Podcasts about Cardiovascular Research

ReferencesCancer Med. 2012 Oct; 1(2): 176–186.Stem Cells. 2007 Feb;25(2):500-10. Cardiovascular Research 2022., cvac159, Nature Metabolism 2019.volume 1, pages 937–946 Nature Cardiovascular Research 2023. volume 2, pages 425–437 Vivaldi, A 1715. Glorias.https://music.youtube.com/watch?v=RMHguvZPcqQ&si=qPFr541Aep0KHle2Kaukonen. 1969."Good Shepard" Jefferson Airplame Volunteers.lphttps://music.youtube.com/watch?v=XtrYVj5e3cs&si=KSmil31KJwmH_P11

Un nuovo studio internazionale coordinato dall’I.R.C.C.S. Neuromed, in collaborazione con l’Università Sapienza di Roma e la Vanderbilt University (USA) e pubblicato su Cardiovascular Research evidenzia il ruolo inedito delle cellule del sistema immunitario nella regolazione della pressione arteriosa. A Obiettivo Salute il commento della prof.ssa Daniela Carnevale, ordinario dell’Università Sapienza e responsabile del Laboratorio di Ricerca Neuro e Cardiovascolare dell’I.R.C.C.S. Neuromed, che ha coordinato lo studio.

In this episode, Deputy Editor Dr. Zamaneh Kassiri (University of Alberta) interviews authors Dr. Oliver H. Wearing (University of British Columbia), Dr. Naomi C. Chesler (University of California Irvine), Dr. Mitchel J. Colebank (University of South Carolina), Dr. Timothy A. Hacker (University of Wisconsin-Madison), Dr. John N. Lorenz (University of Cincinnati), and Dr. Christopher R. West (University of British Columbia) about their new Guidelines in Cardiovascular Research article. This must-read Guidelines article provides a thorough overview of ventricular pressure-volume (PV) measurements in the mouse heart. PV measurements are an invasive method for assessment of heart function, and if done correctly, can provide researchers with valuable information about heart hemodynamics and the relationship between changes in ventricular pressure and volume during a cardiac cycle. The authors discuss PV measurements as the gold standard for assessing cardiac in vivo function. How do PV measurements differ from, and provide a complement to, echocardiography measurements? Listen and find out more.   Oliver H. Wearing, Naomi C. Chesler, Mitchel J. Colebank, Timothy A. Hacker, John N. Lorenz, Jeremy A. Simpson, and Christopher R. West Guidelines for assessing ventricular pressure-volume relationships in rodents Am J Physiol Heart Circ Physiol, published January 2, 2025. DOI: 10.1152/ajpheart.00434.2024

This week's guest is one of the most highly respected Sports Cardiologists in the world and a sub 2:30 marathoner. He is the Head of the Heart, Exercise and Research Trials Lab at St Vincent's Institute and the Victor Chang Cardiovascular Research Institute, as well as being a Cardiologist and Head of Cardiovascular Research at St Vincent's Hospital Melbourne. He completed a PhD at St Vincent's and University of Melbourne and 4 years of post-doctoral research at the University Hospital of Leuven in Belgium. His research and clinical work focuses on the effect of exercise on the human heart. He has more than 300 peer-review publications and text-book chapters, serves on multiple international guideline statements and is regularly invited to present at all major international cardiology conferences. Patreon Link: https://www.patreon.com/insiderunningpodcast Opening and Closing Music is Undercover of my Skin by Benny Walker. www.bennywalkermusic.com Join the conversation at: https://www.facebook.com/insiderunningpodcast/ To donate and show your support for the show: https://www.paypal.com/cgi-bin/webscr?cmd=_s-xclick&hosted_button_id=9K9WQCZNA2KAN

Sometimes negative results can be just as interesting as positive ones. Nivetha Subramaniam, a student at McGill University, discusses her research regarding the potential cardiovascular risks from exposure to mixtures of arsenic and cadmium with co-hosts Anne Chappelle, PhD, and David Faulkner, PhD.About the GuestNivetha Kamalavannan Subramaniam is a PhD student at McGill University in Canada. She is the recipient of the McGill Dr. Morris Karmazyn and Dr. Margaret P. Moffat Fellowship in Cardiovascular Research. The title of her PhD thesis project is "The Pro-atherogenic Effects of Arsenic and Cadmium Mixtures."Ms. Subramaniam serves as the Graduate Student Representative for the SOT Metals Specialty Section, and in 2023, she received the second place prize from the SOT Metals Specialty Section Student Research Award Fund.Send SOT thoughts on the episodes, ideas for future topics, and more.

In our latest episode, Dr. Jeff Saucerman (University of Virginia) interviews authors Dr. Naomi Chesler (University of California, Irvine) and Dr. Mitchel Colebank (University of South Carolina) about their new Guidelines in Cardiovascular Research article on incorporating mechanistic modeling into the analysis of experimental and clinical data to identify possible mechanisms of (ab)normal cardiovascular physiology. The authors' goal is to provide a consensus document that identifies best practices for in silico computational modeling in cardiovascular research. These guidelines provide the necessary methods for mechanistic model development, model analysis, and formal model calibration using fundamentals from statistics. Colebank et al. outline rigorous practices for computational, mechanistic modeling in cardiovascular research and discuss its synergistic value to experimental and clinical data. Would you like to understand how to apply a cone of uncertainty to your experimental data? Listen now to find out more.   Mitchel J. Colebank, Pim A. Oomen, Colleen M. Witzenburg, Anna Grosberg, Daniel A. Beard, Dirk Husmeier, Mette S. Olufsen, and Naomi C. Chesler Guidelines for mechanistic modeling and analysis in cardiovascular research Am J Physiol Heart Circ Physiol, published August 6, 2024. DOI: 10.1152/ajpheart.00253.2024

Professor Robert Byrne, Professor of Cardiovascular Research at the Royal College of Surgeons of Ireland, reacts to new research indicating that some weight loss drugs can also help people live longer.

Thomas Diacovo, MD, is chief of the UPMC Newborn Medicine Program and director of Neonatal Cardiovascular Research at the Heart Institute. Dr. Diacovo discusses how he became interested in Thrombosis research, his journey to Pittsburgh, and his research testing new drugs for neonatal intensive care patients, particularly those with congenital heart disease who are at high risk for forming blood clots. Dr. Diacovo also credits the parents of our patients for the success of his clinical trials.

Prof. Stefan Neubauer and Dr. Thomas Nero discuss two recent papers on the utility of coronary inflammation imaging on CT coronary angiography with Fat Attenuation Index (FAI)FAI score.  The Orfan study demonstrated a 29 fold increased risk in CV event rates with low vs high FAI score and a 10 fold increased event rate in patients with elevated FAI score who have no coronary plaque. FAI score re-categorized 40% of patients in their follow-up studies. Prof. Neubauer is the head of the Division of Cardiovascular Medicine and Director of the Oxford Centre for Clinical Magnetic Resonance Research (OCMR) at the University of Oxford and Past President of the Society for Cardiovascular Magnetic Resonance (SCMR).  He co-authored two recently published landmark papers:Farina NH, Mehta NN, Teague HL, et al. Inflammatory risk and cardiovascular events in patients without obstructive coronary artery disease: the ORFAN multicentre, longitudinal cohort study. Lancet. 2024;403(10392):1823-1835. doi:10.1016/S0140-6736(24)00596-8Farina, C. J., Davidson, M. H., Shah, P. K., Stark, C., Lu, W., Shirodaria, C., Wright, T., Antoniades, C. A., & Nilsson, J. (2024). Inhibition of oxidized low-density lipoprotein with orticumab inhibits coronary inflammation and reduces residual inflammatory risk in psoriasis: a pilot randomized, double-blind placebo-controlled trial. Cardiovascular Research, European Society of Cardiology, March 25, 2024.

Audio Summary by Dr Yuwen Chen

This episode of our podcast takes a deep dive into intermittent fasting and its effects on health. Joining the conversation is Ali Javaheri, MD, PhD, assistant professor of medicine from the Center for Cardiovascular Research at Washington University. Dr Javaheri explains what intermittent fasting does to the body and discusses the benefits and dangers of this eating plan in light of a recent viral study that found 8-hour time-restricted eating may relate to a higher risk of cardiovascular death. 

In our latest episode, Consulting Editor Dr. Kristine DeLeon-Pennell (Medical University of South Carolina) interviews fellow co-authors Dr. Charlotte Usselman (McGill University), Dr. Judy Regensteiner (University of Colorado Anschutz Medical Campus), Dr. Kerrie Moreau (University of Colorado Anschutz Medical Campus), Dr. Austin Robinson (Indiana University Bloomington), Dr. Jesse Moreira-Bouchard (Boston University), and Dr. Quin Denfeld (Oregon Health and Science University) about their recently published guidelines on the use of sex and gender in cardiovascular research. Until recently, the effects of sex and gender in cardiovascular research have been largely ignored in research design and reporting. The result is that women and gender diverse individuals have been understudied in basic and clinical research, leading to a lack of understanding of sex and gender in cardiovascular health and disease. The goal of these guidelines is to provide researchers with practical and actionable advice on best practices to include sex and gender considerations in study design, data collection, analysis, and interpretation. As Dr. Judy Regensteiner points out, “We have to make it doable. We can't just say, ‘Go do this.' We have to show people how to do it.” Ready to get started? Listen now to learn more.   Charlotte W. Usselman, Merry L. Lindsey, Austin T. Robinson, Beth A. Habecker, Chloe E. Taylor, W. David Merryman, Derek Kimmerly, Jeffrey R. Bender, Judith G. Regensteiner, Kerrie L. Moreau, Louise Pilote, Megan M. Wenner, Myles O'Brien, Timur O. Yarovinsky, Nina S. Stachenfeld, Nisha Charkoudian, Quin E. Denfeld, Jesse D. Moreira-Bouchard, W. Glen Pyle, and Kristine Y. DeLeon-Pennell Guidelines on the use of sex and gender in cardiovascular research Am J Physiol Heart Circ Physiol, published December 21, 2023. DOI: 10.1152/ajpheart.00535.2023

This month on Episode 55 of Discover CircRes, host Cynthia St. Hilaireaire highlights two original research articles featured in the December 8th issue of Circulation Research. This Episode also includes a discussion with Dr José Luis de la Pompa and Dr Luis Luna-Zurita from the National Center for Cardiovascular Research in Spain about their study, Cooperative Response to Endocardial NOTCH Reveals Interaction With Hippo Pathway.   Article highlights: Shi, et al. Nat10 Mediated ac4C in Cardiac Remodeling Knight, et al. CDK4 Oxidation Attenuates Cell Proliferation

References Sinatra, Frank. timeless. My Way. https://youtu.be/qQzdAsjWGPg?si=TcpVOHDikKyyQdmC Acta Neuropathol. 2023 Jun;145(6):749-772 Signal Transduction and Targeted Therapy 2022. volume 7, Article number: 175 Cardiovascular Research 2007. 74: 526 – 536 J Investig Med. 2023 Feb;71(2):113-123 --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

Atrial fibrillation (AFib) not only causes shortness of breath and palpitations but puts patients at increased risk of stroke. When medication or other treatments fail to relieve symptoms, cardiologists increasingly perform a catheter ablation procedure. A new study published in the Journal of the American College of Cardiology shows the procedure is successful in most patients, with few side effects. Joining me today to talk about AFib, medication treatments, cardiac ablation and the recent study is Peter R. Kowey, MD. Dr Kowey is a professor of medicine and clinical pharmacology at Sidney Kimmel Medical College at Thomas Jefferson University and the William Wikoff Smith Chair in Cardiovascular Research. In addition, Dr Kowey is the senior author of the study–Initial Findings From the National Cardiovascular Data Registry of Atrial Fibrillation Ablation Procedures Check out the video podcasts at Outbreak News TV on YouTube  

In honor of American Heart Month, we spoke with Dr. Michael Koren, Medical Director and CEO of ENCORE Research Group, as he shares his top tips for heart health – especially for busy professionals working in the clinical research industry. Dr. Koren also explores how cardiovascular research and treatment have progressed over the past several years as well as some exciting new learnings for this vital therapeutic area.

This year marks the 50th anniversary of the Bogalusa Heart Study. Started in 1973, this study looks at the impact of vascular and metabolic changes on health throughout the lifespan. And, it's one of the longest on-going health studies of a biracial, semi-rural southern community.  Director of the Tulane Center for Lifespan Epidemiology Research, Dr. Lydia Bazzano tells us about the profound impact this study has had on various fields of research over the last half century. This weekend, the American Red Cross of Louisiana will head to Baton Rouge for a day of installing free smoke alarms. WWNO's Karl Lengel speaks with Ed Bush, Executive Director, Capital West Chapter in the Louisiana Region for the American Red Cross, to learn more about this event and hear how to mitigate fire risks.  Late last year, the Environmental Protection Agency announced that 53 million dollars would go out to communities across the nation to monitor air pollution. One of those recipients is the Cherokee community in Pascagoula, Mississippi where community members there have been sounding the alarm for a decade. But as the Gulf States Newsroom's Danny McArthur reports, many are skeptical that the new testing will fix their problems. Today's episode of Louisiana Considered was hosted by Alana Schreiber. Our managing producer is Alana Schreiber and our digital editor is Katelyn Umholtz. Our engineers are Garrett Pittman and Aubry Procell.  You can listen to Louisiana Considered Monday through Friday at 12:00 and 7:30 pm. It's available on Spotify, Google Play, and wherever you get your podcasts.  Louisiana Considered wants to hear from you! Please fill out our pitch line to let us know what kinds of story ideas you have for our show. And while you're at it, fill out our listener survey! We want to keep bringing you the kinds of conversations you'd like to listen to. Louisiana Considered is made possible with support from our listeners. Thank you!See omnystudio.com/listener for privacy information.

Mucho se habla del azúcar y de la grasa y poco se habla de la sal y no por ello es más saludable, así que hablemos de sal.La sal en sí misma no es perjudicial, de hecho, es necesaria para nuestro organismo ya que está involucrada en múltiples funciones: nerviosa, de regulación… El problema viene cuando consumimos esa sal en exceso.Los alimentos ya contienen sal de forma intrínseca, es la sal propia de cada alimento. Pero es que además nosotros añadimos más sal, tanto a la hora de cocinar como a la hora de aderezar nuestros platos y es ahí donde viene el problema, si ese consumo de sal supera los 5 g al día.Esta es la cantidad máxima recomendada por la OMS, que nos dice que no debemos tomar más de 2 g de sodio al día, que es lo que equivale a esos 5 g de sal. Sin embargo el consumo medio en la población española está entre 9 y 12 gramos de sal al día. Ya os he explicado en otras ocasiones que la primera causa de muerte en España es por enfermedades cardiovasculares y tanto es así que se estima que cada año se podrían evitar 2,5 millones de defunciones si el consumo de sal a escala mundial se redujera al nivel recomendado. Te explico todo esto porque un nuevo estudio publicado en la Cardiovascular Research ha relacionado el consumo de sal no solo con la hipertensión y enfermedad cardiovascular, sino también con el aumento del cortisol. Este estudio, que traduciendo su título sería algo como "El alto consumo de sal activa el eje hipotalámico-pituitario-suprarrenal, amplifica la respuesta al estrés y altera la exposición tisular a los glucocorticoides en ratones" concluye que los animales expuestos a un mayor consumo de sal tenían niveles más altos de glucocorticoides (cortisol en humanos, corticosterona en ratones), que son hormonas con importantes funciones cardiovasculares, cognitivas y metabólicas y que se liberan como respuesta del organismo a situaciones estresantes o amenazas. Y, aunque nunca podemos trasladar los estudios de ratones a los humanos, la asociación encontrada en esta investigación va en la línea de artículos anteriores que reflejaban una relación entre el consumo de sal y la excreción de cortisol en la orina. En humanos sabemos que el exceso de sal produce más glucocorticoides y aumenta la excreción de los mismos.¿Cuál es pues el tratamiento?El tratamiento dietético especifico de la hipertensión es la dieta DASH, que te hablé de ella en el episodio 246 de este podcast y en la clase 5 del curso como perder peso en situaciones especiales.Si por suerte aún tu consumo excesivo de sal no ha derivado en hipertensión, puedes prevenir esa y otras consecuencias para tu salud reduciendo su consumo. ¿Cómo?No añadas sal a las comidas.Retira el salero de la mesa.Evita los productos muy salados como apertivos, ahumados, salazones, encurtidos,…Reeduca a tu paladar.Quede claro y por delante que es el consumo habitual y en exceso el que genera el problema.FUENTE: https://elpais.com/salud-y-bienestar/2023-01-05/los-riesgos-del-consumo-excesivo-de-sal-hipertension-arterial-y-niveles-mas-altos-de-la-hormona-del-estres.html

Please join authors Loren Field and Sean Reuter, as well as Associate Editor Thomas Eschenhagen as they discuss the article "Cardiac Troponin I-Interacting Kinase Affects Cardiomyocyte S-Phase Activity But Not Cardiomyocyte Proliferation." Dr. Greg Hundley: Welcome listeners, to this January 10th issue of Circulation on the Run, and I am Dr. Greg Hundley, associate editor, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Peder Myhre: I am Dr. Peder Myhre from Akershus University Hospital and University of Oslo in Norway. Dr. Greg Hundley: Well, listeners, this week's feature discussion delves into the world of preclinical science and evaluates cardiac troponin I and its impact on S phase activity in cardiomyocytes, and does that relate to cardiomyocyte proliferation. But before we get to that, how about we grab a cup of coffee and Peder and I will work through some of the other articles in the issue. Peder, how about this week I go first? Dr. Peder Myhre: Go ahead, Greg. Dr. Greg Hundley: Right. So Peder, this first study evaluated whether the burden of positive coronary artery calcification on cardiovascular disease differed by multidimensional individual characteristics, and so the investigators led by Dr. Kosuke Inoue from Kyoto University sought to investigate the heterogeneity in the association between positive coronary artery calcium and incident cardiovascular disease. And so Peder, to examine this question, the authors implemented a cohort study design that included adults aged greater than 45 years, free of cardiovascular disease, from the Multi-Ethnic Study of Atherosclerosis, or MESA, and after propensity score matching in a one-to-one ratio, they applied a machine learning causal forest model to, first, evaluate the heterogeneity in the association between positive coronary artery calcium and incident cardiovascular disease and then, second, to predict the increase in cardiovascular disease risk at 10 years when the coronary artery calcium score was greater than zero, so versus is it zero at all at the individual level? Dr. Peder Myhre: Oh, Greg, that is so cool, so using machine learning for coronary artery calcium and risk prediction, I'm very excited. What did they find? Dr. Greg Hundley: Right, Peder, so the expected increases in cardiovascular disease risk when the coronary artery calcium score was greater than zero were heterogeneous across individuals. Moreover, nearly 70% of people with low atherosclerotic cardiovascular disease risk showed a large increase in cardiovascular disease risk when the coronary calcium score was greater than zero, highlighting the need for coronary artery calcium screening among such low-risk individuals. And Peder, future studies are really needed to assess whether targeting individuals for coronary artery calcium measurements based on not only the absolute ASCVD risk, but also the expected increase in CVD risk when a CAC score is greater than zero and whether that improves overall assessment of cardiovascular outcomes. Dr. Peder Myhre: Wow, that is so clinically relevant and very interesting. And we're actually going to stay clinically relevant with the next paper which is about anti-platelet therapy after PCI. And this paper describes the long-term results of the HOST-EXAM trial. To remind you, Greg, the HOST-EXAM trial was an investigator-initiated prospective, randomized, open label, multicenter trial done at 37 sites in Korea. They enrolled patients who had undergone PCI with DES and maintained dual anti-platelet therapy without any clinical event for a mean 12 months and then they were randomized one to-one to either clopidogrel, 75 milligrams once daily, or aspirin, 100 milligram once daily. The primary results of this trial was published in Lancet in 2021 and showed superiority of clopidogrel over aspirin in prevention of the composite of MACE and major bleeding during 24 months of followup. And then, through the current paper, this describes the results of the post trial extended followup of about five years. Dr. Greg Hundley: Very nice, Peder, so aspirin versus clopidogrel and looking at the maintenance of that monotherapy and cardiovascular outcomes. Wow, so what did they find? Dr. Peder Myhre: Yeah, Greg. They, in this extended followup study, had a total of 5.8 years median followup, and the primary endpoint occurred in 12.8% in the clopidogrel group versus 16.9% in the aspirin group, and that has a range of 0.74 with a 95% conference interval ranging from 0.63 to 0.86. So also the clopidogrel group had lower risk of the secondary thrombotic endpoint and the secondary bleeding endpoint while there was no significant difference in the incident on all caused death. So Greg, to conclude, these very interesting results from the primary analysis of the HOST-EXAM trial was consistent through the longer followup, and this support the use of clopidogrel over aspirin monotherapy from 12 months onwards after PCI. Dr. Greg Hundley: Very nice Peder, beautiful description and sounds like long-term clopidogrel use over aspirin was quite beneficial. Well, the next study comes to us from the world of preclinical science, and it is from the investigative group led by Dr. Yunzeng Zou from Shanghai Institute of Cardiovascular Diseases and the Zhongshan Hospital and Fudan University. Peder, the study pertains to diabetes. So diabetic heart dysfunction is a common complication of diabetes mellitus and cell death is a core event that leads to diabetic heart dysfunction. However, the time sequence of cell death pathways and the precise intervening time of particular cell death type remained largely unknown in diabetic hearts. And so, Peder, this study aimed to identify the particular cell death type that is responsible for diabetic heart dysfunction and propose a promising therapeutic strategy by intervening in this cell death pathway. Dr. Peder Myhre: Wow, Greg, that is really interesting. Heart dysfunction in diabetes is something that we really have to learn more about and I'm so excited to hear what these authors found, Greg. Dr. Greg Hundley: Right. So first, Peder, the authors identified necroptosis as the predominant cell death type at later stages in the diabetic heart. And then second, Peder, the CB2 receptor, and we'll call that CB2-R, recruits transcription factor Bach2 to repress necroptosis and protects against diabetic heart injury while hyperglycemia and MLKL in turn phosphorylates CB2-R to promote ubiquitous dependent degradation of CB2-R, thus forming a CB2-R centric feedback loop of necroptosis. And finally, Peder, cardiac CB2-R or Bach2 expression negatively correlates with both MLKL 10 expression and the extent of diabetic heart injuries in humans. And so the clinical implications of these findings, Peder, are that the CB2-R centric necrotic loop represents a promising target for the clinical treatment of diabetic heart injuries. Dr. Peder Myhre: So Greg, this paper that comes to us from corresponding author Amanda Paluch from University of Massachusetts Amherst, is a meta-analysis of eight prospective studies with device measured steps including more than 20,000 adults who were followed for CVD events. And the mean age of participants in this study was 63 years and 52% were women. And the participants were followed for a median of 6.2 years and 1,523 cardiovascular events occurred. So first, Greg, there was a significant difference in the association of steps per day in cardiovascular disease between older, that is greater or equal to 60 years, and younger, that is less than 60 years adults. So for older adults that has the ratio for cardiovascular disease using Q1 as reference was 0.80 for Q2, 0.62 for Q3, and 0.51 for Q4. And for younger adults that has ratio for cardiovascular disease using Q1 as reference was 0.79 for Q2, 0.90 for Q3, and 0.95 for Q4. And in the paper, Greg, there are some beautiful, restricted cubic lines that really illustrate the association between daily steps and the risk of cardiovascular disease among older adults and in younger adults. So the authors conclude that for older adults taking more daily steps is associated with a progressively lower risk of cardiovascular disease. And monitoring and promoting steps per day is a simple metric for clinician patient communication and population health to reduce the risk of cardiovascular disease. Dr. Greg Hundley: Well, Peder, we've got some other very interesting articles in this issue and how about we dive into that mail bag and discuss a few of those. So I'll go first. The first is a Perspective piece by Professor Powell-Wiley entitled “Centering Patient Voices through Community Engagement in Cardiovascular Research.” A very important topic where can those in the community actually help us design meaningful outcomes for our research initiatives? And next Peder, there is a Research Letter from Professor Evans entitled “Increasing Mononuclear deployed Cardiomyocytes by Loss of E2F7/8, and does that fail to improve cardiac regeneration post myocardial infarction?” Dr. Peder Myhre: Thanks, Greg. We also have an ECG Challenge by Dr. Li entitled, “What Is The Truth Behind Abnormal ECG Changes?” And this is describing a very rare and interesting cause of ST segment elevation. I recommend everyone to read that case. We also have our own Nick Murphy who gives us the Highlights from the Circulation Family of Journals where he summarizes five papers from the Circulation subspecialty journals. First, the experience with a novel visually assisted ablation catheter is reported in circulation A and E. The impact of various exercise training approaches on skeletal muscle in heart failure with preserved the F is presented in circulation heart failure. Gaps in heart failure treatment over a decade are reported in circulation cardiovascular quality and outcomes, and the associations of machine learning approaches to plaque morphology from coronary CTA with ischemia are reported in circulation cardiovascular imaging. And finally, Greg, an observational study of left main PCI at sites with and without surgical backup is reported in circulation cardiovascular interventions. Let's go on to the feature paper today describing the cardiac troponin I interacting kinase and the impact on cardiomyocyte S phase activity. Dr. Greg Hundley: Great, let's go. Welcome listeners to this January 10th feature discussion. Very interesting today as we are going to delve into the world of preclinical science. And we have with us today Dr. Loren Field and Dr. Sean Reuter from University of Indiana in Indianapolis, Indiana. And our own associate editor, Dr. Thomas Eschenhagen from University Medical Center of Hamburg in Hamburg, Germany. Welcome gentlemen. Well, Loren, we're going to start with you. Can you describe for us some of the background information that went into the preparation of your study, and what was the hypothesis that you wanted to address? Dr. Loren Field: Sure. This study actually came about in a rather roundabout fashion. We were doing a study with Kai Wollert in Hanover, Germany, where we were looking at the impact of a CXCR4 antagonist, which is used to mobilize stem cells from the bone marrow. And we had sent our mice over to Kai's lab and we have a mouse model that allows us to track S phase activity in cardiac myocytes, so these are cells are starting to replicate. And Kai crossed them into a different genetic background. And when he sent the mice back to us to analyze the hearts, we observed that we saw things that we never saw before in our experiments here. His injury model was different than ours and now the mouse also had a genetic background, so we had to spend about a year to figure out if it was the injury model or the background. It turned out to be the genetic background, and the phenotype was these mice had about a 15-fold elevated level of cell cycle reentry. So then it became a relatively simple genetics game where we took the progenitor mice, made F1 animals, looked for the phenotype, did backcross animals, and basically identified the gene responsible for the phenotype. Dr. Greg Hundley: Very nice. And so in this study moving forward, what hypothesis did you want to address? Dr. Loren Field: Well, the main hypothesis was to figure out what the gene was and then secondarily to figure out the degree of cell cycle progression. When the cell is proliferating, the first task is to replicate its genome, which is S phase activity that's followed by the nuclei dividing and then finally by the cell itself becoming two cells. So our task was to identify, first, the gene and secondly, how far through the cell cycles the cells progressed. Dr. Greg Hundley: Very nice. And how did you construct your experiment? Dr. Loren Field: It was, again, very straightforward. It was simply setting up the appropriate genetic crosses to produce the animals. For the past 10, 15 years, we've been developing a computer assisted assay that allows us to identify the anatomical position of S phase positive cardiac myocytes in sections of the heart. And basically, we apply that program to the different genetic backgrounds and after that it's a ball of mapping studies, QTL mapping. Dr. Greg Hundley: So really mechanistic understanding. Well listeners, we're next going to turn to Sean, and Sean, can you describe for us your study results? Dr. Sean Reuter: Yes, as Loren stated, we saw a 15-fold increase in the S phase activity within the remote zone. Now we partition the heart in three different zones after injury, so the scar, the border zone, and then the remote zone or injury. And as Loren stated, we saw a 15-fold increase in the S phase activity, cell cycle activity, in the remote zone. And it's only because we have this system in hand that we can anatomically map the S phase activity within the heart that we were able to detect and also quantify this. And I think that's the reason we discovered this particular phenotype. But in addition to that, we performed RNA-seq or Exome sequencing and discovered that TNNI3K was the responsible gene for elevated S phase activity within the remote zone and border zone, but interestingly not in the scar. Dr. Greg Hundley: Very interesting, Sean, and so describe for us the importance of the TNNI3K and its relationship to this S phase. Dr. Sean Reuter: Sure. This particular gene was first discovered around 2000, and it's been studied for a while now, but the targets of this kinase specifically expressed in the heart, and it does get elevated after injury, but the actual targets are not well described or well known. It's believed that it phosphorylates some mild filament fibers and structural proteins, but the actual mechanism and the consequence of this is not known. So when we saw this in the remote zone, the elevated S phase, our current theory is that we believe that it's probably increasing oxidative stress that would basically further out from the at-risk zone or the border zone and then it now is in the remote zone. So we think it's just causing the heart, a pathological area of the heart, basically to expand. And so that's our current theory. Other groups have published on the oxidative stress in over expression of TNNI3K as well. Dr. Greg Hundley: Very nice. Well listeners, next we are going to turn to our associate editor, Thomas many articles come your way and come across your desk. What attracted you to this particular article, and how do we put its results really in the context of cardiac regeneration? Dr. Thomas Eschenhagen: Indeed, there were several arguments. It's a cool paper and the whole field is still very important. As probably most of you know, the field have a rough ride over the last 20 years, went up and down, lots of bad findings. And in the end it turns out that we are there where we have been 20 years ago, the mammalian heart essentially doesn't regenerate. So anything which would improve that would be of very major importance. Why is it a good paper? Because it starts from a very clear finding, one mouse, which looks like strongly regenerating after MI, another mouse line, which doesn't. And so by applying, let's say, classical genetic, very stringent methodology, Loren Field and his group identified this troponin I kinase to be the culprit. And they also proved it, because putting it back in the strain with a low, so-called, regeneration brought it back to the other level. So it's a very clear, nice methodology. And finally, it's also a bit provocative because others in a very prominent paper, actually, have shown that this kinase... Or they concluded more or less just the opposite. The reason for the discrepancy is not quite clear and I was very happy to learn that the two groups actually discussed about it. So it's not just a bad controversy, but something which brings forward science. And finally, I think something we didn't talk about yet today, what I particularly liked, maybe the most, on this paper is that this group didn't stop at the point of DNA synthesis. Everybody else would've probably said, "Okay, here we are, one regenerate the other doesn't." But in the very important extra finding of this paper is that this is just increased DNA synthesis and not more myocytes. And this distinction is so critical to the field because people forget that adult mammalian cardiomyocytes often have several nuclei and individual nuclei have more than one set of chromosomes, so this polyploid. And so if you see DNA synthesis like in this paper, it doesn't necessarily mean more myocytes. And actually here it was shown that it is not more myocytes but more polyploidization and making this difference so clear, I think it's a very important contribution to the field. Dr. Greg Hundley: Very nice. Well, listeners, we're going to turn back to each of our guests today and we'll start with you Loren. Based on your results, what do you see as the next study moving forward in this sphere of research? Dr. Loren Field: I think these results made me appreciate for the first time that the intrinsic level of cell cycle reentry, that's just the S phase, not the cell division, is actually much higher than I had thought previously. And this was because we just fortuitously, or I guess anti-fortuitously, we're using a strain that had low levels of S phase induction. If you calculate the turnover, if every nucleus that it synthesized DNA actually went on to have that cell divide, you could replace a 50% loss of myocytes over the course of about 550 days, give or take. And to me, that's actually telling me that if we could push those cells from just being polypoid, as Thomas was saying, to actually go through cytokinesis, there would be enough intrinsic activity to go forward. So this really tells me that what we should be focusing on is now not trying to induce cell cycle, but to allow the cells that are entering the cell cycle to actually progress through it. Dr. Greg Hundley: Very nice. And Sean? Dr. Sean Reuter: Yes, well, echoing Loren's point there, it's really not necessarily cell cycle induction, it's cell cycle completion to the cytokinetic fate. And that's the key. If we can get to that point, if we can figure out the mechanism to get to that point, then we have a wonderful discovery. However, we're not quite there yet, but we hope to be. Dr. Greg Hundley: And Thomas. Dr. Thomas Eschenhagen: Well, nothing to add really from my side, except that I would like to know what this Troponin I kinase does, because that is somehow still a missing link. How does this kinase lead to more DNA synthesis or the initiation of cell cycling? That would be an important finding and I'm sure there will be more research going on. Particularly also, to solve this discrepancy, I mean, there must be something in it and we don't quite yet know how, but I think we are in a good way. I'm sure there will be papers showing that soon. So I think that's, again, a very good start for this discussion. Dr. Greg Hundley: Well, listeners, we want to thank Dr. Loren Field, Dr. Sean Reuter and Dr. Thomas Eschenhagen for bringing us this really informative study in mammalian myocellular regeneration, highlighting that the level of cardiomyocyte cell cycle reentry in hearts expressing TNNI3 kinase would lead to significant regenerative growth if each cardiomyocyte exhibiting S phase activity was able to progress through cytokinesis. And this in turn suggests that identification of factors which facilitate cardiomyocyte cell cycle progression beyond S phase will be key to unlocking the intrinsic regenerative capacity of the heart. Well, on behalf of Carolyn, Peder and myself, we want to wish you a great week and we will catch you next week on the run. This program is copyright of the American Heart Association 2023. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit ahajournals.org.

