Podcasts about cedar sinai medical center

Our ability to remember or forget is b'yad Hashem. Like always, we're supposed to do our utmost to try and remember things. But we will only remember if Hashem says we should remember. I read a story that an avrech once told, which took place in his wife's classroom. She taught in one of the Netivot Moshe kiruv schools. She told her students one day they were going to get a test the following day and whoever paid attention that day, and got help from Hashem, will do well on the test the next day. The smartest girl in the class who was not raised with any understanding of Hashem said she didn't need anyone's help. She knew if she studied, she would get a hundred. The morah corrected her and said we always need Hashem for everything. But the girl was not fazed. However, the next day it was like a miracle. The girl started crying in the middle of the test saying she couldn't remember any of the answers, despite reviewing numerous times the previous night. She then realized her mistake and publicly said she was sorry to Hashem for the words she said the day before. That day there was an amazing kiddush Hashem in that classroom. Sometimes Hashem lets us see immediate benefits that come about as a result of us forgetting. A man said he prayed Shacharit last week in the house of mourning and accidentally left his tefillin there. The next day he went to his regular shul, and that's when he realized he forgot his tefillin, so he went back to the beit avel to pray. This man is a fundraiser for a certain yeshiva, and the previous year he was not able to locate a man who gave his yeshiva $5,000 annually. On this morning, the man was at the beit avel . So he went over to him and said he had been searching for him but couldn't locate him and asked if he could please donate his annual pledge from last year. The man said okay. Then he asked him if he would give another $5,000 for this year, and once again the man said okay. This fundraiser was so happy that he forgot his tefillin and of course he realized it was all m'et Hashem who made him forget them there. Sometimes we're given wrong information by others. That's also m'et Hashem. There are no mistakes. Everything always happens exactly the way it's supposed to. I heard a story on Stories to Inspire by a rabbi from the Cedar Sinai Medical Center who said someone he knows requested of him to help get them a private room. This man's daughter was beginning chemotherapy treatments and they really wanted privacy. The rabbi was able to help them. One day, when the rabbi walked into the hospital, the head nurse told him that the patient he helped was in room 18. He went there to say hello and when he walked in it seemed like the people in that room were not the ones he knew and helped, so he quickly closed the door. But just to be sure he opened it a crack again and the people asked him to come in. They asked him if he was a rabbi, to which he replied yes. They were practically in tears when they heard that. A woman there explained that her daughter is starting chemo and they have been preparing for this day for a long time wanting everything to go smoothly and quickly. The night before she had a dream in which she saw herself being told to get a blessing from a rabbi for her daughter before the chemo started. She didn't know of any rabbis, and so she and her husband went that day in the streets searching for a rabbi, but they didn't find any. They had just gotten back to their room and, all of a sudden, a rabbi walked in on his own. The rabbi proceeded to give the girl a blessing and the parents were so happy. When the rabbi left the room, the nurse came over and apologized saying she gave him the wrong room number. The patient he helped was in room 19. The rabbi smiled, understanding this was all set up by Hashem. There were no mistakes. This was ratzon Hashem. We should never get frustrated if we're given wrong directions or wrong information or we forget something we needed to remember, because it's always m'et Hashem. We may not always see the reason for it, but we can be confident that it came from Hashem, and it was for our best.

Send us a Text Message.In a special episode of Going Under: Anesthesia Answered, Dr. Brian Schmutzler sits down with Board Certified Trauma Anesthesiologist, Dr. Zain Hasan of Cedar Sinai Medical Center in Los Angeles, CA.Dr. Hasan and Dr. Schmutzler discuss the key differences between Trauma and Clinical Anesthesia, share concerns about where their respective area of practice is headed, and open up about travel!Dr. Zain Hasan: https://www.instagram.com/drzainhasan/?hl=enhttps://www.youtube.com/ @drzainhasan  https://www.facebook.com/drzainhasan/https://linktr.ee/doctarzHave a question for Dr. Brian Schmutzler? Please submit them to any of the social media pages below or on his website at https://www.drbrianschmutzler.com/Facebook: https://www.facebook.com/drbrianschmutzlerInstagram: https://www.instagram.com/drbrianschmutzlerTikTok: https://www.tiktok.com/@drbrianschmutzler?lang=enProvider or Medical Student?? Subscribe to his Patreon Page to get exclusive content and access to Medical Blocks:https://www.patreon.com/user?u=89356957&utm_medium=clipboard_copy&utm_source=copyLink&utm_campaign=creatorshare_creator&utm_content=join_linkSupport the ShowSupport the Show.

In this episode of The Brave Enough Show, Dr. Sasha Shillcutt and Dr. Roxana Mehran discuss:  Stress and the physiological risks that is places on our bodies  How to process and remove the daily stress from your body  How to decrease stress, anxiety and poor sleep as risk factors for cardiovascular disease  How to reinvent yourself as a woman physician  Roxana Mehran, MD, is an internationally renowned interventional cardiologist and clinical research expert in the field of cardiovascular disease. She leads a globally-respected academic research center focused on designing and implementing randomized clinical trials, outcomes research projects, and high impact academic publications. She has served as principal investigator for numerous global studies, developed risk scores for bleeding and acute kidney injury, participates regularly in developing clinical guidelines, and has authored >1,500 peer-reviewed articles. Dr. Mehran currently serving as a member of the American College of Cardiology (ACC) Board of Trustees. She is a founder and Chief Scientific Officer of the Cardiovascular Research Foundation (CRF). Dr. Mehran is named Director of the Women Heart and Vascular Center at Mount Sinai Fuster Heart Hospital, spearheading a new program that represents a collaboration across multiple disciplines and designed to meet the unique needs of women's cardiovascular health. She has been included for the past seven consecutive years in Clarivate Analytics:  “Most Cited Researchers – Top 1%” as well as “The World's Most Influential Scientific Minds” (Thomson Reuters).   Dr. Mehran has spoken and attended over 400 presentations, leading the Lancet Commission on Women's Cardiovascular Diseases, which has brought together leading researchers from around the world to identify and bridge gaps in scientific discovery, clinical trials, and care for women with cardiovascular disease.  She was recently named Director of the Women Heart and Vascular Center at Mount Sinai Heart, spearheading a new program that represents a collaboration across multiple disciplines and designed to meet the unique needs of women's cardiovascular health. In 2019, she founded Women as One, dedicated to advancing opportunities for women in medicine.  Dr Mehran is a recipient of several awards including the 2016 American College of Cardiology Bernadine Healy Leadership in CV disease award, the 2018 Nanette Wenger Award from Women's Heart for excellence in research and education, the 2019 Ellis Island Medal of Honor, and the 2019 ESC Silver Medal and Andreas Grüntzig Lecture plaque. In 2022, she received The Terry Ann Krulwich Physician-Scientist Alumni Award at Mount Sinai; the Linda Joy Pollin Heart Health Leadership Award from Cedar Sinai Medical Center; Doctor Honoris Causa Degree at Università della Svizzera Italiana; Women in Cardiology Mentoring Award from American Heart Association; and the Pulse-Setter Champion Award from The Cardiovascular Research Foundation. Lastly, in 2023, Dr. Mehran was awarded the Bahr Award of Excellence by the American College of Cardiology.  Women as One Quote:  “We all need coaches to help us understand that if you are doing your best, whatever you accomplish in life is enough.” - Dr. Mehran  “Every time you are escalating and climbing the ladder as a woman, you have the responsibility to lift others in the process.” - Dr. Mehran  Episode Links:  BE24 Conference Invite Sasha to Speak Season 12 Sponsor - The Coach Firm The Coach Firm is a women-owned business that certifies life coaches in our signature method that focuses on mindset, coaching tools, and emotional regulation. Follow Brave Enough:   WEBSITE | INSTAGRAM | FACEBOOK | TWITTER | LINKEDIN Join The Table, Brave Enough's community. The ONLY professional membership group that meets both the professional and personal needs of high-achieving women.

This educational podcast will provide learners with the opportunity to enhance clinical decision-making skills about the diagnosis and management of Triple-negative breast cancer (TNBC).   Launch Date: November 9, 2023Release Date: November 9, 2023Expiration Date: October 31, 2024   ACTIVITY DESCRIPTION  In this podcast, Drs. William Gradishar, Yuan Yuan and Rita Nanda will review the latest clinical evidence and patient management approaches in TNBC to enhance patient-centered care.FACULTY BIOSDr. William Gradishar is the Chief of Hematology and Oncology in the Department of Medicine at Northwestern University Feinberg School of Medicine in Chicago, Illinois. Dr. Yuan Yuan is the Director of Breast Cancer Research at Cedar-Sinai Medical Center in Los Angeles, California. Dr. Rita Nanda is the Associate Professor of Medicine at the University of Chicago Medicine in Chicago, Illinois. This podcast provides accredited continuing education credits. To qualify for credit, please read all accreditation information at the provided link below prior to listening to this episode.https://www.practicepointcme.com/CMEHome/treatment-progress-in-triple-negative-breast-cancer-improving-disparities-and-outcomes-with-new-approaches-32

This educational podcast will provide learners with the opportunity to enhance clinical decision-making skills about the diagnosis and management of Triple-negative breast cancer (TNBC).   Launch Date: November 9, 2023Release Date: November 9, 2023Expiration Date: October 31, 2024   ACTIVITY DESCRIPTION  In this podcast, Drs. William Gradishar, Yuan Yuan and Rita Nanda will review the latest clinical evidence and patient management approaches in TNBC to enhance patient-centered care.FACULTY BIOSDr. William Gradishar is the Chief of Hematology and Oncology in the Department of Medicine at Northwestern University Feinberg School of Medicine in Chicago, Illinois. Dr. Yuan Yuan is the Director of Breast Cancer Research at Cedar-Sinai Medical Center in Los Angeles, California. Dr. Rita Nanda is the Associate Professor of Medicine at the University of Chicago Medicine in Chicago, Illinois. This podcast provides accredited continuing education credits. To qualify for credit, please read all accreditation information at the provided link below prior to listening to this episode.https://www.practicepointcme.com/CMEHome/treatment-progress-in-triple-negative-breast-cancer-improving-disparities-and-outcomes-with-new-approaches-32

This educational podcast will provide learners with the opportunity to enhance clinical decision-making skills about the diagnosis and management of Triple-negative breast cancer (TNBC).   Launch Date: November 9, 2023Release Date: November 9, 2023Expiration Date: October 31, 2024   ACTIVITY DESCRIPTION  In this podcast, Drs. William Gradishar, Yuan Yuan and Rita Nanda will review the latest clinical evidence and patient management approaches in TNBC to enhance patient-centered care.FACULTY BIOSDr. William Gradishar is the Chief of Hematology and Oncology in the Department of Medicine at Northwestern University Feinberg School of Medicine in Chicago, Illinois. Dr. Yuan Yuan is the Director of Breast Cancer Research at Cedar-Sinai Medical Center in Los Angeles, California. Dr. Rita Nanda is the Associate Professor of Medicine at the University of Chicago Medicine in Chicago, Illinois.  This podcast provides accredited continuing education credits. To qualify for credit, please read all accreditation information at the provided link below prior to listening to this episode. https://www.practicepointcme.com/CMEHome/treatment-progress-in-triple-negative-breast-cancer-improving-disparities-and-outcomes-with-new-approaches-32

Dr. Mark Pimentel is a professor of medicine and gastroenterology at Geffen School of Medicine UCLA and associate professor of medicine at Cedars-Sinai Medical Center, Los Angeles. He is also the executive director of the Medically Associated Science and Technology (MAST) Program at Cedars-Sinai, https://csmast.com. A pioneering expert in irritable bowel syndrome (IBS), Dr. Pimentel's research led to the first-ever blood tests for IBS, https://ibssmart.com. Dr. Pimentel has served as a principal investigator for numerous clinical investigations of IBS and the relationship between gut flora composition and human disease. Dr. Pimentel is a diplomate of the American Board of Internal Medicine, a fellow of the Royal College of Physicians and Surgeons of Canada, and a member of the American Gastroenterological Association, the American College of Gastroenterology, and the American Neurogastroenterology and Motility Society. Pam Emmer is a GI motility patient who has overcome SIBO, small intestinal bacterial overgrowth. She has been a patient advocate, fundraiser and cheer leader for Cedar Sinai Medical Center in LA and the Mast Program for almost 10 years. Pam and I met with Dr. Pimentel at DDW 2023 in Chicago where we spoke about intestinal methane overgrowth, how to use prokinetics, motility and pooping - what's the difference, biomarkers for malabsorption and its relationship to SIBO and upcoming clinical trials for the MAST program.  Find Pam Emmer at: Website: https://lifeaftersibo.com Facebook: https://www.facebook.com/lifeaftersibo Twitter: https://twitter.com/lifeaftersibo Instagram: https://www.instagram.com/lifeafter_sibo Find Jeffrey Roberts and IBS Patient Support Group at: Website: https://www.ibspatient.org Facebook: https://www.facebook.com/ibspatient Twitter: https://twitter.com/ibspatient Instagram: https://www.instagram.com/ibspatient  Music: Werq Kevin MacLeod (incompetech.com) Licensed under Creative Commons: By Attribution 3.0 License http://creativecommons.org/licenses/by/3.0/

Dr. Suzanne Gilberg-Lenz joins me on Passion Struck to discuss why she is passionate about demystifying menopause and teaching women how to flourish as they age, optimize their health, the truth about hormones, deal with hot flashes, and so much more.  Suzanne Gilberg-Lenz, MD, is deeply connected to her work as an OB-GYN. She is an enthusiastic science nerd with a profound respect for holistic health and life. She earned degrees from the Southern California School of Medicine and California College of Ayurveda and completed a residency at Cedar-Sinai Medical Center in Los Angeles. She is the author of the newly released Menopause Bootcamp: Optimize Your Health, Empower Yourself, and Flourish as You Age (Harper Wave October 11, 2022). --►Purchase Menopause Bootcamp: https://amzn.to/3SYDOFV (Amazon) --► Get the resources and all links related to this episode here: Dr. Suzanne Gilberg-Lenz on Demystifying Menopause and Flourishing (passionstruck.com) --► For information about advertisers and promo codes, go to: https://passionstruck.com/deals/  --► Prefer to watch this interview: https://youtu.be/GfbPTGIRiCs  --► Subscribe to Our YouTube Channel Here: https://www.youtube.com/c/JohnRMiles --► Subscribe to the Passion Struck Podcast: https://podcasts.apple.com/us/podcast/passion-struck-with-john-r-miles/id1553279283  Thank you, Amazon Pharmacy, Indeed, and MasterClass, For Your Support Amazon Pharmacy -  Just Click https://amazon.com/passionstruck Indeed - Head to https://www.indeed.com/passionstruck, where you can receive a $75 credit to attract, interview, and hire in one place. MasterClass - Get 15% off at https://www.masterclass.com/passionstruck  Where to Follow Suzanne Gilberg-Lenz Website: https://thedrsuzanne.com/  Instagram: https://www.instagram.com/askdrsuzanne/  Twitter: https://twitter.com/askdrsuzanne  LinkedIn: https://www.linkedin.com/in/askdrsuzanne/  -- John R. Miles is the CEO, and Founder of PASSION STRUCK®, the first-of-its-kind company, focused on impacting real change by teaching people how to live Intentionally. He is on a mission to help people live a no-regrets life that exalts their victories and lets them know they matter in the world. For over two decades, he built his own career applying his research of passion-struck leadership, first becoming a Fortune 50 CIO and then a multi-industry CEO. He is the executive producer and host of the top-ranked Passion Struck Podcast, selected as one of the Top 50 most inspirational podcasts in 2022. Learn more about John: https://johnrmiles.com/  ===== FOLLOW JOHN ON THE SOCIALS ===== * Twitter: https://twitter.com/Milesjohnr * Facebook: https://www.facebook.com/johnrmiles.c0m * Medium: https://medium.com/@JohnRMiles​ * Instagram: https://www.instagram.com/john_r_miles * LinkedIn: https://www.linkedin.com/in/milesjohn/ * Blog: https://johnrmiles.com/blog/ * Instagram: https://www.instagram.com/passion_struck_podcast * Gear: https://www.zazzle.com/store/passion_sruck_podcast  

This week we review an important report on possible racial disparities amongst children on waiting lists for heart transplantation in the US. How did the 2016 changes to the Organ Procurement and Transplantation Network criteria for listing impact outcomes in listed children and unexpectedly widen racial disparities? What impact did these changes have on mortality and outcomes for white vs. non-white children? Why were differences observed? Dr. Mujeeb Zubair of Cedar-Sinai Medical Center in Los Angeles, CA and Dr. Kurt Schumacher of C.S. Mott Children's Hospital in Ann Arbor, MI share their insights this week. We also speak briefly with Dr. John Triedman of Harvard University about the upcoming Pedirhythmx conference coming in September to Boston, MA. DOI: 10.1161/CIRCULATIONAHA.122.060223

