Podcasts about multi ethnic study

In this week's podcast, a potential new therapeutic target in beta-thalassemia. The E3 ubiquitin ligase AMBRA1 promotes autophagic clearance of free alpha-globin. Researchers describe mutations in the AMBRA1 gene that impair this clearance, exacerbating ineffective erythropoiesis and disease severity. After that: targeting MYD88 mutations. Lasalocid-A is a compound that selectively binds to the MYD88 L265P mutant protein, which is found in a range of B-cell lymphomas. New research shows its potential to inhibit tumor growth, overcome ibrutinib resistance, and synergize with venetoclax. Finally: air pollution is linked to an increased risk of venous thromboembolism in a prospective, community-based cohort study. The findings highlight the harms of pollution, and support the case for global efforts to improve public health.Featured Articles:Mutations in AMBRA1 aggravate β-thalassemia by impairing autophagy-mediated clearance of free α-globinLasalocid A selectively induces the degradation of MYD88 in lymphomas harboring the MYD88 L265P mutationAir pollution is associated with increased risk of venous thromboembolism: the Multi-Ethnic Study of Atherosclerosis

Darshan H. Brahmbhatt, Podcast Editor of JACC: Advances, discusses a recently published original research paper on The mC2HEST Score for Incident Atrial Fibrillation: MESA (Multi-Ethnic Study of Atherosclerosis)

In this episode, Dr. Valentin Fuster discusses a groundbreaking study linking urinary metal levels, particularly non-essential metals like cadmium and uranium, to coronary artery calcification, highlighting their potential role in cardiovascular disease. The findings underscore the urgent need for public health initiatives to address environmental metal exposure, as they could significantly mitigate cardiovascular risks and health disparities.

Dr. Kaitlyn McGraw discusses her study on the relationship between urinary trace metal levels and coronary artery calcification, highlighting the role of environmental exposures in cardiovascular disease risk. The research reveals significant associations between elevated levels of metals like cadmium, tungsten, and uranium with the progression of calcification, comparable to traditional risk factors such as smoking and diabetes. Dr. McGraw emphasizes the need for integrating environmental factors into cardiovascular risk assessments and suggests policy changes to better regulate metal exposure in the population. Moderated by Khurram Nasir, MBBS, FACC.

Darshan H. Brahmbhatt, Podcast Editor of JACC: Advances discusses a recently published original research paper on Interleukin-6 and Cardiovascular Events in Healthy Adults in the Multi-Ethnic Study of Atherosclerosis

Commentary by Dr. Candice Silversides

Join our scientific team in the discussion of the 3 most clinically impactful papers of the month, the crème de la crème of our weekly top picks. This month we're discussing: Aspirin and Cardiovascular Risk in Individuals With Elevated Lipoprotein(a): The Multi‐Ethnic Study of Atherosclerosis DOI: ⁠https://doi.org/10.1161/JAHA.123.033562 Apixaban to Prevent Recurrence After Cryptogenic Stroke in Patients With Atrial Cardiopathy. The ARCADIA Randomized Clinical Trial DOI: ⁠⁠https://doi.org/10.1001/jama.2023.27188 5-year follow-up of the randomised Diabetes Remission Clinical Trial (DiRECT) of continued support for weight loss maintenance in the UK: an extension study DOI: ⁠https://doi.org/10.1016/S2213-8587(23)00385-6 Scientific team: Ricardo Ladeiras Lopes, Mário Santos and João Sérgio Neves Discover Medical Portfolio App weekly top picks - the latest and most relevant papers, curated by our team of experts! ⁠⁠⁠⁠⁠https://linktr.ee/medicalportfolioapp

Commentary by Dr. Candice Silversides

Did you know that the Great Depression—the worst economic downturn in US history—impacted how fast individuals aged biologically decades later according to their epigenetic aging profiles?!Yep… you read that right. Results show that faster epigenetic aging later in life is associated with worse economic conditions, specifically, during the prenatal period, suggesting it may be a sensitive window for the development of later-life disparities in aging. As a result, early-life investments may help postpone age-related morbidity and mortality.In this week's Everything Epigenetics podcast, Dr. Lauren Schmitz speaks with me about just that. We take a deep dive into several of her studies which focuses on using genetic and epigenetic measures alongside data on the social environment from population-based longitudinal studies and randomized control trials. Lauren and I also discuss the methodology she uses for uncovering causal effects from observational data, with the ultimate goal of identifying policy targets that enhance quality of life and extend healthspan. We also chat about her study results that support DNA methylation-based epigenetic aging as a signature of educational inequalities in life expectancy emphasizing the need for policies to address the unequal social distribution of these World Health Organization (WHO) risk factors, as well as, social disadvantages which may contribute additively to faster biological aging.I'm extremely excited and passionate about Lauren's work myself, as it suggests that epigenetic aging measures may contain additional valuable information that could further our understanding of the causes of social disparities in aging and health span.Lauren is now actively working on assessing measures of biological age in a low-income context, specifically “The Malawi Longitudinal Study of Families and Health”.In this Everything Epigenetics episode, you'll learn about:Lauren's atypical, windy road into scienceThe Health and Retirement studyMaternal-fetal epigenetic programmingWhy it's important to look at early-life exposures to adverse eventsHow we can look at early-life exposures to adverse events through the lens of Epigenetics In utero exposure to the Great Depression being reflected in late-life epigenetic aging signaturesHow early-life investments may help postpone age-related morbidity and mortality and extend healthy life spanLauren's study  “The Socioeconomic Gradient in Epigenetic Ageing Clocks: Evidence from the Multi-Ethnic Study of Atherosclerosis and the Health and Retirement Study”Another one of Lauren's study titled: “The Role of Epigenetic Clocks in Explaining Educational Inequalities in Mortality: A Multicohort Study and Meta-analysis”Why is it important to conduct research on the connection between epigenetic pathways of and the socioeconomic gradient and educational inequalitiesEpigenetic ecosystemsApplications of Lauren's work in the real world Where to find Lauren: Website: www.laurenlschmitz.comTwitter: https://twitter.com/laurenlschmitzLinkedIn: https://www.linkedin.com/in/lauren-schmitz-8156785b/Support the showThank you for joining us at the Everything Epigenetics Podcast and remember you have control over your Epigenetics, so tune in next time to learn more about how.

ไลฟ์#68: Lipoprotein particles ชนิดใดบ้างที่อันตรายต่อหลอดเลือดหัวใจ น้องๆมักจะได้ยิน กูรูสุขภาพ เตือนให้เราระวังอันตรายจาก small dense ldl particle บอกว่าเป็น ldl particle ที่เป็นอันตรายต่อหลอดเลือดหัวใจ การเปลี่ยนมากินอาหารแบบคาร์บต่ำไขมันสูง จะทำให้ ldl-particle มีขนาดใหญ่ ไม่เป็นอันตรายต่อหลอดเลือดหัวใจ และให้เราสนใจสัดส่วน TG/HDL ถ้าใกล้เคียง 1 นี่ถือว่าปลอดภัย ไม่ต้องสนใจระดับ total cholesterol และ ldl-cholesterol ที่สูงลิ่ว….จริงหรือ ในไลฟ์#68 เราจะมาทำความเข้าใจกันว่า lipoprotein particles ชนิดใดบ้าง ที่อันตรายต่อหลอดเลือดหัวใจ เราควรสนใจแต่ small dense ldl particle จริงหรือ นอกจากนั้นมาฟังประธาน European Atherosclerosis Society คนปัจจุบัน ซึ่งเป็นแพทย์ผู้เชี่ยวชาญโรคหัวใจ/lipidologist มา 30 ปี ให้สัมภาษณ์พูดถึงสัดส่วน TG/HDL ว่า เป็น parameter ที่ใช้ในการทำนายความเสี่ยงของโรคหลอดเลือดหัวใจได้จริงตามที่ กูรูสุขภาพ ชวนเชื่อเราจริงหรือ งานวิจัยอ้างอิงในไลฟ์#68: Lipoproteins ชนิดใดบ้างที่อันตรายต่อหลอดเลือดหัวใจ 1. Low-density Lipoprotein Particle Number and Risk for Cardiovascular Disease https://moscow.sci-hub.st/817/60bd012... 2. Apolipoprotein B Particles and Cardiovascular Disease: A Narrative Review by Allan D. Sniderman https://www.ncbi.nlm.nih.gov/pmc/arti... 3. LDL particle subclasses, LDL particle size, and carotid atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA) https://pubmed.ncbi.nlm.nih.gov/16765... 4. Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel https://academic.oup.com/eurheartj/ar... 5. Therapeutic Lipidology Chapter 27: Lipoprotein Subfractions in Clinical Practice by Jeffrey W.Meeusen https://link.springer.com/chapter/10.... 6. Metabolism and atherogenicity of apoB containing lipoproteins EAS https://eas-society.org/content/metab...#หาคำตอบสุขภาพจากงานวิจัยไม่ใช่จากเรื่องเล่า #FatOutHealthspans

Commentary by Dr. Valentin Fuster

Commentary by Dr. Valentin Fuster

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.

Studies have demonstrated dysfunction of the left atrium and right atrium were linked to lower ability to walk, and may be a precursor to heart failure. It may be useful to examine the function of the atria on echocardiography to understand one's risk of developing heart failure in the future. In this interview, Ravi B. Patel, MD, MSc and Roger S. Blumenthal MD, FACC, with Aaysha Cader, MBBS, MD, MRCP, discuss Associations of Cardiac Mechanics with Exercise Capacity: The Multi-Ethnic Study of Atherosclerosis.