Rob Hegele is Distinguished University Professor of Medicine and Biochemistry, Western University, and Director of London Regional Genomics Centre at Robarts Research Institute. He holds the Jacob J. Wolfe Distinguished Medical Research Chair in Human Gene Function, and the Martha G. Blackburn Chair in Cardiovascular Research. He cares for > 2400 patients in his lipid clinic at University Hospital. He was among the first in North America to use 5 experimental medications, of which 4 are now available for prescription (rosuvastatin, sitagliptin, lomitapide and evolocumab) to treat high cholesterol or diabetes. In addition, his patients have been among the first in Canada to use mipomersen, anacetrapib, bococizumab, evinacumab, volanesorsen, and inclisiran. His laboratory, alone or in collaboration, discovered the molecular genetic basis of 25 human diseases. He has published > 815 papers, which have been cited > 60,000 times in the medical literature. He is listed in the ISI database of the top 1% of highly cited scientists in the world. In 2021, the website “Expertscape.com” ranked him #1 globally in the area of “hypertriglyceridemia” and #2 for “disorders of lipid metabolism.” He has co-authored many clinical practice guidelines for cholesterol, blood pressure and diabetes, and has contributed to international guidelines on familial hypercholesterolemia and hypertriglyceridemia. He has trained numerous physicians, medical students and graduate students. Purchase Tommy's MetFlex-Rx Diet Book: https://amzn.to/2ZUeMBm Purchase Tommy's Behaviour Change Book on Audible: https://amzn.to/3IjqEOJ Dr.Appleton's Website: https://andrewappletonmd.ca/

Robb MacLellan, MD is the Director of the UW Medicine Heart Institute and our Division Head of Cardiology.   Since 2011 he has ensured our faculty and research goals are aligned with the needs and opportunities in the hospital.  In addition to those important responsibilities, he is an active attending physician and Robert A. Bruce Endowed Chair in Cardiovascular Research.Robb's research interests include:Understand the molecular mechanisms that regulate cardiac failure and develop therapies to regenerate myocardiumUse genetic mouse models in an attempt to correlate molecular insights with whole organ physiologyDevelop stem cell and tissue engineering strategies to repair the heart1:15 - The Canadian Researcher6:00 - Why Cardiology7:27 - Research Training10:45 - Research Fundamentals13:15 - First Trial to the Lab Today26:40 - Complimentary Teamwork Success30:55 - Advice to the Future Academic35:50 - The Argument for the Physician Scientist41:20 - Struggle for Balance in Training and Future Need46:55 - Looking back as Division Head and Director52:30 - Regional Heart Center to Heart Institute56:30 - A new role in Department of Medicine

Eating a high-salt diet, like most Americans do, appears to increase stress. In a new study published in the journal Cardiovascular Research, researchers at the University of Edinburgh in Scotland looked at the effects of high salt consumption on stress and the brain in mice. They observed that eating a large amount of salt-rich food […] The post 332. Eating salt-rich foods might increase stress levels appeared first on Dr. David Geier - Feel and Perform Better Than Ever.

Listen to today's 7-minute Live from the American Heart Association Conference as Dr. Koren tells us what's new in heart health.  Join Dr. Michael Koren and Kevin Geddings each Monday as they give you the quick down-and-dirty truth behind the most recent medical data.  Dr. Michael Koren is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals.  Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital/Memorial Sloan-Kettering Cancer Center/Cornell Medical Center.  On a personal note, Dr. Koren has a life-long interest in history, technology, Public Health, and music. He has written two musical plays.More information and to Participate in Clinical Research Rate, Review, and Subscribe to the MedEvidence! podcast to be notified when new episodes are released.Follow MedEvidence! on Social Media to discover the Truth Behind the Data.FacebookInstagramTwitterLinkedInPowered by ENCORE Research Group at www.ENCOREDOCS.comOriginal Air Date: November 7, 2022#MedEvidence #heart #americanheartassociation #cardiohealth #cardiovasularresearch #LPa #hearthealth #clinicalresearch #clinicaltrials

即刻加入15Mins通勤學英語直播室，每週一9pm等你來說英文 : https://15minsengcafe.pse.is/46hm8k 每日英語跟讀 Ep.K440: How to Get Heart Patients to Take Their Pills? Give Them Just One. Heart disease kills more people than any other condition, but despite advances in treatment and prevention, patients often do not stick to their medication regimens. Now researchers may have found a solution: a so-called polypill that combines three drugs needed to prevent cardiovascular trouble. 死於心臟病的人比死於其他任何疾病的人都多，儘管在治療和預防上取得進展，患者往往不能堅守他們的藥物治療方式。現在，研究人員可能已經找到一個解決方法：一種混合三種預防心血管疾病所需藥物的所謂複方製劑。 In what is apparently the largest and longest randomized controlled trial of this approach, patients who were prescribed a polypill within six months of a heart attack were more likely to keep taking their drugs and had significantly fewer cardiovascular events, compared with those receiving the usual assortment of pills. 在明顯是這種方法規模最大、時間最長的隨機對照試驗中，心臟病發作後6個月內服用複方製劑的患者，跟服用常規藥物患者相比，更有可能繼續服用藥物，心血管事件明顯減少。 The participants also experienced one-third fewer cardiovascular deaths, although their overall risk of death from all causes was not significantly changed. 參與者因心血管疾病死亡人數也減少三分之一，即便他們因為各種原因死亡的總體風險沒有顯著改變。 The study of more than 2,000 heart patients, who were followed for three years, was published Friday morning in The New England Journal of Medicine, as the findings were presented at the European Society of Cardiology Congress in Barcelona, Spain. 這項研究對2000多名心臟病患者進行三年追蹤調查，研究結果周五上午發表在《新英格蘭醫學雜誌》，並在西班牙巴塞隆納舉行的歐洲心臟病學會年會上發表。 The study is the culmination of 15 years of work by researchers led by Dr. Valentin Fuster, director of Mount Sinai Heart at Mount Sinai Hospital in New York City and general director of the National Center for Cardiovascular Research in Spain. 這研究是紐約市西奈山醫院西奈山心臟中心主任、西班牙國立心血管研究中心總監瓦倫丁．福斯特博士帶領研究人員研究15年的結晶。 “Combination pills are easier for the physician and for the patient, and the data are pretty clear — it translates into a benefit,” said Dr. Thomas J. Wang, chair of the department of internal medicine at UT Southwestern Medical Center, who was not involved in the research but wrote an editorial accompanying the study. 未參與研究但為研究報告撰寫社評的德州大學西南醫學中心內科系主任湯瑪斯．王博士說：「複方藥物對醫生和病患來說更簡便，數據非常清楚，它轉化為一種好處。」 The polypill combines a blood-pressure medication, a cholesterol-lowering drug and aspirin, which helps prevent blood clots. 這種複方製劑結合了降壓藥、降膽固醇藥和阿斯匹林，有助防止血栓。 The polypill used in the study has not been approved by the Food and Drug Administration and is not available to patients in the United States right now. Fuster said the results of the new trial would be submitted to the agency shortly in an effort to obtain approval. 這項研究使用的複方製劑還未獲得美國食品藥物管理局批准，目前在美國還不能給患者使用。福斯特 說，這項新試驗結果很快會提交給該機構，以爭取獲得批准。 And since participants became even more likely to keep taking the polypill over time, he said, “The potential results could be even better with more follow-up.” Several studies have shown that only about half of patients, or even less, take all their medications as instructed. 他說，由於參與者會逐漸的更可能繼續服用複方製劑，「若有更多後續研究，潛在結果可能更好」。數項研究顯示，只有大約一半甚至更少患者按照指示服用所有藥物。 The new study, a randomized controlled clinical trial, enrolled just under 2,500 patients at 113 sites in Spain, Italy, France, Germany, Poland, the Czech Republic and Hungary. 這項研究是一項隨機對照臨床試驗，在西班牙、義大利、法國、德國、波蘭、捷克和匈牙利的113個地點招募到近2500名患者。Source article: https://udn.com/news/story/6904/6601708 歡迎留言告訴我們你對這一集的想法： https://open.firstory.me/user/cl81kivnk00dn01wffhwxdg2s/comments Powered by Firstory Hosting

How do the 3 Rs of Research – Refinement, Reduction, Replacement – factor into a methodological paper regarding a novel quantitative method for using an electrocardiogram to determine which animals have infarcts that reflect successful coronary ligation? Listen as Consulting Editor Dr. Ganesh Halade (University of South Florida) interviews lead author and Consulting Editor Dr. Kristine DeLeon-Pennell (Medical University of South Carolina) and content expert Dr. Corey Reynolds (Merck) about the recent work by Broughton et al. What started as an internal project to improve The DeLeon-Pennell Lab's surgical success grew into a research article published as part of a Call for Papers on Innovation in Improving Rigor and Reproducibility in Cardiovascular Research. The DeLeon-Pennell Lab was interested in streamlining infarct size between lab members, students, and technicians during the surgical procedures used for their mouse studies. Aiming for a threshold of 35% infarct size, the DeLeon-Pennell Lab wanted to move beyond looking only at the elevation of the T wave to confirm infarct size. To do so, Broughton et al. designed a new ECG method that provides real-time feedback during the procedure. Broughton et al. found that area under the QRS curve is stronger for predicting successful MI surgeries with an infarct size greater than 35%. This new method will ultimately allow researchers to reduce the time spent performing surgical experiments and the overall number of animals used. Listen now to find out more.   Philip Broughton, Miguel Troncoso, Alexa Corker, Alexus Williams, Dawson Bolus, Gualberto Munoz, Caroline McWhorter, Hallie Roerden, Penny Huebsch, and Kristine Y. DeLeon-Pennell Riding the wave: a quantitative report of electrocardiogram utilization for myocardial infarction confirmation Am J Physiol Heart Circ Physiol, published August 3, 2022. DOI: doi.org/10.1152/ajpheart.00201.2022

Dr. Uwe Schoenbeck, Ph.D., (https://www.pfizer.com/research/science_and_technology/meet_our_scientists/uwe_schoenbeck) is Chief Scientific Officer, Emerging Science & Innovation (ES&I) and Senior Vice President, Worldwide Research and Development & Medical (WRDM) at Pfizer. Part of Worldwide Research, Development & Medical, ES&I is charged with enhancing Pfizer's pipeline through translation of external emerging science into breakthrough therapies for patients and through dedicated outreach to academia, consortia and biotech. Through its Emerging Science Liaisons located around the globe, they work across Pfizer's Therapeutic Areas to harness external cutting edge pre-clinical assets and breakthrough technologies applying a broad range of partnering vehicles, including research collaborations, consortia, licensing, and acquisitions. ES&I also engages in equity investments as well as seed investments and formation of new companies. It has a Target Sciences team which is focused on novel target and biology discovery research to introduce differentiated First-in-Class programs with enhanced confidence in rationale into the WRDM portfolio. And through its new Centers for Therapeutic Innovation (CTI - https://www.pfizercti.com/), ES&I prosecutes cutting edge science sourced from leading academic and medical centers globally, working in close partnership with external PIs and building an exciting pipeline across the range of Pfizer's core areas. Dr. Schoenbeck brings fifteen years of pharmaceutical drug development experience to Pfizer's R&D executive leadership team. Prior to joining the company, he served as Vice President, Emerging R&D Innovation for Wyeth and Vice President, Cardiovascular Research for Boehringer Ingelheim. Before joining industry, he held an Assistant Professor of Medicine position at Brigham & Women's Hospital, Harvard Medical School. He has served as a reviewer for multiple peer-reviewed journals and has published more than 100 peer-reviewed articles, review articles, book chapters and abstracts with particular contributions in molecular and cell biology, cardiovascular research, immunology and metabolism. Dr. Schoenbeck earned his Ph.D. from the University of Kiel, Germany, and completed postdoctoral training in the Division of Cardiovascular Medicine, Brigham & Women's Hospital, Harvard Medical School, before joining as a faculty member.

Commentary by Dr. Valentin Fuster

Dr. Lynn Megeney is a senior scientist in the regenerative medicine program at The Ottawa Hospital. In this episode, he explains why he jumped at the chance to come to Ottawa instead of going south of the border, and the influence Drs. Ron Worton and Michael Rudnicki had on his career. He also shares why sometimes it's good to “rock the boat”, like with his recent global research collaboration on cancer cells, and his need for speed when he's not in the lab. (35:56)

Many environmental factors have been found to influence cardiovascular disease (CVD) risk, progression, and severity. Join Sanjay Rajagopalan, MD, FACC, FAHA, Chief of Cardiovascular Medicine at the University Hospitals, Harrington Heart & Vascular Institute, Director of Cardiovascular Research Institute at Herman K. Hellerstein MD, Professor of Cardiovascular Research, and Professor of the Department of Internal Medicine at Case Western Reserve University, as he is interviewed by Betul Hatipoglu MD, Professor of Medicine at CWRU School of Medicine, Vice-Chair at UH System Clinical Affairs, Department of Medicine, Medical Director of the Diabetes & Obesity Center at Mary B. Lee Chair in Adult Endocrinology, University Hospital Cleveland Medical Center, and Chair of the AACE Disease State Network Lipids & Cardiovascular Health. Dr. Rajagopalan and Dr. Hatipoglu discuss components of the environment that play an important role in health besides general lifestyle factors, including social, economic, and chemical pollutants.

Credits: 0.25 AMA PRA Category 1 Credit™   CME/CE Information and Claim Credit: https://www.pri-med.com/online-education/podcast/frankly-speaking-cme-271 Overview: Given the prevalence of cardiovascular disease (CVD) in the United States, it is key for primary care providers to counsel patients on the importance of exercise for CVD prevention. This brief podcast explores data that will help clinicians understand the need to prescribe exercise and rehabilitation in the primary care setting. You'll walk away with clear guidance to offer patients and ultimately improve outcomes in CVD as well as multiple chronic diseases. Episode resource links: Naci, H., & Ioannidis, J. P. (2015). Comparative effectiveness of exercise and drug interventions on mortality outcomes: metaepidemiological study. British journal of sports medicine, 49(21), 1414–1422. https://doi.org/10.1136/bjsports-2015-f5577rep   Sanchis-Gomar, F., Lavie, C. J., Marín, J., Perez-Quilis, C., Eijsvogels, T. M., O'Keefe, J. H., ... & Blair, S. N. (2021). Exercise effects on cardiovascular disease: from basic aspects to clinical evidence. Cardiovascular Research.  Guest: Mariyan L. Montaque, DNP, FNP-BC   Music Credit: Richard Onorato

Credits: 0.25 AMA PRA Category 1 Credit™   CME/CE Information and Claim Credit: https://www.pri-med.com/online-education/podcast/frankly-speaking-cme-271 Overview: Given the prevalence of cardiovascular disease (CVD) in the United States, it is key for primary care providers to counsel patients on the importance of exercise for CVD prevention. This brief podcast explores data that will help clinicians understand the need to prescribe exercise and rehabilitation in the primary care setting. You'll walk away with clear guidance to offer patients and ultimately improve outcomes in CVD as well as multiple chronic diseases. Episode resource links: Naci, H., & Ioannidis, J. P. (2015). Comparative effectiveness of exercise and drug interventions on mortality outcomes: metaepidemiological study. British journal of sports medicine, 49(21), 1414–1422. https://doi.org/10.1136/bjsports-2015-f5577rep   Sanchis-Gomar, F., Lavie, C. J., Marín, J., Perez-Quilis, C., Eijsvogels, T. M., O'Keefe, J. H., ... & Blair, S. N. (2021). Exercise effects on cardiovascular disease: from basic aspects to clinical evidence. Cardiovascular Research.  Guest: Mariyan L. Montaque, DNP, FNP-BC   Music Credit: Richard Onorato

Despite the establishment of NIH guidelines for inclusion of women in clinical studies, as well as clear expectations for rigor and reproducibility in reporting sex as a biological variable in NIH grant submissions, women and females are still understudied populations in human and animal research. Enter this important primer on incorporating sex as a biological variable into basic and clinical research. Listen as Consulting Editor Austin Robinson, PhD (Assistant Professor, Neurovascular Physiology Laboratory, Auburn University) interviews lead author Quin Denfeld, PhD, RN (Assistant Professor, School of Nursing and Division of Cardiovascular Medicine, School of Medicine, Oregon Health & Science University) and women's health expert Judith Regensteiner, PhD (Director of the Ludeman Family Center for Women's Health Research and Professor of Medicine, Divisions of Internal Medicine and Cardiology, University of Colorado Anschutz Medical Campus).  Denfeld and co-authors heeded the call to action outlined in the recent editorial by the AJP-Heart and Circ Editors on “Reinforcing rigor and reproducibility expectations for use of sex and gender in cardiovascular research”, along with its accompanying podcast episode and Call for Papers on Considering Sex as a Biological Variable in Cardiovascular Research.    In their Perspective article, Denfeld et al. offered practical and actionable ideas for how to include women and females in research studies, demystifying the process for fellow researchers by addressing common concerns such as sample size, cost, statistical analysis, and study participant recruitment challenges. In this episode, our experts tackled these subjects head on, championing the value of looking at data, even pilot data, through the lens of sex differences.   Don't miss hearing about career development opportunities available to researchers from the NIH Office of Research on Women's Health and Building Interdisciplinary Research Careers in Women's Health (BIRCWH) Program.  Including both sexes and genders in research studies is not difficult to accomplish with foresight, planning, and perhaps a little creative thinking. This insightful conversation is invaluable to all researchers. Listen now.   Recommended Reading in AJP-Heart and Circ: Quin E. Denfeld, Christopher S. Lee, and Beth A. Habecker  A primer on incorporating sex as a biological variable into the conduct and reporting of basic and clinical research studies Am J Physiol Heart Circ Physiol, published February 8, 2022. DOI: 10.1152/ajpheart.00605.2021   Austin T. Robinson, Megan M. Wenner, Kanokwan Bunsawat, Joseph C. Watso, Gabrielle E. W. Giersch, and Nisha Charkoudian When it's time for the sex talk, words matter  Am J Physiol Heart Circ Physiol, published December 13, 2021. DOI: 10.1152/ajpheart.00556.2021   Special Article Collection on Considering Sex as a Biological Variable  

The papers behind the pod: 1. Baran SW et al. (2022). Perspectives on the Evaluation and Adoption of Complex In Vitro Models in Drug Development: Workshop with the FDA and the Pharmaceutical Industry (IQ MPS Affiliate). ALTEX, in press. https://doi.org/10.14573/altex.21122032. Borba JVB et al. (2022) STopTox: An in Silico Alternative to Animal Testing for Acute Systemic and Topical Toxicity. Environmental Health Perspectives 130(2). https://doi.org/10.1289/EHP93413. van der Velden J et al. (2022) Animal models and animal-free innovations for cardiovascular research: current status and routes to be explored. Consensus document of the ESC working group on myocardial function and the ESC Working Group on Cellular Biology of the Heart. Cardiovascular Research, in press. https://doi.org/10.1093/cvr/cvab370 It's the third Thursday of March, and you're listening to 3 Minute 3Rs, your monthly recap of efforts to replace, reduce and refine the use of animals in research. This month, we're highlighting three papers focusing on replacement. Follow this link for the full transcript: https://nc3rs.org.uk/3-minute-3rs-podcast-march-2022-transcript See acast.com/privacy for privacy and opt-out information.