This month on Episode 38 of Discover CircRes, host Cynthia St. Hilaire highlights original research articles featured in the Jue 24th, July 8th and July 22nd issues of the journal. This episode also features an interview with the 2022 BCBS Outstanding Early Career Investigator Award finalists, Dr Hisayuki Hashimoto, Dr Matthew DeBerge and Dr Anja Karlstadt.   Article highlights:   Nguyen, et al. miR-223 in Atherosclerosis.   Choi, et al. Mechanism for Piezo1-Mediated Lymphatic Sprouting   Kamtchum-Tatuene, et al.  Plasma Interleukin-6 and High-Risk Carotid Plaques   Li, et al. 3-MST Modulates BCAA Catabolism in HFrEF   Cindy St. Hilaire:        Hi, and welcome to Discover CircRes, the podcast of the American Heart Association's journal, Circulation Research. I'm your host, Dr Cindy St. Hilaire, from the Vascular Medicine Institute at the University of Pittsburgh. And today I'm going to be highlighting articles from our June 24th, July 8th and July 22nd issues of Circulation Research. I'm also going to have a chat with the finalists for the 2022 BCBS Outstanding Early Career Investigator Award, Dr Hisayuki Hashimoto, Dr Matthew DeBerge and Dr Anja Karlstadt.   Cindy St. Hilaire:        The first article I want to share is from our June 24th issue and is titled, miR-223 Exerts Translational Control of Proatherogenic Genes in Macrophages. The first authors are My-Anh Nguyen and Huy-Dung Hoang, and the corresponding author is Katey Rayner and they're from the University of Ottawa. A combination of cholesterol accumulation in the blood vessels and subsequent chronic inflammation that's derived from this accumulation drive the progression of atherosclerosis. Unfortunately, current standard medications tackle just one of these factors, the cholesterol. And this might explain why many patients on such drugs still have vascular plaques. In considering treatments that work on both aspects of the disease, meaning lipid accumulation and inflammation, this group investigated the micro RNA 223 or miR-223, which is a small regulatory RNA that has been shown to suppress expression of genes involved in both cholesterol uptake and inflammatory pathways in both liver and immune cells.   Cindy St. Hilaire:        The team showed that mouse macrophages deficient in miR-223, exhibited increased expression of pro-inflammatory cytokines and reduced cholesterol efflux compared with control cells. Overexpression of miR-223 had the opposite effects. Furthermore, atherosclerosis prone mice, whose hematopoietic cells lacked miR-223, had worse atherosclerosis with larger plaques and higher levels of pro-inflammatory cytokines than to control animals with normal levels of miR-223. These findings highlight miR-223's dual prompt, antiatherogenic action, which could be leveraged for future therapies.   Cindy St. Hilaire:        The second article I want to share is from our July 8th issue of Circulation Research and is titled, Piezo1-Regulated Mechanotransduction Controls Flow-Activated Lymph Expansion. The first author is Dongwon Choi and the corresponding author is Young-Kwon Hong, and they're from UCLA.   As well as being super highways for immune cells, lymph vessels are drainage channels that help maintain fluid homeostasis in the tissues. This network of branching tubes grows as fluids begin to flow in the developing embryo. This fluid flow induces calcium influx into the lymphatic endothelial cells, which in turn promotes proliferation and migration of these cells, leading to the sprouting of lymph tubules. But how do LECs, the lymphatic endothelial cells, detect fluid flow in the first place? Piezo1 is a flow and mechanosensing protein known for its role in blood vessel development and certain mutations in Piezo1 cause abnormal lymphatic growth in humans.   Cindy St. Hilaire:        This script found that Piezo1 is expressed in the embryonic mouse LECs and that the suppression of Piezo1 inhibits both flow activated calcium entry via the channel ORAI1, as well as downstream target gene activation. Overexpression of Piezo1, by contrast, induced the target genes. The team went on to show that mice lacking either Piezo1 or ORAI1 had lymphatic sprouting defects and that pharmacological activation of Piezo1 in mice enhanced lymphogenesis and prevented edema after tail surgery. Together, the results confirmed Piezo1's role in flow dependent lymphatic growth and suggest it might be a target for treating lymphedema.   Cindy St. Hilaire:        The third article I want to share is also from our July 8th issue and is titled, Interleukin-6 Predicts Carotid Plaque Severity, Vulnerability and Progression. The first and corresponding author of this study is Joseph Kamtchum-Tatuene from University of Alberta.   Excessive plasma cholesterol and systemic inflammation are contributing factors in atherosclerosis. While traditional remedies have been aimed at lowering patient's lipid levels, drugs that tackle inflammation are now under investigation, including those that suppress Interleukin-6, which is an inflammatory cytokine implicated in the disease. Focusing on carotid artery disease, this group conducted a prospective study to determine whether IL-6 levels correlated with disease severity. 4,334 individuals were enrolled in the cardiovascular health study cohort. They had their blood drawn and ultrasounds taken at the start of the study and five years later. This group found IL-6 was robustly correlated with and predicted plaque severity independent of other cardiovascular risk factors. This study also determined that an IL-6 blood plasma level of 2.0 picograms/mls, identified individuals with the highest likelihood of plaque, vulnerability and progression. This threshold value could be used to select patients who might benefit from novel IL-6 lowering medications.   Cindy St. Hilaire:        The last article I want to share is from our July 22nd issue of Circulation Research and is titled, Mitochondrial H2S Regulates BCAA Catabolism in Heart Failure. The first author is Zhen Li, and the corresponding author is David Lefer from Louisiana State University. Hydrogen sulfide, or H2S, is a compound that exerts mitochondrial specific actions that include the preservation of oxidative phosphorylation, mitochondrial biogenesis and ATP synthesis, as well as inhibiting cell death. 3-mercaptopyruvate sulfurtransferase, or 3-MST, is a mitochondrial H2S producing enzyme, whose functions in cardiovascular disease are not fully understood.   Cindy St. Hilaire:        This group investigated the global effects of 3-MST deficiency in the setting of pressure overload induced heart failure. They found that 3-MST was significantly reduced in the myocardium of patients with heart failure, compared with non failing controls. 3-MST knockout mice exhibited increased accumulation of branch chain amino acids in the myocardium, which was associated with reduced myocardial respiration and ATP synthesis, exacerbated cardiac and vascular dysfunction, and worsened exercise performance, following transverse aortic constriction. Restoring myocardial branched-chain amino acid catabolism, or administration of a potent H2S donor, ameliorated the detrimental effects of 3-MST deficiency and heart failure with reduced injection fraction. These data suggest that 3-MST derived mitochondrial H2S, may play a regulatory role in branch chain amino acid catabolism, and mediate critical cardiovascular protection in heart failure.   Cindy St. Hilaire:        Today, I'm really excited to have our guests, who are the finalists for the BCVS Outstanding Early Career Investigator Awards. Welcome everyone.   Hisayuki Hashimoto:   Thank you.   Anja Karlstaedt:          Hi.   Hisayuki Hashimoto:   Hi.   Matthew DeBerge:      Hello. Thank you.   Cindy St. Hilaire:        So the finalists who are with me today are Dr Hisayuki Hashimoto from Keio University School of Medicine in Tokyo, Japan, Dr Matthew Deberge from Northwestern University in Chicago and Dr Anja Karlstaedt from Cedar Sinai Medical Center in LA. Thank you again. Congratulations. And I'm really excited to talk about your science.   Hisayuki Hashimoto:   Thank you. Yes. Thanks, first of all for this opportunity to join this really exciting group and to talk about myself and ourselves. I am Hisayuki Hashimoto, I'm from Tokyo, Japan. I actually learned my English... I went to an American school in a country called Zaire in Africa and also Paris, France because my father was a diplomat and I learned English there. After coming back to Japan, I went to medical school. During my first year of rotation, I was really interested in cardiology, so I decided to take a specialized course for cardiology. Then I got interested in basic science, so I took a PhD course, and that's what brought me to this cardiology cardiovascular research field.   Matthew DeBerge:      So I'm currently a research assistant professor at Northwestern University. I'm actually from the Chicagoland area, so I'm really excited to welcome you all to my hometown for the BCVS meeting.   Cindy St. Hilaire:        Oh, that's right. And AHA is also there too this year. So you'll see a lot of everybody.   Matthew DeBerge:      I guess I get the home field advantage, so to speak. So, I grew up here, I did my undergrad here, and then went out in the east coast, Dartmouth College in New Hampshire for my PhD training. And actually, I was a viral immunologist by training, so I did T cells. When I was looking for a postdoctoral position, I was looking for a little bit of something different and came across Dr Edward Thorpe's lab at Northwestern university, where the interest and the focus is macrophages in tissue repair after MI. So, got into the macrophages in the heart and have really enjoyed the studies here and have arisen as a research assistant professor now within the Thorpe lab. Now we're looking to transition my own independent trajectory. Kind of now looking beyond just the heart and focusing how cardiovascular disease affects other organs, including the brain. That's kind of where I'm starting to go now. Next is looking at the cardiovascular crosstalk with brain and how this influences neuroinflammation.   Anja Karlstaedt:          I am like Hisayuki, I'm also a medical doctor. I did my medical training and my PhD in Berlin at the Charité University Medicine in Berlin, which is a medical faculty from Humboldt University and Freie University. II got really interested in mathematical modeling of complex biological systems. And so I started doing my PhD around cardiac metabolism and that was a purely core and computationally based PhD. And while I was doing this, I got really hooked into metabolism. I wanted to do my own experiments to further advance the model, but also to study more in crosstalk cardiac metabolism. I joined Dr Heinrich Taegteyer lab at the University of Texas in the Texas Medical Center, and stayed there for a couple of years. And while I was discovering some of the very first interactions between leukemia cells and the heart, I decided I cannot stop. I cannot go back just after a year. I need to continue this project and need to get funding. And so after an AHA fellowship and NIHK99, I am now here at Cedars Sinai, an assistant professor in cardiology and also with a cross appointment at the cancer center and basically living the dream of doing translational research and working in cardio-oncology.   Cindy St. Hilaire:        Great. So, Dr Hashimoto, the title of your submission is, Cardiac Reprogramming Inducer ZNF281 is Indispensable for Heart Development by Interacting with Key Cardiac Transcriptional Factors. This is obviously focused on reprogramming, but why do we care about cardiac reprogramming and what exactly did you find about this inducer ZNF281?   Hisayuki Hashimoto:   Thank you for the question. So, I mean, as I said, I'm a cardiologist and I was always interested in working heart regeneration. At first, I was working with pluripotent stem cells derived cardiomyocyte, but then I changed my field during my postdoc into directly programming by making cardiomyocyte-like cells from fiberblast. But after working in that field, I kind of found that it was a very interesting field that we do artificially make a cardiomyocyte-like cell. But when I dissected the enhanced landscape, epigenetic analysis showed that there are very strong commonalities between cardiac reprogramming and heart development. So I thought that, hey, maybe we can use this as a tool to discover new networks of heart development. And the strength is that cardiac reprogramming in vitro assay hardly opens in vivo assay, so it's really time consuming. But using dark programming, we can save a lot of time and money to study the cardiac transitional networks. And we found this DNF281 from an unbiased screen, out of 1000 human open reading frames. And we found that this gene was a very strong cardiac reprogramming inducer, but there was no study reporting about any functioning heart development. We decided to study this gene in heart development, and we found out that it is an essential gene in heart development and we were kind of able to discover a new network in heart development.   Cindy St. Hilaire:        And you actually used, I think it was three different CRE drivers? Was that correct to study?   Hisayuki Hashimoto:   Ah, yes. Yeah.   Cindy St. Hilaire:        How did you pick those different drivers and what, I guess, cell population or progenitor cell population did those drivers target?   Hisayuki Hashimoto:   So I decided to use a mesodermal Cre-driver, which is a Mesp1Cre and a cardiac precursor Cre-driver, which is the Nkx2-5 Cre and the cardiomyocyte Cre, which is the Myh6-Cre. So three differentiation stages during heart development, and we found out that actually, DNF281 is an essential factor during mesodermal to cardiac precursor differentiation state. We're still trying to dig into the molecular mechanism, but at that stage, if the DNF281 is not there, we are not able to make up the heart.   Cindy St. Hilaire:        That is so interesting. Did you look at any of the strains that survived anyway? Did you look at any phenotypes that might present in adulthood? Is there anything where the various strains might have survived, but then there's a kind of longer-term disease implicating phenotype that's observed.   Hisayuki Hashimoto:   Well, thank you for the question. Actually, the mesodermal Cre-driver knocking out the DNF281 in that stage is embryonic lethal, and it does make different congenital heart disease. And they cannot survive until after embryonic day 14.5. The later stage Nkx2-5 Cre and Myh6-Cre, interestingly, they do survive after birth. And then in adult stage, I did also look into the tissues, but the heart is functioning normally. I haven't stressed them, but they develop and they're alive after one year. It looks like there's really no like phenotype at like the homeostatic status.   Cindy St. Hilaire:        Interesting. So it's kind of like, once they get over that developmental hump, they're okay.   Hisayuki Hashimoto:   Exactly. That might also give us an answer. What kind of network is important for cardiac reprogramming?   Cindy St. Hilaire:        So what are you going to do next?   Hisayuki Hashimoto:   Thank you. I'm actually trying to dig into the transitional network of what kind of cardiac transitional network the ZNF281 is interacting with, so that maybe I can find a new answer to any etiology of congenital heart disease, because even from a single gene, different mutation, different variants arise different phenotypes in congenital heart disease. Maybe if I find a new interaction with any key cardiac transitional factors, maybe I could find a new etiology of congenital heart disease phenotype.   Cindy St. Hilaire:        That would be wonderful. Well, best of luck with that. Congratulations on an excellent study. Hisayuki Hashimoto:   Thank you.   Cindy St. Hilaire:        Dr DeBerge, your study was titled, Unbiased Discovery of Allograft Inflammatory Factor-1 as a New and Critical Immuno Metabolic Regulatory Node During Cardiac Injury. Congrats on this very cool study. You were really kind of focused on macrophages in myocardial infarction. And macrophages, they're a Jeckel Hyde kind of cell, right? They're good. They're bad. They can be both, almost at the same time, sometimes it seems like. So why were you interested in macrophages particularly in myocardial infarction, and what did you discover about this allograft inflammatory factor-1, or AIF1 protein?   Matthew DeBerge:      Thank you. That's the great question. You really kind of alluded to why we're interested in macrophages in the heart after tissue repair. I mean, they really are the central mediators at both pro-inflammatory and anti-inflammatory responses after myocardial infarction. Decades of research before this have shown that inflammation has increased acutely after MI and has also increased in heart failure patients, which really has led to the development of clinical efforts to target inflammatory mediators after MI. Now, unfortunately, the results to target inflammation after MI, thus far, have been modest or disappointing, I guess, at worst, in the respect that broadly targeting macrophage function, again, hasn't achieved results. Again, because these cells have both pro and anti-inflammatory functions and targeting specific mediators has been somewhat effective, but really hasn't achieved the results we want to see.   Matthew DeBerge:      I think what we've learned is that the key, I guess, the targeting macrophage after MI, is really to target their specific function. And this led us to sort of pursue novel proteins that are mediating macrophage factor function after MI. To accomplish this, we similarly performed an unbiased screen collecting peri-infarct tissue from a patient that was undergoing heart transplantation for end stage heart failure and had suffered an MI years previously. And this led to the discovery of allograft inflammatory factor-1, or AIF1, specifically within cardiac macrophages compared to other cardiac cell clusters from our specimen. And following up with this with post-mortem specimens after acute MI to show that AIF1 was specifically increased in macrophages after MI and then subsequently then testing causality with both murine model of permanent inclusion MI, as well as in vitro studies using bone marrow drive macrophages to dig deeper mechanistically, we found that AIF1 was crucial in regulating inflammatory programing macrophages, which ultimately culminated in worse in cardiac repair after MI.   Cindy St. Hilaire:        That's really interesting. And I love how you start with the human and then figure out what the heck it's doing in the human. And one of the things you ended up doing in the mouse was knocking out this protein AIF1, specifically in macrophage cells or cells that make the macrophage lineage. But is this factor in other cells? I was reading, it can be intracellular, it can be secreted. Are there perhaps other things that are also going on outside of the macrophage?   Matthew DeBerge:      It's a great question. First, I guess in terms of specificity, within the hematopoietic compartment, previous studies, as well as publicly available databases, have shown that AIF1 is really predominantly expressed within macrophages. We were able to leverage bone marrow chimera mice to isolate this defect to the deficiency to macrophages. But you do bring up a great point that other studies have shown that AIF1 may be expressed in other radio-resistant cell populations. I mean, such as cardiomyocytes or other treatable cells within the heart. We can't completely rule out a role for AIF1 and other cell populations. I can tell you that we did do the whole body knockout complementary to our bone marrow hematopoetic deficient knockouts, and saw that deficiency of AIF1 within the whole animal, recapitulate the effects we saw within the AIF1 deficiency within hematopoietic department.   Matthew DeBerge:      It was encouraging to us that, again, the overall role of AIF1 is pro-inflammatory after MI.   Cindy St. Hilaire:        I mean, I know it's early days, but is there a hint of any translational potential of these findings or of this protein?   Matthew DeBerge:      Yeah, I think so. To answer your question, we were fortunate enough to be able to partner with Ionis that develops these anti-sensible nucleotides so that we could specifically target AIF1 after the acute phase during MI. We saw that utilizing these anti-sensible nucleotides to deplete AIF1, again, within the whole mouse, that we were able to reduce inflammation, reduce in heart size and preserve stock function. I think there really is, hopefully a therapeutic opportunity here. And again, with it being, perhaps macrophage specific is, even much more important as we think about targeting the specific function of these cells within the heart.   Cindy St. Hilaire:        Very cool stuff. Dr Karlstaedt, the title of your submission is, ATP Dependent Citrate Lyase Drives Metabolic Remodeling in the Heart During Cancer. So this I found was really interesting because you were talking about, the two major killers in the world, right? Cardiovascular disease and cancer, and you're just going to tackle both of them, which I love. So obviously this is built on a lot of prior observations about the effects of cancer on cardiac metabolic remodeling. Can you maybe just tell us a little bit about what is that link that was there and what was known before you started?   Anja Karlstaedt:          Yeah. Happy to take that question. I think it's a very important one and I'm not sure if I will have a comprehensive answer to this, because like I mentioned at the beginning, cardio-oncology is a very new field. And the reason why we are starting to be more aware of cancer patients and their specific cardiovascular problems is because the cancer field has done such a great job of developing all these new therapeutics. And we have far more options of treating patients with various different types of cancers in particular, also leukemias, but also solid tumors. And what has that led to is an understanding that patients survive the tumors, but then 10, 20 years later, are dying of cardiovascular diseases. Those are particular cardiomyopathies and congestive heart failure patients. What we are trying, or what my lab is trying to do, is understanding what is driving this remodeling. And is there a way that we can develop therapies that can basically, at the beginning of the therapy, protect the heart so that this remodeling does not happen, or it is not as severe.   Anja Karlstaedt:          Also, identifying patients that are at risk, because not every tumor is created equally and tumors are very heterogeneous, even within the same group. To get to your question, what we found is, in collaboration actually with a group at Baylor College of Medicine, Peggy Goodell's group, who is primarily working on myeloid malignancies, is that certain types of leukemias are associated with cardiomyopathies. And so when they were focusing on the understanding drivers of leukemia, they noticed that the hearts of these animals in their murine models are enlarged on and actually developing cardiomyopathies. And I joined this project just very early on during my postdoc, which was very fortunate and I feel very lucky of having met them. What my lab is now studying here at Cedars is how basically those physiological stress and mutations coming from the tumors are leading to metabolic dysregulation in the heart and then eventually disease.   Anja Karlstaedt:          And we really think that metabolism is at the center of those disease progressions and also, because it's at the center, it should be part of the solution. We can use it as a way to identify patients that are at risk, but also potentially develop new therapies. And what was really striking for us is that when we knock down ACLY that in a willdtype heart where the mouse doesn't have any tumor disease, ACLY actually is critically important for energy substrate metabolism, which seems counterintuitive, because it's far away from the mitochondria, it's not part of directly ADP provision. It's not part of the Kreb cycle. But what we found is that when we knock it out using a CRISPR-Cas9 model, it leads to cardiomyopathy and critically disrupts energy substrate metabolism. And that is not necessarily the case when the mouse has leukemia or has a colorectal cancer, which upregulated in the beginning, this enzyme expression. And so we have now developed models that show us that this could be potentially also therapeutic target to disrupt the adverse remodeling by the tumor.   Cindy St. Hilaire:        That is so interesting. So one of the things I was thinking about too is we know that, I mean, your study is showing that, the tumor itself is causing cardiac remodeling, but we also know therapies, right? Radiation, chemotherapy, probably some immune modulatory compounds. Those probably do similar, maybe not exactly similar, but they also cause, adverse cardiac remodeling. Do you have any insights as to what is same and what is different between tumor driven and therapy driven adverse remodeling?   Anja Karlstaedt:          So we do not know a lot yet. It's still an open question about all the different types of chemotherapeutics, how they are leading to cardio toxicities. But what we know, at least from the classic anti-cyclic treatments, is right now at the core, the knowledge is that this is primarily disrupting cardiac mitochondrial function. And through that again, impairing energy provision and the interaction, again, with the immune system is fairly unknown, but we know through studies from Kathryn Moore and some very interesting work by Rimson is that myocardial infarction itself can lead to an increase in risk for tumor progression. And what they have shown as independent of each other, is that the activation of the immune system in itself can lead to an acceleration of both diseases, both the cardiac remodeling, and then also the tumor disease. We don't fully understand which drivers are involved, but we do know that a lot of the cardiomyopathies on cardiotoxicities that are chemotherapeutically driven, all have also metabolic component.   Cindy St. Hilaire:        Nice. Thank you. When I prepare for these interviews, I obviously read the abstracts for the papers, but I found myself also Googling other things after I read each of your abstracts. It was a rabbit hole of science, which was really exciting.                               I now want to transition to kind of a career angle. You all are obviously quite successful, scientifically, at the bench, right? But now you are pivoting to a kind of completely opposite slash new job, right? That of, independent researcher. I would love to hear from each of you, if there was any interesting challenge that you kind of overcame that you grew from, or if there was any bit of advice that you wish you knew ahead of time or anything like that, that some of our trainee listeners and actually frankly, faculty who can pass that information onto their trainees, can benefit from.   Anja Karlstaedt:          I think the biggest challenge for me in transitioning was actually the pandemic. Because I don't know how it was for Hisa and Matt, but trying to establish a lab, but also applying for faculty position during a major global pandemic, is challenging is not quite something that I expected that would happen. And so I think saying that and looking more conceptually and philosophically at this as, you can prepare as much as you want, but then when life just kicks in and things happen, they do happen. And I think the best is to prepare as much as you can. And then simply go with the flow. Sometimes one of my mentors, Dave Nikon, mentioned that to me when I was applying for faculty positions, it's sometimes good to just go with the flow. And as a metabolism person, I absolutely agree. And there are some things that you can do as a junior investigator.   Anja Karlstaedt:          We need to have a good network. So just very important to have good mentors. I was blessed with have those mentors, Peggy Goodell's one of them, Heinrich Taegtmeyer was another. And now with this study that we are publishing, Jim Martin and Dave Nikon were incredible. Without them, this study wouldn't have been possible and I would not be here at Cedars.   Anja Karlstaedt:          You need to reach out to other people because those mentors have the experience. They have been through some of this before. Even if they have never had a major event, like COVID-19 in their life before, because none of us had before, they had other experiences and you can rely on them and they set you then up for overcoming these challenges. And the other thing I would say, is put yourself out there, go and talk to as many people as possible or set conferences, present a poster, not only talks. Don't be disappointed if you don't get a talk, posters are really great to build this network and find other people that you probably wouldn't have encountered and apply for funding. Just again, put yourself out there and try to get the funding for your research. Even if it's small foundations, it builds up over time and it is a good practice to then write those more competitive grants.     Cindy St. Hilaire:        Dr Hashimoto, would you like to go next?   Hisayuki Hashimoto:   Just my advice is that, could be like a culture of difference, but in east Asia, like in Japan, we were taught to, do not disturb people, don't interrupt people and help people. But I realized that I wasn't really good at asking for help. After I am still not like fully independent, but I do have my own group and I have to do grant writing. I still work at the bench and then have to teach grad students, doing everything myself. I just realized it's just impossible. I didn't have time. I need like 48 hours a day. Otherwise, you won't finish it. I just realized that I wasn't really good at asking for help. So my advice would be, don't hesitate to ask for help. It's not a shame. You can't do everything by just yourself. I think, even from the postdoc, even from grad school, I think, ask for help and then get used to that. And then of course, help others. And that is the way I think to probably not get overwhelmed and not stress yourself. Science should be something fun. And if you don't ask for help and if you don't help someone, I think you are losing the chance of getting some fun part from the science.   Cindy St. Hilaire:        That's great advice. I really like that, especially because I find at least, I started my lab seven years ago now. And I remember the first couple months/year, it was extremely hard to let go, right? Like I taught my new people how to do the primary cell culture we needed, but I was terrified of them doing it wrong or wasting money or making too many mistakes. But you realize, you got to learn to trust people. Like you said, you got to learn to ask for help. And sometimes that help is letting them do it. And you doing, you're being paid now to write grants and papers. That's a big brain, you're not paid to do the smaller things. That's really great advice. I like that. Thank you. Dr DeBerge, how about you?   Matthew DeBerge:      So I guess towards a bit of life advice, I think two obvious things is one, be kind, science is hard enough as it is. So I think we should try to lift each other up and not knock each other down. And along those lines as the others have alluded to as well, one of the mantras we sort of adapted on the lab, is a rising tide raises all ships, this idea that we can work together to elevate each other's science and really, again, collaborate.   Towards the career side of things I'll just touch on, because I guess one thing I'll add, there's more than one path, I guess, to achieving your goals. I've been fortunate enough to have an NIH post-doctoral fellowship and had an AHA career development award, but I'm not a K99 recipient. Oftentimes, I think this is the golden ticket to getting the faculty job, so I'm trying to, I guess, buck trend, I just submitted an RO1. So fingers crossed that leads to some opportunity.   Even beyond academia, I'm not certain how much everyone here is involved in science Twitter, it's really become a thing over the last couple years, but I think, kind of the elephant in the room is that academia, it's really hard on the trainees nowadays to have a living wage, to go through this. I mean, I'm really excited to see my, fellow finalists here are starting their own groups and stuff, but for many, that's not the reality for many, it's just not financially feasible. So I think, kind of keeping in mind that there's many, many alternative careers, whether it's industry, whether it's consulting, science writing, etcetera, going back to what Dr Hash says, find what you love and really pursue that with passion.   Cindy St. Hilaire:        I think it's something only, I don't know, five to 10% of people go into or rather stay in academia. And that means, 90 to 95% of our trainees, we need to prepare them for other opportunities, which I think is exciting, because it means it can expand our network for those of us in academia.   Anja Karlstaedt:          I think right now it's even worse because it's about 2% of old postdocs that are actually staying and becoming independent researchers, independent or tenure track or research track. And I think I second, as what Matt said, because I play cello. I do music as a hobby and people always ask me if I'm a musician. And at the beginning I felt like, no, of course not. I'm not like Yoyo Ma. I'm just playing, it's a hobby. And then I, that got me thinking. I was like, no, of course you are because there's so many different types. And what we need to understand is that scientists, like you are always a scientist. It doesn't matter if you are working at Pfizer or if you are working at a small undergrad institution and you're teaching those next generation scientists, you are still scientist and we all need those different types of scientists because otherwise, if everybody is just a soloist, you are never going to listen to symphony. You need those different people and what we need to normalize beyond having those different career paths, is also that people are staying in academia and becoming those really incredible resources for the institutions and labs, quite frankly, of being able to retain those technologies and techniques within an institution. And I think that's something to also look forward to, that even if you're not the PI necessarily, you're the one who is driving those projects. And I hope to pass this on at some point also to my trainees that they can be a scientist, even if they're not running a lab and they become an Institute director and that's also critically important.   Cindy St. Hilaire:        There's lots of ways to do science. Thank you all so much for joining me today. Either waking up at 5:00 AM or staying up past midnight, I think it is now in Japan or close to it. So Matt and I kind of made it out okay. It's like 8:00 or 9:00 AM.   Matthew DeBerge:      Thank you.   Hisayuki Hashimoto:   My apologies for this time zone difference.   Cindy St. Hilaire:        I'm very glad to make it work. Congratulations to all of you, your presentations. I forget which day of the week they are on at BCVS, but we are looking forward to the oral presentations of these and congratulations to all of you. You are amazing scientists and I know I'm really looking forward to seeing your future work so best of luck.   Matthew DeBerge:      Thank you.   Hisayuki Hashimoto:   Thank you.   Anja Karlstaedt:          Thank you so much.   Cindy St. Hilaire:        That's it for the highlights from the June 24th, July 8th and July 22nd issues of Circulation Research. Thank you for listening. Please check out the CircRes Facebook page and follow us on Twitter and Instagram with the handle at CircRes and hashtag Discover CircRes. Thank you to our guests. The BCVS Outstanding Early Career Investigator Award Finalists, Dr Hisayuki Hashimoto, Dr Matthew DeBerge and Dr Anja Karlstaedt. This podcast is produced by Ashara Ratnayaka, edited by Melissa Stoner and supported by the editorial team of Circulation Research. Some of the copy text for the highlighted articles is provided by Ruth Williams. I'm your host, Dr Cindy St. Hilaire. And this is Discover CircRes, you're on the go source for the most exciting discoveries in basic cardiovascular research. This program is copyright of the American Heart Association, 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more information visit ahajournals.org.  

