly grateful. This doesn't affect our opinions.

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, associate editor, director of the Pauley Heart Center, VCU Health in Richmond, Virginia. Dr Carolyn Lam: Greg, guess what we're discussing for the feature discussion? We're talking about sugar sweetened beverage tax. Isn't that interesting? We talk about sugar sweetened beverages and their health impacts, but don't actually look at how tax policies may impact cardiovascular outcomes. So this paper is super interesting, can't wait to get to it, but I really want to get my cup of coffee and discuss a couple of other really cool stuff in today's issue. I'm going to start. Do you think about factor V Leiden much? Dr Greg Hundley: Carolyn, we are early in August and we have all new house officers rotating, and actually we do discuss factor V Leiden, and we think about Protein C and Protein S deficiencies, et cetera. But how about if you tell us about your paper and educate us a little bit more on the topic? Dr Carolyn Lam: Okay. So first of all, it's Leiden or Leiden, I'm not sure. So I'm going to go with your pronunciation. Factor V Leiden is a genetic variant leading to alteration of the inactivation site of factor V, which in turn leads to activate a Protein C resistance and a prothrombotic state, just like you said, Greg. Affecting almost 5% of the Caucasian population, carriers of a factor V Leiden mutation have a fourfold higher risk of venous thromboembolism. However, the risk of arterial atherothrombotic events, such as myocardial infarction or stroke, conferred by the presence of this variant is less certain. So Dr Patel from University College London, and Dr Asselbergs from University Medical Center Utrecht and colleagues assess the association of the factor V Leiden polymorphism with subsequent atherothrombotic events, including mortality in individuals with established coronary heart disease using an individual level data meta-analysis of 25 prospective studies from the genetics of subsequent or GENIUS coronary heart disease consortium. Dr Greg Hundley: Well Carolyn, what did they find? Dr Carolyn Lam: In nearly 70,000 patients with established coronary heart disease, factor V Leiden was not associated with an increased risk of further atherothrombotic events or death compared to non-carriers. A post hoc analysis, however, suggested that factor V Leiden carriers with established coronary heart disease may gain greater protection from subsequent coronary heart disease, death, or myocardial infarction from dual antiplatelet therapy compared to non-carriers. The routine assessment of factor V Leiden genotype to improve risk stratification in secondary prevention settings is therefore unlikely to be of value and is not recommended. However, further work is required to understand if there may instead be a pharmacogenomic role for factor V Leiden status to help personalize treatment with intensive antiplatelet therapy. Dr Greg Hundley: Very nice, Carolyn. Well, my next paper is from Dr Michelle O'Donoghue from Brigham and Women's Hospital, and creates an interesting question for you, Carolyn. Would you be comfortable discontinuing aspirin three months after PCI in lieu of continuing a P2Y12 inhibitor? Dr Carolyn Lam: Ah, big, big question. Not until guidelines change, but tell me, tell me, tell me, Greg, what this paper said. Dr Greg Hundley: Well, before we get some of these more randomized trial, this study included a meta-analysis of 32,145 patients, 14,095, or 43%, with stable coronary artery disease and 18,000, nearly 56%, with ACS from randomized trials during the time period of 2001 to 2020. And they had to study discontinuing aspirin one to three months after PCI with continued P2Y12 inhibitor monotherapy compared to traditional dual antiplatelet therapy. Five trials were included, and the follow-up duration range from 12 to 15 months after PCI. The primary bleeding and MACE outcomes were the pre-specified definitions in each trial. Dr Carolyn Lam: An important study. So what did they find, Greg? Dr Greg Hundley: Well in the experimental arm, background use of a P2Y12 inhibitor with Clopidogrel in 16.5% of cases, and prasugrel or ticagrelor in 84% of patients. In total, 820 patients experienced a primary bleeding outcome and 937 experienced MACE. So the results, discontinuation of aspirin therapy one to three months post PCI significantly reduced the risk of major bleeding by 40% compared to dual antiplatelet therapy with no observed increase in the risk of MACE, myocardial infarction, or death. The findings were