Our inaugural podcast is a discussion between Dr. Paul Thompson, Chief of Cardiology, Emeritus, at Hartford Hospital and Professor of Medicine, Emeritus, at University of Connecticut and Dr. Thomas Nero, Director of Cardiovascular Research at CAFC about coronary artery disease, lipid sub-fractionation and the role of lipoprotein a, aka Lp(a).

Tierversuche erhitzen die Gemüter. Ohne geht es nicht, sagen weite Teile der Forschung. Tierschützer halten entgegen, dass es bereits erprobte Alternativmethoden gibt. Aber wie gut sind die wirklich? In welchen Bereichen können zum Beispiel Organoide die Zahl der Versuchstiere spürbar senken und Tierleid vermeiden helfen? Unsere Autorin Nele Rößler hat sich erklären lassen, wie künstliche Herzmuskel hergestellt werden und wo ihre Grenzen liegen. Im Gespräch mit Host Lucie Kluth erläutert sie, was auf einem Chip nachgestellte Mini-Organe leisten und warum es so schwer ist, in der Medikamentenentwicklung auf Versuche am lebenden Organismus zu verzichten. Außerdem nimmt sie uns mit ins Labor Hamburger Biologinnen, die sich mit Einsatzmöglichkeiten für Schlachtabfälle beschäftigen - und dabei erstmal rausfinden müssen, mit welcher Maschine sich Schweinenieren möglichst dünn und schonend schneiden lassen. Eine Recherche, die Hoffnung macht - und doch zu große Erwartungen dämpft. Mit dieser Episode knüpfen wir an unsere Podcast-Folge 38 an, "Vom Wert der Tiere". DIe Hintergrundinformationen • NDR Synapsen: Vom Wert der Tiere https://www.ndr.de/podcastsynapsen204.html • Video eines Herz-Organoids | Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften: Pulsierende Herzen in der Petrischale, Mai 2021 https://www.oeaw.ac.at/imba-de/ueber-imba/newsroom/news/pulsierende-herzen-in-der-petrischale • Leitfaden zur Reduzierung von Versuchstieren in der kardiovaskulären Forschung | Van der Velden et al: Animal models and animal-free innovations for cardiovascular research: current status and routes to be explored. Consensus document of the ESC Working Group on Myocardial Function and the ESC Working Group on Cellular Biology of the Heart in Cardiovascular Research 2022 https://academic.oup.com/cardiovascres/advance-article/doi/10.1093/cvr/cvab370/6499268?login=true • TED-Talk zur Organ-on-a-Chip-Technologie | Geraldine Hamilton: Körperteile auf Chips, Dezember 2013 https://www.youtube.com/watch?v=CpkXmtJOH84 • Verringert die Organ-on-a-Chip-Methode die Anzahl von Tierversuchen? | Christine Broll, Wenn das Plättchen im Herzschlag pulsiert, Fraunhofer-Magazin, März 2019 https://www.fraunhofer.de/de/forschung/aktuelles-aus-der-forschung/biooekonomie/gesundheit/organs-on-a-chip.html • Reduktion von Tierversuchen in der experimentellen Arzneimittelprüfung | Bundesgesundheitsblatt- Gesundheitsforschung - Gesundheitsschutz, Behrensdorf-Nicol und Krämer, September 2014 https://www.pei.de/SharedDocs/Downloads/wiss-publikationen-volltext/bundesgesundheitsblatt/2014/2014-reduktion-tierversuche-exp-arzneimittelpruefung.pdf?__blob=publicationFile&v=2

Tierversuche erhitzen die Gemüter. Ohne geht es nicht, sagen weite Teile der Forschung. Tierschützer halten entgegen, dass es bereits erprobte Alternativmethoden gibt. Aber wie gut sind die wirklich? In welchen Bereichen können zum Beispiel Organoide die Zahl der Versuchstiere spürbar senken und Tierleid vermeiden helfen? Unsere Autorin Nele Rößler hat sich erklären lassen, wie künstliche Herzmuskel hergestellt werden und wo ihre Grenzen liegen. Im Gespräch mit Host Lucie Kluth erläutert sie, was auf einem Chip nachgestellte Mini-Organe leisten und warum es so schwer ist, in der Medikamentenentwicklung auf Versuche am lebenden Organismus zu verzichten. Außerdem nimmt sie uns mit ins Labor Hamburger Biologinnen, die sich mit Einsatzmöglichkeiten für Schlachtabfälle beschäftigen - und dabei erstmal rausfinden müssen, mit welcher Maschine sich Schweinenieren möglichst dünn und schonend schneiden lassen. Eine Recherche, die Hoffnung macht - und doch zu große Erwartungen dämpft. Mit dieser Episode knüpfen wir an unsere Podcast-Folge 38 an, "Vom Wert der Tiere". DIe Hintergrundinformationen • NDR Synapsen: Vom Wert der Tiere https://www.ndr.de/podcastsynapsen204.html • Video eines Herz-Organoids | Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften: Pulsierende Herzen in der Petrischale, Mai 2021 https://www.oeaw.ac.at/imba-de/ueber-imba/newsroom/news/pulsierende-herzen-in-der-petrischale • Leitfaden zur Reduzierung von Versuchstieren in der kardiovaskulären Forschung | Van der Velden et al: Animal models and animal-free innovations for cardiovascular research: current status and routes to be explored. Consensus document of the ESC Working Group on Myocardial Function and the ESC Working Group on Cellular Biology of the Heart in Cardiovascular Research 2022 https://academic.oup.com/cardiovascres/advance-article/doi/10.1093/cvr/cvab370/6499268?login=true • TED-Talk zur Organ-on-a-Chip-Technologie | Geraldine Hamilton: Körperteile auf Chips, Dezember 2013 https://www.youtube.com/watch?v=CpkXmtJOH84 • Verringert die Organ-on-a-Chip-Methode die Anzahl von Tierversuchen? | Christine Broll, Wenn das Plättchen im Herzschlag pulsiert, Fraunhofer-Magazin, März 2019 https://www.fraunhofer.de/de/forschung/aktuelles-aus-der-forschung/biooekonomie/gesundheit/organs-on-a-chip.html • Reduktion von Tierversuchen in der experimentellen Arzneimittelprüfung | Bundesgesundheitsblatt- Gesundheitsforschung - Gesundheitsschutz, Behrensdorf-Nicol und Krämer, September 2014 https://www.pei.de/SharedDocs/Downloads/wiss-publikationen-volltext/bundesgesundheitsblatt/2014/2014-reduktion-tierversuche-exp-arzneimittelpruefung.pdf?__blob=publicationFile&v=2

Host: Kathryn MacKay Guest: Lida Sarafraz, University of Utah Paper: Understanding and Correcting Sex Disparity in Cardiovascular Disease Research: Ethical and Practical Solutions Transcript: provided by Otter.ai Music: The City Sleeps by Death by Ginger

"Everyone wants to be on the winning team." - Tim Fischell‍Dr. Tim Fischell is a Professor of medicine at Michigan State University and Medical Director of the Department of Cardiovascular Research, as well as Director of the Interventional Cardiology fellowship program at the Borgess Heart Institute in Kalamazoo, Michigan. He has an active practice as an interventional cardiologist at the Borgess Heart Institute in Kalamazoo. After receiving his medical degree from Cornell University Medical Center, Dr. Fischell completed an internship and residency in internal medicine at Massachusetts General Hospital at Harvard University and then completed his cardiology fellowship and interventional cardiology fellowship at Stanford University Medical Center. He was on the faculty at Stanford for five years, and then director of the cardiac cath labs and interventional cardiology at Vanderbilt University from 1992 to 1996. Dr. Fischell is board certified in internal medicine, cardiovascular medicine, and interventional cardiology. Dr. Fischell is an active inventor with more than 100 issued US patents. He has served as principal investigator for five National Institutes of Health grants, as well as several other research grants. Dr. Fischell has research interests in vascular biology, interventional cardiology devices,  such as stents, and renal denervation, and has presented more than 200 papers in the United States and abroad. A member of the editorial board, of Cardiovascular  Revascularization Medicine,  Journal of Invasive Cardiology, and the Journal of Interventional Carademydiology. Dr. Fischell has authored more than 120 papers. He is a founder and a CMO of Ablative Solutions and CEO and Co-founder of CrossLiner Inc., And is a serial entrepreneur and founder of eight other medical device companies. He has received numerous awards and honors, including the Thorax Center Andrius Gruntzig Award for the inventor of the year in 1997, the CRT 2015 Innovation Award, and is a fellow in the National Academy of Inventors.Please enjoy!‍Click here to subscribe to The Sell My Business Podcast to save time and effort. SELECTED LINKS FOR THIS EPISODEDr. Tim Fischell on LinkedInThe Deep Wealth ExperienceBook Your FREE Deep Wealth Strategy Call This podcast is brought to you by Deep Wealth. Your liquidity event is the most important financial transaction of your life. You have one chance to get it right, and you better make it count. But unfortunately, up to 90% of liquidity events fail. Think about all that time, money and effort wasted. Of the "successful" liquidity events, most business owners leave 50% to over 100% of their deal value in the buyer's pocket and don't even know it.Our founders said "no" to a 7-figure offer and "yes" to a 9-figure offer less than two years later. Don't become a statistic and make the fatal mistake of believing that the skills that built your business are the same ones for your liquidity event. After all, how can you master something you've never done before? Are you leaving millions on the table? Learn how the 90-day Deep Wealth Experience and our 9-step roadmap helps you capture the maximum value for your liquidity event.  ‍Click here to book your free exploratory strategy session.‍Enjoy the interview!

It’s no secret there are disagreements about COVID-19 treatments and their mandates among the public, but what about the world’s leading health specialists? U.S. cardiologist and former Chief of Cardiovascular Research at Baylor University Dr. Peter McCullough is one of a […]

Welcome back to this week's #FridayReview.   Today I'd like to share with you the best of the week with these reviews & research on: Fall Community Detox! Cold Brew Coffee Tiny Habits: The Small Changes That Change Everything (book review) Omega-3 & Migraines (research) Omega-3 & Cardiovascular health (research) We're going to review all this and much more on today's #CabralConcept 2058– Enjoy the show! - - -   Show Notes & Resources: http://StephenCabral.com/2058 - - - Dr. Cabral's New Book, The Rain Barrel Effect https://amzn.to/2H0W7Ge - - - Join the Community & Get Your Questions Answered: http://CabralSupportGroup.com - - -  Dr. Cabral's Most Popular At-Home Lab Tests: > Complete Minerals & Metals Test (Test for mineral imbalances & heavy metal toxicity) - - - > Complete Candida, Metabolic & Vitamins Test (Test for 75 biomarkers including yeast & bacterial gut overgrowth, as well as vitamin levels) - - - > Complete Stress, Mood & Metabolism Test (Discover your complete thyroid, adrenal, hormone, vitamin D & insulin levels) - - - > Complete Stress, Sleep & Hormones Test (Run your adrenal & hormone levels) - - - > Complete Food Sensitivity Test (Find out your hidden food sensitivities) - - - > Complete Omega-3 & Inflammation Test (Discover your levels of inflammation related to your omega-6 to omega-3 levels)

LEXINGTON, Ky. (September 23, 2021) – UK's Saha Cardiovascular Research Center recently held its annual Cardiovascular Research Day, an event that showcases innovative research in cardiovascular health. The event features prominent speakers in the field of cardiovascular health, and was the first in-person scientific conference in the field of lipid and lipoprotein metabolism and cardiovascular disease in nearly two years. With 250 attendees from UK and nearly 40 other universities, the event featured a wide variety of research activity from scientists and researchers, from trainees to prominent senior scientists. This week's episode of ‘Behind the Blue' features the director of the Saha Cardiovascular Research Center and chair of the UK Department of Physiology, Dr. Alan Daugherty. Dr. Daugherty is also the Gill Heart Foundation Chair of Preventive Cardiology. He serves as editor-in-chief of the American Heart Association's Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) journal, and his research focuses on molecular mechanisms of vascular diseases, including atherosclerosis and aortic aneurysms. "Behind the Blue" is available on iTunes, Google Play, Stitcher and Spotify. Become a subscriber to receive new episodes of “Behind the Blue” each week. UK's latest medical breakthroughs, research, artists and writers will be featured, along with the most important news impacting the university. For questions or comments about this or any other episode of "Behind the Blue," email BehindTheBlue@uky.edu or tweet your question with #BehindTheBlue. Transcripts for this or other episodes of Behind the Blue can be downloaded from the show's blog page. To discover what's wildly possible at the University of Kentucky, click here.

On today's epsiode, Dr. Jaime has a real "Salty" conversation with Dr. James DiNicolantonio. Dr. DiNicolantonio, is a Doctor of Pharmacy and a cardiovascular research scientist. A well-respected and internationally known scientist and an expert on health and nutrition, he has contributed extensively to health policy and has testified in front of the Canadian Senate regarding the harms of added sugars. He serves as the associate editor of the British Medical Journal's Open Heart, a journal published in partnership with the British Cardiovascular Society, and is on the editorial advisory boards of several other medical journals. Dr. DiNicolantonio is the author or coauthor of over 250 publications in the medical literature. He also is the author of five bestselling health books, The Salt Fix, Superfuel, The Longevity Solution, The Immunity Fix and The Mineral Fix. You can follow him on Instagram and Twitter @drjamesdinic and on Facebook at Dr. James DiNicolantonio. You can visit his website at drjamesdinic.com

Adam, Robin, and Dr. Forbes sit down with Drs Eldrep-Jorgensen and Nelson to discuss in detail the SVS Foundation’s newest initiative, the VISTA program, and one of the first funded pilot projects. Jens Eldrup-Jorgensen, MD is a professor of surgery at Tufts University and Maine Medical Center and medical director for the Society of Vascular Surgery for the Vascular Quality Initiative. He is the innovative force behind the development of the Vascular Volunteers Improve Service to All Program, also known as VISTA. Peter Nelson, MD (@prn19) is the Professor and Chief of Vascular Surgery, Mary Louise Todd Chair in Cardiovascular Research, OU College of Medicine and leads one of the first funded pilot projects working with indigenous communities in Oklahoma.   Relevant Links: Vascular Volunteers Improve Service to All (VISTA) Program Co-host introductions Thomas Forbes, MD (@TL_forbes) is a professor of surgery and RJ Elliot Chair and Division Head of Vascular Surgery at the University of Toronto and was our 4th guest on the podcast and has been a major supporter of our work and will be joining our team more regularly. Robin Osofsky, MD (@OsofskyRobin) is a general surgery resident at the University of New Mexico who is interested in applying for vascular surgery. Follow us @audiblebleeding Learn more about us at https://www.audiblebleeding.com/about-1/ and #jointheconversation.

Adam, Robin, and Dr. Forbes sit down with Drs Lawrence, Nelson, and Eldrep-Jorgensen to discuss the Society for Vascular Surgery Foundation and introduce one of its newest initiatives, the VISTA program. Peter Lawrence, MD is Wiley Barker Professor and Chief of the Division of Vascular and Endovascular Surgery at UCLA and senior editor of the Journal of Vascular Surgery.  He joins us today in his role as the Chair of the SVS Foundation. Peter Nelson, MD (@prn19) is the Professor and Chief of Vascular Surgery, Mary Louise Todd Chair in Cardiovascular Research, OU College of Medicine, and Chair of the Foundation Development Committee of the SVS Foundation. Jens Eldrup-Jorgensen, MD is a professor of surgery at Tufts University and Maine Medical Center and medical director for the Society of Vascular Surgery for the Vascular Quality Initiative. He is the innovative force behind the development of the Vascular Volunteers Improve Service to All Program, also known as VISTA. Donate to the SVS Foundation here. Relevant Links: SVS Foundation SVS Foundation 2020 Annual Report Vascular Volunteers Improve Service to All (VISTA) Program Co-host introductions Thomas Forbes, MD (@TL_forbes) is a professor of surgery and RJ Elliot Chair and Division Head of Vascular Surgery at the University of Toronto and was our 4th guest on the podcast and has been a major supporter of our work and will be joining our team more regularly. Robin Osofsky, MD (@OsofskyRobin) s a general surgery resident at University of New Mexico who is interested in applying for vascular surgery. Follow us @audiblebleeding Learn more about us at https://www.audiblebleeding.com/about-1/ and #jointheconversation.

Hi there!歡迎收聽Look Back Sunday回顧星期天，在這個節目John老師會彙整過去不同國家與主題的熱門跟讀文章，讓你可以在十五分鐘內吸收最精華的世界時事趣聞！我們這週聽聽科學相關的文章，Let's get started!   Topic: Eating a big breakfast could double the amount of calories you burn in the day, according to a new study   Eating a big breakfast could help you burn double the amount of calories than if you eat a larger meal at dinner. 相較於一頓份量較大的晚餐，吃一頓豐盛的早餐可以幫助你燃燒2倍卡路里。   It could be the key to losing weight while also keeping blood sugar levels steady, researchers at Lübeck University in Germany said. 德國盧貝克大學的研究人員表示，這可能是幫你減肥，同時保持血糖水平穩定的關鍵。   Their study found filling up in the morning boosts a metabolism process known as diet-induced thermogenesis （DIT）. 研究人員發現，早上吃飽可以促進「飲食誘導產熱」（DIT）此一新陳代謝過程。   DIT refers to the number of calories the body expends to heat the body and digest food. It was shown to be twice as high for those who ate more at breakfast than at dinner. 飲食誘導產熱指的是身體為保暖和消化食物而消耗的熱量。研究表明，相較於晚餐吃得多的人，早餐吃得多的人的食物誘導產熱是其2倍。   The study also showed increases in blood sugar and insulin concentrations, caused by eating a meal, was diminished after breakfast, but not so much after dinner. 研究還表明，吃飯時升高的血糖和胰島素濃度在早餐後有所降低，晚餐後則下降沒有那麼明顯。   The results also showed eating a low-calorie breakfast caused sweet cravings with a higher appetite. 該研究結果也顯示，吃低卡路里的早餐會導致對甜食的食慾增加。   This suggests those saving all their calories for the end of the day may face consequences because they snack more. 這表明，把一天中高熱量的食物都留到晚上吃的人會得不償失，因為他們會吃更多零食。   Next Article   Topic: Air pollution 'pandemic' shortens lives by 3 years: study 研究：空污「大爆發」 人類減壽3年   A 'pandemic' of air pollution shortens lives worldwide by nearly three years on average, and causes 8.8 million premature deaths annually, scientists said Tuesday. 科學家週二表示，空氣污染「大爆發」，使得全球人口的平均餘命縮短近3年，且每年有880萬人因空污問題提早死亡。   Eliminating the toxic cocktail of molecules and lung-clogging particles cast off by burning oil, gas and coal would restore a full year of life expectancy, they reported in the journal Cardiovascular Research. 根據他們在醫學期刊《心血管研究》發表的研究報告，排除因燃燒石油、天然氣和煤炭所釋出的有毒物質，以及會造成肺阻塞的微粒，將可使人類平均餘命增加整整1年。   Compared to other causes of premature death, air pollution kills 19 times more people each year than malaria, nine times more than HIV/AIDS, and three times more than alcohol, the study found. 該研究發現，相較於其他造成提早死亡的原因，空污每年奪走的人命是瘧疾的19倍、愛滋病的9倍，也是酗酒的3倍。   Coronary heart disease and stroke account for almost half of those deaths, with lung diseases and other non-communicable diseases such as diabetes and high blood pressure accounting for most of the rest. Only six percent of mortality stemming from polluted air is due to lung cancer. 冠狀動脈心臟病和中風的人數，約佔全球提早死亡人數的一半，其餘死因則多半與肺病及糖尿病和高血壓等非傳染性疾病有關。而因空污致死的案例中， 死於肺癌者僅佔6%。   The worst-hit region is Asia, where average lifespan is cut 4.1 years in China, 3.9 years in India, and 3.8 years in Pakistan. 亞洲是受空污影響最嚴重的地區。空污使中國人平均餘命減少4.1年，印度人減少3.9年，巴基斯坦人減少3.8年。 Source article: https://features.ltn.com.tw/english/article/paper/1360772 ; https://features.ltn.com.tw/english/article/paper/1358960   Next Article   Topic: Chemical found in spinach has the same effect as steroids and should be banned for athletes, scientists say   Maybe Popeye was onto something when he ripped open a can of spinach for beating up the bad guys. 當大力水手卜派為了痛毆壞人而打開一罐菠菜時，或許知其所以然。   Scientists in Germany say, ecdysterone, a chemical found in spinach is close to steroids and has a similar effect on humans. Researchers at Freie Universität Berlin ran a 10-week test on nearly 50 athletes and found athletes who took capsules of ecdysterone increased their strength by up to three times. 德國科學家表示，菠菜中發現的化學物質「蛻皮甾酮」（ecdysterone）與類固醇相近，對人體有類似作用。柏林自由大學研究人員對近50名運動員進行歷時10週的測試，發現服用蛻皮甾酮膠囊的運動員，體力最多增加3倍。   The capsules the athletes were given were the equivalent of about nine pounds of spinach but researchers say the capsules could be used as a performance enhancing drug. The study has called on the World Anti-Doping Authority to dig further into ecdysterone and wants the chemical added to the list of banned substances for athletes. 給那些運動員服用的膠囊，約等同於9磅重的蔬菜。但研究人員表示，這些膠囊可能會被用來做為提高成績的藥物。該研究呼籲「世界運動禁藥管制組織」近一步研究蛻皮甾酮，希望將這種化學物質加入運動員禁用物品清單裡。   Next Article:   Topic: Genes, yes, but obesity pandemic mostly down to diet：study 研究：基因有影響，但肥胖流行病主因在飲食   A three-fold jump since 1975 in the percentage of adults worldwide who are obese has been driven mainly by a shift in diet and lack of exercise, but genes do play a role as well, according a large-scale study published Thursday. 根據週四發表的一份大型研究，1975年以來全球成年人口中，肥胖者所佔比例大增3倍，主要由飲食習慣改變和缺乏運動造成，但基因確實也有影響。   For people genetically predisposed to a wider girth, these unhealthy lifestyles compounded the problem, resulting in an even higher rate of weight gain, researchers reported in The BMJ, a peer-reviewed medical journal. 研究人員在同儕審查醫學期刊「英國醫學期刊」發表報告指出，對於基因上易胖的人而言，這些不健康的生活方式加重問題，導致體重更大幅度增加。   To tease out the relative impact of environment and genes on obesity, scientists led by Maria Brandkvist at the Norwegian University of Science and Technology combed through data on nearly 120,000 people in Norway whose height and weight were regularly measured between 1963 and 2008. 為了瞭解環境和基因對肥胖的相對影響，挪威科技大學的布朗克韋斯特領導的一群科學家，探究挪威從1963年到2008年間定期測量身高、體重的近12萬人資料。   Adults began tipping the scales at significantly higher weights in the 1980s and 1990s, they found. Those born after 1970 were far more likely to have a substantially higher BMI as young adults than earlier generations. 他們發現，1980和1990年代成年人的體重顯著增加。1970年以後出生的人，更有可能在年輕時就有比前幾世代人高得多的BMI值。 Source article: https://features.ltn.com.tw/english/article/paper/1312177 ; https://features.ltn.com.tw/english/article/paper/1313703   Next Article   Topic: Science proves that alcohol increases your ability to speak a second language 科學證實，酒精增進你的第二外語口說能力   A new study published in the Journal of Psychopharmacology has found that a bit of Dutch courage might be the key to boosting your ability to speak a second language. 一項發表於《精神藥理學期刊》的最新研究發現，一點酒後之勇可能是促進你第二外語口說能力的關鍵。   Researchers tested 50 native German speakers who had just learned Dutch. Some were given a low dose of alcohol, and others a control beverage with no alcohol, and then were asked to have a conversation in Dutch. 研究人員測試50名以德語為母語的人士，他們剛學習荷蘭語。部分人士被給予低分量的酒精，其他人士則被給予沒有酒精的控制組飲料，之後他們被要求以荷蘭語對話。   The study showed that those who were slightly intoxicated had better pronunciation than their sober counterparts. Alcohol may impair your memory, making it harder to pay attention and recall facts, but on the other hand, it also boosts your self-confidence. 研究顯示，相較於對應他們的清醒受試者，那些微酣受試者的發音更佳。酒精可能損害你的記憶，使你更難專注及回想事情，但另一方面，酒精也會增進你的自信。   However, participants in this study consumed a low dose of alcohol, and that higher levels of alcohol consumption might not have beneficial effects on the pronunciation of a foreign language. The participants knew what they were drinking, so it's not clear if their speech improved because of alcohol's psychological or biological effects. 不過，研究中的受試者只飲用少量酒精，而更多的酒精攝取，可能對外語發音無益。受試者知道自己飲用何物，因此並不清楚他們的口說改善是因為酒精的心理還是生理作用。 Source article: http://iservice.ltn.com.tw/Service/english/english.php?engno=1149846&day=2017-11-07   每日英語跟讀Podcast，就在http://www.15mins.today/daily-shadowing 每週Vocab精選詞彙Podcast，就在https://www.15mins.today/vocab 每週In-TENSE文法練習Podcast，就在https://www.15mins.today/in-tense

Cardiologist University of Alberta Professor in the Division of Cardiology and Director of Cardiovascular Research, and Co-Director of the Canadian VIGOUR Centre The Canadian VIGOUR Centre is a research organization committed to the improving cardiovascular health. Dr. Ezekowitz’s research at the Maz involves the use of machine learning and artificial intelligence to provide insight and discovery out of mountains of invaluable data. Some of the research that he and his colleagues are currently working on will give them the ability to “predict” how patients will respond to certain treatments in advance so doctors can determine best treatment options. See omnystudio.com/listener for privacy information.