With graduate degrees in both business and medicine, Allen has maintained dual exposure throughout his career. Allen has dual surgical board certifications in General Surgery and Colon & Rectal Surgery. He has extensive management experience, having been acting VP at a multi-billion dollar real estate company, a consultant for an international risk-management consulting firm, and has worked at Deloitte. He teaching faculty in the department of surgery at Cedar Sinai Medical Center, and has published books, journals, and textbook chapters, and has spoken at several international conferences. Caring for his community in multiple ways - Allen serves on numerous boards, while simultaneously curing cancer as a surgeon. His breadth of experience in health care and management provides him a uniquely well-rounded perspective on how to tackle the uber-complex field of insurance. Allen is an amateur tri-athlete, residing in Los Angeles with his wife and four children. In this episode Carl White and Dr. Allen Kamrava discuss:What's making it so hard to thrive as a private practice (hint: it's reimbursement)A few “must haves” to succeedBuilding a big referral network fast Want to be a guest on PracticeCare?Have an experience with a business issue you think others will benefit from? Come on PracticeCare and tell the world! Here's where you can get the process started: https://marketvisorygroup.com/practicecare-podcast/ Affiliate PromotionWe're fans of Constant Contact for email campaigns, newsletters, and emails. We use it with our clients. What we like: Very easy to useVery flexibleEasy to find supportHIPAA compliant Get 30% off for the 1st 3 months if you sign up using our partner link. We do receive a commission when you use our link. Constant Contact offers additional prepayment discounts you can choose: 10% off per month for your first 6 months, or 15% off for the year. If you prepay, your discount stacks on top of the 30% discount for the 1st 3 months. Connect with Dr. Allen Kamravahttps://www.linkedin.com/in/allenkamrava/https://drkamrava.com/ Connect with Carl WhiteWebsite: http://www.marketvisorygroup.comEmail:  whitec@marketvisorygroup.comFacebook:  https://www.facebook.com/marketvisorygroupYouTube: https://www.youtube.com/channel/UCD9BLCu_i2ezBj1ktUHVmigLinkedIn: http://www.linkedin.com/in/healthcaremktg

Dr Suzanne Gilberg-Lenz is a self-professed hard-core science nerd with a deep respect for the holistic approach to health and life. She boasts degrees from Southern California School of Medicine and California College of Ayurveda, and she also completed a residency at Cedar-Sinai Medical Center in Los Angeles. She credits her being able to integrate ancient healing traditions into her practice and that has allowed her to go deeper into the study of health and healing. As more natural solutions, medicines, and technologies emerge in the global marketplace, Dr. Suzanne finds herself referring back to Ayurveda, which she calls the original lifestyle medicine. Listen how this incredible doctor chooses herself -- and her mind, body and spirit. This episode is sponsored by TENA. #MyEvolvingBody Become a member of our Patreon page: patreon.com/chooseyounow to have access to exclusive content and send us your questions and comments at chooseyounowpodcast@gmail.com. For more about my Nutrition services and resources, visit me at PlantBasedDietitian.com