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Virologists reveal how poor man's amino acid cure for COVID-19 would abolish need for vaccines Bio-Virus Research Inc (Nevada), September 15, 2021 A natural cure for COVID-19 that is widely available and affordable for even the poorest of people on the planet has been confirmed by a team of virologists who have spent a lifetime studying the underlying causes of viral infections. Backed by decades of research and safety data for herpes-family viruses, U.S.-based researchers at Bio-Virus Research Inc, Reno, Nevada, report on the successful treatment of the first 30 frontline doctors and nurses and a thousand-plus patients given the amino acid lysine to prevent and even abolish COVID-19 coronavirus infections at a clinic in the Dominican Republic.  Astonishingly, symptoms of COVID-19 are reported to have dissipated within hours of this natural treatment. The medical staff at a clinic in the Dominican Republic was coming down with two cases of coronavirus per month before lysine therapy was instituted. The virologists, Drs. Christopher Kagan, Bo Karlicki and Alexander Chaihorsky, strongly suggested the front-line healthcare workers embark on a daily regimen of lysine therapy due to daily exposure to the virus.  Their ground-breaking report is published online at ResearchGate.net. Arginine/lysine balance Lysine therapy interrupts the replication of viruses, including COVID-19 coronavirus, by countering arginine, an amino acid that fosters the eruption of dormant viruses.  Lysine has been safely used for decades to quell herpes virus outbreaks that cause cold sores on the lips (herpes labialis), a treatment pioneered by one of the Bio-Virus Research team members in 1974. Lysine is available in foods and in concentrated form in inexpensive dietary supplements (250 500-milligram lysine tablets can be purchased for under $5 US or 2-cents per tablet), making affordable lysine therapy possible. Lysine/arginine imbalance would explain why patients who have been infected with COVID-19 have recurrent infections, even after vaccination. Lysine Rx in Dominican Republic The daily therapeutic supplement regimen for the medical staff in the Dominican Republic consisted of 2000 milligrams of lysine capsules along with restricted dietary consumption of arginine-rich foods such as nuts, chocolate, orange juice, pumpkin, sesame seeds, wheat germ. The Bio-Virus Research team found doses of supplemental lysine up to 4000 milligrams to be safe and effective. Foods that have a high ratio of lysine over arginine such as eggs, tofu, fish (not raw), sardines, cheese, meats such as pork, poultry and red meat, and yogurt) provide a high ratio of lysine over arginine, thus blocking replication of all coronaviruses including COVID-19. According to the virologists who were interviewed by this reporter, over 1000 patients have now been successfully treated with surprisingly rapid dissolution of symptoms and return to health.  Even severely infected COVID-19 patients have been able to come off the ventilator with lysine therapy, say doctors. Third-party validation for lysine therapy Writing in the International Journal of Infectious Diseases another research team based in New York and Texas reports that arginine depletion is a strategy to quell both coronaviruses and other herpes family viruses. In 2016 researchers documented that lysine impairs the growth of coronaviruses in a lab dish. The Bio-Virus Research team are not loners nor out on a scientific limb.  A report, published in the Journal of Antivirals & Antiretrovirals, is what prompted to the current discovery that was put into clinical practice in the Dominican Republic.  The science was in place prior to the announcement a mutated coronavirus was sweeping the globe which no one had immunity towards. Dietary intake The Recommended Daily dietary intake of lysine is 2660 milligrams for a 154-lb (70 kilogram) adult; 3640 milligrams during pregnancy. Dietary intake of lysine in western populations ranges from 40-180 milligrams per day per kilogram (2.2 lbs.) of body weight, or 2800-12,600 milligrams for a 154 lb. (70 kilogram) adult. It is the balance of arginine to lysine that controls the eruption of dormant viruses in the body.  The average intake of arginine is estimated to be 4000-6000 milligrams per day. Other health benefits Supplemental lysine also has other health benefits.  Lysine increases absorption of calcium, relieves bouts of anxiety, promotes wound healing, and is helpful for other conditions.  Cholesterol is deposited in binding sites within coronary arteries.  When lysine (and vitamin C) occupy those binding sites, cholesterol is not deposited in arteries. Prevalence of herpes viral infections Worldwide many billions of people harbor dormant herpes viruses that erupt into disease from time to time.  In 2016 an estimated 3.7 billion people had herpes simplex virus infection– around 66.6% of the world's population aged 0 to 49. Availability of lysine Lysine is largely produced by the tons for animal feedstuffs.  Roughly 2,200,000 tons of lysine are produced annually.  There is no shortage. Billions may benefit The most frequent medical application of lysine therapy has been the quelling of active herpes infections (on skin, lips, etc.), and eradication of Epstein-Barr infection, Bell's palsy, etc. Researchers bemoan the fact that lysine therapy hasn't become a mainstay in the treatment of herpes infections that affect ~80% of the world's population over expensive and problematic anti-viral drugs because it doesn't generate sufficient profit to attract funding for human clinical trials.  Lysine is superior to various anti-viral drugs. If lysine lives up to its promise as a universal COVID-19 antidote for therapeutic and preventive use, unless billionaire Bill Gates buys up and mothballs all the lysine production plants in the world like he has bought off agricultural land, and bought off news media, vaccine makers and politicians, the need for vaccines will become a moot and meaningless practice for COVID-19. Because of the long-term safety record of this dietary amino acid, the public can take lysine as a non-prescription preventive “medicine.” Epidemiologists baffled by low rate of coronavirus infections in India Despite its large population and poor sanitation, disease trackers are baffled by India's low rate of coronavirus infections.  Maybe it is India's lysine-rich diet of yogurt, lamb, chicken, fish curry that protects its population from viral disease.  The striking difference in the country-to-country prevalence of Herpes Simplex-2 infections (only 9.6% in South East Asian countries and 10.7% in Europe vs. 24.0% in the Americas and 43.9% in Africa) could be explained by the lysine/arginine ratio in native diets. Treat the severely ill; skip the problematic vaccines Vaccination is not fool proof.  Vaccinated patients are testing positive for COVID-19.  Doctors can choose to treat the 3 in 10,000 COVID-19 severely infected patients who are at risk for a mortal outcome with lysine rather than needlessly vaccinate billions of people.  Mass vaccination would not be needed, nor would lockdowns, quarantines and questionable mass face mask use be required.  The pandemic would be rapidly extinguished by a public information campaign regarding lysine-rich foods and dietary supplements.  The public can take action on its own today without adverse consequences.  Literally, trillions of dollars would be saved worldwide.  If not for COVID-19, at least for herpes infections. The shame is on the World Health Organization with a budget of $8.482 billion or the Centers For Disease Control with a budget of $7.875 billion that overlook safe and economical cures like lysine.  This report serves as evidence the world is being gamed to plunder the masses of their health and wealth.  The people of the world need to stop heeding advice from public health officials and practice preventive medicine on their own volition. There is additional evidence that lysine also halts the growth of influenza and coxsackie viruses. Further research Researchers at Bio-Virus Research Inc. are searching for research funds to further document the benefits of lysine therapy.      Omega-3 and Omega-6 supplement improves reading for children   University of Gothenburg, Sweden - September 14, 2021    Supplement of omega-3 and omega-6 fatty acids may improve reading skills of mainstream schoolchildren, according to a new study from Sahlgrenska Academy, at the University of Gothenburg, Sweden. Children with attention problems, in particular, may be helped in their reading with the addition of these fatty acids.   The study included 154 schoolchildren from western Sweden in grade 3, between nine and ten years old. The children took a computer-based test (known as the Logos test) that measured their reading skills in a variety of ways, including reading speed, ability to read nonsense words and vocabulary.   The children were randomly assigned to receive either capsules with omega-3 and omega-6, or identical capsules that contained a placebo (palm oil) for 3 months. The children, parents and researchers did not learn until the study was completed which children had received fatty acids and which had received the placebo. After three months, all children received real omega-3/6 capsules for the final three months of the study.   "Even after three months, we could see that the children's reading skills improved with the addition of fatty acids, compared with those who received the placebo. This was particularly evident in the ability to read a nonsense word aloud and pronounce it correctly (phonologic decoding), and the ability to read a series of letters quickly (visual analysis time)," says Mats Johnson, who is chief physician and researcher at the Gillberg Neuropsychiatry Centre at Sahlgrenska Academy, University of Gothenburg.   No children diagnosed with ADHD were included in the study, but with the help of the children's parents, the researchers could identify children who had milder attention problems. These children attained even greater improvements in several tests, including faster reading already after three months of receiving fatty acid supplements.   Polyunsaturated fats and their role in children's learning and behavior is a growing research area.   "Our modern diet contains relatively little omega-3, which it is believed to have a negative effect on our children when it comes to learning, literacy and attention," says Mats Johnson. "The cell membranes in the brain are largely made up of polyunsaturated fats, and there are studies that indicate that fatty acids are important for signal transmission between nerve cells and the regulation of signaling systems in the brain."   Previous studies in which researchers examined the effect of omega-3 as a supplement for mainstream schoolchildren have not shown positive results, something Mats Johnson believes may depend on how these studies were organized and what combination and doses of fatty acids were used. This is the first double-blind, placebo-controlled study showing that omega-3/6 improves reading among mainstream schoolchildren.   "Our study suggests that children could benefit from a dietary supplement with a special formula. To be more certain about the results, they should also be replicated in other studies," says Mats Johnson. The article Omega 3/6 fatty acids for reading in children: a randomized, double-blind, placebo-controlled trial in 9-year-old mainstream schoolchildren in Sweden was published by The Journal of Child Psychology and Psychiatry.       Elevated stress hormones linked to higher risk of high blood pressure and heart events Kyoto University (Japan) & University of California at Los Angeles, Sept. 13, 2021  Adults with normal blood pressure and high levels of stress hormones were more likely to develop high blood pressure and experience cardiovascular events compared to those who had lower stress hormone levels, according to new research published today in Hypertension, an American Heart Association journal. Studies have shown that cumulative exposure to daily stressors and exposure to traumatic stress can increase cardiovascular disease risk. A growing body of research refers to the mind-heart-body connection, which suggests a person's mind can positively or negatively affect cardiovascular health, cardiovascular risk factors and risk for cardiovascular disease events, as well as cardiovascular prognosis over time. “The stress hormones norepinephrine, epinephrine, dopamine and cortisol can increase with stress from life events, work, relationships, finances and more. And we confirmed that stress is a key factor contributing to the risk of hypertension and cardiovascular events,” said study author Kosuke Inoue, M.D., Ph.D., assistant professor of social epidemiology at Kyoto University in Kyoto, Japan. Inoue also is affiliated with the department of epidemiology at the Fielding School of Public Health at the University of California, Los Angeles. “Previous research focused on the relationship between stress hormone levels and hypertension or cardiovascular events in patients with existing hypertension. However, studies looking at adults without hypertension were lacking,” Inoue said. “It is important to examine the impact of stress on adults in the general population because it provides new information about whether routine measurement of stress hormones needs to be considered to prevent hypertension and CVD events.” Study subjects were part of the MESA Stress 1 study, a substudy of the Multi-Ethnic Study of Atherosclerosis (MESA), a large study of atherosclerosis risk factors among more than 6,000 men and women from six U.S. communities. As part of MESA exams 3 and 4 (conducted between July 2004 and October 2006), white, Black and Hispanic participants with normal blood pressure from the New York and Los Angeles sites were invited to participate in the substudy MESA Stress 1. In this substudy, researchers analyzed levels of norepinephrine, epinephrine, dopamine and cortisol – hormones that respond to stress levels. Hormone levels were measured in a 12-hour overnight urine test. The substudy included 412 adults ages 48 to 87 years. About half were female, 54% were Hispanic, 22% were Black and 24% were white. Participants were followed for three more visits (between September 2005 and June 2018) for development of hypertension and cardiovascular events such as chest pain, the need for an artery-opening procedure, or having a heart attack or stroke. Norepinephrine, epinephrine and dopamine are molecules known as catecholamines that maintain stability throughout the autonomic nervous system—the system that regulates involuntary body functions such as heart rate, blood pressure and breathing. Cortisol is a steroid hormone released when one experiences stress and is regulated by the hypothalamic-pituitary-adrenal axis, which modulates stress response.  “Although all of these hormones are produced in the adrenal gland, they have different roles and mechanisms to influence the cardiovascular system, so it is important to study their relationship with hypertension and cardiovascular events, individually,” Inoue said.  Their analysis of the relationship between stress hormones and development of atherosclerosis found: Over a median of 6.5-year follow-up period, every time the levels of the four stress hormones doubled was associated with a 21-31% increase in the risk of developing hypertension. During a median of 11.2-years of follow-up, there was a 90% increased risk of cardiovascular events with each doubling of cortisol levels. There was no association between cardiovascular events and catecholamines. “It is challenging to study psychosocial stress since it is personal, and its impact varies for each individual. In this research, we used a noninvasive measure — a single urine test — to determine whether such stress might help identify people in need of additional screening to prevent hypertension and possibly cardiovascular events,” Inoue said. "The next key research question is whether and in which populations increased testing of stress hormones could be helpful. Currently, these hormones are measured only when hypertension with an underlying cause or other related diseases are suspected. However, if additional screening could help prevent hypertension and cardiovascular events, we may want to measure these hormone levels more frequently.” A limitation of the study is that it did not include people who had hypertension at the study's start, which would have resulted in a larger study population. Another limitation is that researchers measured stress hormones via a urine test only, and no other tests for stress hormone measurement were used.   Spirulina alleviates high fat diet-induced cognitive impairment via the gut-brain axis Weifang People's Hospital (China), September 9, 2021 Increasing evidence suggested that the gut microbiome-brain axis plays a critical role in regulating cognitive functions. In this study, we aimed to investigate the dietary treatment effect of Spirulina platensis on learning deficits in high fat diet (HFD) fed mice and clarify the potential mechanisms via investigating the gut microbiome-brain axis. Dietary administration of 1% and 2% Spirulina platensis for 16 weeks significantly improved the spatial learning and memory performance of the HFD-fed mice in both Barnes Maze test and Morris water maze test. The Aβ accumulation, tau-hyperphosphorylation, and neuroinflammation in the hippocampus were significantly inhibited by Spirulina platensis. Spirulina platensis also abrogated HFD induced gut microbial dysbiosis and unbalance of gut microbial metabolites indicating its modulating effect on the gut-brain axis. This study provides further evidence for the application of Spirulina platensis as functional supplement for treatment of Alzheimer's disease. Spirulina platensis was frequently used as both a food ingredient and a medical supplement to counteract various metabolic disorders worldwide. In the present study, we found that Spirulina platensis dietary supplementation significantly prevented the cognitive deficits induced by HFD- feeding in mice. For the first time, we identified the inhibition effect of Spirulina platensis on β-amyloid generation, tau-hyperphosphorylation, neuroinflammation, and the gut microbiota dysbiosis. In conclusion, the present study proved the beneficial effect of Spirulina platensis on cognitive impairment in HDF-fed AD mice and cleared Aβ, inhibited tau-hyperphosphorylation, and ameliorated neuroinflammation in the brain. Spirulina platensis also abrogated HFD induced gut microbial dysbiosis and unbalance of gut microbial metabolites indicating that Spirulina platensis might ameliorated cognitive deficits through regulating the gut-brain axis (Fig. 6). This study provides potent evidence for the application of Spirulina platensis as functional supplement for treatment of AD.   Regular exercise may lower risk of developing anxiety by almost 60% University of Lund (Sweden), September 13, 2021 A quick online search for ways to improve our mental health will often come up with a myriad of different results. However, one of the most common suggestions put forward as a step to achieving wellness—and preventing future issues—is doing some physical exercise, whether it be a walk or playing a team sport. Anxiety disorders—which typically develop early in a person's life—are estimated to affect approximately 10% of the world's population and has been found to be twice as common in women compared to men. And while exercise is put forward as a promising strategy for the treatment of anxiety, little is known about the impact of exercise dose, intensity or physical fitness level on the risk of developing anxiety disorders. To help answer this question, researchers in Sweden have published a study in Frontiers in Psychiatry to show that those who took part in the world's largest long-distance cross-country ski race (Vasaloppet) between 1989 and 2010 had a "significantly lower risk" of developing anxiety compared to non-skiers during the same period. The study is based on data from almost 400,000 people in one of the largest ever population-wide epidemiology studies across both sexes. Surprising finding among female skiers "We found that the group with a more physically active lifestyle had an almost 60% lower risk of developing anxiety disorders over a follow-up period of up to 21 years," said first author of the paper, Martine Svensson, and her colleague and principal investigator, Tomas Deierborg, of the Department of Experimental Medical Science at Lund University, Sweden. "This association between a physically active lifestyle and a lower risk of anxiety was seen in both men and women." However, the authors found a noticeable difference in exercise performance level and the risk of developing anxiety between male and female skiers. While a male skier's physical performance did not appear to affect the risk of developing anxiety, the highest performing group of female skiers had almost the double risk of developing anxiety disorders compared to the group which was physically active at a lower performance level. "Importantly," they said, "the total risk of getting anxiety among high-performing women was still lower compared to the more physically inactive women in the general population". These findings cover relatively uncharted territory for scientific research, according to the researchers, as most previous studies focused on depression or mental illness as opposed to specifically diagnosed anxiety disorders. Furthermore, some of the largest studies looking at this topic only included men, were much smaller in sample size, and had either limited or no follow-up data to track the long-term effects of physical activity on mental health. Next steps for research The surprising discovery of an association between physical performance and the risk for anxiety disorders in women also emphasized the scientific importance of these findings for follow-up research. "Our results suggest that the relation between symptoms of anxiety and exercise behavior may not be linear," Svensson said. "Exercise behaviors and anxiety symptoms are likely to be affected by genetics, psychological factors, and personality traits, confounders that were not possible to investigate in our cohort. Studies investigating the driving factors behind these differences between men and women when it comes to extreme exercise behaviors and how it affects the development of anxiety are needed." They added that randomized intervention trials, as well as long-term objective measurements of physical activity in prospective studies, are also needed to assess the validity and causality of the association they reported. But does this mean that skiing in particular can play an important role in keeping anxiety at bay, as opposed to any other form of exercise? Not so, Svensson and Deierborg said, given that previous studies have also shown the benefits of keeping fit on our mental health. "We think this cohort of cross-country skiers is a good proxy for an active lifestyle, but there could also be a component of being more outdoors among skiers," they said. "Studies focusing on specific sports may find slightly different results and magnitudes of the associations, but this is most likely due to other important factors that affect mental health and which you cannot easily control in research analysis.   Gut microbes are key to health benefit delivered by hops compound Oregon State University, September 13, 2021 The health-enhancing performance of a compound found in hops is dependent upon its interactions with intestinal microorganisms, new research by Oregon State University shows. Understanding how xanthohumol, often abbreviated as XN, works is important for unlocking its potential to counter diet-induced obesity and the health risksassociated with a global obesity epidemic, including type 2 diabetes and liver and heart disease, researcher Adrian Gombart says. "We showed that the gut microbiota are necessary for the beneficial effects of XN on glucose metabolism," said Gombart, professor of biochemistry and biophysics in the OSU College of Science and a principal investigator at the university's Linus Pauling Institute. "There is an important interaction between the compound and the microbes in the gut that provides the benefits we see in our studies with mice." Gombart led a team of 20 scientists from three Oregon State colleges in research that compared the glucose metabolism effects of xanthohumol on two sets of mice: "conventional" ones with gut microbiota, and those engineered to be "germ free," i.e. have no gut microbes. Glucose metabolism, the body's ability to convert the sugar into fuel, generally suffers impairment as someone becomes obese, which in turn can lead to the person becoming more overweight. Faulty glucose metabolism also negatively affects brain physiology and is at the root of multiple medical conditions including diabetes and heart disease. In previous studies involving mice, Gombart and colleagues found that XN improved the animals' health and changed the composition of their microbiome, the latter leading them to suspect that the mix of microbes played a role in XN's healthful effects. "In this study, we fed mice either a diet low in calories, high in calories, or high in calories but supplemented with XN for 10 weeks," he said. "We found that only the conventional mice with XN supplementation showed improved glucose metabolism and that XN increased the relative abundance of three bacteria, Akkermansia muciniphila, Parabacteroides goldsteinii and Alistipes finegoldii." Gombart added that the study yielded some evidence that those three microbes are at least partially responsible for the health benefits associated with XN, but the entire microbial community may be playing a role as well. "We can't rule that out," he said. "We know that XN needs the intestinal microbiota to deliver its benefits, and there are complex diet-host-microbiota interactions that bring changes in both microbial composition and functional capacity. Diet is recognized as a major force in shaping gut microbe composition, and future studies will look for insights into the various interactions at play." Earlier mouse model studies by co-author Fred Stevens, professor of pharmaceutical sciences in the OSU College of Pharmacy and also a principal investigator at the Linus Pauling Institute , have shown that XN, a polyphenol found in hops' cones, has a number of anti-obesity properties. It improves cognitive function and it suppresses weight gain associated with a high-fat diet, fat accumulation in adipose tissue and insulin resistance. Insulin resistance is when cells don't respond well to the hormone that allows for the uptake of glucose from the bloodstream. It causes the pancreas to make more and more insulin to keep blood glucose levels within a non-harmful range and is a risk factor for non-alcoholic fatty liver disease.   Antioxidant protects neurons   University of Edinburgh   September 12 2021    Research involving a potent antioxidant, described in Scientific Reports, suggests that the compound could help protect cells in several conditions, including Parkinson's disease, multiple sclerosisand cell transplants. In their report, a team from the University of Edinburgh observe that the flavonoids quercetin and myricetin are among the most potent dietary antioxidants. Structural modification of myricetin has resulted in the development a new compound known as Proxison. In the current research, Proxison demonstrated 10 times the ability to protect against oxidative stress induced by the compound tert-Butyl hydroperoxide (tBHP) in neuroblastoma cells compared to quercetin, while several other antioxidants showed no effects. Proxison, as well as a high concentration of quercetin, also provided significant protection against cell death in tBHP-treated cells. Similar results were obtained in another neural cell line. An investigation of the antioxidants' ability to be taken up by the cells showed significant intracellular levels of quercetin and Proxison, and evidence for some localization of Proxison in the cells' mitochondria. In zebrafish embryos, Proxison helped protect against neuronal cell loss induced by a neurotoxic compound. Quercetin was also protective, but was less potent than Proxison. Neither therapy affected normal embryonic development. “This novel antioxidant can be applied to investigate oxidative stress in disease models, like alpha-synucleinopathies and other neurodegeneration models,” Nicola J. Drummond and colleagues conclude. “In addition, Proxison could have applications for regenerative medicine where oxidative stress has been implicated in poor cell survival of transplanted cells, with the advantage that the molecule can be pre-loaded into cells prior to transplantation. Proxison could also have applications for conditions, such as stroke or cardiac infarction, in which a temporary, but acute, exposure to oxidative stress is experienced, as well as diseases in which oxidative stress and mitochondrial dysfunction are core features.”