consistent among patients who underwent PCI for an ACS in whom discontinuation of aspirin after one to three months reduced bleeding by 50%, to 1.78% versus 3.58%, and did not appear to increase the risk of MACE where both were 2.5% and 2.98%. Dr Carolyn Lam: Nice, Greg. Could you summarize the take home message for us? Dr Greg Hundley: Sure, Carolyn. So in summary, discontinuation of aspirin with continued P2Y12 inhibitor monotherapy reduced the risk of bleeding when stopped one to three months after PCI. An increased risk of MACE was not observed following discontinuation of aspirin, including patients that had previously sustained ACS. Dr Carolyn Lam: Thanks Greg. Well, my next paper is a preclinical one showing that circular RNAs delivered via extracellular vesicles may be a new treatment for ischemic stroke. Dr Greg Hundley: Oh my goodness. Carolyn, can you orient us to circular RNAs and these extracellular vesicles? Dr Carolyn Lam: Sure, Greg. I decided not to quiz you on them. Circular RNAs are a type of endogenous non-coding RNA molecule characterized by back splicing and covalently closed continuous loops, hence circular. Previous studies have demonstrated that multiple circular RNAs have functional roles relating to ischemic brain injury. Although administering circulating RNAs using lentiviruses is efficient for experimental examination, this route is limited for clinical translation due, of course, to disadvantages in onset time and safety issues. So this is where the extracellular vesicles come in as a potential cargo delivering system, if you may, for brain remodeling after stroke. These extracellular vesicles are lipid membrane vesicles of 30 to 150 nanometers in diameter that are released by cells and can cross the blood brain barrier and have been shown capable of carrying proteins, lipids, and nucleotides as their cargo. So today's co-corresponding authors, Dr Yao from Medical School of Southeast University in Nanjing, and Dr Wang from Chinese Academy of Sciences Kunming, Yunnan in China envisioned the potential of delivering candidate circular RNAs to the brain in vivo by constructing engineered extracellular vesicles bearing circular RNAs. They initially explored this circular RNA delivery strategy idea in the context of their ongoing work regarding the functional roles of circulating RNAs in ischemic brain injury. Their microarray based profiling of acute ischemic stroke patients reveal that a circular RNA generated from the SCM-polycomb group protein homolog 1, or SCMH1 gene, is decreased in plasma of acute ischemic stroke patients and confirmed that a similar decrease occurs in stroke model mice. So they successfully engineered extracellular vesicles with circular SCMH1 over-expression and were thus able to experimentally characterize the ischemia related functional benefits of this circular RNA administration in stroke models in both mice and macaque monkeys. Cool, huh? Dr Greg Hundley: Yeah. Very nice, Carolyn. That was a great explanation. My study comes from Dr Juyong Kim from Stanford University School of Medicine, and Carolyn, this study combined RNA sequencing, chip sequencing, ATEC sequencing, and in vitro assays in human coronary artery smooth muscle cells with single cell RNA sequencing, histology, and RNA scope in a smooth muscle cell specific lineage tracing aryl hydrocarbon receptor knockout mouse model of atherosclerosis to better understand the role of the aryl hydrocarbon receptor in vascular disease. This aryl hydrocarbon receptor, heretofore AHR, is an environment sensing transcription factor that contributes to vascular development. Dr Carolyn Lam: Wow, what a comprehensive study. So what do they find? Dr Greg Hundley: The authors identified a novel population of cells derived from smooth muscle cells, termed condramyocytes, which have gene expression features of cartilage and bone formation within an atherosclerotic lesion. In addition, the environment sensing transcription factor aryl hydrocarbon receptor plays an important role in smooth muscle cell differentiation, ossification, and maintains the smooth muscle cell derived fibrous cap structure. Dr Carolyn Lam: Interesting. Okay, you know what I'm going to ask. What are the clinical implications? Dr Greg Hundley: Yeah, I knew you'd ask me that, Carolyn. So human genetics suggests a protective role of the aryl hydrocarbon receptor in the smooth muscle cell during atherosclerosis, and therapies targeted to increase the aryl hydrocarbon receptor activity in smooth muscle cells may confer protection against adverse calcific remodeling