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This month on Episode 31 of Discover CircRes, host Cynthia St. Hilaire highlights two original research articles featured in the December 3 issue of Circulation Research. This episode also features a conversation with Drs Xavier Revelo, and Jop van Berlo from the University of Minnesota about their study, Cardiac Resident Macrophages Prevent Fibrosis and Stimulate Angiogenesis.   Article highlights:   Tong, et al. Alternative Mitophagy Protects Obesity Hearts Soetkamp, et al. Myofilament Phosphorylation in CDC Treated HFpEF   Cindy St. Hilaire:        Hi, and welcome to Discover CircRes, the podcast of the American Heart Association's journal, Circulation Research. I'm your host, Dr Cindy St. Hillaire from the Vascular Medicine Institute at the University of Pittsburgh. And today I'll be highlighting two articles presented in our December 3rd issue of CircRes, and I'll also speak with doctors, Xavier Revelo, and Jop van Berlo from University of Minnesota about their study, Cardiac Resident Macrophages Prevent Fibrosis and Stimulate Angiogenesis.   Cindy St. Hilaire:        The first article I want to share is titled, Alternative Mitophagy Protects the Heart Against Obesity-Associated Cardiomyopathy. The first doctor is Ming Ming Tong, and the corresponding author is Jun Sadoshima from Rutgers University. People with obesity or diabetes have an increased risk of developing cardiomyopathy, a condition which can eventually lead to heart failure. One of the major pathological features of obesity-related cardiomyopathy at the cellular level is a decrease in mitochondrial function. This decrease in mitochondrial function is likely due to a decrease in the canonical mitophagy pathway, which is a process by which dysfunctional mitochondria are degraded. However, a new process termed alternative mitophagy was recently discovered. When mice were fed a high fat diet for 24 weeks after only eight weeks, canonical mitophagy ceased. However alternative mitophagy steadily increased over the 24 weeks. Alternative mitophagy is regulated via the protein ULK1 and Rab9. The team went on to show that suppressing alternative mitophagy by knocking out ULK1, or expressing a loss of function, Rab9 mutant exacerbated the high fat diet induced cardiac dysfunction. Over expression of Rab9 in mouse hearts increased the alternative mitophagy pathway and protected the animals from cardiac dysfunction. These results suggest that pharmacological boosting of this ULK1 Rab9 mediated alternative mitophagy pathway might be a treatment strategy for preventing obesity related cardiomyopathy.   Cindy St. Hilaire:        The second article I want to share is titled Myofilament Phosphorylation in Stem Cell Treated Diastolic Heart Failure. The first doctor is Daniel Soetkamp and the corresponding author is Jenny Van Eyk from Cedar Sinai Medical Center. Weakness, fatigue and troubled breathing are among the symptoms experienced by someone suffering from heart failure with preserved ejection fraction, which is frequently called HFpEF. The pathology of the condition includes hypertrophy, fibrosis and stiffening of the heart and hyperphosphorylation of the cell sarcomere proteins. Because this hyperphosphorylation is a key contributor to HFpEF pathology, and because cardio sphere derived stem cells or CDCs have shown promise as a potential HFpEF treatment, this group investigated whether CDC treatment reduces phosphorylation levels of the sarcomere proteins in the heart. They found that administering CDCs to rats with HFpEF decreased the associated protein hyperphosphorylation, compared with that seen in untreated animals. Bioinformatic analysis revealed that protein kinase C or PKC is a prime suspect behind the phosphorylation. The authors suggest that CDCs alleviate HFpEF in part by reversing PKC-induced phosphorylation, and that PKC inhibition may be a desirable alternative treatment strategy, especially as it avoids regulatory issues associated with cell-based therapies.   Cindy St. Hilaire:        Today, I have Dr Xavier Revelo and Dr Jop van Berlo from the University of Minnesota and they're with me to discuss their study, Cardiac Resident Macrophages Prevent Fibrosis and Stimulates Angiogenesis. And this article is in our December 3rd issue of Circ Res. So, thank you both so much for joining me today.   Jop van Berlo:             Thanks for having us.   Cindy St. Hilaire:        Absolutely. So, your study is investigating the contribution of resident and monocyte drug of macrophages in cardiac remodeling, specifically in hypertrophy remodeling. So can you just introduce the topic of cardiac hypertrophy in humans, why that's not great to have, and then maybe tell us a little bit about what is known or what was known about the role of inflammatory cells in that hypertrophic remodeling.   Jop van Berlo:             Yeah, so absolutely. Cardiac hypertrophy is not a disease in and of itself in humans, but it is often a consequence of pathologies that can happen in patients, such as high blood pressure, hypertension or aortic valve stenosis, or if you've had a myocardial infarction the remaining myocardial may also become hypertrophic. We know that cardiac hypertrophy has downsides to it. People can develop sudden cardiac death when they have hypertrophic heart disease. We notice from population studies like the Framingham Heart Study and other studies, but it also increases the chance of developing heart failure later on. So even though cardiac hypertrophy by itself is not a disease, it is contributing to the cardiac pathology that can develop in patients and that can contribute to the development of heart failure.   Cindy St. Hilaire:        Great. So, what's the base level of knowledge of what is known regarding inflammatory cells in cardiac hypertrophy or cardiac hypertrophic remodeling?   Xavier Revelo:             So previous forecast focused on the role of infiltrating cells, specifically monocyte-derived macrophages, and generally these cells are pro-inflammatory and they aggravate the progression of heart failure. With Jop, we focus on, and what we think is exciting is the role of cardiac resident macrophages. And so, in our experiments, we decided to look at what's the role of these cardiac meta macrophages during pressure overload.   Cindy St. Hilaire:        That's a perfect segue to my next question, which is you obviously modeled this in mice, you used mice as your model and the method that you used to induce this hypertrophy is a technique called Transverse Aortic Constriction. So how does that actually work in a mouse and are there certain pros and cons to using that as a model for cardiac hypertrophy and, does it really recapitulate well, what happens in humans?   Jop van Berlo:             So, you're absolutely right that we use model systems to mimic what happens in humans and every model system has pros and cons to it. What we're trying to do here is to induce essentially acute cardiac pressure overload in a mouse model by inducing a constriction of the transverse aorta, right between the anomia and the left carotid artery. And we do this by ligating a needle on top of the transverse aorta that is of a specific size. And then we pull the needle out of the ligation and that immediately induces constriction. This is known to induce cardiac hypertrophy, and there are thousands of papers about this model as a model to induce cardiac hypertrophy. I think Howard Rockman was the first to publish this as a model of cardiac hypertrophy. Over the past decades, most of the research has focused on how cardiomyocytes within the heart respond to their stress and how they become hypertrophic. And I think what is new about our study is that instead of really focusing on the cardiomyocyte, we are focusing more on the non-cardiomyocyte compartments early after this stress is induced on the heart.   Cindy St. Hilaire:        That was one of the things I liked about this paper. We read about TAC a lot, the transaortic constriction model, but a lot of it is looking at either just the fibrotic cells or the scarring or the cardiomyocytes. So, this was, I thought a really nice unique take. So, one of the things I'm wondering is what are the functional differences between the systemic macrophages and these resident macrophages? I guess, resident to the cardiac tissue. And how does one tell the difference between these cells in the mice, but also in the humans? What is the human equivalent of those cells?   Xavier Revelo:             So, these cells, they rest in the macrophages in the cardiac tissue. One of the key differences from circulatory cells is the origin of the cells. In the heart, these cells self-renew, and they are from embryonic origins, as opposed to circulatory immune cells that come from the bone marrow. In terms of similarities between mice and humans, there are some markers that we can use to specifically study the cardiac resident macrophages. And these markers fortunately seem to be consistent between people and mice, which is advantages.   Cindy St. Hilaire:        That is good. That's always nice when it works out that way. So, you, you actually answered my next question, which was, are these residents macrophages a) able to self-replicate or are they from their own source? And so, regarding that developmental origin, how far apart are these lineages of the circulating monocytes versus the resident or the cardiac resident? How similar and how different, and how far back on the tree do they diverge? If we know it?   Xavier Revelo:             It's a complicated question.   Jop van Berlo:             And it's an active area of study right now, not just by us, but also by many other groups.   Xavier Revelo:             So, what we know is that regardless of origin, the cells are myeloid cells. So, they're the same lineage within the big family of immune cells. Having said that, the function of the cells is dictated by the origin, as well as the issue of residency. I forgot a second part of your question. Cindy St. Hilaire:        I'm wondering how much they diverge functionally from the circulating monocytes?   Xavier Revelo:             They do. It seems like the tissue factors and the residency dictates the function of the cells in general. This is a general comment. Resident cells seem to have a protective role. Sometimes they help with the repair and healing as opposed to infiltrating cells that come into the tissue and they cause inflammation, generally they aggravate disease progression.   Jop van Berlo:             But what I also find fascinating about these resident macrophages is they are not only found in the heart, but they're also found in all organs, and they all come from developmental origins. But if you compare the macrophages between these different organs, they resemble the organ itself more than macrophages between organs and that's based on recent work where people have compared resident macrophages from different organs. And I think that's just fascinating how this develops in the heart, but also in other organs as a way to protect specific organs from potentially dangerous signals.   Cindy St. Hilaire:        Yeah, that's so interesting. So, it's almost like their niche, their new residential home, is really informing their function. So, there's some kind of back and forth between that environment and the cell itself.   Jop van Berlo:             That's what we presume, but I don't think we truly understand how the niche is important in dictating the function of these resident macrophages. And I think we need to do a lot more research into how the niche of tissue resident macrophages has formed and how that then dictates the differentiation of these resident macrophages to give rise to certain functionalities.   Cindy St. Hilaire:        Maybe you can summarize in a couple short sentences or so what, what your key findings were.   Jop van Berlo:             The main findings of our study is that very early after the induction of acute cardiac pressure overload, there is a high level of inflammation happening in the heart. And this allows the replication of resident macrophages and our study showed that these resident macrophages are really important for a protective mechanism within the heart to allow the heart to deal with this increased pressure in a heart. And what they do is they stimulate the formation of new block vessels, also known as angiogenesis and furthermore, they inhibit the formation of scar tissue or fibrosis, and we used different ways to substantiate these conclusions.   Xavier Revelo:             We studied cardiac-resident macrophages as one population. But one thing we learned in this study is that these macrophages are highly diverse. And so, using our techniques, we discover that within cardiac macrophages, we have 11 different subsets. And so, our future studies will be aiming at understanding the precise role of these different subsets that we think have different roles in pressure overload.   Cindy St. Hilaire:        One of the things I was thinking about is these 11 subsets, do they represent kind of end stage fully differentiated resident macrophages, meaning 11 different types, or are they kind of representing maybe the different stages that get to the one end type? Do we have a sense of what's going on?   Xavier Revelo:             I don't think it's completely understood my take on that is that these different subsets they can represent different activation states or functional subsets that we don't really understand why is that we have this diversity?   Jop van Berlo:             I think one of the aspects that we as a field need to work on is to better understand that complexity of immune cells that reside within an organ and associate that complexity to specific functionalities. And right now, the field is mostly lacking in technologies that allow us to do this. For example, we cannot culture these resident macrophages right now. We don't know the proper culturing conditions that allow us to test functional differences between subsets of macrophages. We don't have very good genetic tools to dissect these specific subsets of macrophages. And I think those are important areas that the field and us of course need to work on in the coming years.   Cindy St. Hilaire:        Every layer of discovery, just brings like 10 more layers complexity, or 11 more co-layers of complexity in this case.   Jop van Berlo:             Which is why we all love science!   Cindy St. Hilaire:        Exactly, exactly. It's a drug that, that keeps on giving. So, one of your experiments, I forget which number, I think figure five or six or something like that, but in wild type mice, you went on to use an anti CD115 antibody. And because that treatment others, as well as yourselves has shown depletes the resident macrophages. And, and one thing I thought was really interesting. I just want to hear how you unpack it. And that is in the wild type mice that were treated with the anti CD115 antibody. You found that the depletion of the resident macrophages exacerbated the adverse remodeling and it increased fibrosis, it decreased angiogenesis, but when you did the same thing in a CCR2 knockout mouse in that mouse, they don't have the circulating macrophages, but they also don't have the resident macrophages. They were protected from the increased fibrosis, but there was no change in the angiogenesis. And I was just wondering if you could unpack these results for me and kind of talk about the competing roles of the resident and the non-resident macrophage in this pathogenesis.   Jop van Berlo              So I think you highlight a really important experiment that we performed that try to dissect the protective versus damaging effects of different subsets of macrophages within the heart. We know that if you delete the receptor CCR2, that circulating monocytes cannot extravasate and enter the tissue in response to the cytokine CCL2 that is produced by the myocardium. So, using the CCR2 knockout, we essentially blocked the invasion of circulating monocytes into the myocardium to become monocyte-derived macrophages. And we knew from the literature that, especially the monocyte-derived macrophages, were pro fibrotic. So, we wanted to discern the effects on fibrosis between resident macrophages and monocyte derived macrophages. So, we were happy to indeed see that when we blocked extravasation of circulating monocytes and blocked them to become macrophages, that we indeed reduce the amount of fibrosis that we observed within the heart.                                       I think the difficulty here that we observed that we don't have a very good explanation for right now are the effects on angiogenesis. And I think what this highlights is that there are many, many more complexities than just the resident and recruited macrophages on the development of angiogenesis because when we block tissue resident macrophages, are we actually depleting tissue resident macrophages? We didn't completely block the development of angiogenesis. We merely inhibited this by a little bit. And so, I think there are many more actions happening within the heart in response to stress than just the immune cells. And I think it highlights how complex a living organ really is. And we always try to do reductionist experiments to try to understand the functioning of specific aspects of that organ, but it's much more complex than just one cell type doing one thing and another cell type doing another thing.   Xavier Revelo:             One potential explanation to this complexity is the fact that when we deplete resident macrophages, the monocyte-derived macrophages, the infiltrating macrophages, they can replenish those resident macrophages. And so, whether there's a difference between the original resident macrophages compared to the replacing macrophages is unknown. And so, all these complexities can perhaps explain that different phenotypes that we observed in terms of angiogenesis.   Cindy St. Hilaire:        What do your findings suggest about potential therapies or you even potential therapeutic targets? Is it possible in a human to be able to target one or the other macrophage population? I know a lot of your experiments, because it's an experiment, you're targeting the depletion of macrophages before to see the effects, but are we able to possibly activate or stimulate their production, post MI for example?   Xavier Revelo:             Yeah, absolutely. So, thinking about cardiomyocyte independent interventions that can enhance the preparation process of any stressed heart, we could see potential in manipulating resident macrophages, specifically enhancing the functions of these resident macrophages that will help us heal and prevent fibrosis and enhance angiogenesis. So, we think that future studies need to look at what factors can be manipulated to enhance the function and survival of these resident macrophages.   Jop van Berlo:             One important aspect of our study that we don't highlight is that after this large increase in tissue resident macrophages, that we observed within the first week after cardiac pressure overload, these cells actually disappear. And right now, we don't really know the signals that are important for mediating that disappearing of cells. And we don't know this whether maintenance of these signals could improve longer beneficial effects of tissue resident macrophages.   Cindy St. Hilaire:        Interesting. I guess we know some questions you're going to start to ask in the future.   Jop van Berlo:             Absolutely. There's always more questions to answer in science.   Cindy St. Hilaire:        Well, great. Well, Dr Revelo, Dr van Berlo. Thank you so much for joining me today. Congrats on a wonderful paper and we look forward to these future studies.   Jop van Berlo:             Thank you.   Xavier Revelo:             Thank you.   Cindy St. Hilaire:        That's it for the highlights from the December 3rd issue of Circulation Research. Thank you for listening. Please check out the CircRes Facebook page and follow us on Twitter and Instagram with the handle at @CircRes and #DiscovererCircRes. Thank you to our guests, Dr Xavier Revelo and Jop van Berlo. This podcast is produced by Ishara Ratnayaka, edited by Melissa Stoner and supported by the editorial team of Circulation Research. Some of the copy text for highlighted articles is provided by Ruth Williams. I'm your host, Dr Cindy St. Hillaire. And this is Discover CircRes, your-on-the-go source for the most exciting discoveries in basic cardiovascular research. This program is copyright of the American Heart Association, 2021. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or the American Heart Association for more information visit aha journals.org.  

Stolen BMW police chase in LA. Tiger Woods moved to Cedar Sinai Medical Center. Whistling past the graveyard saying. Al Roker Sharted in the White House. Tiger Woods ex-wife connected to LA Football players pro bowlers. Mark Thorpe talks about the Ontario International Airport success.

Dr. Dre is in the ICU at Cedar Sinai Medical Center in Los Angeles after a brain aneurysm. Sources close to dr. Dre reported he suffered the aneurysm on Monday and was rushed to the hospital where he is currently in Intensive Care Unit with around-the-clock care. --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app Support this podcast: https://anchor.fm/Teddy-G/support

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With me today is Dr. Mark Pimentel who really needs no introduction to the SIBO community. He's the executive director of the MAST program or Medically Associated Science and Technology. He's professor of medicine at Geffen School of Medicine at Cedar-Sinai Medical Center in L.A. A few of Dr. Pimentel's most significant accomplishments include the discovery of rifaximin as a treatment for IBS. He also developed the first blood test for IBS based on IBS being derived from acute gastroenteritis; the antibody testing. He described the association between IBS and bacterial overgrowth, which forms the basis of microbiome therapies in this condition, as well as uncovering that methanogens are causing constipations in humans.

In this episode Dr. V welcomes Dr. Brennan Spiegel of Cedar-Sinai Medical Center and author of VRx - How Virtual Therapeutics Will Revolutionize Medicine (Basic Books). This fast moving conversation covers the power and promise of immersion therapeutics, the coming age of the virtualist (that's actually a thing!) as well as VR's potential limitations in health care. As you'll hear, virtual reality has the capacity to bridge the divide between brain and body and Dr. Spiegel tells us exactly how this is being done. Important Link: https://www.virtualmedicine.health Learn more about your ad choices. Visit megaphone.fm/adchoices

Making sure our gym is safe and cleanly in this new Covid world is our top priority. Our gym isn't just ran by a couple of meatheads. Today we are joined by our business partner and medical advisor, Dr. Katherine Haker. Dr. Haker works at Cedar Sinai Medical Center and has been working on the front lines over the past two months. Today Dr. Haker goes over how she is taking her experience and work with Covid-19 over the past two months to make sure that Pharos is the cleanliest and safest environment for you to train at. Thank you so much to our members who have stuck with us and continue to take part in our challenges from home!Sign up for The Limitless ChallengeWelcome to the Pharos Athletic Club podcast. Please make sure you subscribe wherever you are listening to this show and if you loved this show please leave us a 5 star review in the iTunes store. It is the currency of podcasts and it really goes along in helping us grow our show and impart our values for anyone who wants to live every day reaching for their absolute best self.If you are in Los Angeles swing by our gym at 1316 Glendale Blvd in Echo Park.Check out our website here for class times and follow us on Instagram for more fitness related content See acast.com/privacy for privacy and opt-out information.