Commentary by Dr. Valentin Fuster

Commentary by Dr. Valentin Fuster

Clinical Significance of Micronutrient Supplementation in Critically Ill COVID-19 Patients with Severe ARDS  University Hospital Wuerzburg (Germany), June 12, 2021 Abstract The interplay between inflammation and oxidative stress is a vicious circle, potentially resulting in organ damage. Essential micronutrients such as selenium (Se) and zinc (Zn) support anti-oxidative defense systems and are commonly depleted in severe disease. This single-center retrospective study investigated micronutrient levels under Se and Zn supplementation in critically ill patients with COVID-19 induced acute respiratory distress syndrome (ARDS) and explored potential relationships with immunological and clinical parameters. According to intensive care unit (ICU) standard operating procedures, patients received 1.0 mg of intravenous Se daily on top of artificial nutrition, which contained various amounts of Se and Zn. Micronutrients, inflammatory cytokines, lymphocyte subsets and clinical data were extracted from the patient data management system on admission and after 10 to 14 days of treatment. Forty-six patients were screened for eligibility and 22 patients were included in the study. Twenty-one patients (95%) suffered from severe ARDS and 14 patients (64%) survived to ICU discharge. On admission, the majority of patients had low Se status biomarkers and Zn levels, along with elevated inflammatory parameters. Se supplementation significantly elevated Se (p = 0.027) and selenoprotein P levels (SELENOP; p = 0.016) to normal range. Accordingly, glutathione peroxidase 3 (GPx3) activity increased over time (p = 0.021). Se biomarkers, most notably SELENOP, were inversely correlated with CRP (rs = −0.495), PCT (rs = −0.413), IL-6 (rs = −0.429), IL-1β (rs = −0.440) and IL-10 (rs = −0.461). Positive associations were found for CD8+ T cells (rs = 0.636), NK cells (rs = 0.772), total IgG (rs = 0.493) and PaO2/FiO2ratios (rs = 0.504). In addition, survivors tended to have higher Se levels after 10 to 14 days compared to non-survivors (p = 0.075). Sufficient Se and Zn levels may potentially be of clinical significance for an adequate immune response in critically ill patients with severe COVID-19 ARDS.       Pilot Study of the Tart Cherry Juice for the Treatment of Insomnia and Investigation of Mechanisms Louisiana State University, June 20, 2021 Insomnia is common in the elderly and is associated with chronic disease, but use of hypnotics increases the incidence of falls. Montmorency tart cherry juice has improved insomnia by self-report questionnaire. Study Question:  Is insomnia confirmed by polysomnography and is tryptophan availability a potential mechanism for treating insomnia? Study Design:  A placebo-controlled balanced crossover study with subjects older than 50 years and insomnia were randomized to placebo (2 weeks) or cherry juice (2 weeks) (240 mL 2 times/d) separated by a 2-week washout. Measures and Outcomes:  Sleep was evaluated by polysomnography and 5 validated questionnaires. Serum indoleamine 2,3-dioxygenase (IDO), the kynurenine-to-tryptophan ratio, and prostaglandin E2 were measured. In vitro, Caco-2 cells were stimulated with interferon-gamma, and the ability of cherry juice procyanidin to inhibit IDO which degrades tryptophan and stimulates inflammation was measured. The content of procyanidin B-2 and other major anthocyanins in cherry juice were determined. Results:  Eleven subjects were randomized; 3 with sleep apnea were excluded and referred. The 8 completers with insomnia increased sleep time by 84 minutes on polysomnography (P = 0.0182) and sleep efficiency increased on the Pittsburgh Sleep Quality Index (P = 0.03). Other questionnaires showed no significant differences. The serum kynurenine-to-tryptophan ratio decreased, as did the level of prostaglandin E2 (both P < 0.05). In vitro, cherry juice procyanidin B-2 dose-dependently inhibited IDO. Conclusions:  Cherry juice increased sleep time and sleep efficiency. Cherry juice procyanidin B-2 inhibited IDO, increased tryptophan availability, reduced inflammation, and may be partially responsible for improvement in insomnia.         Many with migraines have vitamin deficiencies, says study   Cincinnati Children's Hospital, June 10, 2021    A high percentage of children, teens and young adults with migraines appear to have mild deficiencies in vitamin D, riboflavin and coenzyme Q10—a vitamin-like substance found in every cell of the body that is used to produce energy for cell growth and maintenance.   These deficiencies may be involved in patients who experience migraines, but that is unclear based on existing studies.   "Further studies are needed to elucidate whether vitamin supplementation is effective in migraine patients in general, and whether patients with mild deficiency are more likely to benefit from supplementation," says Suzanne Hagler, MD, a Headache Medicine fellow in the division of Neurology at Cincinnati Children's Hospital Medical Center and lead author of the study.   Dr. Hagler and colleagues at Cincinnati Children's conducted the study among patients at the Cincinnati Children's Headache Center. She will present her findings at 9:55 am Pacific time Friday, June 10, 2016 at the 58th Annual Scientific Meeting of the American Headache Society in San Diego.   Dr. Hagler's study drew from a database that included patients with migraines who, according to Headache Center practice, had baseline blood levels checked for vitamin D, riboflavin, coenzyme Q10 and folate, all of which were implicated in migraines, to some degree, by previous and sometimes conflicting studies. Many were put on preventive migraine medications and received vitamin supplementation, if levels were low. Because few received vitamins alone, the researchers were unable to determine vitamin effectiveness in preventing migraines.   She found that girls and young woman were more likely than boys and young men to have coenzyme Q10 deficiencies at baseline. Boys and young men were more likely to have vitamin D deficiency. It was unclear whether there were folate deficiencies. Patients with chronic migraines were more likely to have coenzyme Q10 and riboflavin deficiencies than those with episodic migraines.   Previous studies have indicated that certain vitamins and vitamin deficiencies may be important in the migraine process. Studies using vitamins to prevent migraines, however, have had conflicting success.     Research suggests mask-wearing can increase struggles with social anxiety University of Waterloo (Canada), June 21, 2021 People who struggle with social anxiety might experience increased distress related to mask-wearing during and even after the COVID-19 pandemic. A paper authored by researchers from the University of Waterloo's Department of Psychology and Centre for Mental Health Research and Treatment also has implications for those who haven't necessarily suffered from social anxiety in the past. "The adverse effects of the COVID-19 pandemic on mental health outcomes, including anxiety and depression, have been well-documented," said David Moscovitch, professor of clinical psychology and co-author of the paper. "However, little is known about effects of increased mask-wearing on social interactions, social anxiety, or overall mental health. "It is also possible that many people who didn't struggle with social anxiety before the pandemic may find themselves feeling more anxious than usual as we emerge out of the pandemic and into a more uncertain future -- especially within social situations where our social skills are rusty and the new rules for social engagement are yet to be written." Social anxiety is characterized by negative self-perception and fear that one's appearance or behaviour will fail to conform with social expectations and norms. Social anxiety disorder is an extreme manifestation that affects up to 13 per cent of the population.  The researchers reviewed existing literature addressing three factors that they hypothesized might contribute to social anxiety associated with mask-wearing: hypersensitivity to social norms, bias in the detection of social and emotional facial cues, and propensity for self-concealment as a form of safety behaviour. "We found that mask-wearing by people with social anxiety is likely to be influenced by their perception of social norms and expectations, which may or may not be consistent with public-health guidelines and can vary widely by region and context," said Sidney Saint, an undergraduate psychology student at Waterloo and lead author of the paper. The paper also highlights that people with social anxiety have difficulty detecting ambiguous social cues and are likely to interpret them negatively. These individuals also tend to worry about sounding incomprehensible or awkward. "We believe that both issues are likely to be magnified during interactions with masks," Saint said. Another highlighted impact is that masks can function as a type of self-concealment strategy that enables people with social anxiety to hide their self-perceived flaws. Therefore, the desire for self-concealment may motivate their use of masks over and above their desire to protect themselves from contagion. "Due to their self-concealing function, masks may be difficult for some people to discard even when mask-wearing is no longer required by public health mandates," Saint said.  In addition to contributing insights to guide clinicians toward effective assessment and treatment, the paper shows that people with social anxiety may be particularly vulnerable to periods of norm transitions where expectations for mask-wearing are in flux or become a matter of personal choice.       Going with your gut can result in better decision-making than using detailed data methods, study shows City University London, June 21, 2021 Managers who use their gut instinct together with simple decision-making strategies may make equally good, but faster, decisions as those who use data to reach an outcome, a new study has found. The report, co-authored by academics at the Business School (formerly Cass), King's Business School, and the University of Malta, finds that the reliance on data analysis in decision-making might be counterproductive as this reduces decision-making speed without ensuring more accuracy. The research, based on information from 122 advertising, digital, publishing, and software companies, finds that using data to inform decision making under high uncertainty is often not optimal. This may explain why 12 different publishers initially rejected the opportunity to publish "Harry Potter and the Philosopher's Stone' – because it had no data to inform its potential. A recent survey revealed that 92 percent of Fortune 1000 companies were reporting increased investment in data initiatives, although it appears this may not always be necessary. The authors asked managers how they made decisions on their most recent innovation project, including the extent to which they used data, instinct, and other simple heuristics (mental strategies). The findings outlined that among those decision-making methods were: Majority—choosing what the most people wanted Tallying—picking the choice with the greatest quantity of positive points Experience—selecting the option that the most experienced individual on the team wanted. Managers were asked whether they think they made the right decision and how fast they were in reaching that decision. Results showed that managers relied on their own instinct as much as data, using 'tallying' more than any other metric. Dr. Oguz A. Acar, Reader in Marketing at the Business School and co-author of the report, said: "This research shows that data-driven decision-making is not the panacea in all situations and may not result in increased accuracy when facing uncertainty. "Under extreme uncertainty, managers, particularly those with more experience, should trust the expertise and instincts that have propelled them to such a position. The nous developed over years as a leader can be a more effective than an analytical tool which, in situations of extreme uncertainty, could act as a hindrance rather than a driver of success." "Choosing among alternative new product development projects: The role of heuristics" is published in Psychology and Marketing.   Pretreatment by rosemary extract or cell transplantation improves memory deficits of Parkinson disease Damghan University (Iran) June 21 2021 According to news originating from Damghan, Iran, research stated, “The therapeutic effect of adipose tissue-derived stem cells (ADSCs) or RE on hippocampal neurogenesis and memory in Parkinsonian rats were investigated. Male rats were lesioned by bilateral intra-nigral injections of 6-OHDA and divided into six groups: 1. Lesion 2 and 3: RE and water groups were lesioned rats pretreated with RE or water, from 2weeks before neurotoxin injection and treated once a day for 8weeks post lesion. 4&5: Cell and alpha-MEM (alpha-minimal essential medium) received intravenous injection of BrdU-labeled ADSCs or medium, respectively from 10days post lesion until 8weeks later. 6: Sham was injected by saline instead of neurotoxin.” Our news journalists obtained a quote from the research from Damghan University, “Memory was assessed using Morris water Maze (MWM), one week before and at 1, 4 and 8weeks post 6-OHDA lesion. After the last probe, the animals were sacrificed and brain tissue obtained. Paraffin sections were stained using cresyl violet, anti-BrdU (Bromodeoxyuridine / 5-bromo-2'-deoxyuridine), anti-GFAP (Glial fibrillary acidic protein) and anti-TH antibodies. There was a significant difference of time spent in the target quadrant between groups during probe trial at 4 and 8 weeks' post-lesion. Cell and RE groups spent a significantly longer period in the target quadrant and had lower latency as compared with lesion. Treated groups have a significantly higher neuronal density in hippocampus compared to water, alpha-MEM and lesion groups. BrdU positive cells were presented in lesioned sites. The GFAP (Glial fibrillary acidic protein) positive cells were reduced in treated and sham groups compared to the water, alpha-MEM and lesion groups.” According to the news editors, the research concluded: “Oral administration of RE (Rosemary extract) or ADSCs injection could improve memory deficit in the Parkinsonian rat by neuroprotection.”     Inadequate vitamin D levels associated with interstitial lung disease Johns Hopkins University, June 20 2021.    An article appearing in the Journal of Nutrition documents a link between decreased vitamin D levels and a greater risk of early signs of interstitial lung disease (ILD), a group of disorders characterized by inflammation and scarring that can lead to lung damage. Although ILD can be caused by environmental and other factors, some cases have unknown causes. The investigation included 6,302 participants in the Multi-Ethnic Study of Atherosclerosis who had information available concerning their initial serum 25-hydroxyvitamin D concentrations and computed tomography (CT) imaging that included partial views of the lungs. Ten years after enrollment, 2,668 participants had full lung CT scans that were evaluated for presence of scar tissue and other abnormalities. Subjects who had deficient vitamin D levels of less than 20 ng/mL had more spots on their lungs that were suggestive of damage in comparison with subjects whose vitamin D was adequate. Among those who had full lung CT scans, deficient or intermediate (between 20-30 ng/mL) vitamin D levels were associated with a 50-60% greater risk of abnormalities suggestive of ILD. "We knew that the activated vitamin D hormone has anti-inflammatory properties and helps regulate the immune system, which goes awry in ILD," commented senior author Erin Michos, MD, MHS. “There was also evidence in the literature that vitamin D plays a role in obstructive lung diseases such as asthma and COPD, and we now found that the association exists with this scarring form of lung disease too." "Our study suggests that adequate levels of vitamin D may be important for lung health,” she concluded. “We might now consider adding vitamin D deficiency to the list of factors involved in disease processes, along with the known ILD risk factors such as environmental toxins and smoking.”