Nick talks with junior Aidan Swanson about nuclear energy. They discuss some misconceptions about nuclear energy and the role nuclear energy can plan in a zero-carbon future. References:Calabrese, E. J. (2011). Muller’s Nobel lecture on dose–response for ionizing radiation: ideology or science?. Archives of toxicology, 85(12), 1495-1498.Cui, J., Yang, G., Pan, Z., Zhao, Y., Liang, X., Li, W., & Cai, L. (2017). Hormetic response to low-dose radiation: Focus on the immune system and its clinical implications. International journal of molecular sciences, 18(2), 280.Brenner, D. J., Doll, R., Goodhead, D. T., Hall, E. J., Land, C. E., Little, J. B., ... & Ron, E. (2003). Cancer risks attributable to low doses of ionizing radiation: assessing what we really know. Proceedings of the National Academy of Sciences, 100(24), 13761-13766.Brook, B. W., Alonso, A., Meneley, D. A., Misak, J., Blees, T., & van Erp, J. B. (2014). Why nuclear energy is sustainable and has to be part of the energy mix. Sustainable Materials and Technologies, 1, 8-16. Hirth, L. (2013). The market value of variable renewables: The effect of solar wind power variability on their relative price. Energy economics, 38, 218-236.Jordan, B. R. (2016). The Hiroshima/Nagasaki survivor studies: discrepancies between results and general perception. Genetics, 203(4), 1505-1512.Lelieveld, J., Pozzer, A., Pöschl, U., Fnais, M., Haines, A., & Münzel, T. (2020). Loss of life expectancy from air pollution compared to other risk factors: a worldwide perspective. Cardiovascular Research.Lelieveld, J., Klingmüller, K., Pozzer, A., Burnett, R. T., Haines, A., & Ramanathan, V. (2019). Effects of fossil fuel and total anthropogenic emission removal on public health and climate. Proceedings of the National Academy of Sciences, 116(15), 7192-7197.National Research Council. (2006). Health risks from exposure to low levels of ionizing radiation: BEIR VII phase 2 (Vol. 7). National Academies Press.Putnam, F. W. (1998). The atomic bomb casualty commission in retrospect. Proceedings of the National Academy of Sciences, 95(10), 5426-5431.Sepulveda, N. A., Jenkins, J. D., de Sisternes, F. J., & Lester, R. K. (2018). The role of firm low-carbon electricity resources in deep decarbonization of power generation. Joule, 2(11), 2403-2420.Suzuki, Y., Yabe, H., Yasumura, S., Ohira, T., Niwa, S. I., Ohtsuru, A., ... & Abe, M. (2015). Psychological distress and the perception of radiation risks: the Fukushima health management survey. Bulletin of the World Health Organization, 93, 598-605. United Nations. Scientific Committee on the Effects of Atomic Radiation. (2015). Developments since the 2013 UNSCEAR Report on the levels and effects of radiation exposure due to the nuclear accident following the great east-Japan earthquake and tsunami: A 2015 White Paper to guide the Scientific Committee's future programme of work. UN. World Health Organization. (2012). Preliminary dose estimation from the nuclear accident after the 2011 Great East Japan Earthquake and Tsunami. World Health Organization.

THE WARRIOR RABBI by David R. Gross SAMUEL HA-LEVI IBN NAGRELA, KNOWN AS HA NAGID, LIVED FROM 993-1056 AD. Raised in Cordoba he became the Prime Minister of the city/ state of Granada, the General-in-Chief of its armies, and the head Rabbi of all of Andalusia. As a General he never lost a war. He wrote and published books on Jewish law and poetry, the latter in both Arabic and Hebrew. He conducted an active correspondence with Jewish communities throughout the Diaspora reaching as far north as England and Ireland and as far east as India and the Khazar Empire. Much of his poetry, some of his legal writings, and a bit of his correspondence has survived. Some of his poetry is included in Jewish prayer books to this day. Ha Nagid fled from Cordoba, became a scribe, then assistant to the financial vizier of Granada and, by dint of hard work and extraordinary intelligence and skill, rose to positions of real authority. Palace intrigue, the near constant threat of war from neighboring taifa, and never-ending struggles to protect his people dominated his life. He was a moral person forced, by his position and dedication to the welfare of the Jewish community, to participate in immoral activities. His son Joseph, whom he groomed from an early age to succeed him, was intelligent and educated but lacked the ruthlessness, leadership skills, and warrior nature of his father. Dr. Gross graduated from Colorado State University with the DVM degree in 1960. After ten years in veterinary practice he enrolled at the Ohio State University and earned the MS and Phd degrees in cardiovascular physiology. He did research and taught at Texas A & M University for 16 years, then accepted a position as Professor and Director of the Cardiovascular Surgery Research Labs at the University of Kentucky, College of Medicine. He retired after 12 years as Professor and Head of the basic science department in the College of Veterinary Medicine at the University of Illinois, Champaign-Urbana. During his academic career Dr. Gross co-edited three multi-authored textbooks and over one hundred scientific articles and abstracts. The first, second, and third editions of his single author text, Animal Models in Cardiovascular Research, can be found in most medical libraries. Since retirement, he has published 3 historical novels, 3 memoirs, and a self-help book for students. His most successful book, so far, is the memoir of his first year in veterinary practice entitled “Animals Don’t Blush”. He is now working on a 4th historical novel about the Hanna family, 6 generations ranching on the same property in the Sand Hills of north central Nebraska. https://www.amazon.com/Warrior-Rabbi-David-Gross/dp/1645506436 https://docdavesvoice.com/ http://www.bluefunkbroadcasting.com/root/twia/westwoodbooks12.mp3

Ira Pastor ideaXme life sciences ambassador interviews Dr. Gulden Camci-Unal, Ph.D. Assistant Professor, Department Chemical Engineering, Francis College of Engineering, UMass Lowell. Ira Pastor comments: A few episodes ago ideaXme hosted the University of Michigan’s Dr. Bruce Carlson. We spoke to him about the interesting topic of the importance of "substrate" in regenerative processes, for both the maintenance of normal tissue functions, and in the migration of cells or changes to tissue architecture that are part of healing processes. Substrate is broadly defined as the surface or material on, or from which, cells / tissues live, grow, or obtain nourishment, and have both biochemical, as well as biomechanical functions. Today, on ideaXme we are joined Dr. Gulden Camci-Unal, Ph.D. Assistant Professor, Department Chemical Engineering, Francis College of Engineering, UMass Lowell. Dr Camci-Unal received her Ph.D. in Chemistry at Iowa State University (USA) and her M.Sc. and B.Sc. degrees both in Chemical Engineering at Middle East Technical University (Turkey). Dr. Camci-Unal’s research is at the interface of biomaterials and bioengineering, including the design, synthesis, and characterization of functional biomaterials for applications in tissue engineering and regenerative medicine, development of in vitro disease models for personalized medicine, as well as work in the area low-cost point of care diagnostics. Her work interestingly brings in another interesting theme that we’ve touched on past shows, that of biomimicry, and looking at structures in nature, such as eggshells, plant leaves, marine sponges, and origami paper(!), to help guide viable and cost-effective bioengineering strategies. The overarching goal of her research is to improve human health and quality of life and she has made important contributions in generation of novel engineered platforms for cardiac, cardiovascular and bone tissue engineering. Dr. Camci-Unal’s research and teaching achievements include various awards such as the Iowa State University Teaching Excellence Award, Wakonse Fellowship, NSF ADVANCE Travel Award, Chevron-Phillips Award, Procter & Gamble Fellowship, and finalist for BioFlux Innovation Award. Her research has resulted in dozens of published manuscripts and conference abstracts, and patent applications so far. Dr. Camci-Unal’s work has been published in high impact journals such as Advanced Materials, Nature Asia Materials, JACS, Biomaterials, Lab on a Chip, Soft Matter, and Tissue Engineering. She is an Editorial Board member of Scientific Reports (Nature Publishing Group), Journal of Biomaterials and Tissue Engineering, Regenerative Medicine Research, International Journal of Cardiovascular Research, International Journal of Bioprinting, and Journal of Materials Science and Chemical Engineering. On this episode we will hear from Dr. Camci-Unal about :  - Her background - how she developed an interest in science, in chemical engineering, and in regenerative medicine - An overview of her work in the area of novel bio-materials for regenerative medicine and the importance of inexpensive substrates for wide scale, cost effective use within the global population - An overview of the themes of "origami-inspired tissue engineering", and "organ-on-paper disease models" - Her future visions for clinical translation of such tools  - Current work in the field of low-cost point of care diagnostics for Covid-19. Credits: Ira Pastor, ideaXme ambassador interview. This interview is in American English. Visit ideaXme www.radioideaxme.com Follow ideaXme on Twitter:@ideaxm On Instagram:@ideaxme To discuss collaboration and or partnerships please contact the founder of ideaXme: andrea@ideaxme.com Find ideaXme across the internet including on Apple Podcasts, YouTube, SoundCloud, Radio Public, TuneIn Radio, I Heart Radio, Google Podcasts, Spotify, Amazon Podcasts and more. ideaXme is a global podcast, creator series and mentor programme. Our mission: Move the human story forward!™ ideaXme Ltd.

Dr. Jeffrey Berger is an Associate Professor of Medicine and Surgery (on tenure track) with appointments in Cardiology, Hematology, and Vascular Surgery, and Director of Cardiovascular Thrombosis at New York University School of Medicine. During his training, he received a Master's degree in clinical research from the NIH K30 program at Albert Einstein College of Medicine. He completed fellowships in Cardiology at Duke University, Cardiovascular Research training at Duke Clinical Research Institute, and Vascular Medicine and Thrombosis and Hemostasis at the University of Pennsylvania. Dr. Berger has been the recipient of several grants, honors and awards, including the American Heart Association's Fellow Faculty award, amongst many others. He has also established an independent NIH-funded research program, investigating the role of platelet activity and thrombotic biomarkers in cardiovascular disease. How can we develop a more positive environment in medicine? For starters, says Dr. Jeffrey Berger, is finding ways to bring out the best in those around us. On top of that, Dr. Berger believes hard work, perseverance, and curiosity are the key principles for success. Today, he teaches us how to construct the mindset we need to persevere in medicine—and how to help others succeed along the way, too. Pearls of Wisdom: 1. Ask yourself the questions you want to answer and do not pursue meaningless paths in life. Ask yourself how you can make fresh contributions to your field that few others are making. 2. Be different. Do not conform to a specific mold but be willing to go places, do stuff, and try things others might not attempt. 3. Create an environment of encouragement. Do your best to bring out the best in those around you. 4. Persevere through difficult seasons. Be curious and willing to try hard, fail, and then try again.

Dr. Gershony was the Founder of Vascular Solutions, Inc. (Minneapolis, MN), which had a successful IPO in 2000, and for which he served as Chief Medical Officer and a member of the Board of Directors from 1996-2002. Dr. Gershony was the principal inventor of the DuettTM Vascular Sealing Device manufactured by Vascular Solutions. Dr. Gershony was also the Co-Founder and Chief Medical Officer of AngioScore, Inc. (Fremont, CA), a medical device company devoted to developing unique angioplasty scoring balloon catheters to address a variety of important clinical needs during coronary and peripheral interventional procedures. He was a member of the senior management team from 2003 until AngioScore’s successful acquisition in 2014. Dr. Gershony has served on the adjunct faculty of the Stanford Biodesign Innovation Program. He also completed an Executive Program in finance and accounting (FANFE) at the Stanford Graduate School of Business in 2007. Dr. Gershony is the author of 10 issued medical device patents. He has been a member of the scientific advisory board or a consultant to numerous medical device companies and venture capitalists in the Bay Area and elsewhere. Dr. Gershony is an active early-stage MedTech company investor and mentor, a member of Life Science Angels Medical Device and Digital Health Committee, and a member of the Band of Angels.

What are the best practices for animal models of exercise training? Associate Editor Mario Delmar (New York University) kickstarts a conversation with expert physiologists David Poole (Kansas State University), Timothy Musch (Kansas State University), Steven Copp (Kansas State University), Michael Sturek (Indiana University), Donal O’Leary (Wayne State University), and our own Editor in Chief Irv Zucker (University of Nebraska Medical Center) about the new Guidelines in Cardiovascular Research article by Poole et al. This landmark Guidelines article is designed to provide researchers with comprehensive information as they navigate selecting the most appropriate animal species and exercise paradigm to use in their exercise studies. As Tim Musch points out, “Exercise tests are many times the best strategy for determining the presence and severity of disease.” As the authors explain, animal models offer researchers the ability to control for disease severity and duration, confounding drug treatments, invasive procedures, as well as acute and chronic exercise interventions. We cover rat, mouse, dog, pig, and rabbit exercise training, and discuss everything from which incentive (dark chocolate or cocoa puffs?) rats prefer to thoroughbred racehorses! Listen now.   David C. Poole, Steven W. Copp, Trenton D. Colburn, Jesse C. Craig, David L. Allen, Michael Sturek, Donal S. O’Leary, Irving H. Zucker, Timothy I. Musch Guidelines for animal exercise and training protocols for cardiovascular studies Am J Physiol Heart Circ Physiol, published April 21, 2020. DOI: doi.org/10.1152/ajpheart.00697.2019

The Filtrate:Joel TopfSwapnil HiremathSamira FaroukJennie LinMatt SparksAnd special guests:David J. Cohen: Professor of Medicine at the University of Missouri-Kansas City and Director of Cardiovascular Research at Saint Luke’s Mid America Heart Institute. In addition, he is Medical Director of the Medical Economics and Technology Assessment Group at Mid America Heart Institute. He was previously Associate Director of Interventional Cardiology at Beth Israel Deaconess Medical Center where he was also Associate Professor of Medicine at Harvard Medical School and Director of Economics and Quality of Life Research at the Harvard Clinical Research Institute. He is on Twitter at @djc795Keith Bellovich: Chief Medical Officer Ascension St John. He is also on the board of directors of the renal physician association where he currently the treasurer/secretary.Show Notes:Ischemia CKD trial: https://www.nejm.org/doi/full/10.1056/NEJMoa1915925The most famous figure in nephrology: https://jasn.asnjournals.org/content/10/7/1606(This figure was originally published in AJKD, but is now behind a paywall, hence the JASN link https://www.ajkd.org/article/S0272-6386(98)00339-4/pdf)Should Statins Be Banned from Dialysis? https://jasn.asnjournals.org/content/28/6/1675Ischemia trial (not CKD) https://www.nejm.org/doi/full/10.1056/NEJMoa1915922Courage trial from 2007: https://www.nejm.org/doi/full/10.1056/NEJMoa070829Drug eluting stents approved in 2003: https://en.wikipedia.org/wiki/Drug-eluting_stentCéline Dion, Courage: https://www.youtube.com/watch?v=WN-ZHOHmvcwDr. Farouk hanging with her close personal friend Ms. Dion: https://twitter.com/ssfarouk/status/1246448332039471107https://twitter.com/ssfarouk/status/1235935956152311808A lot of the enrollment of CKD-Ischemia was from Asia, 25%Methods: 19:40Avoiding the Oculostenotic Reflex: https://www.acc.org/membership/sections-and-councils/fellows-in-training-section/section-updates/2016/02/12/16/29/avoiding-the-oculostenotic-reflexBeta blockers in dialysis patients: https://www.ncbi.nlm.nih.gov/pubmed/10201019Mehran Score: https://www.mdcalc.com/mehran-score-post-pci-contrast-nephropathyUltra-low contrast coronary angiography and zero-contrast percutaneous coronary intervention for prevention of contrast-induced nephropathy: step-by-step approach and review: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727230/Capsulology 32:30Antiplatelet treatment of STEMI with P2Y12 inhibitors https://en.wikipedia.org/wiki/P2Y12#Antiplatelet_treatment_of_STEMIImpact of concomitant use of proton pump inhibitors and clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826890/Jennie is an intermediate metabolizer so she will be sluggish to activate P2Y12 inhibitor pro-drugs (which is just about all of them) https://www.mdmag.com/conference-coverage/acc-2018/realtime-genetic-data-impacts-physician-prescribing-behavior-following-stent-proceduresSt John's Wort Supplements Endanger the Success of Organ Transplantation: https://jamanetwork.com/journals/jamasurgery/fullarticle/212243Results 37:10Frank Harrell https://twitter.com/f2harrellHis blog: https://www.fharrell.comDiscussion 46:56Samira does not work at NYU.The Argument for Abolishing Cardiac Screening of Asymptomatic Kidney Transplant Candidates https://pubmed.ncbi.nlm.nih.gov/31492488/Coronary-Artery Revascularization before Elective Major Vascular Surgery. The CARP study https://www.nejm.org/doi/full/10.1056/NEJMoa041905A Single Ventilator for Multiple Simulated Patients to Meet Disaster Surge https://onlinelibrary.wiley.com/doi/pdf/10.1197/j.aem.2006.05.009Joel’s enthusiasm for Remdesivir: The COVID Diaries 3: Ladies and Gentleman, I think this tweet is going to get me in trouble… http://pbfluids.com/2020/05/the-covid-diaries-3-the-tweet-heard-round-the-world/Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31022-9/fulltextNIH Clinical Trial Shows Remdesivir Accelerates Recovery from Advanced COVID-19 https://www.niaid.nih.gov/news-events/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19

The Caribbean Tourism Organization's Communications Specialist Johnson Johnrose speaks to Professor Clive Landis, the Chairman of the University of the West Indies Covid-19 Task Force. Professor Clive Landis has held a number of leadership positions at the University of the West Indies. He has fostered collaborations both inside and outside the university; in Professor Landis' view: "collaboration is the engine of my productivity as an academic and an administrator". Currently, he is the Por-Vice-Chancellor for Undergraduate Studies and Research and is also Professor of Cardiovascular Research, George Alleyne Chronic Disease Research Centre, The University of the West Indies, Barbados. From 2015 – 2019, Professor Landis served as the Deputy Principal, of the Cave Hill Campus, The University of the West Indies, Barbados and from 2013 – 2015, he held the position of Director, ofGeorge Alleyne Chronic Disease Research Centre, The University of the West Indies, Barbados. His ongoing research remains focused on the role of inflammation, particularly the resolution of inflammation, in vascular diseases and recovery from surgery. Recently, he ihas focused on viral research: established viruses such as HIV as well as emerging viruses such as Zika and COVID-19. Professor Landis has sought to help build preparedness and capacity in the Caribbean to deal with such pandemics as Zika andCOVID-19 as Chair of the UWI Zika Task Force in 2016 (www.uwi.edu/zika) and Chair of the UWI COVID-19 Task Force in 2020. Over the years, Professor Landis has successfully secured a number of research grants and engaged in fundraising for The University of the West Indies.

Hosted by Dr. Jacinta Delhaize by herself! Dr. Daniel Cunnama will rejoin her with the next show. Season Two of The Cosmic Savannah is on it’s way! But in the meantime, our science-savvy listeners can get their fix at a very exciting live event that happened in Cape Town! Soapbox Science South Africa happened on Saturday 28th September 2019 at the Pierhead V&A Waterfront in Cape Town from 12pm until 3pm. It is a pop-up event where incredibly talented female scientists will stand on soap boxes and tell passers-by all about their jobs. Science topics ranged from astronomy to archaeology, forensics to atomic physics, gut bacteria to sea creatures, vaccines to renewable energy, and more! Today we hear from some of our speakers:   Ms. Harshna Jivan (@HershiesJ), School of Physics, University of the Witwatersrand, “At the centre of it all: The Atomic Nucleus.”   Dr. Kerryn Ashleigh Warren (@kerryn_warren / https://bonevolution.wordpress.com/ ), Dept of Archaeology, University of Cape Town, “There and back again: Excavating at Rising Star Caves.”   Ms. Mieke du Plessis (@the_patient_scientist / https://www.linkedin.com/in/mieke-du-plessis-71014183/ ), the Hatter Institute for Cardiovascular Research in Africa, University of Cape Town, “Bugs and brains: how your microbes influence your mind.”   Dr. Michelle Lochner (@doc__loc / http://doc-loc.blogspot.com/ ), African Institute for Mathematical Sciences/ South African Radio Astronomy Observatory “Mysteries of the universe unravelled by the rise of the machine.”   Dr. Marise Heyns ( http://www.forensicscience.uct.ac.za/ ), Division of Forensic Medicine and Toxicology, Department of Pathology, University of Cape Town, “CSI: Cool Science Interrogates.”   Dr. Edina Amponsah-Dacosta (@eddiedacosta2 / http://soapboxscience.org/we-should-all-be-talking-about-vaccines-meet-dr-edina-amponsah-dacosta/ ), Vaccines for Africa Initiative, University of Cape Town, “Vaccines Are Us!”   Dr. Natasha Karenyi (@Natasha_Karenyi / http://www.biologicalsciences.uct.ac.za/bio/staff/academic/karenyi ), University of Cape Town, “What lies beneath the waves: small players on a large stage.”   Dr. Natasha Ross (@NatashaUWC), Department of chemistry, University of the Western Cape “It is your attitude, not your aptitude, that determines your altitude # Unlike protons, I don’t deal with negativity! :-)”   Associate Professor Liesl Zuhlke (@lieslzuhlke / http://www.chdru.uct.ac.za/ ), Red Cross war memorial children’s hospital, “Peas, almonds and fists: saving children’s hearts.”   Ms. Edith Phalane  (@EdithPhalane1 / http://www.nwu.ac.za/ ), North-West University, “Keeping your heart healthy: five easy steps to follow.”   Dr. Lucia Marchetti, Chief organizer of Soapbox Science South Africa.   We've added a new way to donate to 365 Days of Astronomy to support editing, hosting, and production costs. Just visit: https://www.patreon.com/365DaysOfAstronomy and donate as much as you can! Share the podcast with your friends and send the Patreon link to them too! Every bit helps! Thank you! ------------------------------------ Do go visit http://astrogear.spreadshirt.com/ for cool Astronomy Cast and CosmoQuest t-shirts, coffee mugs and other awesomeness! http://cosmoquest.org/Donate This show is made possible through your donations. Thank you! (Haven't donated? It's not too late! Just click!) The 365 Days of Astronomy Podcast is produced by Astrosphere New Media. http://www.astrosphere.org/ Visit us on the web at 365DaysOfAstronomy.org or email us at info@365DaysOfAstronomy.org.

Hallie Arnott, President of the Canadian Biomaterials Ottawa Student Chapter, talks to Dr. Jane Freedman about her work on inflammation and cardiovascular research. Dr Freedman also shares with us how she envisions Circulation Research, the Journal where she is the Editor in Chief, is transforming how Cardiovascular research is being made available to the community using Social Media.

How can researchers ensure that Doppler ultrasound measurements of human resistance vessel function are both accurate and repeatable? Listen as Editor in Chief Dr. Irving H. Zucker (University of Nebraska Medical Center) interviews the lead authors of this Guidelines in Cardiovascular Research article— Jacqueline K. Limberg (University of Missouri), Jaume Padilla (University of Missouri), Darren P. Casey (University of Iowa), Joel Trinity (University of Utah). The authors discuss the need for clear inclusion and exclusion criteria for human subjects, as well as the necessity of avoiding several key environmental stressors for a period of time prior to assessments. As a result of collaborating with experts around the globe, the authors developed a comprehensive figure and tables to outline considerations surrounding medication use and the potential impact of medication on vascular function, as well as other concerns for study participants such as caffeine intake, alcohol use, posture, and sleep. What is the best ambient room temperature to avoid confounding results related to skin blood flow when evaluating total limb blood flow to skeletal muscle? For the answer to this key question and more, listen now.   Jacqueline K. Limberg, Darren P. Casey, Joel D. Trinity, Wayne T. Nicholson, D. Walter Wray, Michael E. Tschakovsky, Daniel J. Green, Ylva Hellsten, Paul J. Fadel, Michael J. Joyner, Jaume Padilla Assessment of resistance vessel function in human skeletal muscle: guidelines for experimental design, Doppler ultrasound, and pharmacology  Am J Physiol Heart Circ Physiol, published January 31, 2020. DOI: doi.org/10.1152/ajpheart.00649.2019

Dr. Benjamin Levine is the founder and Director of the Institute for Exercise and Environmental Medicine (IEEM) at Texas Health Presbyterian Hospital Dallas where he also holds the S. Finley Ewing Chair for Wellness and the Harry S. Moss Heart Chair for Cardiovascular Research. He is Professor of Internal Medicine/Cardiology and Distinguished Professor of Exercise Sciences at the University of Texas Southwestern Medical Center. He is a wealth of information on some of our nation's most cutting-edge research on taking better care of your heart. This is the full un-cut interview where Dr. Levine describes some of the studies his Institute has been involved with and the amazing findings, especially for how much exercise is required to maintain a healthy cardiovascular system. See acast.com/privacy for privacy and opt-out information.