This month on Episode 12 of the Discover CircRes podcast, host Cindy St. Hilaire highlights three featured articles from the May 8 issue of Circulation Research and gives listeners an inside scoop of the cutting edge ideas in the May 22nd Compendium on Obesity. This episode also features an in-depth conversation with Dr Eduardo Marbán concerning COVID-19 and its effects on the heart.   Article highlights:   Roberts et al.  LYN Regulates Monocyte Heterogeneity and Lifespan Lu, et al. Acute Hyperglycemia Activates CaMKII-ROS Pathway Yan, et al. Epicardium and Atrial Cardiomyopathy Transcript Dr Cindy St. Hilaire: Hi. Welcome to Discover CircRes, the podcast of the American Heart Association's journal, Circulation Research. I'm your host, Dr Cindy St. Hilaire, from the Vascular Medicine Institute at the University of Pittsburgh. Today, I'm going to share with you articles selected from the May 8th issue of Circulation Research as well as give you a hint at the cutting-edge ideas in the May 22nd Compendium on Obesity. We'll also have discussion with Dr Eduardo Marbán from the Smidt Heart Institute at Cedar Sinai Medical Center about his Review on COVID-19 and its effects on heart. So, first the highlights. The first article I'm sharing with you is titled Deep Phenotyping by Mass Cytometry and Single Cell RNA Sequencing reveals LYN Regulated Signaling Profiles Underlying Monocyte Subset Heterogeneity and Lifespan. The first authors are Morgan Roberts and Maunish Barvalia and the corresponding author is Kenneth Harder and they're from the University of British Columbia. Monocytes can be separated into two main groups, conventional monocytes which enter tissues from the bloodstream and differentiate into macrophages, and patrolling monocytes, which developed from conventional monocytes but tend to remain in the blood vessel walls where they can scavenge cells and tissue debris. It's thought that patrolling monocytes help to prevent a range of diseases like atherosclerosis by helping to clean up the vessel walls. Studies in mice harboring genetic mutations in a gene called Nr4a1 cause mice to have less than normal numbers of patrolling monocytes. In these mice, the development of atherosclerosis is exacerbated. In addition to Nr4a1, this group has now identified another factor regulating the survival of patrolling monocytes, the tyrosine kinase LYN, L-Y-N. Genetic deficiency of LYN caused the upregulation of Nr4a1 and other genes involved in patrolling monocytes development and survival. This in turn led to the accumulation of patrolling monocytes in the blood, also in the bone marrow, spleen, and the aorta. Loss of LYN was also protective against atherosclerosis in mouse models of this disease. These results not only provide novel insights into patrolling monocyte biology, but also suggest that targeting LYN could offer novel treatments for diseases like atherosclerosis, where boosting the patrolling monocyte numbers could be beneficial. The second article I want to highlight is titled Hyperglycemia Acutely Increases Cytosolic Reactive Oxygen Species via O-linked GlcNAcylation and CaMKII Activation in Mouse Ventricular Myocytes. The first author is Shan Lu and the corresponding author is Don Bers, and they're from the University of California, Davis. Diabetes affects more than 400 million people worldwide and puts these individuals at a higher risk for developing heart failure. When heart failure does occur, the outcomes for these patients with diabetes are likely to be far worse than for individuals without the diabetic condition. Both heart failure and diabetes have been associated with excessive production of reactive oxygen species and also with increased activation of a protein kinase in the cells of the heart called CaMKII. Both ROS and CaMKII are induced by hypoglycemia, where there is an increased amount of extracellular glucose levels in the blood. This study shows that reactive oxygen species in CaMKII are causally linked. When CaMKII was inhibited or genetically deleted in mouse cardiomyocytes, high extracellular glucose levels were unable to induce reactive oxygen species production, which is what would normally occur. The team also discovered that O-GlcNAcylation post-translational modification of CaMKII is induced by the extracellular glucose and this modification is necessary for the enzyme's reactive oxygen species- boosting effects. Lastly, they found that the enzyme NADPH oxidase 2 or NOX2 was the source of this CaMKII induced reactive oxygen species. This work uncovers the molecular pathway linking hyperglycemia, cardiomyocyte-damaging reactive oxygen species production, and it helps explain why heart failure pathology is exacerbated in diabetic patients. The next article I want to share with you is Reactivation of the Epicardium at the Origin of Myocardial Fibro-Fatty Infiltration During the Atrial Cardiomyopathy. The first author is Nadine Suffee and the corresponding author is Stéphane Hatem and they're from Inserm in Montpellier, France. Fatty tissue surrounding the heart is linked to an increased risk for atrial fibrillation, which is the most common form of arrhythmia. It seems that a combination of fat cells, which are called adipocytes and the fibroblast localized within the heart's epicardium, builds up and expand into the subepicardial layers, and this is a feature that is called fibro-fatty infiltration. These fibro-fatty infiltrations cause disturbances to the electrical rhythms that regulate the heart beating. Although generally quiescent in the adult heart, epicardial cells possess the ability to proliferate and have been shown that they harbor the ability to differentiate into adipocytes and fibroblast. This team hypothesized that the epicardial cells were the source of the damaging fibro-fatty infiltrations. Sure enough, when they looked at human heart sections, they found that within the epicardial layer, there were cells that were expressing fibroblast and adipocyte progenitor cell markers. In culture, these epicardial cells with fibroblast progenitor markers could be differentiated into fibroblasts by treatment with angiotensin II and cells with the adipocyte progenitor markers could be differentiated into adipocytes by treatment with atrial natriuretic peptide. The team also showed that these epicardial fibro-fatty infiltrations occurred in a mouse model of atrial cardiomyopathy. Together this work highlights the pathogenesis of epicardial fibro-fatty infiltrations and suggest a novel model in which to study its progression to AFib. The last thing I want to share with you before we switch to our interview with Dr Marbán is that the May 22nd issue of Circulation Research is our Obesity Compendium. Obesity is a major threat to cardiovascular health worldwide. While early studies focused on body mass index as a generalized measure of obesity and focused on the BMIs relation to cardiovascular disease, studies within the last decade have now tried to more fully understand adipose tissue physiology and the overall impact of obesity on cardiovascular disease. The articles in this compendium are obesity phenotypes, diabetes and cardiovascular diseases, basic mechanisms of diabetic heart disease, leukocyte heterogeneity and adipose tissue including obesity, an eclectic cast of cellular actors orchestrates innate immune responses and the mechanisms driving obesity and the metabolic perturbation, metabolic inflammation and insulin resistance in obesity, genetic insights into the relationship between Type 2 diabetes and coronary heart disease, metabolomics and proteomics in Type 2 diabetes, metabolic and molecular imaging in diabetic cardiomyopathy and treatment of obesity and mitigating metabolic risk. This compendium reflects the collective work of leading investigators in the space of diabetes, cardiometabolic disease, and cardiovascular disease with the ultimate goal of providing a summary of selected aspects of obesity and metabolic physiology central to cardiovascular disease development. So, I have with me here today, Dr Eduardo Marbán, the founder of the Smidt Heart Institute at Cedars-Sinai Medical Center in Los Angeles, California. He's a leading physician scientist in the fields of electrophysiology, cardiac progenitor cells, and next generation cell-free therapeutics. Dr Marbán, thank you very much for taking the time out of your busy schedule to speak with us today about your article COVID-19 and the Heart, which is now freely available on the Circulation Research webpage. Dr Eduardo Marbán: It's my pleasure to talk to you Cynthia. Dr Cindy St. Hilaire: First off, how are you and how are things at your hospital center in LA? Dr Eduardo Marbán: We seem to have dodged the bullet here in the sense that we were pretty progressive in terms of quarantine and stay at home orders. Given that, we seem to have peaked at a level that is very manageable in terms of our surge capacity. So, we feel for those who are worse off, but at least knock on wood here, we seem to be surviving so far. Dr Cindy St. Hilaire: Yeah, that's similar to how we are in Pittsburgh. We shut down about the same time that Philadelphia, who was already surging was shutting down. So, we are feeling safe but still prepared. So, I was extremely excited to read this article because as we know, cardiac injury is happening in between 20% to 30% of the COVID-19 patients and cardiac injury is also the cause of about 40% of the COVID-19 related deaths. So, my first question is, what are the types of cardiac injuries or events that you're seeing in these COVID-19 patients and are there any particular characteristics that the subpopulation of patients shares that's different from non-cardiac injury COVID patients? Dr Eduardo Marbán: What seems to be extremely common in COVID-19 patients is elevations of circulating biomarkers, things like troponin I, troponin T, BNP as an indicator of heart failure, but what's much less certain is whether these biomarker elevations have any clinical significance. At the level of isolated case reports, there's fulminant myocarditis, ventricular tachycardia, arrhythmias, occasional acute coronary syndromes, but there seems to be a disconnect between the almost ubiquitous nature of the circulating biomarker elevations and the relative rarity of clinical events. Dr Cindy St. Hilaire: So, do these patients, do a majority of them have a history of cardiovascular disease or is this all new developments? Do we know? Dr Eduardo Marbán: Underlying cardiovascular disease, diabetes, hypertension, and recently obesity and, of course age, have all been implicated as general risk factors for being critically ill with COVID, but there's no specific indication epidemiologically yet that those with underlying cardiovascular disease have a particular predilection to manifesting worse heart symptoms or signs during COVID-19. It makes sense that that would be the case, but so far, the epidemiology is somewhat more general. Dr Cindy St. Hilaire: When you were first writing this article, I'm sure between then and now we even have more epidemiological data points that are constantly changing. Dr Eduardo Marbán: Since the article was published online on April 7th, I've given four updated versions of the webinar to various audiences. Every time we do so, the slides need to change subtly. It's a very rapidly evolving field. Dr Cindy St. Hilaire: Yeah, that's amazing. In the first SARS outbreak, which was in 2002-2003, scientists discovered that this type of Coronavirus enters the cell by binding to angiotensin converting enzyme II as a receptor. So, ACE2 as it's called. It's not a receptor in the canonical sense of the word, but it's a cell surface enzyme and it's involved in the renin angiotensin aldosterone system, which regulates a handful of cardiovascular homeostatic processes and is quite frankly, rather complicated. So, I don't want to talk specifically about that, but I'm wondering if you could tell us a little bit about what ACE2 is, what cells it's found on, and what that might mean for the implications of this virus and its effects on the cardiovascular system? Dr Eduardo Marbán: Well as you correctly stated, ACE2 is central to cardiac physiology in the sense that it creates the bioactive form of angiotensin. In so doing, its regulation is central to that of blood pressure, human dynamics. What is less appreciated and to me was a bit of a revelation is the fact that it's expressed fairly richly on the surface of epithelial cells of the lung and the SARS-CoV virus family seems to have co-opted the presence of that in order to create a handy sort of hook to get into the cells in the first place. Whether there are broader ranging implications of ACE2 other than the particular mode of entry into the cell for a viral infection is a topic of great speculation at this point. Dr Cindy St. Hilaire: Yeah. In some of my preparation for this and also just my curiosity regarding this virus and the vascular system, when you look at things like the human protein atlas, you can see that ACE2 is highly expressed, not only on the lung epithelial like you say, but they're also expressed on cardiovascular cells in nearly all of the tissue. I'm thinking of cells like the smooth muscle cell and the endothelial cell. Is the virus binding to ACE2 positive cells part of the reason for the cardiac events or these cardiac events secondary to systemic toxicity? So, I guess the real question is, do we know anything about the direct versus the indirect effects of the virus on the heart? Dr Eduardo Marbán: No question in vitro that SARS-CoV can infect cardiac myocytes and most surely almost any other cell that expresses these two on its surface. In vivo, how frequently that happens as opposed to triggering secondary cardiac damage due to the systemic inflammation is uncertain, but I can tell you from the various case reports that have actually analyzed human tissue either at autopsy or an endomyocardial biopsy in cases of fulminant myocarditis, the frequency of direct viral infection seen either by culturing viral particles or more frequently by electron microscopy and visualization of inclusion bodies within cells points to perhaps a third of the cases being due to direct infection and two thirds of the cases likely being due to some bystander effect of systemic inflammation. Dr Cindy St. Hilaire: Interesting. So, are the phenotypes different between those patients where it seems to be direct versus indirect? Does the myocarditis appear similar or the cytokine profiles, anything like that? Dr Eduardo Marbán: There are too few patients to make really good conclusions about whether or not the phenotypes differ greatly when there's direct versus indirect cardiac involvement, but certainly from the literature as it exists now, there's no reason to believe that we could outsmart the clinical picture. They all look pretty much the same from the bedside. Dr Cindy St. Hilaire: So from the first SARS outbreak, do we know anything about the long-term effects of this type of viral infection on the cardiovascular system or on the heart specifically? Dr Eduardo Marbán: Yeah. COVID-19 of course the follow-up is limited to a few months since the first cases probably didn't emerge until late October early November and weren't really recognized as such until late '19 early 2020, but for SARS from the 2002-2003 epidemic, some of the long lasting sequelae are unanticipated and include hypertension, hyperlipidemia, pulmonary fibrosis, avascular necrosis. So, it seems that even when a patient is out of the woods, perhaps they're not really out of the woods in terms of long-term sequelae. We need to be watchful for long-term sequelae in COVID-19 survivors. They're going to be many more of them than there were from the SARS epidemic. Dr Cindy St. Hilaire: So, one of the things that's come out recently, which I've been really mulling about because my background is vascular biology and specifically smooth muscle cells and endothelial cells, but one of the findings is about the later stage or more sick patients. These are patients who are going on ventilators and about 50% of them going on the ventilators are dying and/or just not responding to ventilator therapy as doctors expect. So, just to give a little background about ventilators, they're normally used when a patient's blood oxygen level drops too low. So, normal levels are between 95% and 100%. However, patients with pneumonia or acute respiratory symptoms are put on ventilators sometimes when their oxygen drops below 90%, but some of the COVID-19 patients are exhibiting blood oxygen levels at 70% or sometimes even lower, but they don't have outward signs of distress and they can still hold conversations. So, I'm wondering if you can give me any insight into possibly what's going on there with the lens of vascular remodeling, what might be happening to the vasculature in the lung that is unique to this ventilator response and COVID response? Dr Eduardo Marbán: The observation you described is common that sometimes a patient will be profoundly hypoxemic but chatting away or surfing the internet as if nothing were happening. We're not used to seeing this in other cases of ARDS or viral sepsis where the patient usually is in extremis by the time the blood oxygen levels get that low. It begs the question as to whether perhaps there's something about the cerebral circulation, and this is complete and rampant speculation. Whether there's something about the cerebral circulation that makes it somewhat resistant to the effects of systemic hypoxia, perhaps there's a compensatory vasodilation that occurs that compensates for the otherwise deadly systemic hypoxemia. It would be quite interesting to monitor oxygen tensions within the cerebral parenchyma to test that, but all I can say with any certainty right now is that the clinical observation is robust. We see this not infrequently in patients who in the sort of clinical jargon have no right to look that good. Dr Cindy St. Hilaire: Yeah. Yeah. It's like your numbers, you really have those numbers? Yeah. There's just so many questions. It's really unprecedented. So, I guess we've been talking a lot about the disease itself and the symptoms and the pathogenesis, but I want to switch to ask about potential therapies. There's been several therapies that have been suggested by a variety of people and there's, I don't even know how many clinical trials. I looked a week ago and there's really a great response of pharmaceutical companies and university hospital systems trying what they can with the tools they have. So, things like antivirals, HIV protease inhibitors, inhibitory antibodies, and even antimalarial drugs have been suggested that they could possibly work. So, I'm wondering if you could give us some insight from a cardiovascular standpoint, what are the potential implications or potential adverse side effects of using these different therapies off label and what might that mean for the heart in addition to treating the viral infection? Dr Eduardo Marbán: You're correct in the explosion of clinical trials in this area or at least, clinical interventions. At our IRB, as of today, there are 56 active COVID protocols. Imagine nobody even cared about COVID until mid-February, right? Dr Cindy St. Hilaire: That's just at Cedars-Sinai. Dr Eduardo Marbán: Yeah. Now, we have 56 active protocols. So, not all of those are interventional. Some of them are epidemiological or biomarker studies, but still there's an incredible plethora. You're right, the approaches of targeted anything from the viral infection to the viremia to the downstream consequences of viral infection including the hyper inflammation and cytokine storm. The rationale for anti-malarials is actually fairly thin and resides on in vitro observations that actually were just from February that SARS-CoV-2 infection in vitro is somewhat retarded by exposure to hydroxychloroquine. This didn't come out of the blue. There had been an extensive literature and quite controversial literature, I should say, that anti-malarials might be useful in influenza and other infections. In a very general sense, there was a lot of hype created by early in vitro studies, which turned out to be neutral or in some cases even harmful clinically, but this has led to an almost universal adoption of hydroxychloroquine in patients with COVID-19 coupled sometimes with the antibacterial agent azithromycin for which the rationale is even thinner. There's no reason to believe that an antibacterial per se would help in a viral infection, but azithromycin is said to have antioxidant properties, which may or may not potentiate the effects of hydroxychloroquine, but for sure what they do together is prolong repolarization of the heart and lead to a clinical syndrome known as prolonged QT, which is a known substrate for toxic arrhythmias like polymorphic ventricular tachycardia. So, in prescribing some of these agents, one needs to weigh the uncertain benefits against the very certain risk that they entail. Dr Cindy St. Hilaire: Yeah. I think that's a really important point. I think one of the scary things that has the potential of happening during this crisis is too quick of a jump to conclusions. While there is a need for as rapid a response as possible, we still need to make sure that we're taking in all the scientific information we have and that that science is good and strong. I think one of the things that you mentioned in the Review is the lack of power in some of those initial anti-malarial studies. I think it's really important thing I want to emphasize that it's an emergency, but we still need to make proper good scientific decisions. Dr Eduardo Marbán: Well, one of the problems is that hydroxychloroquine and other agents in some cases, remdesivir and you know, you choose, have gotten so popular and hyped that there's almost no possibility of being an ethical clinical trial because the patients want to be on them. So, it may be easier in some settings than in others, but it's certainly not going to be a trivial thing to sort out the true risk benefit ratio of these drugs in this illness. Dr Cindy St. Hilaire: So right now, doctors and scientists, we're all in crisis mode, but once things settled down, we could really start to sit down and think about more mechanistic questions that might be able to be tested that will really help us flush out our understanding of COVID-19 disease pathogenesis and its effects on the cardiovascular system. So, what do you see after this initial crisis is under control, what do you see as the immediate next questions that basic scientists and translational scientists need to address that can help the next time that this comes again? Dr Eduardo Marbán: First of all, it's quite clear that we've all become consumed by COVID-19 and SARS-CoV-2. We can't think of anything else often. It's really hard to even focus on work from the laboratory that doesn't have to do with SARS-CoV-2 and COVID. It's so ubiquitous in public perception and the way we're living our lives that it just makes it incredibly difficult to think about anything else. I think there's going to be a correction in which we're going to get frankly tired of SARS-CoV-2 and COVID and want to think about other things, but among the lasting questions and the ones that will have greater biological merit above and beyond how to deal with this particular virus and this particular pandemic are the following. What is the role of ACE2 in human biology? Clearly here, there's an experiment of nature in which this surface enzyme has been co-opted for viral entry and a tremendous amount of speculation surrounds the question of whether high ACE2 values are protective and detrimental and ACE inhibitors and angiotensin receptor blockers might be detrimental or beneficial. All of these fundamental mechanisms need to be sorted out and now there's motivation to do so because of the epidemic. Some of this work is easier than others and those institutions that happen to have a BSL-3 level facility for being able to directly study the effects of the virus on various tissues should do so with alacrity because it's a limited resource right now where the number of questions really far exceed the ability to answer them just physically. Another question which I think is going to be motivated by our experience with COVID-19 is that of the mechanisms of cytokine storm and hyper thrombotic states. These are things that characterize the critically ill patient with COVID-19. Dr Cindy St. Hilaire: Can you just explain what is a cytokine storm? What does that exactly mean? Dr Eduardo Marbán: So, patients who are critically ill with COVID-19 manifest a late stage of the illness, which is often fatal, in which circulating levels of various inflammatory biomarkers, interleukin 6, C-reactive protein, ferritin being among them, but basically anything that goes up in an inflammatory state. And some of these appeared not to just be markers of inflammation. Something like C-reactive protein is probably just a biomarker of inflammation, but interleukin 6 for example, is a highly bioactive cytokine that itself probably causes tremendous tissue injury and there's some enthusiasm for the use of anti IL6 antibodies and anti IL6 receptor antibodies to treat the critically ill with some anecdotal dramatic success I should say. So perhaps the cytokine storm isn't just a marker of those who are critically ill, perhaps it's causative. If that presumption is real, then it makes good sense to target the cytokine storm, but from a scientific point of view, what causes it in the first place? How does a viral infection lead to massive production of cytokines and inflammatory biomarkers and how can that be mitigated? One of the ways of dealing with that is by understanding precisely how it happens in the first place and there's not that much literature on it. There's a recent study which I found quite provocative that glucose metabolism and the whole process known as O-GlcNAcylation might actually be a trigger in the production of cytokines during viral infections like COVID-19, but I think understanding how it happens will lead to much more targeted therapeutics and perhaps enable us to eventually divorce the infection from the overreaction. Really what's happening is friendly fire. The body's immune system is turning against itself in a sort of vain effort to control the virus. Sometimes the viremia is actually almost gone by the time that these inflammatory biomarkers increase, and the cytokine storm surges. Dr Cindy St. Hilaire: So, it's almost like the inflammatory response reaches some point beyond which it doesn't need virus anymore. It is just full force feeding forward and causing more damage by itself. Dr Eduardo Marbán: Yeah, exactly. It's almost as if there's an eroding cliff and even though the river may be back down to normal levels, the cliff is still unstable and the whole hillside could come crashing down. Dr Cindy St. Hilaire: Are there long terms effects of that? I wonder how long that would last after the infection or is it only during a viral titer in the system? Dr Eduardo Marbán: Well, you raised yet another interesting question to the extent that patients who have survived SARS- CoV-2 infection develop long-term sequelae, what's the mechanism of those long-term sequelae? Why should patients who are previously well develop hyperlipidemia and hypertension after the infection, if in fact they do, so are any of these related to micro thrombotic events? It's quite conceivable. Dr Cindy St. Hilaire: Great. Well, thank you so very much for taking the time to speak with me today. I don't think I found a ton of answers. I found a lot more questions, but hopefully as this develops and we get it under control, maybe we can talk again and talk about some of those new mechanistic findings and potential therapies. Dr Eduardo Marbán: Absolutely. You're welcome, and I hope you and all the listeners stay safe during this pandemic. Dr Cindy St. Hilaire: You too, and your clinical team. That's it for highlights from the May 10th and May 22nd Obesity Compendium issues of Circulation Research. Thank you so much for listening. Please check out the Circulation Research Facebook page and follow us on Twitter and Instagram with the handle @CircRes and #DscoverCircRes. Thank you to our guest, Dr Eduardo Marbán. This podcast is produced by Rebecca McTavish, edited by Melissa Stoner, and supported by the editorial team of Circulation Research. Some of the copy text for highlighted articles is provided by Ruth Williams. I'm your host, Dr Cindy St. Hilaire, and this is Discover CircRes, your on-the-go source for the most up-to-date and exciting discoveries in basic cardiovascular research.  