of the atherosclerotic plaque. This study also highlights a methodological advance, and further characterization of the pathways that direct the modulation of smooth muscle cells during atherosclerosis at the single cell level may be able to identify potential therapeutic targets to mitigate the risk of atherosclerosis. Dr Carolyn Lam: Oh, I like that summary, Greg. Thanks. Now, let's move on to other things in today's issue. There's a perspective by Dr Al-Lamee on the ISCHEMIA trial asking was it worth the wait? There's also a perspective by Dr Levine on the ISCHEMIA-CKD trial, providing contemporary randomized clinical data at last in this important population. There's a white paper by Dr Emmaullee on Fontan-Associated Liver Disease, screening, management, and transplant consideration. And finally, there are letters to the editor from Dr Helgestad, Chieffo, and Waksman, with replies from Dr Amin on the article The Evolving Landscape of Impella Use in the United States Among Patients Undergoing PCI With Mechanical Circulatory Support. Dr Greg Hundley: Very good, Carolyn. Well, I have a few other items in the mail bag. Xiang Cheng has a research letter entitled Cardiac Troponin I is an Independent Predictor for Mortality in Hospitalized Patients with Coronavirus Disease 2019. Also, Corinne Frere has a research letter regarding the Systemic Inflammatory Response Syndrome is a Major Contributor to COVID-19-Associated Coagulopathy, and they provide insights from a perspective single center cohort study. And finally, Dr Jeffrey Wagner has an ECG challenge regarding the infamous is it VT or not VT? Well, Carolyn, how about we get on to that feature discussion. Dr Carolyn Lam: Let's go, Greg. Beverage Texas are a promising policy approach to reduce consumption of sugar sweetened beverages. And as we know, these are linked to adverse health outcomes, such as Type 2 diabetes and obesity. Now these taxes have been adopted by seven localities in the United States, and in more than 40 countries around the world using different tax designs, but until now a critical answered question where we lack empirical data is the health impact of these beverage taxes. That is until today's feature paper, and I'm so pleased to have with us, Dr Yujin Lee from Friedman School of Nutrition Science and Policy, Tufts University, as well as our associate editor, Dr Naveed Sattar from University of Glasgow. Welcome both, and Yujin, could I start with you please? What an interesting and important idea to look at this. Could you start by perhaps first explaining to us what are the different types of tax designs? Dr Yujin Lee: There are three types of tax design. First, the volume tax is taxing sugar sweetened beverages based on the volume. For example, a penny per owns for volume tax. So the tax rate is same whether a beverage contains 5 or 20 grams of added sugar for 8 ounces. The second design is the absolute sugar content tax, which is taxing beverages based on the sugar content regardless of the volume. So for example, one cent per one teaspoon of sugar, or one cent per one gram of sugar. Lastly, tier tax is hybrid of volume and absolute sugar content tax. For example, creating different tiers products based on the sugar content and taxing based on the volume at different rates. So for example, the American Heart Association suggested three tiers. First, no tax on beverages with less than five grams of added sugar per eight ounces. And second, 1 cent per ounce on beverages with 5 to 20 grams of added sugar per 8 ounces. And lastly, 2 cents per ounce on beverages with more than 20 grams of added sugar per 8 ounces. Dr Carolyn Lam: Great. So thank you for explaining that. I mean, to be honest, I didn't even realize there were so many different tax designs. Now, could I understand a bit better? So in the US, are they mostly volume-based? And then perhaps you could tell us how did you go about your study of comparing these things, and looking on their impact on outcomes. Dr Yujin Lee: Sure. So as you mentioned, all seven US locality have been implementing the volume tax, and in this study, this is the modeling study, so we're using the nationally representative data and using a microsimulation model, and we wanted to compare and estimate the health and economic impact of the volume, absolute sugar content. And the tier tax designs in the United States. Dr Carolyn Lam: Great. And tell us what you found. Dr Yujin Lee: What we found is we found that implementing a volume-based sugar sweetened beverage tax could prevent 850,000 cardiovascular events and 