February is Heart Month and we kick it off with one of the premier cardiologists in the DFW Metroplex, Dr. Benjamin Levine of Texas Health Presbyterian Hospital and UT Southwestern Medical school. Dr. Levine is the founder and Director of the Institute for Exercise and Environmental Medicine (IEEM) at Texas Health Presbyterian Hospital Dallas where he also holds the S. Finley Ewing Chair for Wellness and the Harry S. Moss Heart Chair for Cardiovascular Research. His degrees are from Brown University and Harvard Medical School.Next, Stephen Love facilitates an in-depth discussion about the impending Medicaid 1115 Waiver, which is set to expire next legislative session and will create a multi-billion dollar shortfall that will have to be picked up by Texas taxpayers. This is a huge looming issue that you likely haven't heard about, but need to be aware. We are joined by Charles Smith, a consultant and advisor who helped write the current Waiver, State Senator Nathan Johnson of Dallas, and Richard Carter, CEO of Hunt Regional Healthcare in Greenville.The radio program, hosted by DFWHC President/CEO Stephen Love and KRLD's Thomas Miller, will run throughout 2020 on Sunday's from 1:00 p.m. to 2:00 p.m. CST on KRLD-1080-AM Dallas, Texas or listen to KRLD live on Radio.com from anywhere in the world.You can also listen to broadcasts on:SpotifyAppleGoogleStitcheriHeart PodcastsYouTubeFor information or program ideas, you can contact radio@dfwhc.org. See acast.com/privacy for privacy and opt-out information.

It’s well known that myocardial cell death leads to cardiac remodeling and heart failure. It is, however, less well known exactly which mechanisms lead to myocyte cell death in the heart. In our latest podcast, Associate Editor Junichi Sadoshima (Rutgers New Jersey Medical School) interviews lead authors Paras Mishra (University of Nebraska Medical Center), Joseph Hill (University of Texas Southwestern Medical Center), Peter Kang (Beth Israel Deaconess Medical Center), James Downey (University of South Alabama) and Takashi Matsui (University of Hawaii at Manoa) about their recent comprehensive Guidelines in Cardiovascular Research article on evaluating myocardial cell death. Listen as our experts—all of whom are global thought-leaders in their individual fields—delve into the 6 main mechanisms of cell death in the heart: apoptosis, ferroptosis, autophagic cell death, necroptosis, MPT-mediated necrosis, pyroptosis, autosis.   Paras K. Mishra, Adriana Adameová, Joseph A. Hill, Christopher P. Baines, Peter M. Kang, James Downey, Jagat Narula, Masafumi Takahashi, Antonio Abbate, Hande C. Piristine, Sumit Kar, Shi Su, Jason K. Higa, Nicholas K. Kawasaki, Takashi Matsui Guidelines for evaluating myocardial cell death Am J Physiol Heart Circ Physiol, published October 23, 2019. DOI: doi.org/10.1152/ajpheart.00259.2019

This month on the Discover CircRes podcast, host Cindy St. Hilaire highlights five featured articles from recent issues of Circulation Research and talks with Matthew Stratton, Rushita Bagchi, and Tim McKinsey about their article on Dynamic Chromatin Targeting of BRD4 Stimulates Cardiac Fibroblast Activation. Article highlights: Vincentz, et al. HAND1 Enhancer Variation Impacts Heart Conduction   Zhuang, et al. EC-Klf2-Foxp1-Nlrp3 Regulates Atherogenesis   Quintanilla, et al. Robust Targets for Persistent AF Ablation   Lambert et al. Characterization of Kcnk3-Mutated Rats   Myagmar et al. Gq Mediates Cardioprotection Transcript Cindy St. H:       Hi, welcome to Discover CircRes, the monthly podcast of the American Heart Association's journal, Circulation Research. I'm your host, Dr Cindy St Hilaire, and I'm an assistant professor at the University of Pittsburgh. My goal as host of this podcast is to share with you highlights from recent articles published in the August 30th and September 13th issues of Circulation Research. We'll also have an in-depth conversation with Drs. Matthew Stratton, Rushita Bagchi, and Tim McKinsey, who are the lead authors of one of the exciting discoveries presented in the September 13th issue. Cindy St. H:         The first article I want to share with you is titled, "Variation in a Left Ventricle–Specific Hand1 Enhancer Impairs GATA Transcription Factor Binding and Disrupts Conduction System Development and Function." The first author is Joshua Vincentz and the corresponding author is Anthony Firulli, and this work was conducted in the Departments of Pediatrics, Anatomy, and Medical and Molecular Genetics at Indiana Medical School in Indianapolis, Indiana. Cindy St. H:         The heart's ventricular conduction system, or VCS, is composed of specialized muscle cells that propagate electrical signals through the working myocardium of the ventricles to coordinate the rhythmic contractions of the heart chambers. Disorders of the VCS can lead to certain types of arrhythmia. Genome-wide association studies have identified a number of single nucleotide polymorphisms, or SNPs, that appear to increase the risk of VCS-mediated arrhythmias. Two such SNPs are located in the upstream region of a gene encoding for Hand1. And Hand1 is a transcription factor that is involved in left ventricle development. Conditional cardiac Hand1 ablation during embryogenesis leads to ventricular septal defects and hyperplastic arterial ventricular valves, and a reduction in Hand1 expression could lead to morphological, and therefore functional defects. Vincentz and colleagues hypothesized that these SNPs might reside in an enhancer element, and that's a region of DNA and a promoter that allows for the increased expression of a gene. The region containing the SNPs is highly conserved from mammals to reptiles and includes two sequences that allow for the binding of GATA transcription factors. And GATA transcription factors are well known to drive cardiac development. So this team used CRISPR-Cas9 technology to show that the deletion of the enhancer impaired normal VCS morphology and therefore function. And they did this in a mouse model and in the in vitro electromobility shift assay (which frankly was one of my favorite love-to-hate experiments of my PhD). So this group did their own electromobility shift essay and showed that GATA-4 binds to these enhancer sites. And together, these results support a role for Hand1 in the formation and function of the VCS and offer insights to possible arrhythmia etiologies. And what I really love about this paper is that they could actually go from a SNP in a GWAS to a functional role of a protein, which is great. A lot of times with GWAS studies, you have no clue what the heck is going on. So this was a beautiful study where they actually could link a single nucleotide polymorphism to differential expression of a gene. Cindy St. H:         The next article I'd like to highlight is titled, "Endothelial Foxp1 Suppresses Atherosclerosis via Modulation of Nlrp3 Inflammasome Activation." The first authors are Tao Zhuang and Jie Liu, and the corresponding authors (there's three of them) are Zhongmin Liu, Muredach Reilly, and Yuzhen Zhang. The Liu and Zhang teams are from the Key Laboratory of Arrhythmias of the Ministry of Education of China, and the Research Center for Translational Medicine at Shanghai East Hospital, which is part of Tongji University School of Medicine in Shanghai. And the Reilly team is from the Cardiology Division in the Department of Medicine and the Irving Institute for Clinical and Translational Research at Columbia University in New York, New York. And I have to say my good friend Rob Bauer is also a coauthor on this article. So Rob, I hope you're listening. Cindy St. H:         Chronic inflammation contributes to atherosclerotic disease and is a major pathological mechanism contributing to the dysfunction of the vascular endothelium. So leukocytes, which are inflammatory cells that float around in your blood, leukocytes can adhere to the endothelial layer, and then they can migrate through the endothelial wall into the wall of the vasculature. And it's this activity, along with the uptake of oxidized LDL and the formation of a little fatty streak, that is the start of atherosclerosis. And now Zhuang and colleagues have identified that the transcription factor Foxp1 is a potential regulator of vascular endothelial health. So first they showed that while healthy arteries express Foxp1 robustly, atherosclerotic endothelium from both mice and humans exhibits reduced expression of this transcription factor. The team then generated atheroprone mice that either lacked Foxp1 or overexpressed Foxp1 specifically in the endothelium. The mice lacking Foxp1 were shown to have exacerbated athero with much larger plaque sizes and increased macrophage infiltration into the vessels, while overexpression of Foxp1 had largely the opposite effect. It actually curtailed progression of atherosclerotic disease. The team went on to examine the atherosclerosis-suppressing mechanism of Foxp1, showing that the factor suppressed expression of the inflammasome components in the endothelial cells. Cindy St. H:         So all together, these results highlight that Foxp1-mediated regulation of the inflammasome is a potential targetable pathway for atherosclerotic treatments, and having a new targetable pathway is important, as the CANTOS trial, which provides proof of concept of the inflammation hypothesis of atherosclerosis in humans, showed robust effects in only a small subset of the population tested. Thus, there is a need to identify other means, a plan B if you will, by which we can control the inflammation that contributes to atherosclerosis. Cindy St. H:         The next paper I want to highlight is titled, "Instantaneous Amplitude and Frequency Modulations Detect the Footprint of Rotational Activity and Reveal Stable Driver Regions as Targets for Persistent Atrial Fibrillation Ablation." The first author is Jorge Quintanilla, who is also a corresponding author alongside David Filgueiras-Rama, and they are from the National Center for Cardiovascular Research and the Center for Biomedical Research in Cardiovascular Diseases Network in Madrid, Spain. Uncoordinated contractions of the atria to the ventricles of the heart is called atrial fibrillation, or AFib, and AFib causes symptoms such as heart palpitations, dizziness, and taken to the extreme, AFib can actually cause death. To correct such rhythm problems, doctors can ablate certain regions of the heart suspected to be driving this misfiring. In an ablation procedure, a catheter is inserted through the blood vessels and into the heart. An electrophysiologist then identifies the locations of the heart that are sending abnormal electrical impulses, and with either delivery of tiny pulses of painless, low-level energy or using a catheter that has a cold tip to freeze the misfiring areas, the electrophysiologist can ablate and hopefully stop  AFib. The problem is that this approach often fails, and AFib still occurs or can reoccur after a length of time. So Quintanilla and colleagues wanted to develop a more personalized medicine approach to treating AFib. So to do this, they wanted to make it something simple, something affordable, and something that hospitals currently have access to. So they used the standard electroanatomical mapping system to track the amplitude and also the frequency modulations of the electrical signals from the hearts with AFib. And they found that regions with high and stable instantaneous frequency signals were the drivers of fibrillation in the hearts. When these regions were ablated in pigs with persistent AFib, the misfiring stopped in almost all cases and was sustained. The team went on to test the system in three patients with Afib, and two of the three remained arrhythmia-free without drugs for at least 16 months. So with further development and testing, this frequency mapping could potentially replace systems that are currently in use, and more importantly, this could provide a more accurate and patient-tailored way to find and ablate the drivers of AFib. Cindy St. H:       The next paper I want to highlight is titled, "Characterization of Kcnk3-Mutated Rat, a Novel Model of Pulmonary Hypertension." Oh, now that was a nice title. That was nice and short. The first author is Mélanie Lambert, and the corresponding author is Fabrice Antigny, and they are from the INSERM Hôpital Marie Lannelongue in Le Plessis Robinson, France. Cindy St. H:       Pulmonary hypertension is a rare but life-threatening condition where the adverse remodeling of the pulmonary arteries causes an increase in the blood pressure that's needed to push the blood through the lungs, and this high blood pressure causes the heart to work harder, and it leads ultimately to right ventricular hypertrophy and heart failure. So genome-wide association studies have identified a number of mutations that have been linked to pulmonary hypertension and these include several loss-of-function mutations in the gene encoding for a potassium channel, and that's a protein that can release potassium from a cell to the extracellular environment. And the particular one that has been found to be mutated in pulmonary hypertension patients is Kcnk3. And this channel regulates the resting membrane potential of pulmonary artery smooth muscle cells. To date, it is not known how the loss of Kcnk3 contributes to pulmonary hypertension. To start to unravel this mystery, Lambert and colleagues created a full-body knockout of Kcnk3 in rats, and they used rats because that's a much more robust model for studying pulmonary hypertension than some of the murine models available. These knockout animals exhibited an increased pulmonary artery pressure. They also had faster heart rates and they were more susceptible than their wild-type counterparts to both pharmacological or hypoxia-induced pulmonary hypertension. These Kcnk3 knockout rats also had evidence of remodeled pulmonary vasculature, and this vasculature showed signs of endothelial dysfunction, altered vaso transcription, and altered neomuscularization. In in vitro studies, they used pulmonary artery smooth muscle cells that they isolated from these knockout rats, and these cells showed increased activation of proliferation markers, which is another signature of pulmonary hypertension. And this was also mirrored in human pulmonary artery smooth muscle cells that were treated with a Kcnk3 inhibitor. So together, this work starts to uncover the role of Kcnk3 in pulmonary hypertension pathogenesis. And it also provides the field with a novel model system from which people can learn more about the role of membrane potential of pulmonary artery smooth muscle cells in pulmonary hypertension. Cindy St. H:       The last paper I want to highlight before our interview is titled, "Coupling to Gq Signaling Is Required for Cardioprotection by an Alpha-1A-Adrenergic Receptor Agonist." The first author is Bat-Erdene Myagmar, and the corresponding author is Paul Simpson from the VA Medical Center in San Francisco, California. So like their name says, G-protein coupled receptors interact with G-protein subunits to propagate the signal when a ligand binds. The protein G alpha q has long been considered a key mediator of cardiac hypertrophy. And that's because in mice, when this Gq protein was overexpressed, it induced hypertrophy, myocardial apoptosis, and contractile failure. However, this sub unit Gq can interact with a multitude of G-protein coupled receptors that themselves bind a variety of ligands. So which receptor or which signaling pathway specifically is responsible for the hypertrophic phenotype? Recent studies by others had shown that stimulation of the alpha-1A adrenergic receptor prevents cardiotoxicity and heart failure. So Myagmar and colleagues asked whether this cardio-protective alpha-1A stimulation is dependent on the alpha q subunit. So using mice with a mutant version of alpha-1A that allows the binding of the ligand but does not couple with the Gq subunit, the team found that alpha-1A induced cardioprotection was absent. The mutant animals were more likely to die than their wild-type counterparts when hypertrophy was induced pharmacologically or surgically. And furthermore, in the mutant myocytes themselves, the group observed that alpha-1A induced ERK signaling, which is essential for the receptors cardioprotective activity, was impaired. So together these results showed that alpha-1A-induced cardioprotection is dependent on alpha q, and actually it showed that alpha q signaling is not always maladaptive. Cindy St. H:       Now we're going to move to our interview with Drs. Matthew Stratton, Rushita Bagchi and Tim McKinsey and we're going to talk about their great paper titled "Dynamic Chromatin Targeting of BRD4 Stimulates Cardiac Fibroblast Activation." Cindy St. H:       Okay, so now we're going to have our interview with Drs. Stratton, Bagchi, and McKinsey on their paper titled, "Dynamic Chromatin Targeting of BRD4 Stimulates Cardiac Fibroblast Activation." So welcome, everyone. Dr Tim M:          Thank you. Dr Rushita B:    Thank you. Dr Matt S:          Thank you. Cindy St. H:       I was wondering if you could just all maybe go around and introduce yourselves. Dr Tim M:          Sure. I'm Tim McKinsey. I'm a professor in the Division of Cardiology at the University of Colorado Anschutz Medical Campus. I also direct a newly formed fibrosis center on campus. It's called the CFReT, the Consortium for Fibrosis Research and Translation, and our goal is to understand new mechanisms that regulate fibrosis and develop new therapies to treat scarring, or fibrosis, in organs. Dr Rushita B:    I'm Rushita Bagchi. I'm currently a postdoctoral fellow in Dr McKinsey's lab. I grew up in India, and that's where I did my undergrad and master's degrees. Then I moved to Canada to do my PhD focusing on transcriptional regulation of cardiac fibrosis under the supervision of Dr Michael Czubryt. After that, I transitioned to Dr McKinsey's lab here in Denver to enhance or add to my expertise of transcription by studying epigenetics, and especially trying to find the underlying mechanisms that cause cardiovascular disease. The nice thing about this position for me has been that I have been able to constantly build up on my experience studying tissue fibrosis, but at the same time, Tim has been very generous and has let me develop projects of my own as well. Cindy St. H:       You're lucky. That's awesome. Thank you for joining us. And Dr Stratton. Dr Matt S:          I'm Matt Stratton. I'm an assistant professor in the Department of Physiology and Cell Biology at Ohio State University. I did my graduate training at Colorado State University in neurodevelopment and neuroendocrinology and then moved to Tim's lab for a postdoc and assumed my current position this past December. Cindy St. H:       Wow. How's it going? Dr Matt S:          It's going well. Starting a lab is a lot of fun and a lot of stuff going on. Cindy St. H:       Yeah, I'm four years in now and at the same time you feel brand new and excited and then, oh my God, what am I doing? So that's great. Well thank you all for joining me. So I really like this paper, mostly because I'm also a vascular biologist. I kind of focus more on the heart valves, but I have a real interest in cell phenotype transitioning and cell shifting, and so when you started to talk about chromatin remodeling and bromodomain protein, I was really interested and wanted to hear more. So maybe we can start by telling everyone what is the clinical need that your paper at base is trying to address? Dr Tim M:          Well before we get into that, could I start by saying that we're honored to have our work published in Circulation Research. We're really grateful for that. I also want to point out that this is the result of a very detailed collaborative effort involving at least six other labs, including the labs of Charles Lan at Baylor College of Medicine, Jun Qi at the Dana-Farber Cancer Institute, Kunhua Song and Maggie Lam here in Colorado, as well as Sap Haldar and Deepak Srivastava at the Gladstone Institutes in San Francisco. Without this collaborative effort, none of this would have been possible. Cindy St. H:       That's great to hear and I'm really happy you mentioned that. Team science is so important, and I feel like we almost can't get these big, groundbreaking papers unless we really work as a good team, so thank you for highlighting that. Dr Tim M:          So we're really interested in fibrosis, which is a hallmark of heart failure. Fibrosis can actually be a good thing for the heart. If you have a myocardial infarction, you need a strong scar to form to prevent the ventricle from rupturing. But in response to chronic stress like hypertension and other things, you can get this longstanding fibrosis that results in cardiac dysfunction. That's because fibrosis is essentially a scarring process and one of the things that that does is to create a stiff in the left ventricle that can't relax effectively. Unfortunately, despite the well-known roles of fibrosis in cardiac disease, there are no targeted anti-fibrotic therapies for the heart, and that's really our focus in the lab. We've had a long-standing interest in epigenetic regulation of heart failure and cardiac fibrosis, and we've known for some time that inhibitors have a family of epigenetic reader proteins called the bromodomain and extraterminal proteins, the BET proteins. Inhibitors of those BET proteins can block cardiac fibrosis in rodent models and improve cardiac function. What we knew going into this work is that systemic delivery of those compounds was efficacious. But as you know, the heart is made up of many different cell types. So we really wanted to understand if the efficacy of these compounds was related to effects in resident cardiac fibroblasts. Cindy St. H:       Excellent. So what is the role of a cardiac fibroblast in a healthy cell, and where does that go awry? Dr Matt S:            So in a undiseased heart, fibroblasts are necessary to provide structure, right? They lay down the extracellular matrix that really holds the heart together. Without them, you would not have a good pump function. Where they go awry, I mean, that's one of the things that we're trying to study, right? They become proliferative, they become contractile, and they secrete, or we call them super-secretors, of extracellular matrix. So TGF-beta is really a known signaling molecule that kicks the fibroblasts into this activated or myofibroblast state. We use that in the paper as a agonist for our cultured cells. Cindy St. H:         Great, thank you. So what was the hypothesis you were testing in this paper? Dr Matt S:            So what we wanted to know, if BRD4 and BET proteins are important for this activation of cardiac fibroblasts? So going from a quiescent fibroblast to a proliferative and super-secretor of extracellular matrix fibroblast in the heart. And those experiments hit right away. I mean, we did those experiments, and it was quite dramatic that if you use JQ1 to inhibit these BET proteins, you completely blocked this myofibroblast differentiation. We went in and did some siRNA and shRNA work to show that really BRD4 appears to be the main culprit of the BET protein families. Cindy St. H:         Rushita, could you tell us a little bit about what a bromodomain protein is and what maybe specifically BRD4 is in relation to the other bromodomain proteins? Dr Rushita B:      Sure. So when we talk about the chromatin, there are various players in there that are known as, in general, chromatin modifiers. So you have enzymes that add acetylation mark on lysine residues on histone tails, which is basically DNA is wound around these histones and those histones have lysine tails, but you have the big acetyl group sitting. Now when you have this acetyl group sitting, this makes it more accessible for the transcriptional machinery and allowing gene transcription to happen. Those enzymes are known as histone acetyltransferase, the ones that add the acetyl mark there. The ones that take it away, which is what our lab has been studying for a long time, and Tim is a known world expert in the field, those are known as histone deacetylases, or HDACs, which basically remove those acetyl marks and compact the chromatin, thereby suppressing gene expression. This BET proteins or bromodomains are transcriptional coactivators. So this bromodomain is actually in charge or takes up the duty of identifying these acetyl marks on the lysine residues and therefore, tells the transcription machinery to come in and allow gene transcription to happen. There are a few BET proteins. Of them, BRD4 has been studied extensively in cancer as well as in the heart. But as Tim mentioned, the role of BRD4 has been studied vastly in the heart in terms of the cardiac myocytes, but not so much in the non-myocyte population, which is where our work stands out really well and starts highlighting the role of this specific chromatin modifier protein in activation or control of profibrotic gene expression. Cindy St. H:         Yeah. So correct me if I'm wrong, but my understanding is, you're going to need a little bit of the cardiac fibroblasts remodeling in the early phase. But where it is really detrimental is when that overcompensates and overproliferates and throws down too much matrix and then is bad. So do you see your study as a way to kind of target that window of where a potential treatment might be applicable? Dr Tim M:            Yeah, we think that BRD4 is a nodal regulator of cardiac fibrosis and therefore, an excellent therapeutic target. The challenge will be developing selective BRD4 inhibitors that are safe, as well as effective. We know that BRD4 is not only expressed in cardiac fibroblasts-it's all over the body. But we think our work provides an entry point to the development of highly selective BRD4 inhibitors for fibrotic indications, including heart failure. Cindy St. H:         So that's one of the things I was wondering, how specific your drug is to BRD4 versus the other ones, but also you mentioned the myofibroblast versus the immune cells infiltrating the heart. Do we know what BRD4 is doing in those cells in this system? Dr Tim M:            BRD4 is definitely pro-inflammatory, and BET protein inhibitors like JQ1 are anti-inflammatory, that's for sure. Interestingly, there's a BET family inhibitor called Apabetalone, RVX-208, that's in Phase III clinical testing for people with atherosclerosis. So if that's successful, it will provide proof of concept that you can target this family of epigenetic readers to treat cardiovascular disease. I also wanted to point out that JQ1 was initially discovered by Jay Bradner's lab, in particular Jun Qi, who is a coauthor and collaborator on this paper. Cindy St. H:         Oh, very nice. Okay, good conflict of interest too, I guess. So maybe you guys can talk a little bit about how you managed to get this huge team of scientists together efficiently, and what were any hang-ups? Matt is laughing a bit, but you two are the lead authors, Matthew and Rushita. How did you two kind of lead the way on this and divvy up this huge project? Dr Matt S:            So it is definitely a project management-style approach I think you have to take. I mean, there's a lot of communication, really a lot of communication with bioinformatics, analysts, and getting the right sequencing done, and that was fun, but it took a lot of effort. And once you get this big data, how do you present it in an intelligible story and how do you pick things out that may lead to new discoveries, right? So we highlight Sertad4 in here as a gene that's very much BRD4-dependent. And I think this is a proof of concept for using this genomics, and particularly BRD4, as kind of a molecular string to pull on to unwind this puzzle. So that was a lot of fun. And you know, Rushita was super awesome in helping with this project. Dr Rushita B:      Yeah, I think having stared at cardiac fibroblasts for six years during my PhD definitely gave me the confidence that I could step up to the plate and deliver what was necessary. And like Matt said, there was a lot of omics-based stuff that we did in the paper. And that is actually one of the key highlights, because we see papers or manuscripts that are published that have RNA-Seq, ChIP-Seq and proteomics, but I believe the strength in our article is the combination of all three. So we were actually able to do overlapping ChIP-Seq and RNA-Seq experiments, and then there was proteomics involved. So we are looking at it at the genomic transcriptome and protium-wide changes that are happening all together, put in one manuscript. And the beauty of this work is it has now created data sets that people can mine and get more information out of. And this is something that will definitely continue to drive our future studies in the lab as well. Cindy St. H:         Can you maybe expand on that? Could you maybe describe briefly for the audience what ChIP-Seq is and what RNA-Seq is, and really the power that is created when you can couple those techniques with the same samples? Dr Matt S:            Sure. So BRD4 was the center point of the paper, right? So we did BRD4 ChIP-Seq and RNA Pol II ChIP-Seq in fibroblasts treated with TGF-beta or not. So in ChIP-Seq, you basically immunoprecipitated your target protein, and that brings with it, if it's bound to chromatin, that brings with it the DNA that it's bound to. And then you can sequence the DNA that comes out of your immunoprecipitation and map that to the genome, and you get a very nice picture of where is BRD4 enriched, and where does it go after stimulation like TGF-beta, when the fibroblast becomes a myofibroblast. So you can line all these up and you can pick out what gene changes we think are directly dependent on BRD4. That's something that we like, because we now know that BRD4 is a good target, right, so that kind of pulls it together. Cindy St. H:         Great. Thank you. What else do you want to bring up? Dr Matt S:            I think understanding how signals get translated to changes in gene expression is obviously something that the field is very much interested in. And because BRD4 is basically a step away from RNA polymerase II, it gives you a little bit more specificity in knowing that that's a disease-activated pathway, right? So trying to figure out what directs BRD4 to new locations in the chromatin and cause it to be removed from previous locations in the chromatin is really an interesting area of research. So we did a pathway screen basically using inhibitors, and we use Sertad4 as the readout, right. And we found that a p38 inhibitor was able to block the ability of TGF-beta to induce Sertad4. And we were able then to show that p38 had a role in targeting BRD4 specifically to the Sertad4 locus. Dr Tim M:            I wanted to say, you know, one of the challenges with this project is that fibroblasts are difficult to work with. You would think that they would be easier to work with than a myocyte. But when a fibroblast hits a plastic cell culture dish, it rapidly transforms into an activated cell, because that plastic has a very high tensile strength. So it took a lot of optimization to figure out methods to culture these cells to maintain them in a quiescent state. Cindy St. H:         What did you do? What was that trick? Dr Tim M:            I mean, it involves changing cell density, changing the constituents of the medium, and doing other things. Cindy St. H:         Science magic. Dr Tim M:            Yeah. Dr Rushita B:      And I'll just add to that. The nice thing about being able to contribute to a study like this is also that, like Tim said, fibroblasts, they change phenotype rapidly. You take them out of a biological system, whether it's a heart or any other tissue, you plate them out in cell culture, they start changing. The nice thing about the in vivo study, the RNA-Seq that was done using the in vivo study with JQ1, was that we used a very simple pressure overload model known as the TAC model, which is a very well-established and accepted model worldwide in the field of cardiovascular disease, treating animals with JQ1. So we isolated fibroblasts, but the time from the isolation of cells to the time an RNA was prepared was an hour or two. So we made sure that we minimally exposed them to culture conditions in the lab, so we retained their biology. So what we did on plastic dishes before, although they were plated on plastic, and we had RNA-Seq done on those cells, like Tim said, we did optimize the conditions. And then being able to similarly treat or use the cells that come from an animal directly and both of them contributing to a similar cohort of genes or pathways that we can look at, that has definitely given immense strength to this manuscript. Cindy St. H:         And that's why it's in Circ Research, so it's a beautiful paper. Very well done. So I can't imagine all these hearts that you had to isolate and get single cells of and culture. What kind of days were you pulling? What was the actual boots on the ground of getting this done? How did that work? Dr Tim M:            It wasn't uncommon for me to get emails from Matt and Rushita at very odd hours of the night or early in the morning. Dr Rushita B:      Yeah, it was like we had the animals being sacrificed, hearts taken, and running to the cell culture room to do everything under sterile conditions. Most important thing- I think what worked out really well is we made sure we had all the reagents prepared ahead of time, so that once the heart is out, it's weighed, because we were also looking at hypertrophy because of the TAC model. We weighed the heart and it goes into your BST right away. Cindy St. H:         I try to teach that to my lab. It's like the cooking idea of mise en place. I make them lay out everything in the cell culture hood ahead of time, and it's all in the order and you just boom, boom, boom, boom. Dr Rushita B:      And a lot of our experiments were done later in the evening, so the nice thing was we had access to multiple centrifuges, which is usually a huge plus. And I still remember Matt being on one side, I'd be on the other. And then we had help from members of the lab as well. They were running between the cell culture room and the centrifuge. So it was actually quite fun. It turned out really well. Cindy St. H:         I'm picturing like those old water brigades to put out a fire where like a bucket is just passed. Is that what this was? Dr Rushita B:      That was very similar to the situation you just talked about. Cindy St. H:         That's great. It sounds kind of painful, but also kind of fun. I guess lastly, maybe one of you can end with telling us what are the bigger picture results of this, and what are the next steps in terms of maybe possibly translating this to the clinic? Dr Tim M:            Well as I mentioned, one of the things we're trying to do is to selectively inhibit BRD4. We're also trying to inhibit it only in cardiac fibroblasts with the hope that we'll be able to improve the therapeutic index of BRD4 inhibition. So create a situation where patients can tolerate this anti-fibrotic therapy better than if it was delivered systemically. We're also looking at other regions of BRD4. BRD4 contains the bromodomains, and those are the targets of JQ1, but there are other interesting domains on BRD4 that we're actively pursuing. Cindy St. H:         Thank you. And Matthew, what are you doing in your new lab, or is it just set up right now? Dr Matt S:            Well I have a K Award from the National Institute of Aging. Cindy St. H:         Congratulations. Dr Matt S:            Thank you. To look at BRD4's role in the heart and cardiac aging. And I also have a couple projects based on some of the mining that we've done from these datasets. So hopefully those lead to good publications and follow-on grants. Cindy St. H:         Well, if this is a good start, I'm sure they will. And Rushita, what are your next plans? How long have you been with Tim? Dr Rushita B:      So I've been here with Tim for almost four years now, so I'm pretty much in the final leg of my postdoctoral training. So I'm still continuing to work on tissue fibrosis projects, including the heart. But I have been able to develop a new field of interest and something that Tim has entrusted me to carry on in the lab in the field of cardiometabolic disease, but definitely with an epigenetic focus. So hopefully in a year's time I see myself having an independent academic scientist position. My dream job will be to be at an academic institute where I can lead a research team which focuses on deciphering or trying to even find the most basic molecules that define the underlying mechanisms of tissue fibrosis and cardiometabolic disease. Cindy St. H:         That sounds like a great plan. Very best luck to you. Dr Rushita B:      Thank you. Cindy St. H:         Do you guys want to add anything else? Dr Tim M:            The field of cardiovascular epigenetics is in its infancy and we still have a lot to learn. Cindy St. H:         And I'm sure all of you will do your parts in moving that field forward. So with that, we're going to end our interview with Drs. Stratton, Bagchi, and McKinsey. Thank you all for joining me and thank you to the listeners for listening. Have a great day. Dr Tim M:            Thank you. Dr Rushita B:      Thank you. Dr Matt S:            Thank you. Cindy St. H:         That's it for highlights from the August 30th and September 13th issues of Circulation Research. Thank you for listening. This podcast is produced by Rebecca McTavish, edited by Melissa Stoner, and supported by the editorial team of Circulation Research. Copy text for highlighted articles is provided by Ruth Williams. I'm your host, Dr Cindy St Hilaire, and this is Discover CircRes, your source for the most up-to-date and exciting discoveries in basic cardiovascular research.