Commentary by Dr. Valentin Fuster

Should I quit drinking diet soda? And if so, how??? What gets Carolyn up in the morning, and the power of our gratitude practice, especially for health care workers.  LET’S TALK THE WALK! Wellness While Walking Facebook page Wellness While Walking on Instagram Wellness While Walking on Twitter Wellness While Walking website for show notes and other information wellnesswhilewalking@gmail.com   RESOURCES AND SOURCES (some links may be affiliate links) DIET SODAS AND ARTIFICIAL SWEETENERS Do Sweet Drinks Have Anything to Do With Dementia? foodpolitics.com Just How Bad is Diet Soda For You? clevelandclinic.org 21 Healthy, Low-Sugar Soda Alternatives That Make It Easy to Quit Color, eatthis.com Effects of Sweeteners on the Gut Microbiota: A Review of Experimental Studies and Clinical Trials, ncbi.nlm.nih.gov Diet Soda By Itself May Not Cause Weight Gain, Study Says, But Combining With Carbs Can, cnn.com Measuring Artificial Sweeteners Toxicity Using a Bioluminescent Bacterial Panel, ncbi.nlm.nih.gov Artificial Sweeteners: Sugar-Free, But at What Cost? health.harvard.edu Diet Soda Intake and Risk of Incident Metabolic Syndrome and Type 2 Diabetes in the Multi-Ethnic Study of Atherosclerosis, diabetesjournals.org Coca-Cola Discontinues TaB Diet Soda in the US, beveragedaily.com Stickk app  Habitica app  Pact app – (not recommended) LOVE OF LEARNING Character Strengths, VIACharacter.org Science of Well-Being (Yale) class, coursera.org GRATITUDE AND HEALTH CARE WORKERS Thanks! How Practicing Gratitude Can Make You Happier, Robert Emmons Improving Mental Health in Health Care Practitioners: Randomized Controlled Trial of a Gratitude Intervention, researchgate.net Improving Mental Health in Health Care Practitioners: Randomized Controlled Trial of a Gratitude Intervention, pubmed.ncbi.nlm.nih   DISCLAIMER Neither I nor most of my podcast guests are doctors or healthcare professionals of any kind, and nothing on this podcast or associated content should be considered medical advice. The information provided by Wellness While Walking Podcast and associated material, by Whole Life Workshop and by Bermuda Road Wellness LLC is for informational and entertainment purposes only. It is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment, and before undertaking a new health care regimen, including walking.     Thanks for listening to Wellness While Walking, a walking podcast.