270,000 diabetes over a lifetime of current US adults aged 35 years or older. And this tax design could save tens of billions of dollars in healthcare costs. In addition, taxing sugar sweetened beverage based on their sugar content, for example, the tier or absolute sugar content based tax design, could generate about double the health and economic benefits compared to the volume tax. Dr Carolyn Lam: Wow, that is so intriguing. Naveed, I have to bring you in here. So in the UK they use a tier tax. Do you? And what are your thoughts? Dr Naveed Sattar: Oh, well clearly, Carolyn, I mean, I think taxation of sugar sweetened beverages is something that all of us can agree on is beneficial. I think it's really important that many other countries and states consider this. I'm surprised that only seven states in the US are currently doing this. And in some respects, this papers is very timely. It's based on modeling. I mean maybe you can come back to Yujin about how good the modeling is, but if you think about the issue we have now in terms of health inequalities and COVID related deaths, going forward we need mechanisms to help reduce health inequalities. And this particular paper will flag up that places need to think about sugar sweetened beverage taxes and how best to do them. And I completely agree, they should be based on sugar content. I don't see why they should be more convoluted than that. And although Yujin explained it, it still seems a bit complex to me, the different mechanisms, but I think your paper is very timely and very important. And for me, the key question for Yujin is people looking at this may say well, how robust is that model? How do we know how accurate you've been in terms of the money saved, because that's going to be really important going forward, and in particular, the number of lives or cardiovascular and diabetes cases prevented? Dr Yujin Lee: Sure. So let me explain how we estimated how many cases of cardiovascular disease and Type 2 diabetes were prevented. So we use a microsimulation model, which is a computer simulation model, which is developed by the research team, led by Dr Thomas Casiano and Harvard School of Public Health. So this model predicts the probability of an individual experiencing cardiovascular disease or diabetes based on each person's risk factor, such as sex, age, total cholesterol, or smoking or diabetes, and also their SSB-consumption also be part of this input. So it estimate the probability of one person, individual, developing the future cardiovascular disease, or Type 2 diabetes, and it estimate how this prevention can save healthcare costs associated with these diseases. So in this study, this model simulates the status quo, so the way things now stand, and also it assimilate the three different tax design. After that, we compute the health outcome and costs associated with this policy options and, by comparing this model, outputs for these three tax design with the status quo. Dr Naveed Sattar: Has any country got long enough perspective data that have implemented such taxes to validate the model, or is that still to come? I mean it would be nice to get it validated in real life, but I think most people would accept that reducing sugar in beverages is a really good thing, and presumably the part of the mechanisms by reducing weight, and reducing all of the implications of excess calorie intake, particularly refined sugar, on a variety of different diseases. Is that fair? Dr Yujin Lee: Yeah, and I wanted to make a point that, since this is a modeling study, so our study cannot prove the health and economic impacts of this tax design in the United States, so rather our estimates provide evidence that can be considered and incorporate into the design, and implementation, and evaluation of future SSB taxes. Dr Carolyn Lam: That's a really good point. And maybe just to round up, Yujin, could I just ask you to were any particular individuals in the population simulated to experience larger gains? We know that it's exactly like Naveed said, it's the minorities, it's perhaps lower income region individuals who might need this more. I mean did your simulation show anything to that effect? Dr Yujin Lee: We also investigate this tax design and how this influence in sub population. Particularly we found that the SSB taxes have a larger benefit among younger adults, minorities, and adults with the lower income. Given that these population, their SSB consumption is higher than the other group, so this SSB tax implementation gives them a greater health and economic benefit to these