With Borja Ibanez, Spanish National Centre for Cardiovascular Research - Spain & Allan Davies, Hunter New England Health - Australia.

Lead administrator and physician from Bellin Health share their journey of navigating the corridor from volume to value-based healthcare and address these important questions:•What does volume-to-value mean for you?•How are physicians reacting to this new population health model?•Why have you decided to focus on understanding cost of care?•From a population health perspective, what focus areas are you targeting for 2019?Andrea Werner, MSW is Senior Vice President for Cardiovascular and Pulmonology; Neurosciences, Orthopedics, and Sports Medicine; and Pathology and Radiology for Bellin Health in Green Bay, Wisconsin. James Rider, MD is the Director of Cardiovascular Research, Nuclear Cardiology, and the CHF program for Bellin Health in Green Bay, Wisconsin. Lori Walsh, MHSA is Vice President - Membership and Senior Consultant for MedAxiom.

This week, we interview Dr. Paula Harvey, Physician in Chief, Clinician Investigator and Associate Professor in the Department of Medicine, University of Toronto and Women’s College Hospital. Dr. Harvey's research focuses on cardiovascular disease in women across the lifespan. She is particularly interested in addressing the differences in cardiovascular disease risk between men and women to improve disease outcomes, but also is interested in cardiovascular disease prevention through lifestyle interventions. Dr. Harvey works collaboratively across various specialities such as rheumatology and exercise physiology to address cardiovascular disease in women with multiple comorbidities.

With Tomasz Guzik, Univ. of Glasgow, Editor-in-Chief of Cardiovascular Research and Pasquale Maffia, Univ. of Glasgow, Deputy Editor of Cardiovascular Research Link to paper Link to editorial

Dr Carolyn Lam:                Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr Greg Hundley:             And I'm Greg Hundley, also associate editor from VCU Health Systems, the Poly Heart Center in Richmond, Virginia. Dr Carolyn Lam:                So arrhythmogenic cardiomyopathy that will make most of us think of right ventricular disease and fatty infiltration of the muscle, but could arrhythmogenic cardiomyopathy really be a bi-ventricular disease? Well you've got to stay tuned to find out more in a fantastic interview coming right up after our little coffee chat. So Greg, what are your picks this week? Dr Greg Hundley:             My first paper is from Chris Lim at NYU in New York. And it's looking at the relationship between Mediterranean diet, air pollution and cardiovascular events.                                                 So, it's unknown whether usual individual dietary patterns can modify the association between long-term air pollution exposure and health outcomes. And so, in this large cohort with detailed diet information at the individual level, they had 548000 individuals across six states and two cities within the U.S. and a follow up period of 17 years. And that occurred between 1995 and 2011. And they evaluated whether a Mediterranean Diet modified the association between long-term exposure to ambient air pollution and then cardiovascular disease and mortality risk. And so, the average exposures to parts per billion and nitric oxide air pollution that the residential census track level were measured, and the investigators found that for the particulate matter there were elevated significant associations with cardiovascular disease. So, a hazard ratio of 1.13, ischemic heart disease similar hazard ratio and cerebrovascular disease with also a similar hazard ratio.                                                 For the nitric oxide, there were also significant associations with cardiovascular disease, as well as ischemic heart disease. And then the analysis indicated that Mediterranean diet modified the relationships. Those with a higher Mediterranean diet score had significantly lower rates of air pollution related mortality. These results therefore indicate Carolyn, that Mediterranean diet reduce cardiovascular disease mortality related to long-term exposure to air pollutants in a large perspective, U.S. cohort. Can you believe increased consumption of foods rich in antioxidant compounds actually may aid in reducing the considerable disease burden associated with ambient air pollution? Dr Carolyn Lam:                Oh wow. That is hugely interesting. Gosh, what do we do about this clinically now?  Dr Greg Hundley:            Remember, first of all, this is an associate study, so we can't infer cause effect. And what we need next are some more independent studies from other cities around the world, prospective cohorts, examinations of clinical outcomes and randomize interventions. And so, I think the results add to a growing body of literature suggesting that dietary patterns may help reduce cardiovascular events in these high air pollution exposure areas. And how does this work? Well, potentially through augmenting antioxidants and reducing oxidative stress. Dr Carolyn Lam:                That's really cool. So from one region, talking about air pollution to another region that often reports about air pollution and that's China. But this study from China is actually the largest registry study to evaluate sex related differences and hospital management and outcomes of patients with acute coronary syndrome in China.                                                 This is from corresponding author Dr Zhao from Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Disease. With colleagues of the improving care for cardiovascular disease in China, Acute Coronary Syndrome project, which is an ongoing nationwide registry of the American Heart Association and the Chinese Society of Cardiology. So, the authors use data from this project and evaluate at sex differences in the acute management, medical therapies for secondary prevention and in hospital mortality in more than 82000 patients admitted for acute coronary syndrome in 192 hospitals across China from 2014 to 2018. Dr Greg Hundley:             What did they show in this study? Dr Carolyn Lam:                They showed that women hospitalized for acute coronary syndrome in China less frequently received acute treatments and strategies for secondary prevention and had a higher in hospital mortality rate than men. Now the observed sex differences in this in hospital mortality were likely due to older age, worse clinical profiles and fewer evidence base acute treatments provided to women. And that's because the sex differences were no longer observed after adjustment for these clinical characteristics and acute treatments.                                                 What this all means though is specifically targeted quality improvement programs may be warranted to narrow these sex related disparities in patients with acute coronary syndrome in China.  Dr Greg Hundley:            Very interesting. I'm going to take sort of the next paper and it's looking at a different aspect of acute myocardial infarction. And these papers from Yong Wang from the Division of Molecular and Translational Cardiology at Hannover Medical School in Hanover, Germany.                                                 Now as we know, the heart can undergo deleterious changes and left ventricular geometry and function during that vulnerable period before scar formation has stabilized the infarct area. And so inflammatory cell trafficking from hematopoietic organs like the spleen to sites of tissue injury is coordinated by chemokine chemokine receptor networks. Therapeutically modulating these chemokine chemokine receptor interactions may promote infarct healing by limiting excessive inflammation induced tissue damage or by enhancing the recruitment of angiogenic cell populations to the infarct or the wound. Inflammatory cell trafficking after a myocardial infarction is controlled by a CXC motif chemokine ligand 12 or CXCL12 and its receptor CXC motif chemokine receptor 4. CXC receptor 4 antagonists, mobilize inflammatory cells and promote infarct repair. But the cellular mechanisms are unclear.                                                 So, what do these investigators do? In mouse models, the investigators found that inflammatory cell trafficking between a hematopoietic organs and sites of tissue injury is controlled by CXCL12 and its receptor CXC receptor 4. And bolus injectives of a highly selected peptidic macrocycles CXC receptor 4 antagonist, enhanced tissue repair and functional recovery after re-perfused acute myocardial infarction in mice. And interestingly, the therapeutic effects require a dendritic cell priming and we're specifically mediated by t-regulator cells. Intermittent CXC R4 blockade mobilized the t-regulator cells from their splenic reservoir. Leading to their enhanced recruitment to the infarct region. Dr Carolyn Lam:                So bring it home for us, Greg. What does this mean clinically for MI management in humans? Dr Greg Hundley:             Right. Highlighting the translational potential. What we might infer is that CXC receptor 4 blockade reduces infarct volume and improved systolic function in a porcine close chest model of re-perfuse acute myocardial infarction.                                                 And so, the results of both the mouse experiments and this sort of translational model in pigs should stimulate further research into therapeutic potential of CXC R4 blockade after MI and in other acute conditions were excessive, innate or adaptive immune responses cause immunopathology. Dr Carolyn Lam:                Fascinating. So from one preclinical paper to another, but this time focused on heart failure. And focus specifically on titin. Titin is this giant elastic protein that spans the half-sarcomere from the Z-disk to the M band, and it acts like a molecular spring and a mechanosensor that has been linked to striated muscle disease. Now the pathways that govern tight independent cardiac growth and contribute to disease are diverse and have been really difficult to dissect. And so corresponding author Dr Gotthardt, from Max Delbruck Center for Molecular Medicine and the German Center for Cardiovascular Research and his colleagues aimed to study titin deficiency versus titin dysfunction.                                                 And how they did that is they generated and compared striatum muscles specific knockouts with progressive postnatal loss of the complete titin protein. And that's by removing Exxon 2. Or an M-band truncation that eliminates the proper structure and integration, but retains all the other functional domains. So they then evaluated cardiac function, cardiomyocytes mechanics, and the molecular basis of the phenotype. Now, what they found was that progressive depletion of titin led to sarcomere disassembly an atrophy in striated muscle. And in the complete knockout, remaining titin molecules had increased strain resulting in mechanically induce trophic signaling and eventual dilated cardiomyopathy.                                                 On the other hand, the truncated titin helped maintain passive properties and thus reduced mechanically and do signaling. In other words, truncations versus loss of titin, differentially affected cardiac pathology with atrophy versus dilated cardiomyopathy respectively. And together, these findings really contribute to the molecular understanding of why titin mutations differentially affect cardiac growth and have implications importantly for genotype, phenotype relations that support a personalized approach to the diverse titinopathy. Dr Greg Hundley:             Interesting, Carolyn. All this information on titin. So why is it clinically important? Dr Carolyn Lam:                Well, first of all, tightened mutations are the most common genetic basis of heart disease and the findings are clinically relevant, as I said, for understanding the genotype phenotype relations at the Titin mutation. But understanding the integration of Titin based signaling and sarcomere biology could indeed help personalize diagnostics by improved clinical decisions and maybe identify suitable therapeutic targets for these titinopathy. But that of course requires much further work. Well that brings us to the end of our summaries. Let's go to our feature discussion.  Dr Greg Hundley:            Welcome everyone to our second segment of our program. We're discussing an interesting paper today entitled Sudden Death and Left Ventricular Involvement in Arrhythmogenic Cardiomyopathy. And we want to welcome our coauthors Elijah Behr and Mary Sheppard from St George's University in London. And also, our own associate editor, Sami Viskin to discuss this paper. Mary, can you tell us a little bit about your study design here, the population and the hypothesis and some of your results? Dr Mary Sheppard:          I am a cardiac pathologist of 20 years and I have a special interest in sudden death. Over this time, I've established a national pathology database, where pathologists throughout the country when they have a sudden death, which is likely cardiac and non-ischemic, they will send the heart or tissue blocks insides to me for my opinion concerning the death. We have as a result developed a large number, over 5200 cases which has now built up to 6000. It's the largest pathological series in the world.                                                 And I was also discovering the pathologists were either under or over diagnosing all types of cardiomyopathy but particularly ergogenic cardiomyopathy. And that is why with Chris Miles, our research fellow, we looked in detail at what I had diagnosed, or the pathologist as ergogenic cardiomyopathy and we actually honed are pathological diagnostic criteria for this very important entity. Establishing that left ventricular is five and ventricular and left and ventricular is the norm almost. That right or left ventricular is unusual by themselves and even in 20%, one in five, the heart can look macroscopically normal. So that histology is essential when you're making this diagnosis. You cannot make the diagnosis pathologically without histologically examining the heart. Dr Greg Hundley:             Very good, Mary. And did you also examine some genetic markers in some of the subsets of the patients? And how did you decide who those individuals would be that received the genetic analysis? Dr Mary Sheppard:          A small subset and I will hand over to Elijah Behr, my colleague concerning that. Dr Elijah Behr:                   The genetic tissue is only available in a minority of cases. We've developed a pipeline now with the referring pathologists who are increasingly they're sending samples of spleen suitable for DNA extraction that allow us then to do a retrospective postmortem genetic testing or molecular autopsy. But unfortunately, in this particular series we only had a small proportion. I think there were roughly about 24 out of the 202 cases, so just over ten percent. And interestingly, while we didn't necessarily mirror the expected yield of genetic testing that is seen in clinical cases, where you may see about 40% carrying pathogenic variance. We certainly picked up some important pathogenic variance, particularly those that are often associated with highly penetrant and more severe disease. In particular TMEM43 and desmoplakin. These findings may reflect the small size of the sample, but it also may reflect where the greatest risk for sudden death from ergogenic cardiomyopathy lies. Dr Greg Hundley:             Elijah, getting back to some of the patients that experienced the sudden death in the study population Mary was referring to, were there characteristics that were associated with the sudden death? For example, those that might be related to gender or activity? Dr Elijah Behr:                   So the majority of the cases were male. The majority has never had prior symptoms. These were unheralded deaths. The majority did not have a family history and I think the majority were addressed, but those that were athletes, we're much more likely to have died during exertion. So as we found with ergogenic cardiomyopathy in general and exertion is a trigger to sudden death. The risk was higher and compared to the athletes in death during exertion was associated with being younger as well. I think exertion and sports clearly play a role in ergogenic cardiomyopathy. It didn't appear to play a role in whether there was left ventricular involvement or not, but certainly a role at more severe presentation.  Dr Greg Hundley:            Maybe both Mary and Elijah answering this. You found histopathological evidence of fibrosis and fatty infiltration. How extensive was that? And do you think that could be identified with a test like maybe magnetic resonance imaging? Dr Mary Sheppard:          Yes. Our diagnostic criteria which is illustrated in the addendum is that it was at least two blocks of tissue. We always look at 10 to 12 to 15 blocks of tissue from both right and left ventricle. And at least two of the blocks had to have fibrosis with fat in 20% of the area examined. We did not include inflammation because inflammation is, an important histological criterion in our experience. We were very precise about that because you need that much at least to make the diagnosis. A little bit of fibrosis or a little bit of fat is not sufficient by itself. Dr Greg Hundley:             When you mention a block, for us clinically, how much myocardium would that be? For example, on an imaging test like an echo or an MRI scan. Dr Mary Sheppard:          One to two centimeters squared. Dr Greg Hundley:             So quite a bit. Dr Elijah Behr:                   You're looking at probably around two to four millimeters of potential depth of fibrosis. And what we've seen clinically in LV involvement of MRI scans is miss two epicardial late enhancement. Now the question is whether our scans are sensitive enough to pick that up? Given the technology available or a sense to the histopathology and I think that's why maybe some of the clinical studies have tended to miss the true proportion of left ventricular involvement. Because of the relative subtlety of the fibrosis compared to the technological ability to discriminate it. I mean certainly when you look at our cases that were diagnosed previously with cardiomyopathy, either they were arrhythmogenic or dilated, many did have imaging findings if MRI was performed, that would indicate or suggest some left ventricular involvement. But as you know, the task force criteria for arrhythmogenic cardiomyopathy having very much right ventricular focus. An LV imaging findings and LV ECG findings are just not part of those at the moment. Dr Greg Hundley:             Was there a particular location within the heart where there was a predilection toward the findings of fibrosis and fat? Dr Mary Sheppard:          In the posterior basal wall particularly, transmural involves going from the epicardium to the sub endocardium and also the interior walls of the left ventricular were the predilection areas. Dr Elijah Behr:                   I think that's what we see on our MRI scans as well. When you look at these patients, that posterior basal area, is the one that tends to light up the most. Dr Mary Sheppard:          It is believed that increased stress in that area gives more damage because of the stretching away from the septum. Dr Greg Hundley:             Very interesting. So Elijah, you had mentioned task force criteria. I want to shift to Sami now and ask, Sami, can you help us put this in perspective relative to the existing task force criteria and then the findings in this study? And how that could lead to subsequent changes down the road?  Dr Sami Viskin:                 Okay, so it is difficult to place this in the context of the task force because mentioned by Elijah, the taskforce are focused on a disease that is believed to be in the right ventricle. And the study shows that many of the sudden death cases will involve the left ventricle. One of the most important messages of this paper is importance of her forensic examination. And importance of making it for anything examination in the center of expertise. We know of patients that will travel a thousand miles to undergo surgery or an ablation procedure, but families do not think that way when there is casualty or family dies. You may take a postmortem as a given, but in many countries, including my own, most cases of sudden death would not be followed by a post mortem and will not go into center of expertise. And you cannot overemphasize the importance of doing that because then you have to know what you are looking for in the remaining relatives is extremely important. Dr Greg Hundley:             Very good. How about from the perspective as an electrophysiologist? Does this impact in any way how you might evaluate a younger person with syncope? Dr Sami Viskin:                  Well, it is difficult to conclude from this paper about how to evaluate patients with syncope because most of the cases in this series don't have symptoms at all. But this paper calls to very interesting investigations by Mario del Mar and others in New York. Looking about the electrophysiology consequences of a disease like right ventricle are like a bit mechanical in [inaudible 00:21:58] The tissues becomes editing the disease, the electrical properties how the patients in brugada can cause malfunction of this sodium channel and create a disease that is more like brugada and dysplasia at the beginning. So, the entire correlation between a morphologic disease and the metrical disease and we used to think they are two different things. And now we see that we can actually put them together and you can go through stages where one disease is before an electrical disease and only at later stages it becomes a morphological evident disease.  Dr Greg Hundley:            A fantastic discussion on pathologic findings. Sami making the point that certainly in cases for young individuals having a postmortem examination performed at centers that have expertise such as what Mary's described, can be very important. And then Elijah, helping us to understand with arrhythmogenic cardiomyopathy, number one, findings are not, we shouldn't just be thinking about the right ventricle in isolation, but also the left ventricle. Fibro fatty infiltration, particularly in the posterior basal wall could be an important thing to look for, for those that are performing the magnetic resonance imaging exams. And then lastly, many of the patients in the study like this, the first presentation was of sudden death. And we need to be cognizant that this condition could be prevalent in the population and not necessarily appreciated by some of our current task force guidelines and examinations. So, what an outstanding discussion. And I think for today, we want to thank our authors and our associate editor and wish everyone a great week.                                                 On behalf of Carolyn and myself, we look forward to seeing you next week. Thank you very much. Dr Carolyn Lam:                This program is copyright American Heart Association 2019.  

This week we review a recent randomized and controlled trial from the NEJM on the use of the novel Medtronic TYRX envelope for the prevention of pacemaker or ICD infections in adult high risk patients. Did the use of this antibiotic envelope result in reduced incidences of infection? Were there complications associated with its use? Should this be used in only in high risk patients? Is this a cost effective solution? These are amongst the many questions we tackle with co-author of this important trial, Dr. Suneet Mittal who is the Director of Cardiovascular Research at Valley Hospital in Ridgewood, NJ. Dr. Mittal offers great insights into this trial and possible implications of these important findings. DOI: 10.1056/NEJMoa1901111

This week we review a recent randomized and controlled trial from the NEJM on the use of the novel Medtronic TYRX envelope for the prevention of pacemaker or ICD infections in adult high risk patients. Did the use of this antibiotic envelope result in reduced incidences of infection? Were there complications associated with its use? Should this be used in only in high risk patients? Is this a cost effective solution? These are amongst the many questions we tackle with co-author of this important trial, Dr. Suneet Mittal who is the Director of Cardiovascular Research at Valley Hospital in Ridgewood, NJ. Dr. Mittal offers great insights into this trial and possible implications of these important findings. DOI: 10.1056/NEJMoa1901111

Thomas Diacovo, MD, is chief of the UPMC Newborn Medicine Program and director of Neonatal Cardiovascular Research at the Heart Institute. Dr. Diacovo discusses how he became interested in Thrombosis research, his journey to Pittsburgh, and his research testing new drugs for neonatal intensive care patients, particularly those with congenital heart disease who are at high risk for forming blood clots. Dr. Diacovo also credits the parents of our patients for the success of his clinical trials.

Welcome back to the #FridayReview!  I can’t wait to share with you all of the research, product reviews and our super nutrient of the week! Today we are going to be going over some large-scale research studies showing the proven benefits of specific B vitamins and antioxidants in a diet. I also have a fun and inexpensive product tool that will make avocado slicing and dicing that much easier… And we also have a very special super-food super nutrient of the week that is loaded with electrolytes and able to help cool and calm your digestion… Tune into today's #CabralConcept 1029 for all the details - Enjoy the show! - - - Specific Show Notes & Resources: http://StephenCabral.com/1029 - - - Dr. Cabral's New Book, The Rain Barrel Effect https://amzn.to/2H0W7Ge - - - Join the Community & Get Your Questions Answered: http://CabralSupportGroup.com - - -   Dr. Cabral’s Most Popular Supplements: > “The Dr. Cabral Daily Protocol” (This is what Dr. Cabral does every day!) - - - > Dr. Cabral Detox  (The fastest way to get well, lose weight, and feel great!) - - - > Daily Nutritional Support Shake  (#1 “All-in-One recommendation in my practice) - - - > Daily Fruit & Vegetables Blend  (22 organic fruit & vegetables “greens powder”) - - - > CBD Oil  (Full-spectrum, 3rd part-tested & organically grown) - - - > Candida/Bacterial Overgrowth, Leaky Gut, Parasite & Speciality Supplement Packages - - - > See All Supplements: https://equilibriumnutrition.com/collections/supplements  - - -   Dr. Cabral’s Most Popular At-Home Lab Tests: > Hair Tissue Mineral Analysis (Test for mineral imbalances & heavy metal toxicity) - - - > Organic Acids Test (Test for 75 biomarkers including yeast & bacterial gut overgrowth, as well as vitamin levels) - - - > Thyroid + Adrenal + Hormone Test  (Discover your complete thyroid, adrenal, hormone, vitamin D & insulin levels) - - - > Adrenal + Hormone Test (Run your adrenal & hormone levels) - - - > Food Sensitivity Test (Find out your hidden food sensitivities) - - - > Omega-3 Test (Discover your levels of inflammation related to your omega-6 to omega-3 levels) - - - > Stool Test (Use this test to uncover any bacterial, h. Pylori, or parasite overgrowth) - - - > Genetic Test (Use the #1 lab test to unlocking your DNA and what it means in terms of wellness, weight loss & anti-aging) - - - > Dr. Cabral’s “Big 5” Lab Tests (This package includes the 5 labs Dr. Cabral recommends all people run in his private practice) - - - > View all Functional Medicine lab tests (View all Functional Medicine lab tests you can do right at home for you and your family!)