There’s more than one way to measure how fast you’re ageing. There’s chronological age - the number of years you’ve been alive - and then there’s biological age, which you can think of as the total damage your body has accumulated over the years. Your chronological age may differ from your biological age, in which case it’s interesting to understand why. The good news is you can reduce your biological age by improving your lifestyle, which in turn can lengthen lifespan and healthspan. The question is, then, how to quantify biological age? On this podcast, NBT Scientific Director Megan Hall talks about PhenoAge: a measure of biological age that can be determined by analyzing a shortlist of common blood markers. We talk about why PhenoAge is important and valid as a reliable measure of biological status, and how you can get your PhenoAge score. Megan also offers tips for improving your PhenoAge once you’ve got your baseline. This episode has a ton of information, so be sure to follow along with Megan’s outline. Here’s the outline of this interview with Megan Hall: [00:00:25] Arden Pope, PhD; Studies on the effects of air pollution on human health. [00:01:15] Puppy update. [00:05:54] Is ageing a disease? Article: Bulterijs, Sven, et al. "It is time to classify biological aging as a disease." Frontiers in genetics 6 (2015): 205.   [00:06:35] Primary vs secondary ageing. [00:08:02] Book: Lifespan: Why We Age - and Why We Don't Have To, by David A. Sinclair PhD. [00:08:16] Ken Ford; STEM-Talk Podcast. Ken Ford on the NBT Podcast: Optimal Diet and Movement for Healthspan, Amplified Intelligence and More. [00:09:19] Measuring ageing. [00:13:09] Theories of ageing - more than 300 theories; Articles: Tosato, Matteo, et al. "The aging process and potential interventions to extend life expectancy." Clinical interventions in aging 2.3 (2007): 401. 2. da Costa, Joao Pinto, et al. "A synopsis on aging—Theories, mechanisms and future prospects." Ageing research reviews 29 (2016): 90-112. 3. Jin, Kunlin. "Modern biological theories of aging." Aging and disease 1.2 (2010): 72.  [00:13:34] Grandmother hypothesis; Podcast: The Postmenopausal Longevity Paradox and the Evolutionary Advantage of Our Grandmothering Life History, with Kristen Hawkes, PhD. [00:14:48] Program Theories and Damage Theories. [00:17:45] Epigenetic clock theory of aging; Steven Horvath; Study: Horvath, Steve, and Kenneth Raj. "DNA methylation-based biomarkers and the epigenetic clock theory of ageing." Nature Reviews Genetics 19.6 (2018): 371.  [00:19:02] Steven Horvath's TEDx talk: Epigenetic Clocks Help to Find Anti-Aging Treatments. [00:20:47] Book: Masters of Doom: How Two Guys Created an Empire and Transformed Pop Culture, by David Kushner. [00:21:43] DNA methylation; Article: Horvath, Steve. "DNA methylation age of human tissues and cell types." Genome biology 14.10 (2013): 3156. [00:23:13] Offspring of semi-supercentenarians have lower epigenetic age; Study: Horvath, Steve, et al. "Decreased epigenetic age of PBMCs from Italian semi-supercentenarians and their offspring." Aging (Albany NY) 7.12 (2015): 1159.  [00:23:36] Methylation based biological age associated with: 1.  breast cancer risk: Kresovich, Jacob K., et al. "Methylation-based biological age and breast cancer risk." JNCI: Journal of the National Cancer Institute 111.10 (2019): 1051-1058. 2. Frailty: Breitling, Lutz Philipp, et al. "Frailty is associated with the epigenetic clock but not with telomere length in a German cohort." Clinical epigenetics 8.1 (2016): 21; 3. All-cause mortality: Marioni, Riccardo E., et al. "DNA methylation age of blood predicts all-cause mortality in later life." Genome biology 16.1 (2015): 1-12 and Christiansen, Lene, et al. "DNA methylation age is associated with mortality in a longitudinal Danish twin study." Aging cell 15.1 (2016): 149-154. [00:24:46] PhenoAge as a biomarker of ageing for lifespan and healthspan; Study: Levine, Morgan E., et al. "An epigenetic biomarker of aging for lifespan and healthspan." Aging (Albany NY) 10.4 (2018): 573. [00:29:06] Nine blood markers that make up PhenoAge. [00:29:57] PhenoAge related to COVID-19; Study: Kuo, Chia-Ling, et al. "COVID-19 severity is predicted by earlier evidence of accelerated aging." medRxiv (2020).  [00:30:34] Combining PhenoAge with DNA methylation data as a predictor of mortality. [00:33:28] Episode 59 of HumanOS podcast: Are You Biologically Older or Younger Than Your Chronological Age? [00:33:58] Dr. Josh Turkett’s 4-quadrant model. [00:34:00] Lifestyle factors that accelerate ageing: Sleep: Li, Xiaoyu, et al. "Association between sleep disordered breathing and epigenetic age acceleration: Evidence from the Multi-Ethnic Study of Atherosclerosis." EBioMedicine 50 (2019): 387-394; Socioeconimic status, childhood and adult adversity: Liu, Zuyun, et al. "Associations of genetics, behaviors, and life course circumstances with a novel aging and healthspan measure: Evidence from the Health and Retirement Study." PLoS medicine 16.6 (2019): e1002827; Education: Zhao, Wei, et al. "Education and lifestyle factors are associated with DNA methylation clocks in older African Americans." International journal of environmental research and public health 16.17 (2019): 3141. [00:35:59] Protein; Podcast: Why You’re Probably Not Eating Enough Protein (How to Know for Sure), with Megan Hall. [00:36:50] Book: The Good Gut: Taking Control of Your Weight, Your Mood, and Your Long-term Health, by Justin Sonnenburg and Erica Sonnenburg. [00:37:23] Bloodsmart.ai. [00:38:35] Patreon: nbt.link [00:39:33] Age reversal possible in humans? Study: Fahy, Gregory M., et al. "Reversal of epigenetic aging and immunosenescent trends in humans." Aging cell 18.6 (2019): e13028.  [00:40:15] Simon Marshall, PhD. [00:41:00] Interpreting your blood markers to understand PhenoAge. [00:46:11] PhenoAge vs Predicted Age.

Commentary by Dr. Valentin Fuster

Medscape.com recently reported on the results of the Multi-Ethnic Study of Atherosclerosis (MESA) relative to, “high plasma levels of the kinds of fatty acids (omega 3) found in fish oil (EPA/ eicosapentaenoic acid & DHA/ docosahexaenoic) were associated with a lower long-term risk for new heart failure, whether with reduced or preserved ejection fraction, in a community-based cohort of more than 6,000 people.”

→ Join us on Patreon ← Dr. Peter Attia, MD is the founder of Attia Medical, PC, a medical practice that focuses on increasing healthspan by minimizing the risk of chronic disease and preserving quality of life. Peter trained for five years at Johns Hopkins in general surgery and then spent two years at NIH as a surgical oncology fellow.  He has since been mentored by some of the most experienced and innovative physicians and scientists in the US and Canada. On this podcast Dr. Tommy Wood, MD talks with Peter about the critical components of lifespan and healthspan, including the factors he has identified as most important. They also discuss the controversial role of statin medication and take a close look at the necessity and sufficiency of risk factors for atherosclerosis. If you want to learn more about Peter’s work, he has a blog, a podcast and an active social media presence. Here’s the outline of this interview with Peter Attia: [00:00:35] Mellow Johnny’s Bike Shop. [00:04:01] Eddy Merckx. [00:04:16] Healthspan. Video: Peter Attia - Reverse engineered approach to human longevity. [00:05:23] Components of healthspan: cognitive, physical, emotional. [00:07:21] Lewis Hamilton; Ayrton Senna. [00:08:35] Reverse engineering healthspan. [00:11:34] Strength, power, aerobic and anaerobic fitness, flexibility. [00:14:57] Injuries affecting healthspan. [00:16:27] Exercise dosing studies: Marshall, Simon J., et al. "Translating physical activity recommendations into a pedometer-based step goal: 3000 steps in 30 minutes." American journal of preventive medicine 36.5 (2009): 410-415; Merghani, Ahmed, Aneil Malhotra, and Sanjay Sharma. "The U-shaped relationship between exercise and cardiac morbidity." Trends in cardiovascular medicine 26.3 (2016): 232-240. [00:17:26] Atrial fibrillation; mitochondrial injury. [00:18:39] Study: Nakayama, Hiroyuki, and Kinya Otsu. "Mitochondrial DNA as an inflammatory mediator in cardiovascular diseases." Biochemical Journal 475.5 (2018): 839-852. [00:19:28] Functional threshold power (FTP). [00:23:58] Podcast: The High-Performance Athlete with Drs Tommy Wood and Andy Galpin. [00:23:59] Twin study: Bathgate, Katherine E., et al. "Muscle health and performance in monozygotic twins with 30 years of discordant exercise habits." European journal of applied physiology 118.10 (2018): 2097-2110. [00:24:50] The emotional component of healthspan. [00:24:56] The Drive Podcast: Paul Conti, M.D.: trauma, suicide, community, and self-compassion. [00:25:59] Dave Feldman; Podcast: How to Drop Your Cholesterol. [00:26:40] Sam Harris: Meditation. [00:29:30] Video: Commencement speech by David Foster Wallace from 2005 at Kenyon College, This is Water. [00:30:45] Vulnerability as a practitioner. [00:33:46] Time-restricted feeding. [00:34:23] Continuous glucose monitoring (CGM); Oura ring. [00:35:38] Factors contributing to longevity: deprivation of calories and rapamycin. [00:37:54] Benefits of fasting. [00:41:04] Free T3:Reverse T3 ratios during fasting. [00:42:50] Study: Finkelstein, Joel S., et al. "Gonadal steroids and body composition, strength, and sexual function in men." New England Journal of Medicine 369.11 (2013): 1011-1022. [00:43:30] Robert Lustig. [00:45:07] Multi-Ethnic Study of Atherosclerosis (MESA). [00:46:09] Statins; side effects. [00:48:36] Lipoprotein(a) - Lp(a). [00:49:19] Coronary Artery Calcium (CAC) scan. [00:54:03] The Drive podcasts: Dave Feldman, Ron Krauss, Tom Dayspring: (parts 1, 2, 3, 4, 5). [00:54:32] Risk factors for atherosclerosis: necessity and sufficiency. [00:56:16] Lead study: Lanphear, Bruce P., et al. "Low-level lead exposure and mortality in US adults: a population-based cohort study." The Lancet Public Health 3.4 (2018): e177-e184. [00:59:03] LDL cholesterol; ApoB. [01:01:15] Familial Hypercholesterolemia (FH). [01:04:41] Hyper-responders. [01:06:25] Saturated fat/cholesterol study: Jones, P. J., A. H. Lichtenstein, and E. J. Schaefer. "Interaction of dietary fat saturation and cholesterol level on cholesterol synthesis measured using deuterium incorporation." Journal of lipid research 35.6 (1994): 1093-1101. [01:09:43] Feldman Protocol. [01:11:48] The Drive podcast; peterattiamd.com.