Johanna Cronin is a survivor of COVID-19. She joins the podcast to talk about her symptoms, the difficulties surrounding getting tested and her overall experience. Johanna lives in Los Angeles, CA and details what it was like going into Cedar Sinai Medical Center in the middle of the night after waking up gasping for air. Now recovered, she hopes by sharing her story, people will be more careful and take the coronavirus seriously. 13 News Reporter Richard Bodee, who is Johanna's cousin, hosts this episode of 815 Live.

Dr. Sam Fink is an internal medicine specialist in private practice in Tarzana, California. He’s currently treating patients with coronavirus and has been on the frontline of educating the public on COVID-19 on KTLA, CNN, FOX, and more.   Dr. Fink’s daughter, Sarrica Fink is a registered nurse who practiced at Cedar Sinai Medical Center in LA. She’s currently working at a Digital Health Innovation Nonprofit in Tel-Aviv, Israel. Following in her father's footsteps, she too is passionate about educating others.   You'll love this father and daughter, doctor, and nurse duo, a.k.a. The Fink Tank, who are here today to give us factual and realistic answers about the current situation of Covid-19 so we can beat the Coronavirus together.   SHOW NOTE LINKS: Fink Tank- Facebook LIVE on Sundays (12:30pm PST, 3:30pm EST, & 10:30pm Israel) via Dr. Fink’s profile Fink Tank Updates on Instagram Dr. Samuel Fink, MD Website Sarrica Fink, RN's Facebook   CONNECT WITH US! *Dear Family, Podcast Page *Write Now Rachel Website *Rachel's Blog @Medium *Rachel’s Twitter *Facebook *Instagram   PLEASE JOIN: *Dear Family Members, the Private Facebook Group     WAYS TO HELP THE PODCAST: *PLEASE Leave a 5-Star Review and ***Listen and Subscribe via iTunes!!!  ***Listen and Subscribe via Stitcher!!! ***Listen and Subscribe via Spotify!!!   Thank you! Your support means the world to me. Wishing you love, happiness, and good mental health always.

DESMOND DOGAN--Following high school, Desmond served his country for five years in the US Navy. Throughout his military term he further developed leadership skills as a Navy Corpsman in Yokosuka, Japan. His hard work and dedication once again exceeded expectations leading to the prestigious Meritorious Unit Commendation Medal, which he and his shipmates were awarded for “Superb medical support” that was provided between July 1986 with the unit he was attached to. Although Desmond had a thriving military career, he was ready to explore new heights and pursue his love of the arts, fitness, and healthy/ wellness development. The road to success didn't come easy. He took the skills he learned in the Navy and landed a position with the prestigious Cedar Sinai Medical Center in Los Angeles. He worked an Operating Room Technician in the mornings and auditioned for dance jobs in the afternoon. His 12-year medical career included assisting with the open-heart surgery, liver and kidney transplants and all other surgical practices. Desmond simultaneously continued his pursuit of a viable dance role. His talent didn't go unnoticed. LA Models began to represent him and eventually a major breakthrough presented itself. “Hip Hop Body Shop,” a fitness and dance show on ESPN II that Desmond co-created and co-hosted received 5 stars from Fitness Magazine.

DESMOND DOGAN--Following high school, Desmond served his country for five years in the US Navy. Throughout his military term he further developed leadership skills as a Navy Corpsman in Yokosuka, Japan. His hard work and dedication once again exceeded expectations leading to the prestigious Meritorious Unit Commendation Medal, which he and his shipmates were awarded for “Superb medical support” that was provided between July 1986 with the unit he was attached to. Although Desmond had a thriving military career, he was ready to explore new heights and pursue his love of the arts, fitness, and healthy/ wellness development. The road to success didn’t come easy. He took the skills he learned in the Navy and landed a position with the prestigious Cedar Sinai Medical Center in Los Angeles. He worked an Operating Room Technician in the mornings and auditioned for dance jobs in the afternoon. His 12-year medical career included assisting with the open-heart surgery, liver and kidney transplants and all other surgical practices. Desmond simultaneously continued his pursuit of a viable dance role. His talent didn’t go unnoticed. LA Models began to represent him and eventually a major breakthrough presented itself. “Hip Hop Body Shop,” a fitness and dance show on ESPN II that Desmond co-created and co-hosted received 5 stars from Fitness Magazine.

DESMOND DOGAN--Following high school, Desmond served his country for five years in the US Navy. Throughout his military term he further developed leadership skills as a Navy Corpsman in Yokosuka, Japan. His hard work and dedication once again exceeded expectations leading to the prestigious Meritorious Unit Commendation Medal, which he and his shipmates were awarded for “Superb medical support” that was provided between July 1986 with the unit he was attached to. Although Desmond had a thriving military career, he was ready to explore new heights and pursue his love of the arts, fitness, and healthy/ wellness development. The road to success didn’t come easy. He took the skills he learned in the Navy and landed a position with the prestigious Cedar Sinai Medical Center in Los Angeles. He worked an Operating Room Technician in the mornings and auditioned for dance jobs in the afternoon. His 12-year medical career included assisting with the open-heart surgery, liver and kidney transplants and all other surgical practices. Desmond simultaneously continued his pursuit of a viable dance role. His talent didn’t go unnoticed. LA Models began to represent him and eventually a major breakthrough presented itself. “Hip Hop Body Shop,” a fitness and dance show on ESPN II that Desmond co-created and co-hosted received 5 stars from Fitness Magazine.

From gray hair to menopause, Jackie and Dr. Suzanne Gilberg Lenz talk choices that can help you thrive in midlife and beyond.    Plus, your common questions answered:   What exactly is peri-menopause? How do you know menopause is about to happen? What kinds of changes can you expect? What kind of impact will it have on your sense of well being?     About Dr. Suzanne Gilberg Lenz   I’m a hard-core science nerd with a deep respect for the holistic approach to health and life. Believe it or not, there is a science to self-care!   After earning my medical degree at Southern California School of Medicine and completing my residency at Cedar-Sinai Medical Center in Los Angeles, California, I wanted to expand my knowledge beyond conventional medicine.   In 2010 I graduated from California College of Ayurveda as a Clinical Ayurvedic Specialist, which has truly expanded and informed my practice of medicine. Being able to integrate this incredible ancient healing tradition has been a game changer and allowed me to go deeper into the study of health and healing.   As more “natural” solutions, medicines, and technologies emerge in the global marketplace, I find myself referring back to Ayurveda- the original lifestyle medicine, which incorporates the mind, body, and spirit.   Get your ticket to Dr. Suzanne's Menopause Bootcamp HERE! Promo Code: FORTYTHRIVE   Mentioned in this episode: Joy Lamay Erica Chidi Cohen The Wing Rebecca Benenati The Wisdom of Menopause (Revised Edition): Creating Physical and Emotional Health During the Change Insight Timer   Follow Dr. Suzanne: Website Facebook Instagram   Are you subscribed to the Forty Thrive podcast? Well let’s make that happen!  Not only will it update you each time there’s a new episode, I’m working on some bonus content that you definitely don’t want to miss. So subscribe now!  Annnd… if you find value in this conversation, please consider giving the show an honest rate and review. I just may feature your review on an upcoming episode!  

Unless you’re living under a rock, you know October is Breast Cancer Awareness Month. But before you run out and buy that pink kitchen utensil or a bottle of (potentially cancer-causing) pink alcohol… take a listen to this episode.   Dr. Suzanne Gilberg-Lenz and I talk the surprising truth behind Breast Cancer Awareness Month. We answer:   • Where does your money actually go? • Which organizations truly help women? • What can you do to make a real impact this month.   Plus, Dr Suzanne shares her own experience being diagnosed with breast cancer 6 years ago — even after doing “everything right.”   7 Ways to Create Impact in October What are some of the ways you can really make an impact to prevent and support?    1. Understand your own breasts (self breast exams each month are a must) 2. Make sure you’re donating time, money and efforts to an organization where you understand the goal 3. Be mindful of what you’re consuming; food, drink, air, chemicals, media. What we put into our brains and hearts is as important as what we put into our bodies.  4. Decrease stress and/or engage stress-relieving activities like yoga and meditation. (Moving your body is key) 5. Support Planned Parenthood or another organization that provides care for women who may otherwise not be able to afford it.  6. Support someone in your community with meals. You can use an app like MealTrain to organize meals in your community.  7. Advocate for yourself! You are the most important person when it comes to healthcare.    Resources   Dr. Susan Love   Sharsheret   Episode 21: Will I even make it to 40? (Jackie's story)   I Did Everything Right and I Still Got Breast Cancer by Dr. Suzanne Gilberg-Lenz     About Dr. Suzanne   I’m a hard-core science nerd with a deep respect for the holistic approach to health and life. Believe it or not, there is a science to self-care!   After earning my medical degree at Southern California School of Medicine and completing my residency at Cedar-Sinai Medical Center in Los Angeles, California, I wanted to expand my knowledge beyond conventional medicine.   In 2010 I graduated from California College of Ayurveda as a Clinical Ayurvedic Specialist, which has truly expanded and informed my practice of medicine. Being able to integrate this incredible ancient healing tradition has been a game changer and allowed me to go deeper into the study of health and healing.   As more “natural” solutions, medicines, and technologies emerge in the global marketplace, I find myself referring back to Ayurveda- the original lifestyle medicine, which incorporates the mind, body, and spirit.   Follow Dr. Suzanne: Website Facebook Instagram    