1. Physical Therapy Management of Congenital Muscular Torticollis: A 2018 Evidence-Based Clinical Practice Guideline from the American Physical Therapy Association Academy of Pediatric Physical Therapy AUTHORS: Sandra L. Kaplan, Colleen Coulter and Barbara Sargent (https://journals.lww.com/pedpt/Fulltext/2018/07000/Informing_the_Update_to_the_Physical_Therapy.2.aspx) This update of the 2013 CMT clinical practice guideline informs clinicians and families as to whom to monitor, treat, and/or refer, and when and what to treat. It links 17 action statements with explicit levels of evidence and expert opinion to implementation recommendations. Pediatric Physical Therapy journal Editor-in-Chief Linda Fetters PhD PT FAPTA of the University of Southern California, Los Angeles, reviews the guideline and pinpoints key clinical messages. 2. Effects of a gaming platform on balance training for children with cerebral palsy (Pediatr Phys Ther 2018;00:1–6) Hsieh, Hsieh-Chun, PhD, OTR, Department of Special Education, National Tsing Hua University, Hsinchu City, Taiwan talks about her study using a platform requiring multi-dimensional trunk movement that facilitated postural balance in children with cerebral palsy. 3.  Physical Therapist Coaching to Improve Physical Activity in Children with Brain Tumors: A Pilot Study   (Pediatr Phys Ther 2018;0:1–8) Jessica Ovans PT DPT, Physical Therapist, Department of Rehabilitation, Children’s Hospitals and Clinics of Minnesota, Minneapolis discusses the use of a fitness tracker intervention combined with tailored coaching by a physical therapist to increase physical activity and quality of life and decrease fatigue in children with brain tumors. 4.  Physical therapists’ use and alteration of standardized assessments of motor function in children. (Pediatr Phys Ther 2018;0:1–8) Deanne Fay, PT, DPT, PhD, Professor & Director of Curriculum, Physical Therapy Program, AT Still University, Mesa, Arizona reports on how physical therapists in the real world are assessing motor function in children with disability. This study presents survey responses of pediatric physical therapists’ use and alteration of standardized assessments of motor function in children aged 2-10 years.  5.  Adapted Motivational Interviewing to Promote Exercise in Adolescents with Congenital Heart Disease: A Pilot Trial  (Pediatr Phys Ther 2018;0:1–9) Adam McKillop PhD, Hospital for Sick Children, Toronto, Canada, describes his study to assess a motivational interviewing intervention to improve moderate-to-vigorous physical activity in adolescents with congenital heart disease. Although their standard approach using telephone calls was achievable and accepted he expects electronic methods and social media to beckon in the future—especially with young patients. 6.  The Effect of Transcranial Direct Current Stimulation (Tdcs) on Motor Function, in Pediatric Cerebral Palsy: A Systematic Review  (Pediatr Phys Ther 2018;00:1–11) A bold approach to therapy for children with cerebral palsy that uses transcranial electrical stimulation has analyzed findings from nine published articles. First author Angela Hamilton, University of Newcastle, New South Wales, Australia explains how determining the effects of transcranial direct-current stimulation (tDCS) on motor function for children with cerebral palsy could help their brains develop. 7.  Stepping activity in children with congenital myotonic dystrophy (Pediatr Phys Ther 2018;00:1–5) Heather A. Hayes, DPT, PhD NCS, Utah Neurological Physical Therapy Residency Director and Associate Clinical Professor, Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City discusses her observational research on therapy for the rare condition congenital myotonic dystrophy (CDM) and explains how their investigation of physical activity levels in children who have CDM could determine whether clinical and functional characteristics correlate to physical activity and help find  keys to improving activity levels and quality of life. 8.  Whole-body vibration training designed to improve functional impairments after pediatric inpatient anticancer therapy: pilot study (Pediatr Phys Ther 2018;00:1–9) A new form of physical therapy called whole body vibration has been investigated as a way of helping children to recover good physical activity after treatment for cancer. Vanessa Oschwald (née Rustler) MA, Molecular & Cellular Sports Medicine Department, Sports and Exercise Science Department, Institute of Cardiovascular Research & Sports Medicine, German Sport University, Cologne, Germany talks about the way functional, motor, balance and strength impairments children after inpatient anticancer therapy were assessed after training on a platform that vibrates. Feasibility, adherence, program acceptance and fields of effectiveness were assessed.

The watchful eye of Big Pharma still has a lot of control on the purse strings of the medical industry. Why is content and the education of ordinary consumers so necessary in changing this? What are some of the world’s most advanced institutions getting wrong about health and diet? Should you consider ketogenic dieting? On this episode, Russ Scala is back to talk about how to get rid of the lab coat savior mentality. We got about 150 high level pharmaceutical drugs currently on the market, and the ketogenic diet and intermittent fasting impact more metabolic pathways than any drug. -Russ Scala Three Takeaways Ketogenic dieting: a lot of people don’t realize that excess protein gets converted through gluconeogenesis into sugar. When you elevate your blood sugar, you cause a lot of oxidative stress. Carbs have the same opiate pathways as heroin; just not as hard. At the start of the show, Russ gave an update on what he’s been working on, and why it’s so powerful to teach ordinary people to ask the right questions. We also discussed muscle wasting, the dangers of carb addiction and how to control your own insulin. We also discussed: How bereft of real data the mainstream system is What people get wrong about ketogenic dieting Why we need to de-patternize our brains around how we see doctors There’s something very powerful and transforming about people being able to think critically and ask their doctors the questions that will really change their health. If we continue teaching people the basics of biology, it is going to create a viral market of people who are in the know. Forget SSRIs and all the pharmaceuticals out there, ketogenic diet and intermittent fasting are the best tools to keep you in the game, keep you healthy, and keep your insulin and blood-glucose levels down. The only way to change perceptions is to educate people through content. Guest Bio Russ is the founder of Scala Precision Health, the organization found in select elite medical practices for the purposes of enhancing and extending the services offered to patients. It was created from Russ’ lifelong research and development of breakthrough protocols through The Institute of Nutritional Medicine and Cardiovascular Research. Through the Institute, protocols have been developed for chronic illness, athletic performance, brain health, weight loss, aging and longevity. He is also the author of American Biohacker. Go to https://scalaprecisionhealth.com/ or find out about his book.

Dr. Paul Wong:                  Welcome to the monthly podcast, On The Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wong, editor in chief, with some of the key highlights from this month's issue. We'll also hear from Dr. Suraj Kapa, reporting on new research from the latest journal articles in the field. In our first article, Ratika Parkash and associates examined whether the outcomes following escalated antiarrhythmic drug therapy, or catheter ablation, depended on whether ventricular tachycardia with amiodarone refractory or sotalol refractory in patients with prior myocardial infarction in the VANISH study. At baseline, 169, or 65%, were amiodarone refractory, while the remaining were sotalol refractory. Amiodarone refractory patients had more renal insufficiency; 23.7% versus 10%. Worse, new ARC Heart Association class, 82.3% versus 65.5% class II or III; and lower ejection fraction, 29% versus 35%. Within the amiodarone refractory group, ablation resulted in a reduction of any ventricular arrhythmias compared to escalated drug therapy, with a hazard ratio of 0.53, P = 0.02. Sotalol refractory patients had trends towards higher mortality in VT storm with ablation, with no effect on ICD shocks. Within the escalated drug arm, amiodarone refractory patients had a higher rate of composite endpoint, with a hazard ratio of 1.94 and a P value of 0.01. In a trend toward higher mortality, hazard ratio 2.4, P = 0.07. While mortality was not different between amiodarone and sotalol refractory patients within the ablation treatment group. In our next study, Junaid Zaman and associates examined 57 cases in which local ablation of persistent atrial fibrillation terminated to sinus rhythm or organized tachycardia. The authors analyze unipolar electrograms collected during atrial fibrillation from multi-polar basket catheters to reconstruct isochronal activation maps for multiple cycles, and computational modeling and phase analysis were used to study mechanisms of map variability. At all signs of atrial fibrillation termination, localized, repetitive activation patterns were observed, 21% with complete rotational activity, 46% with partial rotational circuits, and 33% with focal patterns. In computer simulations incomplete segments of partial rotations coincided with areas of slow conduction, characterized by complex, multi-component electrograms. In our next article, Matthew Kalscheur and associates sought to use a novel machine-learning approach to predict outcomes following resynchronization therapy in the companion trial. The random forest algorithm resulted in the best performing model. In 595 CRTD patients in the companion trial, 105 deaths occurred, with a median follow-up of 15.7 months. The survival difference across subgroups differentiated by bundle branch block morphology and cure restoration did not reach significance, P = 0.08. The random forest model, however, produced quartiles of patients with an eight-fold difference in survival between those with the highest and lowest predictive probability for events, hazard ratio 7.96 with a P value of less than 0.0001. The model also discriminated the risk of composite endpoint of all cause mortality, or heart failure hospitalization, better than subgroups based on bundle branch block morphology and cure restoration. Future studies are needed to validate this model in other populations. In our next paper, Amr Barakat and associates examined the clinical outcomes of trans-venous lead extraction for CIED infection based on renal function. The authors examined 1,420 consecutive patients undergoing trans-venous lead extraction of infected CIEDs over a 14 year period. Groups with normal renal function, Group 1, consisting of 1,159 patients, Group 2, 163 patients with renal dysfunction not requiring dialysis, and Group 3, 98 patients on dialysis. Complete procedural success rates were comparable in the three groups: 94%, 96%, and 94% in Groups 1, 2 and 3, respectively. This was not statistically significant. The mortality rates were significantly higher in dialysis patients at one month. The procedure-related complication was 12.2% in dialysis patients versus 6.5% in Group 1 and 6.1% in Group 2. Other factors associated with mortality were lead material retention, functional New York Heart Association Class, and occurrence of procedural complications. In our next paper, Eric Johnson and associates studied the contribution of the current ITO, two left ventricular re-polarization in the human heart, since the current has been shown to have an important role in animal models. The authors found that using whole-cell voltage clamp recordings from myocytes, isolated from the left ventricle, non-failing human hearts, that there were two, distinct transient currents, ITO fast and ITO slow. The two currents have significantly different rates of recovery from inactivation and pharmacological sensitivities. ITO fast recovers in about 10 milliseconds, 100 times faster than ITO slow, and it's selectively blocked by KV4 channel toxin SNX 482. Using current clamp experiments, they found that regional differences in action potential wave forms, with a notch in phase one in the left ventricular subepicardial myocytes. In failing, left ventricular subepicardial myocytes, ITO fast was reduced, while ITO slow was increased. In addition, the notch and plateau potentials were depolarized, and action potential durations were prolonged, both statistically significantly. Slowing ITO fast inactivation results in a dramatic action potential shortening. The authors concluded that remodeling of ITO fast in failing, human left ventricular subepicardial myocytes, attenuates transmural differences in action potential wave forms. In our next paper, Ravi Vaidyanathan and associates examine the interaction between Caveolin 3 domain in the inward rectifier potassium channels. Although the IK1 current is mainly composed of Kir2.1, there are Kir2.2 and Kir2.3 heterotetromerisoforms that occur and modulate the IK1 current, but these have not been studied. Kir2.x isoforms have unique, subcellular co-localization in human cardiomyoctyes and co-immunoprecipitate with Cav3. Using induced pluripotential stem-cell-derived cardiomyocytes, the LQT9 Cav3 mutation, F97CCav3 resulted in actual potential prolongation. Based on the technique FRET, which is Fluorescent Resonance Energy Transfer, the authors calculated the distance between KR2.2 and cath ray proteins to be 6.61 nanometers. LQT9 is caused by Cav3 mutations. Prior work has shown that F97CCav3 mutation increases the late sodium current, and decreases KR2.1 current density by distinctive mechanisms. This study extends the authors' previous observations on the impact of LQT9 Cav3 mutation on Kir2.1 current, by demonstrating that mutation affects the Kir2.2 current. LQT9 causing Cav3 mutation differentially regulates current density and cell surface expression of Kir2.x homomeric and heteromeric channels. The authors show that the mutation does not affect Kir2.3 current, but the heterotetromer Kir2.2-2.3 demonstrated loss of function. Using the Li-Rudy [inaudible 00:09:45] model and myocyte mathematical model, the authors' data suggest that both loss of IK1 and increased sodium L are required for arrhythmia generation in LQT9. In our next study, Christophe Teuwen and associates use high resolution epicardial mapping electrodes, 128 or 192, with an inter-electrode distance of 2.0mm of the entire atrial surface in 164 patients. These patients were undergoing open-chest cardiac surgery. This study was designed to examine the conduction of atrial extrasystoles. The authors found that a higher degree of aberrancy was associated with a higher instance of conduction disorders. Most conduction disorders were provoked by atrial systoles emerging as epicardial breakthroughs. Atrial extrasystoles cause most conduction disorders in patients with left atrial dilatation or diabetes mellitus. In our next paper, Yuki Komatsu and associates examine 31 patients with idiopathic ventricular arryhthmias, using a two french microcatheter placed in a communicating vein between the great cardiac vein and small cardiac venous system, which passes between the aortic and pulmonary annulae, and is located in close associated with the left ventricular summit. They found that 14 patients had summit ventricular arryhthmias. The remaining 17 patients control group had ventricular arryhthmias originate from the right ventricular outflow track in the aortic cusps.  In patients with summit ventricular arryhthmias, the earliest activation during ventricular arryhthmias in the summit, preceded to cure as onset by 34 milliseconds. The summit ventricular arryhthmias exhibited inferior axes, negative polarity in lead one, deeper Q wave in AVL than AVR, nonspecific bundle branch morphology with an RS ratio in lead V1 of 0.67, distinguishing them from arryhthmias originating from the right ventricular outflow track or right ventricular cusp. Overall, ablation success was achieved in 10, or 71% of patients with summit ventricular arryhthmias, and 88% in the control group, P = 0.24. In our final paper, Deepak Padmanabhan and associates examine differences in mortality in patients with non-MRI conditional CID undergoing brain MRI compared to controls. Patients with CIDs undergoing brain MRI were compared with three control groups matched for age, sex, imaging year, and type of CID. These groups included 1) no CID and brain MRI, 2) CID in brain-computed CT, and 3) no CID in brain CT. They estimated all cause mortality at five years for CID MRI group, was not significantly different from patients who underwent CT, with or without a device. There was a significant increase in the mortality between CIED versus no CID MRI groups, hazard ratio 1.46 with a P value of 0.04. That's it for this month, but keep listening. Saraj Kapa will be surveying all journals for the latest topics of interest in our field. Remember to download the podcasts On the Beat. Take it away Saraj. Saraj Kapa:                          Thank you Paul, and welcome back to On the Beats where this month we'll be focusing on articles that are particularly hard-hitting, published across the literature in December of 2017. It's my pleasure to introduce 20 different articles that seem to have either particular interest or might change the field in the future. First, within the area of atrial fibrillation, we'll focus within the area of anticoagulation and stroke prevention. In the Journal of the American College of Cardiology, Vivek Reddy et al published on the five-year outcomes after left atrial appendage closure, from the Prevail and Protect AF trials. They included a total of 1,114 patients, with a total of 4,343 patient years of follow-up, randomized two to one to closure versus Warfarin. While ischemic stroke and systemic embolism of [inaudible 00:14:32] were numerically higher with closure, this did not reach statistical significance in terms of hemorrhagic stroke, unexplained death, and post-procedure bleeding favor left atrial appendage closure. These findings further support a role for left atrial appendage closure in the specific groups of patients enrolled in the Protect and Prevail Studies. Of course, we always need to understand, that extrapolation to patients who may not have met inclusion criteria will be difficult. In particular, given both trials had their own fundamental limitations in the Prevail study. There was a relatively low rate of [inaudible 00:15:09] in the Warfarin arm. And in turn, there was a relatively high complication rate in Protect AF with left atrial appendage closure. Part of the differences might be due to the fact that, with more experience, complication rates might decrease. Furthermore, a comparison with more novel agents, such as the new oral anticoagulants, remains to be seen. Next, within the realm of cardiac mapping and ablation for atrial fibrillation, we review an article by Vlachos et al published in the Journal of Cardiovascular Electrophysiology entitled Low-Voltage Areas Detected by High-Density Electroanatomical Mapping for Recurrence of Ablation after a Paroxysmal Atrial Fibrillation. They presented the results from a series of 80 patients undergoing ablation for paroxysmal atrial fibrillation, performing high-density voltage mapping to characterize the total area involved by low voltage. They demonstrated, when low voltage areas, defined as less than 0.4 millivolts, were seen in greater than 10% of the left atrial surface area, this served as an independent predictor of atrial fibrillation recurrence. These data support prior research, including that of MRIs, suggesting the characterization of the atrial substrate may correlate with likelihood of ablation success. Identifying methods however, to accurately and reproduce will identify these patients with more atrial substrate prior to ablation, remains to be seen. The importance of this, however, is our ability to better counsel patients on the likelihood of treatment success. Next within the realm of atrial fibrillation, we review elements of risk stratification managements. First, in the December issue of the Journal of American College of Cardiology, Takimoto et al published on how Eplerenone may reduce atrial fibrillation burden without preventing atrial electrical remodeling. In a randomized controlled ovine atrial tachy pacing model of atrial fibrillation. The authors provided daily, oral Eplerenone and compared this with a placebo. They showed that Eplerenone significantly reduced the rate of left atrial dilatation, with less smooth muscle actin protein, atrial fibril [inaudible 00:17:17]. Furthermore, Eplerenone further prolonged the time to persist in atrial fibrillation in 26% of animals. However, interestingly, Eplerenone did not prevent AF-induced electrical remodeling.  These data suggest that Eplerenone, or other medications that can be used to prevent or reverse structural remodeling, may offer an upstream therapy to reduce atrial fibrillation burden, and decrease likely the persistent atrial fibrillation. Giving the ever-growing population of patients suffering from atrial fibrillation, identifying upstream approaches to prevent it will be critical. Of course, these need to be taken with due consideration, however. Specifically, the model used here, namely that of an atrial tachy pacing model, might not be applicable to all human atrial fibrillation. Thus, whether or not such therapies actually offer benefit in clinical models, is as of yet unclear. Finally, from the realm of atrial fibrillation, we review the article by Rowin et al published in circulation entitled Clinical Profile of Consequences of Atrial Fibrillation Hypertrophic Cardiomyopathy. In patients presenting with hypertrophic cardiomyopathy, atrial fibrillation is known to be a significant co-morbidity. However, the implications of atrial fibrillation in terms of worsening of heart failure status, or long-term morbidity mortality are less clear. Rowin et al reviewed the natural history of atrial fibrillation amongst 1,558 patients, prospectively followed at a single center. Nearly 20% of the population developed atrial fibrillation with the majority having symptomatic paroxysmal atrial fibrillation. However, atrial fibrillation was not associated with any increase in cardiovascular mortality or worsening of heart failure status. Furthermore, mortality that was directly related to atrial fibrillation was nearly exclusively related to thrombolic stroke. Anticoagulation [inaudible 00:19:13] reduced this risk. The traditional scoring systems fared poorly in assessing the stroke risk of this population. About 121 patients underwent invasive rhythm control approaches, including 72 patients undergoing maze and 49 catheter ablation. The success rate of maze was significantly greater at around 75%. These data are important when counseling hypertrophic cardiomyopathy patients presenting with new-onset atrial fibrillation. While it is clear that paroxysmal atrial fibrillation has a significant impact on symptoms and quality of life, it does not cause worsened, overall, long-term outcomes. However, it does highlight the importance of anticoagulation in this population, nearly irrespective of the underlying risk score. In terms of rhythm control options, it appears that rhythm control options can be successful in these patients. Finding that catheter ablation is associated with a 40 to 50% success rate is in keeping with prior published data. Thus, consideration of when a patient needs to be referred to maze, needs to be considered in the clinical inpatient context. Changing gears, we will next review articles within the realm of ICDs, pacemakers, and CRT. In the New England Journal of Medicine this past month, Nazarian et al published on their experience regarding the safety of magnetic resonance imaging in patients with cardiac devices. They performed a prospective non-randomized study of the safety of, specifically, 1.5 tesla-strength MRI scans on legacy. In other words, not MRI conditionally-safe pacemakers and defibrillators. A total of 2,103 scans were done among 1,580 patients. They demonstrated no long term clinically significant adverse events. Nine patients did experience a reset to a backup mode, though eight of which were transients. The most common change seen acutely was a decrease in PVA amplitude in one percent of patients, and in a long term follow-up, 4% of patients experiencing a decrease in PVA amplitude, increase in atrial catheter sheer threshold, or increase in right or left ventricular capture threshold. However, none of these events were considered clinically significant. Furthermore, there was not a good [inaudible 00:21:23] group to know if this long term change in amplitudes or thresholds might have been seen in patients who had devices that were not exposed to MRI. These findings are complimentary to multiple, prior, published reports, indicating the safety of performing MRIs under clinical protocol in legacy pacemakers and defibrillators. It calls into question whether MRI conditional devices truly offer an additional safety factor furthermore, over legacy devices. Next we review an article by Lakkireddy et al published in Heart Rhythm entitled A Worldwide Experience, the Management of Battery Failures and Chronic Device Retrieval of the Nanostim Leadless Pacemaker. Lakkireddy et al reported their large multi-center experience on the overall risk of battery failure. Amongst 1,423 implanted devices there were 34 battery failures occurring, on the average, three years after implants. Furthermore, about 73 patients underwent attempted device retrieval, and this was successful in 90%, with the seven failures of retrieval being due to either inaccessibility of the docking button, or dislodgement of the docking button in one patient, in whom it embolized to the pulmonary artery. An additional 115 patients interestingly received an additional pacemaker after release of the device advisory. These data suggest that there may be as high as an overall 2% risk of battery failure with the Nanostim device, even late after implants. This highlights the need for close follow-up, even if the battery appears relatively stable up to two year after implants. Furthermore, almost 10% of devices cannot be successfully retrieved. However, in those patients, even with re-implantation of a separate device, there was no device-device interaction seen. Further innovation will be needed to optimize device longevity, and close follow-up of all patients undergoing implantation will be critical to understand the overall long term efficacy and safety when compared to other traditional devices. Finally, within the realm of device care, we focus on an article by Kiehl et al, again published in Heart Rhythm this past month entitled Incidence and Predictors of Late Atrial Ventricular Conduction Recovery Among Patients Requiring Permanent Pacemaker for complete heart block after cardiac surgery. They reviewed the likelihood of recovery of conduction in their retrospective cohort of 301 patients. Interestingly, 12% of patients had recovery of AV conduction on average six months after surgery. Those who did not recover tended to more likely have preoperative conduction abnormalities. Saraj Kapa:                          Findings that suggested a higher likelihood of long term conduction recovery included female sex and the existence of transient periods of AV conduction postoperatively. These data highlight that recovery of AV conduction is possible in a significant number of patients undergoing cardiac surgery. However, being able to predict long term recovery may assist in device selection, to avoid more costly device implantations that may not be needed over chronic follow-up. Prospective studies amongst larger numbers of patients are needed to better understand mechanisms of block, mechanisms of recovery, an optimal device in patient selection. Changing focus, we will next review two articles within the realm of supraventricular tachycardias. First we read an article by Han et al published in JACC Clinical Electrophysiology, entitled Clinical Features in Sites of Ablation for Patients With Incessant Supraventricular Tachycardia From Concealed Nodofascicular and Nodoventricular Tachycardias. Han and group describe three cases of concealed nodovascicular, nodoventricular re-entrant tachycardias, and focus on the different mechanisms of proving their participation in tachycardia. In all cases, atrial ventricular re-entering tachycardia was excluded. Successful ablation for these tachycardias occurred either at the slow pathway region, the right bundle branch, or the proximal coronary sinus. This is the first described case of incessant, concealed tachycardias related to these pathways. The importance of this article highlights an understanding the mechanisms proving the contribution to tachycardia, and the importance of recognition when performing electrophysiology studies, and being unable to reveal traditional mechanisms, which exist in most patients, such as atrial tachycardia, AVNRT or AVRT. Next we review an article by Guo et al published in Europace entitled Mapping and Ablation of Anteroseptal Atrial Tachycardia in Patients With Congenitally Corrected Transposition of the Great Arteries: Implications of Pulmonary Sinus Cusps. They reviewed three separate cases of anteroseptal atrial tachycardias in the setting of congenitally corrected transposition. They demonstrated that in these cases, there was successful ablation performed with the pulmonary sinus cusps. The result is successful and durable suppression. The reason this article is important lies in the fact that it's critical to understand both cardiac anatomy and cardiac nomenclature. The pulmonary valve in CCTJ is affectively the systemic ventricular arterial valve, given that the right ventricle is the systemic ventricle. Thus, mapping in this region of CCTJ abides the same principles as mapping the aortic valve in structurally normal hearts for similar tachycardias. However, understanding the nomenclature and that despite the variant anatomy, the utility of similar approaches to mapping of the systemic outflow are important when matching these complex, congenital anatomy or arrhythmia patients. Changing gears yet again, we review an article within the realm of sudden death and cardiac arrest. Baudhuin et al published in Circulation and Genetics entitled Technical Advances for the Clinical Genomic Evaluation of Sudden Cardiac Death. Baudhuin et al reviewed the utility of formal and fixed paraffin-embedded tissue, which is routinely obtained in an autopsy, to perform post-mortem, genetic testing. One of the main limitations to advising family members who have had prior family history of sudden death in closely related relatives, is that blood is often not available to perform DNA screening late after death. DNA however is often degraded in the tissues that are commonly available at autopsy, namely the formal and fixed paraffin-embedded tissues. The authors sought to evaluate if your next generation techniques could make these types of tissue adequate for diagnosis. They demonstrated amongst 19 samples, that performance characteristics were similar between whole blood and these tissue samples, which could be as old as 15 years. It can be critical to identify disease-causing mutations in family members, as individuals who might not yet be affected, but at risk, need to know about that overall risk. Given that decision to sequence might also not be universally applied at all centers, or in all situations, oftentimes these paraffin-embedded tissues might be the only available option, sometimes over a decade after death. This represents the first report of using next-generation sequencing approaches to successfully and accurately sequence for specific mutations using paraffin-embedded tissue. This may offer additional options to help family members achieve diagnoses for sudden death-inducing conditions. Within the realm of cellular electrophysiology, we review an article by Lang et al published in Circulation Research entitled Calcium-Dependent Arrhythmogenic Foci Created by Weakly Coupled Myocytes in the Failing Heart. Lang et al reviewed the effect of cell-cell coupling on the likelihood of triggered arryhthmias. In a [inaudible 00:28:45] model, they demonstrated the myocytes that are poorly synchronized with adjacent myocytes were more prone to triggered activity due to abnormal calcium handling when compared to myocytes with normal connection to adjacent cells. Thus, adequate coupling leads to voltage clamping during calcium waves, thus preventing triggering arrhythmias. While poorly coupled myocytes aren't able to to this due to a weakened currency, making them more prone arrhythmogenesis. These data highlight another critical cellular basis for arrhythmogenesis. In heart failure, while the focus for clinical management is typically areas of scar, there's clearly a role at the cellular level where cell-cell coupling abnormalities can lead to dynamic changes that can increase tendencies to arrhythmogenesis. The role in understanding the varying, arrhythmogenic risk based on varying factors, is important, and might have importance in the future advances in mapping technologies. Changing gears, we review an article published in the Journal of the American College of Cardiology by Mazzanti et al within the realm of genetic channelopathies entitled Hydroxyquinoline Prevents Life-Threatening Arrhythmic Events in Patients With Short QT Syndrome. They reviewed a cohort of 17 patients and demonstrated that hydroxyquinoline resulted in a reduction of arrhythmic events from 40% to 0% of patients. QTc prolongation was seen in all patients. These data clearly demonstrate that hydroxyquinoline plays a role in lowering the incidence of arrhythmic events in patients suffering from short QT syndrome. However, it's important to note that in many markets, quinoline has been difficult to access. In the specific case of QT syndrome thus, there's clearly a role for hydroxyquinoline. However, it also must be noted, the comparative efficacy with more commonly available drugs still needs to be evaluated. This past month has been of particular interest in the realm of ventricular arrhythmias, with multiple, potentially ground-breaking articles. One of the well-recited articles published this past month already is by Cuculich et al entitled Noninvasive Cardiac Radiation for Ablation of Ventricular Tachycardia published in the New England Journal of Medicine. Cuculich et al reported the first in-human data on the use of stereotactic body radiation therapy to perform noninvasive ablation of ventricular arryhthmias. Using a combination of noninvasive electrocardiographic imaging curing ventricular tachycardia, and stereotactic radiation, patients were treated with a single fraction of 25 [inaudible 00:31:15] while awake. A total of five patients were included with a mean ablation time of only 14 minutes. During the three months prior to treatment, there was a total of 6,577 VT episodes seen, and during a six week post-ablation period, considered a blanking period, there were 680 episodes. After this blanking episodes, there were only four episodes of VT seen over the ensuing 46 patient months. This study is important because it reflects the first in-human proof of concept that noninvasive ablation using radiation therapy traditionally as for treatment of solid tumors, may be affective in targeting cardiac tissue. Furthermore, modern techniques such as noninvasive electrocardiographic imaging might allow for a fully noninvasive experience for the patients. This is a vast advance seen within the realm of cardiac electrophysiology. In the early days, all we could do was map invasively and then have to go to much more invasive, open-heart surgery to treat arryhthmogenic substrates. Since the advent of catheter and radiofrequency ablation, surgical ablation is relatively fallen by the wayside, to a less invasive approaches. A completely noninvasive approach to successfully targeting tissue is potentially ground-breaking. However, there are several limitations in this study that can only be ascertained by reading the actual article. When we actually review the patients included, the long term follow-up was limited to only four patients, as one patient actually died within the blanking period, and in fact, this patient suffered from the largest burden overall of VT. Furthermore, amongst the remaining four patients, one required a redo ablation within the blanking period, and one had to be restarted on amioderone after the blanking period was over. Thus further data is really needed to clarify efficacy, given the overall success rate appears to be less than 50% on a per patient basis. Though on an overall episode basis, there was significant reduction. The exact type of radiation to be used also needs to be considered, within the realm of solid oncology. Stereotactic radiation is considered an older modality, with proton beam, and more recently, carbon beams offer more directed therapy. Thus, a lot more data is required to identify the promise of radiation therapy. Though again, this is a significant advance. Next, within the realm of invasive electrophysiology, we review an article by Turagam et al published in the JACC Clinical Electrophysiology entitled Hemodynamic Support in Ventricular Tachycardia Ablation: An International VT Ablation Center Collaborative Group Study. The utility of hemodynamic support during VT ablation is relatively unclear. Studies have been variable and limited. This group included 1,655 patients who underwent 105 VT ablations using hemodynamic support with a percutaneous ventricular assist device. Those undergoing support overall tend to be sicker, including lower ejection fractions and [inaudible 00:34:07] classes, and more VT events, including ICD shocks and VT storm. Hemodynamic support use interestingly, was an independent predictor of mortality with a hazard ratio of 5, though there was no significant difference in VT recurrence rates irrespective of the subgroup considered. These data indicate that, while patients are receiving hemodynamic support were overall sicker, there was no clear incremental benefit in use of hemodynamic support in terms of long term outcomes. In the area of substrate ablation, whether use of hemodynamic support to facilitate mapping during VT, actually alters outcomes remains to be seen. This study highlights the potential importance of randomized clinical approaches to better evaluate whether hemodynamic support truly alters the long term outcomes of the VT ablation. Next, we review an article by Munoz et al that focuses more on prediction of those patients who might be at risk for ventricular arrhythmias, again published in the last edition of JACC Clinical Electrophysiology and entitled Prolonged Ventricular Conduction and Repolarization During Right Ventricular Stimulation Predicts Ventricular Arrhythmias and Death in Patients With Cardiomyopathy. Munoz et al reviewed the relationship between paced QRS and pace Qtc and long term risk. A total of 501 patients with mean ejection fractions of 33% were included. Longer paced ventricular QRS and Qtc was associated with a higher risk of ventricular arrhythmia, and all caused death or arrhythmia, irrespective or ejection fraction. A paced QRS duration of 190 milliseconds was associated with 3.6 fault higher risk of arrhythmia, and a 2.1 fault higher risk of death or arrhythmia. These data suggest that findings during [inaudible 00:35:47] pacing and otherwise normal rhythm, including paced QRS and QTc may independently result in elevation of overall risk of ventricular arrhythmia and death. Physiologically these data make sense. In light of the fact that longer cure restorations are probably related to a greater degree of myopathy. While these data offer a prognostic indication, whether they alter outcomes or decision making regarding ICM implantation, remains to be seen. Next, also published in JACC Clinical Electrophysiology, Vandersickel et al reviewed a more cellular basis for toursades in an article entitled Short-Lasting Episodes of Toursades de Pointes in the Chronic Atrial Ventricular Model Have Focal Mechanism While Longer-Lasting Episodes are Maintained by Reentry. Vandersickel et al reviewed the mechanisms underlying toursades, and demonstrated that both focal and reentry mechanisms may exist. In five canines they used broadly distributed neuro electrodes to simultaneously map across the heart. They demonstrated that initiation and termination was always focal, but longer and non-terminal episodes always had reentry mechanisms. These data suggest that the mechanisms underlying toursades actually reflect a spectrum of potentially dynamic, electrophysiologic phenomenon the heart, including both focal and reentry activity. Understanding these mechanisms, and the fact that focal mechanisms almost universally underlie initiation may bring into consideration the optimal treatments whether in the form of pacing and defibrillation techniques or medication techniques for toursades. Finally, in the realm of ventricular arrhythmia, we review an article published in the last month's edition of Heart Rhythm by Penela et al entitled Clinical Recognition of Pure Premature Ventricular Complex-Induced Cardiomyopathy at Presentation. As we know, it's sometimes difficult to recognize patients when they present with frequent PVCs and a depressed injection fraction in terms of, whose injection fractions are purely caused by the presence of PVCs, and whose PVCs are only exacerbated by the presence of an underlying myopathy. The group included 155 patients and excluded all patients who did not normalize their elevated ejection fraction, or who had previously diagnosed structural heart disease, leaving a total cohort under consideration, of 81 patients. About 50% were diagnosed as having a PVC-induced cardiomyopathy on the basis of normalization of elevated function after PVC suppression. While the remainder was considered to have PVC exacerbated cardiomyopathy on the basis that things did not entirely resolve, and thus had an independent mechanism for nonischemic myopathy. Characteristics that suggested patients with a lower likelihood of EF normalization included those with longer intrinsic QRSs, above 130 milliseconds, a lower PVC burden of baseline, considered less than 17%, and larger [inaudible 00:38:33] greater than 6.3 cm. PVCs as a cause of [inaudible 00:38:35] are obviously a well-recognized treatable cause of myopathy, however again, it might be difficult to differentiate. Those patients whose PVCs are a result of the underlying myopathy versus those whose PVCs are the cause, and for whom ablation or suppression may reverse the myopathic process. The work of Penela et at offers an initial attempt at helping differentiate these processes, however validation of larger cohort is necessary. Next we review an article within the realm of syncopy entitled Prohormones in the Early Diagnosis of Cardiac Syncopy by Badertscher et al published in the Journal of the American Heart Association this month. They review the utility of circulating prohormones [inaudible 00:39:14] autonomic dysfunction or neurohormonal abnormalities, to differentiate cardiac from non-cardiac causes of syncopy in the emergency departments. They measured four novel prohormones in a multi-center study. In the emergency departments there is a specific protocol used to determine the perceived likelihood of the cause of syncopy to be cardiac versus non-cardiac. In addition to this, the prohormones are drawn. After this, everyone's final diagnosis was reached. Two independent cardiologists reviewed the cases to determine if it was a truly cardiac or non-cardiac cause of syncopy. Among 689 patients included, 125 overall were adjudicated as cardiac syncopy. Measure of the specific marker MR-proANP in combination with emergency department suspicion of syncopy, performed better than suspicion alone, to differentiate cardiac causes of syncopy. A combination of a circulating MR-proANP, less than 77, picomoles per liter, an [inaudible 00:40:17] probability of cardiac syncopy could be less than 20%, had a very high sensitivity negative predictive value of 99%. The significant resources are often used to manage patients with syncopy presenting to the emergency departments, and it's often extremely difficult at this stage to differentiate cardiac from non-cardiac causes of syncopy. And the amount of evaluation that can be done in the emergency department is often limited. Cardiac caused of syncopy are not good to miss, however, since these can include ventricular arrhythmias, and transient AV block, that might result in death as well. As is well-recognized, emergency department evaluation in clinical [inaudible 00:40:49] are limited in terms of their utility. This raises the utility of objective measures to help differentiates. These data suggest that circulating prohormones [inaudible 00:40:59] your hormonal function drawn during your emergency department evaluation, may be a useful adjunct to differentiate cardiac from non-cardiac syncopy. Whether they can be used to prospectively differentiate those patients requiring inpatient admission or now, however, remains to be seen. The last two articles we'll choose to focus on will fall under the realm of broader, other EP concepts. The first article we will review is by Varghese et al published in Cardiovascular Research entitled Low-Energy Defibrillation With Nanosecond Electric Shocks. Varghese et al reviewed the potential of low-energy nanosecond duration shocks for defibrillation in rapid hearts. In induced fibrillation examples, the repeated defibrillated nanosecond impulses as low as three kilovolts demonstrated effective defibrillation. The energy required is significantly lower than from monophasic shocks and longer pulse durations. Furthermore, there was no detectable evidence of electroporation, namely cardiac or so injury after defibrillation. Using nanosecond impulses, it may be feasible to defibrillate the heart with significantly lower energies. The implications for patients experiencing defibrillation, for example pain, is unclear without in-human studies. However, the ability to use lower energies could have implications in battery life. Further [inaudible 00:42:11] studies will be critical to study ambulatory efficacy as this research is performed in [inaudible 00:42:19] hearts. Finally, we review an article published in Circulation entitled Mortality in Supravascular Events After Heart Rhythm Disorder Management Procedures by Lee et al. Amongst three centers, a retrospective cohort study regarding the mortality and risk of supravascular events, was performed. They included a variety of heart rhythm [inaudible 00:42:40] procedures, including defibrillation threshold testing, lead extraction, device implant, and invasive electrophysiology studies and ablation procedures. Amongst 48,913 patients, 62,065 procedures were performed and an overall mortality of .36% was seen. Supravascular [inaudible 00:42:58] was lower at .12%. Interestingly, and expectedly, the highest risk was seen with lead extraction patients, with an overall mortality risk of 1.9%. Less than half of the deaths seen, however, were directly attributable to the procedure itself. The most common cause of procedural death was cardiac tamponade, largely seen amongst device implant patients. This is critical, as the number of ablation and other invasive electrophysiology procedures performed, is increasing. These data provide a large, contemporary experience regarding the overall risk attributable to a variety of heart rhythm disorder procedures. Interestingly, half of the procedure related deaths were associated with device implantation procedures. With the predominant cause being tamponade, highlighting the importance of early recognition of this treatable complication. Tamponade may not always be considered as a major issue after device implantation, however these data clearly suggest that it is. In addition, extraction, as expected, carried the highest incident of both supravascular events and mortality. Though, this is likely related to the higher rate of core morbidity in this population, including active infection. In summary, this month, we have reviewed 20 articles in various areas of electrophysiology published across the literature. Particularly high impact articles range from those reviewing experience regarding left atrial appendage closure and the efficacy of this, to the utility of using atrial fibrillation to predict risk and long term morbidity and mortality in hypertrophic cardiomyopathy, to further evidence regarding the safety of magnetic resonance imaging in legacy pacemakers and defibrillators, and novel considerations regarding supraventricular tachycardias and there diagnosis and management, especially invasively. Other potential groundbreaking articles included evidence that we can successfully use formal and fixed paraffin-embedded tissue that can be as old as 15 years, to successfully identify genetic mutations that might be responsible for sudden death. And evidence that using novel techniques, we might be able to perform completely noninvasive therapies for arrhythmias by using radiation therapies. However questions were also raised such as regarding the role of hemodynamic support for VT ablation. How to better differentiate those patients who will have recovery of AV conduction from those who won't, as they meet class I indications post cardiac surgery? And whether other factors such as right ventricular pacing during [inaudible 00:45:28] study might further differentiate patients at risk for ventricular arrhythmias in spite of a low ejection fractions. Many of the papers had to deal with tranlational work that still remains to be proven in terms of value at a clinical level, such as demonstrating mechanisms underlying trousades de pointes. Or the potential value of low-energy defibrillation with nanosecond electric shocks. Clinical protocols involving the use of prohormones in the early diagnosis of cardiac syncopy. How to differentiate PVC induced from other causes of myopathy, and how to manage, in the long term, these devices. Also, likely requires further study. Finally, covering all areas of electrophysiology, we reviewed one large article focusing on mortality in supravascular events after heart rhythm management disorder procedures at large. This article highlights the importance of considering institutional experience and reporting it to use as a benchmark to help better optimize our counseling of patients, as well as our procedures and protocols. I appreciate everyone's attention to these key and hard-hitting articles that we just focused on from this past month of cardiac electrophysiology across the literature. Thanks for listening. Now, back to Paul. Dr. Paul Wong:                  Thanks Seraj. You did a terrific job surveying all journals for the latest articles on topics of interest in our field. There's not an easier way to stay in touch with the latest advance. These summaries, and a list of all major articles in our field each month, can be downloaded from the Circulation Arrhythmia and Electrophysiology website. We hope you'll find the journal to be the go-to place for everyone interested in the field. See you next month.  