Dr Paul Wang:   Welcome to the monthly podcast, On The Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor-in-chief, with some of the key highlights from this month's issue.                                 In our first paper, Ruairidh Martin and associates used ultra-high-density mapping to access the ventricular tachycardia circuit dependent upon re-entry, with scar regions in 36 tachycardias in 31 patients. The author has found that 11 of the ventricular tachycardia circuits and isthmuses were single-loop, and 25 were double-loop. Three had two entrances, five had two exits, and fifteen had dead-end activation. Isthmuses were defined by barriers which included anatomical obstacles, lines of block, and slow conduction in 27 out of 36 isthmuses. The barrier to conduction in isthmus appeared to be partially functional in 75% of circuits. Isthmus voltage is often higher in ventricular tachycardia than in sinus or paced rhythms. The authors found that conduction velocity in the VT isthmus slowed at the isthmus entrances and exits when compared with mid-isthmus. The mean conduction velocity was 0.08 meters per second in entrance zones, 0.29 meters per second in isthmus regions, p < 0.0001, and 0.11 meters per second in exit regions. P = 0.002.                                 In our next paper Daniel Duprez and associates found that plasma collagen biomarkers, particularly at elevated levels, were associated with excess risk of atrial fibrillation. In a stratified sample of the Multi-Ethnic Study of Atherosclerosis (MESA), initially age 45 to 84 years, the authors examined in 3,071 participants plasma Procollagen Type III N-Terminal Propeptide, also known as P3NP, which reflects collagen synthesis in degradation in Collagen Type I Carboxy-Terminal Telopeptide, also known as ICTP, which reflects collagen degradation at baseline. The authors aimed to determine if the levels of these biomarkers were associated with incident atrial fibrillation in participants initially free of overt cardiovascular disease. Incident atrial fibrillation in ten-year follow-up was based on a hospital ICD code for atrial fibrillation or atrial flutter, in or outpatient Medicare claims, or ECG ten years after baseline. The authors found that baseline levels of these markers were positively related, both p < 0.0001 to incident atrial fibrillation in a model adjusting for age, race, ethnicity, and sex. These findings were attenuated but remain statistically significant after further adjustment for systolic blood pressure, height, body mass index, smoking, and renal function.                                 In our next paper, Ahmet Adiyaman and associates conducted a randomized controlled trial comparing the safety and efficacy of minimally invasive thoracoscopic pulmonary vein isolation with left atrial appendage ligation versus percutaneous catheter ablation pulmonary vein isolation. In 52 patients with symptomatic paroxysmal or early persistent atrial fibrillation, paroxysmal atrial fibrillation was present in 74% of patients. The authors found that percutaneous pulmonary vein isolation with a 56% single procedure arrhythmia-free survival at two years was not inferior to minimally invasive thoracoscopic pulmonary vein isolation with left atrial appendage ligation, which had a 29% arrhythmia freedom, p = 0.059. Procedure-related major adverse events occurred in 21% of patients undergoing minimally invasive thoracoscopic pulmonary vein isolation, compared to none undergoing percutaneous catheter ablation with p = 0.029.                                 In the next paper, Richard Ang and associates examined whether the glucagon-like peptide-1 receptor agonist exendin 4 has an effect on ventricular action potential duration in susceptibility to ventricular arrhythmia in the rat heart in vivo and ex vivo. Ventricular monophasic action potentials recorded in anesthetized rats in vivo in isolated profused rat hearts in sinus rhythm and/or ventricular pacing. In vivo systemic administration of exendin 4 increased heart rate and this effect was abolished by beta adrenoceptor blockade. Despite causing sympathetic activation, exendin 4 increased axon potential duration at 90% repolarization, APD90, during ventricular pacing by 7% and reversed the effect of beta adrenoceptor agonist Dobutamine on APD90. In isolated profused hearts, 3 nanomolar exendin 4 increased APD90 by 14% with no effect on heart rate. Exendin 4 also reduced ventricular arrhythmia inducibility in conditions of beta adrenoceptor stimulation with Isoproterenol. Exendin 4 effects on action potential duration in ventricular arrhythmia susceptibility were prevented in conditions of muscarinic receptor blockade or inhibition of nitric oxide synthase. The authors concluded that glucagon-like peptide-1 receptor activation effectively reverses the effects of beta adrenoceptor stimulation on cardiac ventricular excitability and reduces ventricular arrhythmic potential. The effect of glucagon-like peptide-1 receptor activation on the ventricular myocardium is indirect, mediated by acetylcholine and nitric oxide, and, therefore, might be explained by stimulation of cardiac parasympathetic neurons.                                 In our next paper, Michael Barkagan and associates examined the role of modulating baseline impedance on ablation lesion dimension. Radiofrequency ablation was performed using an irrigated catheter at a fixed power setting of 30 watts 20 seconds and a multi-step impedance load from 100 to 210Ω ex vivo in 20 swine hearts and in vivo in the right atrium and in thigh preparations. Ablation was performed using similar power settings at three baseline impedances: low, 90 to 130Ω; intermediate, 131 to 180Ω; and high, 181 to 224Ω. The relationship between baseline impedance, current, and lesion dimensions were examined. Baseline impedance had a strong negative correlation with current squared for all of these experimental models with R either -0.93 or -0.94. Lesion dimensions at similar power setting were directly related to current squared with R = 0.853 for width and R = 0.814 for depth. In thigh muscle lesion depth was greatest at low impedance, 8.2 millimeters, compared to 6.5 millimeters and intermediate impedance and 4.2 millimeters at high impedance, p < 0.0001. In right atrial lines, low baseline impedance resulted in wider lines, 7.2 millimeters, relative to intermediate 5.8 millimeters and high impedance, 4.7 millimeters, p < 0.0001.                                 In the next study, Virginie Dubes and David Benoist and associates examined the origin of ventricular arrhythmias in animal model of repair of tetralogy of Fallot. They studied six piglets undergoing tetralogy of Fallot repair-like surgery compared to five sham-operated piglets. Twenty-three weeks post-surgery, the authors found that right ventricular dysfunction was present, while left ventricular function was preserved in tetralogy of Fallot pigs. Optical mapping showed longer action potential duration on the tetralogy of Fallot left ventricular epicardial and endocardium. Epicardial conduction velocity was significantly reduced in the longitudinal direction but not the transverse direction in tetralogy of Fallot ventricles compared to sham. Elevated collagen content was found in left ventricular basal and apical sections from the tetralogy of Fallot pigs. The tetralogy of Fallot left ventricles had a lower threshold for arrhythmia induction using incremental pacing protocols.                                 In our next study, Meera Varshneya and associates sought to understand the individual roles of slow and rapid delayed rectifier potassium currents, IKS and IKR, and quantify how effectively each stabilize the actions potential, protecting cells against arrhythmias across multiple species. The authors compared ten mathematical models describing ventricular myocytes from human, rabbit, canine, and guinea pig. They examined variability within heterogeneous cell population, tested the susceptibility of cells to a pro-rhythmic behavior, and studied how IKS and IKR responded to changes in the action potential. They found, one, models of higher baseline IKS exhibited less cell-to-cell variability in action potential duration; two, models with higher baseline IKS were less susceptible to early afterdepolarizations induced by depolarizing perturbations; three, as action potential durations lengthened, IKS increases more profoundly than IKR, thereby providing negative feedback that resists excessive action potential duration prolongation; and four, the increase in IKS that occurs during β-Adrenergic stimulation is critical for protecting cardiac myocytes from early afterdepolarizations under these conditions. The authors concluded that slow, delayed rectifier current is uniformly protected across a variety of cell types, suggesting that IKS enhancement could be potentially anti-arrhythmic.                                 In our final paper, Piotr Podziemski and Stef Zeemering and associates performed a direct one-to-one comparison between phase and activation time mapping in high-density epicardial direct contact mapping files of human atrial fibrillation. The authors examined 38 unipolar electrum files of ten seconds duration recorded in 20 patients with atrial fibrillation using a 16 x 16 electrode array placed on the epicardial surface of the left atrial posterior wall or right atrial free wall. Using sinusoidal recomposition and Hilbert Transform, 138 phase singularities were detected, with 104 out of 138 phase singularities detected within on electro distance, 1.5 millimeters, from a line of conduction block between non-rotating wave fronts determined by activation mapping. Only 18 rotating wave fronts were detected out of 8,219 detected waves based on wave mapping. Fourteen out of these 18 cases were detected as phase singularities in phase mapping. Phase analysis of filter electrograms produced by simulated wave fronts separated by conduction block also identified phase singularities on the line of conduction block. The authors found that phase singularities identified by phase analysis of filter epicardial electrograms colocalized with conduction block lines identified by activation mapping. The authors concluded that detection of phase singularity using phase analysis has a low specificity for identifying rotating wave fronts using activation mapping of human atrial fibrillation.                 That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time.

This podcast discusses the article "Coronary Artery Calcium Score for Long-term Risk Classification in Individuals With Type 2 Diabetes and Metabolic Syndrome From the Multi-Ethnic Study of Atherosclerosis." As the incidence of type 2 diabetes mellitus rises in the United States, understanding the cardioprotective effects of new drug classes will prepare you to better treat your patients. Learn how the classification of diabetes mellitus has changed from describing a homogenous group to a heterogeneous group and how that affects treatment.