Jane Ferguson:                Hello, I'm Jane Ferguson and you are listening to Getting Personal: Omics of the Heart, the podcast from Circulation: Cardiovascular genetics, and the functional genomics and translational biology council of the AHA. This is episode ten, from November 2017.                                            November is always a big month for AHA and the annual Scientific Sessions were held in Anaheim, California, November 11th through 15th. For those of you who were able to attend, hopefully you came away feeling refreshed and invigorated and with your desired level of Disney merchandise. For those of you who could not attend, or who didn't make it to all of the genomic sessions, this month's episode should catch you up.                                            For the past several years, the FGTB Council has been organizing boot camps at AHA sessions to give people a chance for hands on learning in a flipped classroom model. This year was no exception and in addition to a clinical genomics boot camp focused on patient centric genomics including single gene testing, whole genome sequencing and pharmacogenomics there was also a new boot camp focused on tackling big data network systems analysis for high input data interpretation.                                            These boot camps are always very well attended and popular, so if you're interested in attending one next year, make sure to get in early and sign up during registration. There was also a hands on session in collaboration with the AHA's Precision Medicine Institute to teach people how to use the precision medicine platform to further their research.                                            In addition to this, there was a full day of programming related to precision medicine in the precision medicine summit, which is held on the Tuesday of Sessions. That covered topics ranging from big data, electronic health records, collaborations and the All of Us initiative to rapid fire reports from ongoing consortium, large scale analysis to disease specific approaches in cardiomyopathy.                                            We were planning to have an in depth focus on the Institute for Precision Cardiovascular Medicine in a future podcast episode, so stay tuned for more on that coming soon. There were a number of individuals who were recognized for their contributions to science and we would like to congratulate all of these outstanding individuals.                                            The FGTB medal of honor was awarded to Stuart Cook from the Duke National University of Singapore. The FGTB mentoring award was awarded to Robert Gerszten from Beth Israel Deaconess Medical Center. The FGTB distinguished achievement award went to Sekar Kathiresan from the Broad Institute. And the functional genomics and epidemiology mid-career research award went to Kiran Musunuru from the University of Pennsylvania. Congratulations to all of these.                                             One of the highlights for the FGTB council at sessions is the FGTB young investigator award. This award celebrates early career investigators and recognizes outstanding research in basic science, populations science, genetic epidemiology, clinical genetics and translational biology. Four finalists presented their research on the Sunday afternoon sessions and I had the chance to chat with all four of them before and after their presentations. So listen on for a behind the scenes over view of the finalists research and the announcement of the winner.                                            Mark Benson is a cardiology fellow at Brigham and Women's Hospital and is working on post-doctoral research at the Beth Israel Deaconess Medical Center in Boston with Dr. Robert Gerszten. His talk was entitled "The Genetic Architecture of the Cardiovascular Risk Proteum." Mark Benson:                  My name's Mark Benson. I'm just finishing up a cardiology fellowship at Brigham and Women's Hospital and am in the middle of post doc in Robert Gerszten’s lab at Beth Israel. Jane Ferguson:                Great, and congratulations on being chosen as a finalist for the FGTB Young Investigator Award. We would love to hear a little bit more about what you’re working on and what you're gonna be telling us. Mark Benson:                  Yeah, absolutely. So the goal of the project was really to integrate proteomic data with genomic data, with the idea that we may be able to use the overlap between those data sets to identify potentially novel biological pathways that underlie very early cardiovascular disease risk.                                            And the thinking behind that was that the lab had just finished up applying DNA-aptamer-based proteomic platform to profile over 110 proteins and the Framingham-Offspring Cohort and from that work, we had identified a very specific signature of 156 proteins in plasma that were each very strongly associated with cardio-metabolic risk.                                            The idea was while those associations were very strong, it was unclear if we were capturing cart or horse or how these associations were fitting together. We wanted to incorporate the genomic data to try to get a better handle on that, to try to connect those pathways to see how these proteins might actually associate with the end phenotype of risk. Jane Ferguson:                It's a sort of Mendelian randomization-esque. Mark Benson:                  Exactly, yeah. So what we were able to find in doing this, we were able to use peripheral blood samples from participants at the Framingham-Offspring study. With a validation in participants of the Swedish Malmo Cancer and Diet Study. Then we did protein profiling using commercial DNA aptamer platform, soma scan. What we were able to find is we were able to detect very strong associations between these circulating cardio metabolic risk-proteins and genetic variance.                                            What was fascinating was we were able to see many things. We were able to start mapping where are these associations, where are these genetic variance in relation to, for example, the gene that's coding the protein that we're measuring. That had some interesting implications because for about half of the protein that had significant associations, we could track those genetic variance back to the gene. It was coding the protein that we were measuring, which was interesting because it's validating the specificity of the proteomic platform that we're using. Jane Ferguson:                Right that's nice, because so often you found a gene that's nothing related to what you think it's going to be so it's nice actually the gene you expect. Mark Benson:                  Yeah, it's very reassuring too when you're looking at rows and rows and rows of data. When the top association of the p value of 10 in the minus 300 is the actual gene you thought would be coding the protein that you're measuring. So that was very reassuring, but we also found dozens and dozens and dozens of associations that were totally unexpected and that may point to completely unexplored biological pathways in cardiovascular disease. So that was obviously very exciting.                                            That actually led us to do two things. One was to make all these data available publicly on dbGaP because as a resource for cardiovascular research there is just way too much data for one group or a handful of groups to digest. The other thing that was fun about the project, is we were able to take one association that was particularly interesting for a number of reasons and experimentally validate it in a tissue-culture model. Jane Ferguson:                So how did that work? Mark Benson:                  So this was an interesting challenge where we all of a sudden got all of these hits back, which was probably to be expected, but to try to figure out which of these dozens and dozens and dozens of new, unexpected hits, what do you do? There was one hit, one association, that was particularly strong and it was between several variance around this gene. That's a phosphatase called PPM1G. It's a transcription factor.                                            These variants, which was interesting, were associated with several different circulating cardio metabolic risk proteins. So our idea was, isn't that interesting? Is it possible that this is mapping to some central regulator? And so it fit that that would be ... that the nearest gene to these variants was a transcription factor and could be a central regulator.                                            What made it more interesting to us was that several variants in the GLGC had recently been described that were highly associated with circulating levels of total cholesterol and triglycerides and they were located around this PPM1G locus as well. The association between those variants and circulating cholesterol didn't have a clear biological connection.                                            So what our work had shown is that those same variants were associated with circulating levels of apolipoprotein E. So wouldn't that be interesting if these variants mapped to PPM1G, the transcription factor, this PBM1G in turn regulated circulating apolipoprotein E and that would provide some insight into the biology behind the GLGC findings.                                            So sure enough we were able to knock down PPM1G using SRNA and hepatocytes and then see that that led to a significant down regulation of the transcription of Apo-B and extra-cellular presumably secreted Apo-B in this model, which is kind of a nice proof of principal that this idea of integrating proteomics and genomics may lead to some novel biological pathways. Jane Ferguson:                Yeah, it's really interesting. So what's next. There are probably a lot more associations that you're going to have to go after? Mark Benson:                  Yeah, I think that what this showed us is that this seems like a powerful tool. Joining these orthogonal data sets to find new pathways and so we're continuing to pursue that with an increasing number of proteins for example, so we're doing genome-wide association studies and x-gamma rays. We've gone from 156 to 1100 to 1300 and are now going beyond that and so as those numbers get higher, you start to see these central nodes come together and more interesting targets and potential pathways. It's also interesting to use these data to find new associations or new tools that you would never think to look for as ways to modulate protein levels.                                            So you can imagine, for example, one thing that we've been exploring for the last few months is can we identify, for example, SNP associated with an interesting circulating protein. That SNP maps to an enzyme or some other druggable mechanism and very preliminary studies, it seems like the answer is probably yes, but there is still a lot of work to be done. Jane Ferguson:                Well that's cool. That sounds really interesting. Mark Benson:                  Yeah, I think the key thing is that all these data will soon be out there and so it's a very rich data set and I think there are many ways that we could use the data. Jane Ferguson:                So is that the genomic data and all the proteomic data or it's the summary of the those associations? Mark Benson:                  All the genomic data, all the proteomic data and the associations as well. You can do the associations yourself if you'd like to. Jane Ferguson:                We can find that  dbGaP. Awesome, well thank you for talking to us. Mark Benson:                  Thank you. It's been fantastic. Jane Ferguson:                Congratulations again. Mark Benson:                  Thanks so much. ... Jane Ferguson:                Jenny Lin is an instructor at the University of Pennsylvania, working with Dr. Kiran Musunuru. Her presentation was entitled, "RNA binding protein A1CF Modulates Plasma Triglyceride Levels through Transcriptomic Regulation of Stress-Induced BLDL Secretion".                                            Jenny, can you take a moment to introduce yourself? Jenny Lin:                          Yes, hi. Thank you for this opportunity to participate. I'm Jenny Lin. I'm an instructor of medicine at the University of Pennsylvania, a nephrologist by clinical training, but training in cardiovascular research in Kiran Musunuru's lab. Jane Ferguson:                So congratulations for getting selected as a finalist for the Young Investigator Award. We'd love to hear a little bit more about what you've been presenting and what you've been working on. Jenny Lin:                          Thank you. So basically, what I've been working on over the past year is functional follow-up of this A1CF locus, which is a novel locus for triglycerides. So say Sek Kathiresan's group recently published in Nature Genetics and x and y association study on plasma lipids involving more than 300,000 individuals.                                            One of the key findings from that study is this strong association between a lo-frequency coding variant and elevated plasma triglycerides. So we wanted to delve more deeply into the biology for why we have that genotype/phenotype connection. One of the key things that we wanted to do was ... A1CF is not a stranger to lipo-protein metabolism, but we wanted to see what else it may be doing outside of its canonical role of facilitating the editing of Apo-B messenger RNA.                                            It really took us on a little bit of a wild journey using different unbiased approaches to try to figure out some of the mechanisms that could be behind it. Jane Ferguson:                So you had to do a lot of different types of experiments to really get at this question. Jenny Lin:                          Yeah. So again, one thing we wanted to see was: if you lose A1CF function, whether or not you would have differences in Apo-B 100-B48. We actually found that A1CF isn't even needed for that editing reaction and that our mice that we were able to create with crispr cas9 genome editing, so knocking in the mutation and knocking out the gene, actually have the phenotype even though they don't have changes in editing.                                            But what surprised us was that we know that A1CF as an RNA binding protein binds Apo-B transcript, yet it somehow does not alter transcriptional abundance of the Apo-B messenger RNA. And it has nothing to do with Apo-B synthesis so we basically had to think, what is A1CF doing outside of Apo-B biology?                                            We found that you have A1CF loss of function, you have increased triglycerides secretion. There is more Apo-B secretion, but that seems to be a downstream effect of other processes going on in the cell and to really try to figure out what those processes are, we had to take an unbiased approach using enhanced clipseek to figure out binding targets and also doing some transcriptional profiling with RNA sequencing and found that it's not necessarily regulating that transcriptum on a differential expression level, but there are some key alternative splicing events as well as messenger RNA binding to affect translational efficiency of some key targets that could be driving the biology. Jane Ferguson:                That's really interesting and you wouldn't have been able to find that by just looking at levels of protein or levels of mRNA, you really had to do these additional clipseek and some experiments to really get at this splicing. Jenny Lin:                          Yeah, so it's been interesting. Clipseek is not as commonly performed method, so we had to collaborate with some brilliant people over at UCSD, to help us facilitate this. But again, finding that A1CF binds many more transcripts than Apo-B itself is a novel finding and the fact that it can regulate alternative splicing is also a very novel finding as well. Jane Ferguson:                So what was the most challenging part of this whole project? Jenny Lin:                          I think the challenging part was that when we saw there wasn't necessarily a direct effect on Apo-B abundance and having to then cast this wide net and then figure out from all of the different unbiased data we have and integrating it find different pathways that may be relevant. In this case, it may all be relevant to ER stress, which is a field that is a little bit controversial in VLDL secretion in terms of directionality, but certainly is important in the biology. Jane Ferguson:                So is that something that you're going to have to start doing in the future? Are you going to start looking at ER stress or what kind of other experiments do you think you're going to keep doing to move this project forward? Jenny Lin:                          Yeah, so actually, I think focusing in on A1CF as an RNA-binding protein and pursuing some of these additional targets will also be relevant, so I think in terms of ER stress, we could be looking at different targets, but there other processes going on in the cell that's mediated by A1CF, that could contribute maybe doing some isoform specific studies just to really prove that these alternative-splicing changes are driving some of the biology.                                            There's a lot of work to do as I would joke to anyone on study section listening to this, perhaps four to five years of work for an RO1. Jane Ferguson:                Sounds very appropriate. Jenny Lin:                          Yeah, there's a lot of exciting work to do. A1CF is actually also a locus for other cardio-metabolic relevant traits such as uric acid, gout and kidney function so there could be something very interesting going on. There could be cross talk among cellular processes that could lead to these different phenotypes. Jane Ferguson:                Really interesting project and a lot of really great work. Congratulations again on being selected as finalist and on this really interesting paper. Jenny Lin:                          Thank you. Jane Ferguson:                Thanks.                                            Sarah Parker is based in Cedar Sinai Medical Center in LA and her mentor is Dr. Jenny Van Eyk. The title of her presentation was "Identification of Putative Fibrous Plaque Marker Proteins by Unsupervised Deconvolution of Heterogeneous Vascular Proteomes ". And I apologize in advance for the quality of this recording. The background noise wasn't that noticeable at the time, but that recording really gives you that full immersive audio experience of a busy hotel lobby.                                            Hey Sarah. Thank you for joining us. Could you just take a few moments to introduce yourself to the audience? Sarah Parker:                   So I'm Sarah Parker. I'm a project scientist at Cedar Sinai Medical Center where I'm doing work to study the basic mechanisms of vascular biology of various indolent conditions. Jane Ferguson:                So congratulations on being selected as a finalist for the Young Investigator Award. It's a great achievement. I'd love to hear a bit more about your project, how that started and what you found. Sarah Parker:                   The work that I did was under the overarching umbrella of a project called the Genomic and Proteomic Architecture of Atherosclerosis. So with this project, we're using tissues that we're able to obtain from individuals who are young and have passed away from traumatic and violent and so non-cardiovascular causes of death. Because of the presence of atherosclerosis in the population, we get this range of lesion, both fatty streak and fibrous-plaque lesions in these asymptomatic or non-diseased individuals and this gives us this opportunity to do some molecular profiling to really try to find protein-signatures of early stage plaque formation, that could ultimately and hopefully be used for biomarker development. Jane Ferguson:                That's really cool and that's such a valuable sample resource. Sarah Parker:                   Yeah so we've essentially, in this project I was able to set up a pipeline that enabled us to do these proteomics on such a large scale, because that's actually really difficult in label free quantitative proteomics and to use other forms becomes very expensive and cost-limiting.                                            So we were able to find a panel of proteins that we think are a putative early set of fibrous plaque markers and with this panel, we took them to see if any of these tissue derived markers would then be detectable and informative in plasma, because that's the next really big translational leap with these discovery-type data sets. Of our 58 initial candidates, we were able to detect 39 of them and about a handful 10-13 are showing informative behavior in the plasma of initial cohort of women with known coronary-artery disease. Jane Ferguson:                So out of the 58 that you first found, how many of them were potentially known to be involved in disease and how many were novel? Sarah Parker:                   I would say, going through the list, it was probably about 50/50 in terms of background data that shows role as a biomarker, so there are a lot of apolipoproteins, which have all been characterized as potential biomarkers. There were a lot that could feasibly be linked through the literature to atherosclerosis. Most of them made a lot of sense, but having been proposed as potential biomarkers, some of them were more rare. Jane Ferguson:                Were there any of them that were sort of in different directions, let's say were elevated in tissue, but then were lower in plasma? Sarah Parker:                   Funny you should ask. That actually has us scratching our heads a little bit right now. There were a couple of apolipoproteins that are more associated with HDL biology that we saw as being elevated in the tissue but then lower in the plasma [inaudible 00:23:34] so that's a really interesting observation so something about the role of these proteins to scavenge cholesterol and then once they're in the blood, they're cleared really quickly relative to normal, or something. So we're really trying to figure out what that biology means. Jane Ferguson:                Maybe if they're building up in the tissue, that's bad. But while in circulation, they're fine. Sarah Parker:                   Yeah, maybe they're trapped in the circulation. We have a lot of exciting hypotheses to test along that front. Jane Ferguson:                So what's next? Are you following up some of these proteins? Sarah Parker:                   Yep, so we have a huge discovery arm to the project where we're looking for more molecular mechanisms like why do we have these things in the tissue versus plasma and then we are working to really validate and optimize these multi-plexes in much more generalized large-scale populations to determine whether this strategy of instead of one or two biomarkers, more of a signature-style panel can be informative, especially as we try to press towards a precision medicine approach where different substratum might be informed by different protein signatures. Jane Ferguson:                Right, so you might have to have a specific panel based on sex or age or race or some other demographic. Sarah Parker:                   Yes and to find those signatures, it's going to be very big numbers, with very accurate, careful quantitation. Jane Ferguson:                So you have a lot of work to do. Sarah Parker:                   Yes. Jane Ferguson:                Alright, well thank you for talking to us and congratulations again.                                            Louie Wang, a cardiologist and PhD student came all the way from the Victor Chang Cardiac Research Institute in Syndey, Australia. His mentor is Dr. Diane Fatkin. The title of his talk is "A novel zebrafish model of human A-band truncated titan exhibits alternated ventricular diastolic compliance in vivo and reveals enhanced susceptibility to the effects of volume overload in mutation carriers.                                            So thank you for joining me. Could you take a few minutes to introduce yourself? Louie Wang:                     So I'm Louie Wang. I'm a cardiologist based in Australia. I work and live in Sydney. I'm a PhD student at the Victor Chang Cardiac Research Institute and I'm an NHMRC (National Health and Medical Research Council and National Heart Foundation of Australia post-graduate scholar). I have previously been based at St. Vincent's Hospital. Jane Ferguson:                Great. So we'd love to hear a little bit in advance of what you're working on and what you're planning to present. Louie Wang:                     So basically what I'm presenting is what I think is a different form of functional of genomics. What we're actually looking at is the impact of genetic changes, specific genetic change on function of the heart at an organ level. So there is a problem out there that is very common in cardiology and it's a big problem in cardiology and that is there are mutations in the sarcomere protein titan, truncating variants which actually are associated with dilated cardiomyopathy.                                              Now they're pretty common in idiopathic dilated cardiomyopathy, present in about 15-20% of the cases depending on which cohort study you look at. But they're also widely prevalent in the general population. Somewhere between 0.3 to 1% of the general population carries this truncating variants or various forms of this truncating variant.                                            So it's not sure whether these are disease-causing in their own right or if it's just a genetic susceptibility factor for heart failure and so what our work involves is that we actually, by chance, at St. Vincent's Hospital and at Victor Chang Cardiac Institute, two families who had the identical genetic truncation in the A-band region of his human titan gene where the individuals in the family, typically who carried the gene, typically developed systolic heart failure, which is a mild phenotype and occurred at middle age, but in two individuals, they developed severe onset accelerated disease trajectory in a very severe phenotype when exposed to conditions associated with chronic volume overload.                                            We suspect and this was a hypothesis, not only was this genetic-truncation disease-causing, but at volume overload was disease-modifying and given that volume overload is a very common condition present in birth, a lot physiological processes like lung endurance, exercise, pregnancy as well as a lot of pathological disease states in cardiovascular disease, this was actually a very important modifiable factor.                                            So what we did, was we created a novel zebrafish model of this human A-band truncated variant. We then studied the animals when they became adults to look at their heart structure and function and we used zebrafish echocardiography. So reversed translated all the techniques you can do in human echocardiography so they can be used in the zebrafish.                                            What we found was, yes, this animal, or heterozygotes developed dilated cardiomyopathy but also the volume overload exacerbated this condition. So this is a phenomenon that has conserved this by four hundred million years of vertebrate evolution so this is a pretty important mechanism. Jane Ferguson:                So what kind of next steps do you see for this project? Louie Wang:                     So one thing is that we obviously have shown that there is an association with volume overload in precipitous disease. The corollary of our work is that perhaps interventions that could reduce volume load in these genetic susceptible individuals or alternatively in people who can't avoid volume overload. Because a lot of volume overload conditions can be modifiable and perhaps this could be protective and that would have wide-ranging population benefits. Jane Ferguson:                Thank you for sharing that soundbite of your work and good luck. Congratulations again on becoming a finalist. Louie Wang:                     Thank you. ... Jane Ferguson:                Each of these four finalists gave compelling presentations of their research and the judges were highly impressed of the quality of the research and level of accomplishments of these early career investigators.                                            Just getting selected as a finalist for this award is a huge accomplishment. But there did have to be one winner. I'm delighted to announce that Jenny Lin was selected as the 2017 FGTB Young investor award winner. Congratulations, Jenny, and thanks to all four finalists for agreeing to appear on this podcast.                                            And that's all for this month. We'll be back at the end of December with a new episode. Subscribe to the podcast through iTunes or your favorite podcast app. to get new episodes delivered automatically and thank you for listening.