When addiction centers fail to treat the metabolism of addicts, they get repeat business. How is the addiction treatment protocol changing with TRT? When will the medical industry begin to recognize the benefits of TRT? How will community supported healthcare and wellness make doctors insignificant? On this episode, Russ Scala is back to talk about addiction, weight loss and the current state of medicine. When we want to grow new brain tissue, we give someone testosterone. -Russ Scala Takeaways If you have low-circulating dopamine levels, you are more susceptible to addiction. One area addiction treatment isn’t paying attention to is the opiate bowel. 95% of men who present with a deficiency in testosterone won’t get the treatment they need from doctors. The community is doing a lot more to help people attain and maintain health than doctors. At the start of the show, Russ shared on the work he’s doing including biochemical individuality, and his interest in the aging workforce. Next, we talked about the current model of healthcare and how competition will shift it towards preventative healthcare and wellness. We also talked about an LA times article about the struggle many Americans are having with obesity. We went on to talk about the many benefits of TRT and testosterone as rehab in the HPA axis. Towards the end of the show, we shared on how testosterone protects the brain. Russ also shared insights on; Why we need addiction treatment protocols designed for metabolism The warrior gene and its connection to addiction Opiate induced neuroplasticity Why addicts have with muscle waste Why doctors will become insignificant As medicine remains bogged down in Pharma-controlled, backward practices that aren’t helping people, the community is going to step up and help people get better, not doctors. People are going to continue to crowdsource their health solutions to tribes that are already adhered to a practice, and people who have the foundational principles and real world quantifiable results. This can change the game for addicts, testosterone deficient men and other people who aren’t being served well by the doctors who are meant to help them. Guest Bio Russ Scala is a former paramedic and SWAT team member who went on to found Scala Precision Health and the Institute of Nutritional Medicine and Cardiovascular Research. He’s developed specific protocols for everything from brain health to athletic performance, from active longevity to rapid recovery. Go to http://scalaprecisionhealth.com/ for more information. To Download Your FREE PDF Copy of the Amazon Best Seller: The Definitive Testosterone Replacement Therapy MANual, Click Here  For a FREE Paperback Copy. The TRT MANual has helped hundreds of thousands of men around the world reclaim their health and vitality. Don’t suffer in silence a moment longer! PS. As an added bonus, upon finishing the book-once you provide a Thoughtful, High Quality Review on Amazon (hopefully 5 STAR), we will send you our new unreleased eBook 7 Lies You’ve Been Told About Testosterone for FREE.* (To receive book, email jay@trtrevolution.com a screenshot of your posted review.)

Patient care and health are on the verge of a paradigm shift, and personalized health professionals are on the tip of the spear. What are the biggest factors responsible for this shift? On this week’s episode I discuss this with the founder of Scala Precision Health, Russ Scala and touch on the current problems in healthcare, the drop in testosterone and TRT’s role in battling mental health issues and heart problems. Three Takeaways Low testosterone can accelerate blockages of the coronary arteries. Assuming that the doctors know everything is a common mistake many are making. Many patients are scared of using testosterone, it gets a bad name. This can only be combated by encouraging people to learn about it. We kicked off the show with a bit of Russ Scala’s story and his interest in how stress compromises the body. This interest goes back to when he worked in the ER and later on as a SWAT team member. This led to him starting Scala Precision Health, an institution driven by the need to empower people to take their health into their own hands. There’s going to be a huge paradigm shift in health spurred on by the fact that healthcare in its current state cannot deal with a lot of health concerns. We discussed the common stereotype - people thinking that doctors know everything. I asked Russ how he combats this way of thinking when dealing with older patients. Next we discussed the issue of low testosterone and the reasons behind it. Russ stresses the importance of environmental factors like pesticides, shampoo and other products the patient may have been exposed to. Russ went onto mention the importance of a “a virus of knowledge” and creating content that educates the masses about taking their health into their own hands. This content should be aimed at families, and not doctors. Next we discussed the cardio protective elements of testosterone and what it does for your arteries on the cellular level. Towards the end of the show we discussed how testosterone also combats PTSD and diabetes. We also discussed Russ Scala’s perspective on ketogenic dieting. The reality of healthcare is that doctors have filters that stand between them being able to really meet the needs of patients. This has left a space for a huge paradigm shift that will see people having more control over their own health. TRT is part of this shift, and through it we can begin to see changes in how we tackle mental illness and diabetes. The shift also means you can be the CEO of your own health. Guest Bio Russ Scala is a former paramedic and SWAT team member who went on to found Scala Precision Health and the Institute of Nutritional Medicine and Cardiovascular Research. He’s developed specific protocols for everything from brain health to athletic performance, from active longevity to rapid recovery.   To Download Your FREE PDF Copy of the Amazon Best Seller: The Definitive Testosterone Replacement Therapy MANual, Click Here  For a FREE Paperback Copy. The TRT MANual has helped hundreds of thousands of men around the world reclaim their health and vitality. Don’t suffer in silence a moment longer! PS. As an added bonus, upon finishing the book-once you provide a Thoughtful, High Quality Review on Amazon (hopefully 5 STAR), we will send you our new unreleased eBook 7 Lies You’ve Been Told About Testosterone for FREE.* (To receive book, email jay@trtrevolution.com a screenshot of your posted review.)

1) Mid-life exercise blood pressure, heart rate and fitness relate to brain volume two decades later2) What's Trending: Antibiotic-associated encephalopathy 3) Topic of the month: Migraine awareness seriesThis podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Jeff Burns interviews Dr. Nicole Spartano about her paper on the mid-life exercise blood pressure, heart rate and fitness and how it relates to brain volume two decades later. Dr. Ted Burns is interviewing Dr. Shamik Bhattacharyya for our “What's Trending” feature of the week about his paper on antibiotic-associated encephalopathy. Dr. Tesha Monteith interviews Dr. Aarno Palotie about the topic of migraine genetics: What have we learned. DISCLOSURES: Dr. Jeff Burns serves on the editorial board for Journal of Alzheimer's Disease; receives royalties for the publications of Early diagnosis and treatment of mild cognitive impairment and Dementia: An atlas of investigation and diagnosis; is a consultant for PRA International and receives research support from the NIH, Alzheimer's Drug Discovery Foundation, Elan, Janssen Pharmaceuticals Inc., Wyeth, Pfizer Inc, Novartis Pharmaceuticals Ltd, Danone, Avid Radiopharmaceuticals, Merck Serono and for clinical trials.Dr. Spartano receives research support from the NIH.Dr. Ted Burns serves as Podcast Editor for Neurology®; and has received research support for consulting activities with UCB, CSL Behring, Walgreens and Alexion Pharmaceuticals, Inc.Dr. Monteith serves as an editorial advisory board member for Neurology Now and receives research support from the NIH.Dr. Palotie serves as a member of the Pfizer Genetics Scientific Advisory Panel; receives research support from Finnish Academy, European Union NIH, NINDS, Juselius Foundation and Finnish Foundation for Cardiovascular Research.

James Clark and Graham Sattler discuss how to improve hemodynamic study outcome consistency by monitoring vital signs during surgery.

James Clark and Graham Sattler discuss how to improve hemodynamic study outcome consistency by monitoring vital signs during surgery.

Commentary by Dr. Valentin Fuster

Host: Alan S. Brown, MD, FNLA A paradigm shift in the management of lipid disorders has been witnessed of late based on evidence reviews by the AHA and the ACC. Where the clinical dogma once focused on targeting specific lipoproteins, clinicians are now trending toward using appropriate dosages of statins for lowering non-HDL cholesterol. What are the ramifications of this change in approach, and how does the NLA weigh in on recommendations for targets and goals? To address these and other questions, host Dr. Alan Brown welcomes Kevin Maki, PhD, FNLA, CLS, Chief Science Officer for Midwest Center for Metabolic and Cardiovascular Research and Adjunct Faculty in Biostatistics and Applied Epidemiology at DePaul University, Chicago, IL.

Host: Alan S. Brown, MD, FNLA What's the evidence for LDL and other non-HDL targets for primary and secondary prevention of heart disease? What are the comparative benefits versus toxicities of all lipid-lowering medications in clinical use? Addressing these and other questions from the standpoing of recent NLA recommendations is Kevin Maki, PhD, FNLA, CLS, Chief Science Officer for Midwest Center for Metabolic and Cardiovascular Research and Adjunct Faculty in Biostatistics and Applied Epidemiology at DePaul University, Chicago, IL. Produced in partnership with

Guest: Kevin C. Maki, PhD, FNLA, CLS Host: Alan S. Brown, MD, FNLA At the most recent National Lipid Association (NLA) meeting, host Dr. Alan Brown welcomes Kevin Maki, PhD, FNLA, CLS, Chief Science Officer for Midwest Center for Metabolic and Cardiovascular Research and Adjunct Faculty position in Biostatistics and Applied Epidemiology at DePaul University, Chicago, IL. Drs. Brown and Maki discuss the evidence of the relationship of statin use and risk of new onset of diabetes; as well as, the relationship of statin use and the possiblity of worsening glycemia in those patients who have diabetes. What are the conclusions? What should clinicians be screening for? Download and listen to this great conversation! Sponsored by