subpopulations. Dr Carolyn Lam: Thank you so much, Yujin, for this really, really, I think, novel and very important data. Naveed, could I give you the last say as the associate editor who is managing this, and you even invited an editorial, which I liked very much, the title, Simple is Better for Local Beverage Tax Policy Diffusion. It's kind of in line with what you've been saying, but maybe some take home messages? Dr Naveed Sattar: Obviously in Circulation, we get lots of beautiful papers that very molecular depth and various other factors, but actually this paper brings us back to the reality that for many of the diseases that we treat, diet and drink intake is really relevant to our diseases and the likelihood of diseases, and there are simple mechanisms whereby we can help people in the community to actually lead better lifestyles that also are actually economically beneficial. And I think that in this paper, if it was to be implemented and looked at seriously by many states in the US, by many other countries to go along this route would have huge potential benefits on health, And it's really important at this time, given what's happened with the pandemic, and as we move forward over the next 5 to 10 years. So I think it's really timely and I congratulate the authors on it. Dr Carolyn Lam: Well, listeners, you heard it right here, novel, impactful data. That's what Circulation is about. Thank you for listening to Circulation on the Run. Don't forget to tune in again. Next week. Dr Greg Hundley: This program is copyright the American Heart Association, 2020.  

Keisha and Lexie discuss participating In DC Is Blind, a local, virtual spinoff of Love Is Blind. They spill some tea regarding the couples from the show, their feelings, the downward spiral that occurred, and their feelings on being In the group with the people that watched them. The also have Naveed on the podcast to discuss DC Is Blind from a man's perspective and tells us what kind of girl he's looking for and how to slide Into his DMs.

While working at his post doc at Oxford University, Dr. Akbar focuses on the signals the immune system uses and resulting actions through extracellular vesicles research. He discusses: How our body's healing mechanisms post-heart attack can both benefit and undercut healthy arteries through immune-induced inflammation. The difference between a healthy blood vessel and atherosclerosis plaque build up and how the epithelial cell cascade that the body sends to heal the area ends up progressing the inflammatory condition. Why his research to turn on and off these inflammatory signals may aid in better healing from heart disease. Dr. Naveed Akbar focuses on extracellular vesicles research and how the vesicles relate to metabolic disease. Atherosclerosis, which causes heart attacks and strokes, tends to be much thicker in a diabetic patient. He believes this junction of immunological and metabolic disease is an important crossroads.  He explains that while atherosclerosis builds up over decades due to many other lifestyle causes, we don't understand is why diabetic patients are more apt to get fattier plaques that are more aggressive and more prone to rupture, which ends in the heart attack and stroke events. Therefore, he has studied how immune systems responds to damage within the blood vessel and why immune cells accumulate within the wall of an artery to drive these attacks. They've discovered that as the monocytes try and engulf the fat in an artery, this action attracts more immune cells, causing more inflammation. Trying to understand what signals turn on and off the message to cause inflammation may lead to better healing. Finally, he describes a current project: extracellular vesicles research into what happens after a heart attack and splint placement. Immune cells go to the heart and create more inflammation, which is harmful—a healing that has a defective element. Understand what's controlling their switch is important therapeutically. For more information, see his page on the Oxford University site: https://www.rdm.ox.ac.uk/people/naveed-akbar

You might know Naveed from his writing at Newsweek and his appearances on MSNBC. He’s also the co-author of How to Catch a Russian Spy: The True Story of an American Civilian Turned Double Agent, which is currently in development as a feature film. Follow Naveed on Twitter @NaveedAJamali. Today we’ll dig into the impeachment, the Trump Crisis, Naveed’s work for the FBI as a double agent, and even the Snowden matter from 2013.

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