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. Today's feature discussion centers on the population burden of sudden death associated with hypertrophic cardiomyopathy. These are novel data from the ongoing Oregon sudden unexpected death study, results that may surprise you. Stay tuned and that's coming up right after these summaries.                                              The first original paper in this week's journal tells us that risk reductions from air pollution control yields health benefits comparable to the control of systolic hypertension and smoking in a high risk segment of the urban Chinese population. First author Dr Huong, corresponding author Dr Gu and colleagues from Fu-Wai hospital in Beijing China projected the life years gained if urban China were to reach one of three air quality goals. First, Beijing Olympic games level. Second, China class 2 standard. Third, the WHO standard. They further compared projected air pollution reduction control benefits with the potential benefits of reaching WHO hypertension and tobacco control goals.                                              Now to do this, the authors used the Cardiovascular Disease Policy Model: China, which is a computer simulation state transition mathematical model of coronary heart disease and stroke incidence, prevalence, mortality, non-cardiovascular deaths, and costs of health care in the Chinese population. They found that air quality improvement under the different scenarios could lead to a great health benefit, ranging from 241,000 life years gained to much greater benefits, benefits that were greater to or equal to the combined benefits of a 25% improvement in systolic hypertension control, and a 30% smoking reduction. Thus, the authors called for joint efforts of the whole society for air quality improvement in China.                                              The next study describes six differences and similarities in atrial fibrillation epidemiology, risk factors, and mortality in the community. First author Dr [Magnusson 00:02:42], corresponding author Dr [Schnabel 00:02:44] and colleagues from University Heart Center Hamburg Eppendorf studied 79,793 individuals without atrial fibrillation diagnosis at baseline from 4 community-based European studies, namely, FINRISK, DanMONICA, Molisani, and Northern Sweden, all followed for a medium of 12.6 years. They found that cumulative incidence increased markedly after the age of 50 years in men and after the age of 60 years in women. The lifetime risk was similar in more than 30% for both sexes.                                              Subjects with incident atrial fibrillation had a three and a half fold higher risk of death compared with those without atrial fibrillation. Among the classical risk factors, body mass index explained the largest proportion of atrial fibrillation risk. Six interactions were seen for the risk associations of body mass index and total cholesterol, wherein body mass index was associated with a greater risk increase in men than women, whereas total cholesterol was inversely associated with incident atrial fibrillation with a greater risk reduction in women than men.                                              The next study describes a novel circular RNA as a potential target in diabetic proliferative retinopathy. Circular RNAs are a novel class of non-coding RNAs that regular gene expression and they're characterized by closed loop structures with neither five-prime, nor three-prime polarity nor a polyadenylated tail. In today's study, first author Dr [Shah 00:04:33], corresponding authors Drs. [Yen 00:04:33] and [Zhao 00:04:36] from Shanghai Medical College Fudan University in China characterized the expression and regulation of the circular RNA, circHIPK3 in retinal endothelial cells and diabetic retinal vascular dysfunction.                                              CircHIPK3 expression was significantly up regulated upon high glucose stress in vivo and in vitro and regulated retinal endothelial cell function and vascular dysfunction by acting as an endogenous microRNA 30A-3P sponge that sequestered and inhibited its activity. In summary therefore, the circular RNA circHIPK3 plays a role in diabetic retinopathy by blocking microRNA 30A function, leading to increased endothelial proliferation and vascular dysfunction. These data suggest that the circular RNA may be a potential target for diabetic proliferative retinopathy.                                              The next study identified important new principles of endogenous chromatin structure that have key implications for epigenetic therapy. In this study from first author Dr Rosa-Garrido, corresponding author Dr Vondriska, and colleagues of David Geffen School of Medicine in UCLA, the authors examined changes in chromatin configuration in cardiomyocytes isolated from mouse hearts subjected to transverse aortic constriction or hearts subjected to Tamoxifen inducible cardiac specific excision of CTCF, which is a ubiquitous chromatin structural protein.                                              There was several important findings from this work. Firstly, the authors found that depletion of CTTF was sufficient to induce heart failure in mice and human heart failure patients receiving LVADs also showed increase CTCF abundance. Pressure overload or CTCF depletion selectively altered the boundary strength between topologically associated domains, which are regions of DNA in which physical interactions occur frequently. The authors showed that there were changes in the compartmentalization of active chromatin and inactive chromatin segments, which is a measure of genomic accessability.                                              Heart failure involved decreased stability of chromatin interactions around disease causing genes. In summary, these finding provide a high resolution chromatin architectural resource for cardiac epigenomic investigations and also demonstrate that global structural remodeling of chromatin underpins heart failure.                                              The final study is the first to provide insights into the fluid mechanics of transcatheter valve thrombosis. First author Dr Midha, corresponding author Dr Yoganathan and colleagues from Georgia Institute of Technology and Emory University in Atlanta analyzed post-procedural four dimensional volume rendered CT data of transcatheter aortic valve replacement, or TAVR patients, enrolled in the Resolve trial, excluding patients on anticoagulation. Patients were classified as having transcatheter heart valve thrombosis if there was any evidence of hypoattenuated leaf thickening. The authors studied the flow characteristics within the neo sinus which is formed followed deployment of a transcatheter valve into a native aortic valve.                                              The authors found that post deployment valve geometry and final implant position affected the flow within the neo sinus, which in turn, may affect the predisposition to thrombus formation. The impact of geometry and position varied according to the different valve types. A supra-annular transcatheter heart valve deployment resulted in a nearly seven fold decrease in stagnation zone size when compared to an intro-annular deployment. In addition, the in vitro model indicated that the size of the stagnation zone increased as cardiac output decreased. In summary, deployed transcatheter heart valve geometry may have implication on the occurrence of thrombosis and a supra-annular neo sinus may reduce thrombosis risk due to reduced flow stasis. While additional prospective studies are clearly needed, these results may help identify patients at higher thrombosis risk and aid in the development of the next generation of devices with reduced thrombosis risk.                                              Well, that wraps it up for our summaries. Now for our feature discussion.                                              Sudden death in hypertrophic cardiomyopathy has been and still is a very hot topic in cardiology. Of course it's understandable given all the high profile deaths that have occurred in young athletes ascribed to hypertrophic cardiomyopathy and the fact that these deaths may potentially be preventable with implanted defibrillators. However, we're so proud to have in this week's journal, some of the first data on the population-based burden of sudden death associated with hypertrophic cardiomyopathy. I'm so happy to have with us the corresponding author of this research letter, Dr Sumeet Chugh from Cedar Sinai Medical Center, as well as Dr Mark Link, associate editor from UT Southwestern. Welcome, gentlemen. Dr Sumeet Chugh:            Thank you. Dr Mark Link:                    Thank you. Dr Carolyn Lam:               Sumeet, you know as I said in the introduction, sudden death in hypertrophic cardiomyopathy, we've talked about it a lot. There's been lots published. What makes your data so novel? Dr Sumeet Chugh:            There is indeed a large body of work related to hypertrophic cardiomyopathy but most of it came from registries. Probably what's a bit unique about our work is that it was done in one large, US community over a number of years. Dr Carolyn Lam:               Indeed. So population-based statistics, not just of hypertrophic cardiomyopathy, but of sudden death related to it, isn't it? Dr Sumeet Chugh:            That's correct, Carolyn. Dr Carolyn Lam:               I think the other thing that we were just actually chatting about is the fact that it's contemporary. Could you tell us maybe the period you're looking at and then give us your findings? Dr Chugh:                           Yes. The study was initiated in 2002 and is now in it's 16th year, so this particular analysis was conducted between the time period 2002 and 2015. What we do in the process of this community-based work is that we track prospectively every cardiac arrest that happens in the community centered around Portland, Oregon in the USA. The work in performed in the process of doing a multiple-source ascertainment where we take the help of the first responders or the ambulance personnel, the hospital emergency rooms, as well as the police, and the coroner network. It's a fairly comprehensive way of ascertaining sudden cardiac arrest. Dr Carolyn Lam:               That is a very unique and valuable data set. Could you summarize the top line results, because they were rather surprising? Dr Sumeet Chugh:            We are already learning that over time, with more awareness, education, and modern management of hypertrophic cardiomyopathy, the risk of sudden cardiac arrest and the overall morbidity from hypertrophic cardiomyopathy may be on its way down. What this study is showing is, that actually the risk of sudden cardiac arrest and the burden of sudden cardiac arrest from hypertrophic cardiomyopathy in the community may be quite low. Those are the main findings. Dr Carolyn Lam:               Yeah. In fact, I was just so impressed because first of all, you excluded the individuals in this population and found that hypertrophic cardiomyopathy was responsible for 1 in 30 of the cardiac deaths, but that the incidence of the sudden deaths were 0.2 to 0.3% among these hypertrophic cardiomyopathy patients, perhaps less than others may have expected.                                              Mark could I bring you in on this for a moment? What do you think are the take home messages for something like this, because in a young and middle age population, is any rate really too low? Dr Mark Link:                    I think this is great data because it encompasses an entire population, so it gets us good data on the true incidence of sudden cardiac death. In the study, if you look at the total number of patients that either had an ECHO or had an autopsy, about 5%, a little over 5% of them, had hypertrophic cardiomyopathy. Roughly 5% of the individuals dying suddenly, under age 60 are dying secondary to hypertrophic cardiomyopathy. That's the sort of data that we really didn't have before because we didn't have such a nice population-based study.                                              It was interesting also, they tended to be younger, 10 years younger than the others dying suddenly, so it was a younger cohort. They more often had ventricular fibrillation or ventricular tachycardia than the others dying suddenly. It really does give us some nice data on the true incidence of sudden death due to HCM in the community. Dr Carolyn Lam:               What I thought was also valuable was the fact that the diagnosis of hypertrophic cardiomyopathy was quite often missed prior to the cardiac arrest and I'm trying to wrap my head around about what that implies. Dr Sumeet Chugh:            That's a very important point, Carolyn. These findings also give us the message that our risk classification methodology continues to need more work. The fact remains that a significant proportion of patients with hypertrophic cardiomyopathy are also going to be asymptomatic. Sometimes they just don't come to our attention.                                              Another important point, however, that's related to this work is that there may have been during the course of this time period, at least a few patients in this community who would have received an implantable defibrillator and their sudden cardiac arrest would have been averted, so we're not able to count those individuals who were already found and managed. Dr Mark Link:                    That's a very important point because if a person is found with HCM and has risk factors, they would get a implantable defibrillator. Those individuals would not show up in this database because they wouldn't die. Dr Carolyn Lam:               Mm-hmm (affirmative)-                                              That's a very, very important point. Thank you for highlighting that. I think it goes back to why these data are so important, because they are contemporary as well and we really need such estimates, so congratulations Sumeet and thank you for giving us these valuable data.                                              I'd like to switch tracks a little bit though, and point out this was a research letter, a big data set, important findings, but published as a research letter. Should I even say but? Mark could you comment a little bit about research letters in circulation versus original articles? Dr Mark Link:                    We increasingly are using research letters in circulation for original research that drives home a basic single point. If that basic single point can be made in 1,200 words, we actually like the research letter format. It's a quick read, people remember it, it's cited. It is something that authors that we ask to turn a full length manuscript into a research letter, should be taking that as a positive sign, because that means that we're interested in the topic and would like to see it in print. Dr Carolyn Lam:               I completely agree and in fact, Sumeet, if I could ask you to weigh in. Sometimes it's harder, isn't it, to write a research letter than to write a full length manuscript? How was your experience? Dr Sumeet Chugh:            I have to admit that the first responses as you said, where you feel, "Oh, I've spent a lot of effort in writing this large paper, and now I have to squeeze it into 1,200 words," but the second thought for me was, "The fact is that this is a one bullet message and why not make it shorter and snappier as it is?" I think I've come around in the appropriate situation to appreciating this opportunity of writing a research letter. Dr Mark Link:                    when you read the research letters, they're very succinct. I actually like them. They get the message across quickly and I think it's a great way to produce science and to show what you've done. Dr Carolyn Lam:               Yeah. The thing is that we also restrict to a single figure, or a single table and I cannot tell you how many times I've referred to that single figure because it usually tells the full story and it's beautiful summary.                                              So, listeners, you've heard about the research letters in circulation. Please have a look at them. I'm pretty sure that you will fall in love with the format just like we all have.                                              Thank you so much, Sumeet and Mark for joining me today. I'm afraid our time is up, but I've so enjoyed talking to you. Thank you, listeners, for following us today. Don't forget to tune in again next week.  

Guest Dr. Clive Svendsen is the Director of the Board of Governors Regenerative Medicine Institute and Professor of Biomedical Sciences at Cedar Sinai Medical Center. One focus of his current research is to derive cells…

Back from Christmas break, we talk about Star Wars, tornadoes in Texas, and $400 per person for an Olive Garden meal at Times Square. We talk to Dr. Dean Sherzai and his colleague and wife Dr. Ayesha Sherzai, of Cedar Sinai Medical Center, about the detection and prevention of Alzheimer disease and dementia. Find out about this cruel disease and how you can get involved and lower your risk.

Back from Christmas break, we talk about Star Wars, tornadoes in Texas, and $400 per person for an Olive Garden meal at Times Square. We talk to Dr. Dean Sherzai and his colleague and wife Dr. Ayesha Sherzai, of Cedar Sinai Medical Center, about the detection and prevention of Alzheimer disease and dementia. Find out about this cruel disease and how you can get involved and lower your risk.

A Los Angeles native, Andrew Weiss, M.D. graduated from the Harvard School and then left Southern California to attend college and play soccer at the University of Pennsylvania. After graduating Magna Cum Laude, with a Bachelor of Arts in the Biological Basis of Behavior, Dr. Weiss returned to Los Angeles and taught high school biology and algebra. He subsequently attended medical school at the University of California, Los Angeles School of Medicine where he graduated with honors/Alpha Omega Alpha and then completed an orthopedic surgery residency at UCLA-Harbor Medical Center. During his residency, Dr. Weiss had extensive exposure to general orthopedics and orthopedic trauma. Afterwards, he completed a sports medicine fellowship at UCLA Medical Center, where he served as a team physician for the UCLA football, volleyball, and baseball teams. In addition to his background in general orthopedics, orthopedic sports medicine, and orthopedic trauma, Dr. Weiss loves working with children and has developed expertise in treating pediatric orthopedic trauma, including the operative and non-operative management of broken bones and other injuries. He has written many articles on laser surgery and the MRI evaluation of articular cartilage and has lectured extensively on the evaluation and management of sports related injuries. As an avid runner, competing in both marathons and triathlons, he has firsthand knowledge of the physical and mental challenges athletes face. Dr. Weiss is a Board certified Diplomate of the American Board of Orthopaedic Surgery and a member of the American Association of Orthopaedic Surgeons. He serves on staff at Cedar Sinai Medical Center. Outside of work, Dr. Weiss enjoys traveling, watching college athletics, and, most of all, spending time with his wife and three young daughters.

A Los Angeles native, Andrew Weiss, M.D. graduated from the Harvard School and then left Southern California to attend college and play soccer at the University of Pennsylvania. After graduating Magna Cum Laude, with a Bachelor of Arts in the Biological Basis of Behavior, Dr. Weiss returned to Los Angeles and taught high school biology and algebra. He subsequently attended medical school at the University of California, Los Angeles School of Medicine where he graduated with honors/Alpha Omega Alpha and then completed an orthopedic surgery residency at UCLA-Harbor Medical Center. During his residency, Dr. Weiss had extensive exposure to general orthopedics and orthopedic trauma. Afterwards, he completed a sports medicine fellowship at UCLA Medical Center, where he served as a team physician for the UCLA football, volleyball, and baseball teams.In addition to his background in general orthopedics, orthopedic sports medicine, and orthopedic trauma, Dr. Weiss loves working with children and has developed expertise in treating pediatric orthopedic trauma, including the operative and non-operative management of broken bones and other injuries. He has written many articles on laser surgery and the MRI evaluation of articular cartilage and has lectured extensively on the evaluation and management of sports related injuries. As an avid runner, competing in both marathons and triathlons, he has firsthand knowledge of the physical and mental challenges athletes face.Dr. Weiss is a Board certified Diplomate of the American Board of Orthopaedic Surgery and a member of the American Association of Orthopaedic Surgeons. He serves on staff at Cedar Sinai Medical Center. Outside of work, Dr. Weiss enjoys traveling, watching college athletics, and, most of all, spending time with his wife and three young daughters.

If you have had a transplant, blood transfusion or a child, you might have antibodies that prevent you from getting transplanted. Dr. Stanley Jordan of Cedar Sinai Medical Center describes this breakthrough treatment called "desensitization" which allows people with high antibodies to receive a successful kidney transplant. Listen to Lori's story about how she underwent this treatment protocol which made it possible for her to receive her 4th kidney transplant.

Dr. Robert Reyna is a Diplomat of the American Board of Sleep Medicine and a fellow of the American Academy of Pediatrics. He has been involved in Sleep Medicine since he was trained as a sleep technician during his undergraduate work at Stanford University in the early 80’s. After receiving his medical degree from the University of California, San Diego, he completed his residency in Pediatrics at Cedar-Sinai Medical Center. He helped to develop and expand sleep services in Southern CA in 1992 becoming Medical Director of Sleep Services in 2002 when he received his board certification from the American Board of Sleep Medicine. He has also been involved in research in the field of insomnia at the Instate Sleep Center in Cincinnati, studying the clinical importance of certain brain waves called CAPS( Cyclic Alternating Patterns). Dr Reyna worked in concert with other medical centers in Southern CA to create a multi-specialty Cognitive Behavior Therapy insomnia program and helped implement a self­-directed web based program utilized by a local health maintenance organization. He joined The Sleep Center of Nevada in February of 2009, moving to Las Vegas with his wife and two children. “I accepted the position here in Las Vegas so I could help in educating the community on the importance of sleep and the role sleep has in promoting a healthy lifestyle.”http://randinternational.net/sleep/