In this episode Pete and Emmy talk about the allure and draw of artificalial sweeteners and why they are not as good a choice as we may have previously believed. Sweeteners are a broad class of non-nutritive compounds—things that taste like sugar but provide little or no calories and no nutrition. People who drink an artificially sweetened (diet) soda daily have a 36% greater chance of developing the metabolic syndrome and a whopping 67% increased risk of type 2 diabetes. BUT WHY? Maybe... Something Called “CPIR”: Some sweeteners elicit an insulin response.  This phenomenon is known as the cephalic phase insulin response (CPIR). It helps prepare the body for the inevitable carbohydrate load that comes with it.  The CPIR is simply the body’s way of releasing a little insulin in anticipation. There are countless sweeteners, but the main ones may cause a CPIR, including aspartame, and saccharin People who eat artificial sweeteners tend to eat more later (people think they can eat more fries because they are having a diet coke). People who eat artificial sweeteners tend to crave and eat higher sugar foods as well. (reinforces addiction) Stimulates hunger Your body expects calories but doesn't get them - wants caloriesI notice gum makes me hungry and if I have to chew I have to chew piece after piece or I will eatSalt on tongue seems to do the opposite for me Affect the gut microbiomeCreates a gut microbiome which makes it hard to lose weight Can be used in moderation healthily and likely better than things like corn syrup Many “more natural” products have added crap  Choose monk fruit, stevia but understand it’s still a processed food Ideas for reasonable us: in baked Keto desserts occasionally. In tea  or coffee occasionally but recognize addiction will not be kicked. Gum on airplane Recognize the importance of harm reduction (tea with monk fruit vs monster vs a bag of skittles). If diabetic stevia sweetened cookies vs refined sugar. If not Keto and if you have metabolic flexibility consider real maple syrup or honey. We do this with our kids. “There is an overwhelming amount of evidence that [artificial sweeteners] can be useful as a tool for weight management, when people are actually cognitively engaged in trying to lose weight … as part of a program or following a plan.” — John C. Peters, PhD, professor, chief of strategy and innovation, University of Colorado Anschutz Health and Wellness Center, Aurora   Nettleton JA, Lutsey PL, Wang Y, Lima JA, Michos ED, Jacobs DR, Jr.: Diet soda intake and risk of incident metabolic syndrome and type 2 diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA). Diabetes Care 2009, 32:688-694. http://www.insuliniq.com/3-not-so-sweet-insulin-effects-of-artificial-sweeteners/ http://time.com/4859012/artificial-sweeteners-weight-loss/ https://endocrinenews.endocrine.org/sweet-lowdown-artificial-sweeteners-weight-gain/

Dr Carolyn Lam:                Welcome to "Circulation On The Run," your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr. Carolyn Lam, Associate Editor, from the National Heart Center, and Duke National University of Singapore. Our featured paper today is so important for cardiac surgeons and their patients. It answers a question of whether targeting a higher versus a lower blood pressure during cardiopulmonary bypass helps to prevent cerebral injury. Curious? Well, more soon right after these summaries.                                                 In the first original paper this week, MicroRNA-22 is shown to be a novel mediator of vascular smooth muscle cell, phenotypic modulation, and neointima formation. Co-first authors, Drs. Yang and Chen, co-corresponding authors, Dr. Zhang from Zhejiang University and Dr. Xiao from Queen Mary University of London and their colleagues used wire injury mouse models to show that MicroRNA-22 controls vascular smooth muscle cell phenotype and injury-induced arterial remodeling by modulating multiple target genes, including methyl-CpG-binding protein 2, histone deacetylase 4, and ecotropic virus integration site 1 protein homolog.                                                 The authors observed that MicroRNA-22 expression was suppressed in human femoral arteries with atherosclerotic plaques, and that there was an inverse relationship between MicroRNA-22 and its target genes in healthy and diseased arteries. Furthermore, local delivery of MicroRNA-2 in the injured arteries prevented adverse arterial remodeling, thus suggesting that site-specific delivery of MicroRNA-22 mimics may be a potential therapy for in-stent restenosis.                                                 The next paper adds to our understanding of the pathobiology of pulmonary hypertension related to left-sided heart failure and importantly adds histomorphometric evidence from human lung specimens at autopsy or surgery.                                                 First author Dr. Fayyaz, corresponding author Dr. Redfield, and colleagues from the Mayo Clinic studied patients with heart failure with preserved or reduced ejection fraction and pulmonary hypertension and compared these to normal controls, as well as patients with primary pulmonary veno-occlusive disease.                                                 They found that patients with heart failure and pulmonary hypertension had global pulmonary vascular remodeling with thickening of the media and intima in arteries and thickening of the intima in veins and small pulmonary vessels compared to normal control subjects.                                                 This venous and small-vessel intimal thickening was more severe than the arterial intimal thickening in heart failure with a pattern that was similar to patients with pulmonary veno-occlusive disease. In fact, the severity of pulmonary hypertension correlated most strongly with venous and small vessel remodeling rather than arterial remodeling.                                                 These findings expand our understanding of the pathobiology of pulmonary hypertension in heart failure. It also suggests that pulmonary venous remodeling in heart failure may predispose to worsening alveolar edema with pulmonary vasodilators as in primary pulmonary veno-occlusive diseases.                                                 Are there sex and race differences in the lifetime risk of HFpEF versus HFrEF? First author Dr. Pandey, corresponding author Dr. Berry from UT Southwestern Medical Center, and their colleagues used participant level data from two large respective cohort studies, the Cardiovascular Health Study, and the Multi-Ethnic Study of Atherosclerosis to determine remaining lifetime risk estimates for heart failure with preserved and reduced ejection fraction at different index ages.                                                 They found that compared to women, men have a higher lifetime risk of HFrEF, heart failure reduced ejection fraction with a similar lifetime risk of HFpEF, or heart failure preserved ejection fraction. Compared with blacks, non-blacks have a similar lifetime risk of developing HFrEF but a higher risk of HFpEF.                                                 Lifetime risks of HFpEF and HFrEF were similar and substantially higher in those with versus without antecedent myocardial infarction.                                                 In summary, these findings provide novel insights on sex and race differences in the lifetime risks of HFpEF and HFrEF, and may help health policymakers in appropriate resource allocation for targeting HFpEF and HFrEF specific preventive therapies at the at-risk population.                                                 What are evidence-based blood pressure targets during pediatric cardiopulmonary resuscitation? Well, first and corresponding author Dr. Berg from Children's Hospital of Philadelphia and his colleagues studied a multi-center population of children with invasive arterial blood pressure monitoring during in-hospital ICU cardiac arrest, and the Collaborative Pediatric Critical Care Research Network Intensive Care Units, between 2013 and 2016.                                                 They found that a mean diastolic blood pressure greater or equal to 25 millimeters of mercury during cardiopulmonary resuscitation in infants, and greater or equal to 30 millimeters of mercury in children 1 year old or greater, was associated with a 70% greater likelihood of survival to hospital discharge, and a 60% higher likelihood of survival with a favorable neurologic outcome.                                                 On the other hand, survival rates were markedly lower with mean diastolic pressures less than 20 in infants and less than 25 in children 1 year or older. Thus, clinicians should consider targeting diastolic blood pressure of 25 or greater in infants, and 30 or greater in children 1 year old or older during cardiopulmonary resuscitation when invasive arterial blood pressure is monitored.                                                 That wraps up our summaries for this week. Now for our featured discussion.                                                 Does a higher versus a lower blood pressure target during cardiopulmonary bypass surgery reduce the risk of cerebral injury? Well, the feature paper today provides some answers, and we have the first and corresponding author, Dr. Anne Vedel from University of Copenhagen with us today, as well as our associate editor, Dr. Timothy Gardner, who's a cardiac surgeon from University of Pennsylvania.                                                 Thank you so much for being with us today and this was a terrific trial, a very difficult trial to carry out. Could you please tell us a bit more about it? Dr Anne Vedel:                 Cerebral injury is an important complication after cardiac surgery with the use of cardiopulmonary bypass. Up to half of our patients suffer these perioperative silent strokes. Therefore, in Copenhagen we conducted a trial investigating the importance of two distinct blood pressure levels during cardiopulmonary bypass. Now, on this subject of optimal perfusion strategy during bypass, there are many opinions, but also a stunning lack of convincing evidence, for instance, when it comes to blood pressure management.                                                 Now, the question is whether normal physiological principles, such as cerebral autoregulation therapy, whether they apply during bypass, or if perfusion pressure indeed does play a less important role when blood flow is mechanically provided in an uncomplicated and sufficient way by the heart and lung machine.                                                 So, in a patient on the assessor-blinded randomized trial, we allocated patients to a higher or a lower MAP target, 70 to 80, or 40 to 50 millimeters of mercury, respectively, by titrating intravenous norepinephrine during bypass.                                                 Pump flow levels were set at 2.4 liters per minute per square meter of body surface, and our primary outcome was the total volume of new ischemic cerebral lesions, expressed as a baseline MRI, and opposed to the difference between the baseline MRI and the postop MRI on day three to six. Secondary outcomes were a number of new ischemic lesions and newer psychological test evaluations.                                                 Now among the 197 patients enrolled who were scheduled for coronary artery bypass, or heart valve repair surgery, or a combination of both, we found that 53% of patients in the low target group as opposed to 56 in the high target group had new cerebral lesions on their postop cerebral MRI.                                                 The primary outcome of volume of new cerebral lesions was comparable between groups, and so was the total number of newer lesions. No significant difference was observed in stroke rates in frequencies of postoperative cognitive dysfunction, or in severe adverse event rate.                                                 Therefore, we concluded that among patients undergoing on-pump cardiac surgery, targeting higher versus a lower mean arterial pressure did not seem to affect the volume or number of new infarcts. Dr Carolyn Lam:                Wow, thank you so much, Anne. Tim, you think about these issues a lot more than I do as a non-surgeon. Could you tell me what your insights were? Dr Tim Gardner:                You know, it's a very difficult study to do a randomized control trial in this environment, and they're really to be congratulated for doing it. As Anne acknowledges, this is not an area where randomized trials are very frequent.                                                 The first thing about the trial, I think, is a growing awareness among all of us that there seems to be a lot of imaging evidence of what we call injury or changes based on diffusion-weighted imaging in patients after cardiopulmonary bypass. This is not the first study that shows that.                                                 But the question is are these incidental, trivial lesions? I'd have to, again, ask Anne to clarify how many of the patients in either group, what percentage had what we would consider evidence of overt strokes? Dr Anne Vedel:                 Well, overt strokes, as opposed to silent strokes, 1 patient in the lower target group had stroke and 6 patients in the high target group, which corresponds to 1 as opposed to 7%. Dr Tim Gardner:                That was not quite statistically significant difference but headed in that direction with the assumption that if you have a larger sample size there might be, in fact, some association with overt stroke using the high target vasopressor approach, is that right? Dr Anne Vedel:                 We can only speculate. But as you do, yes, I agree. Dr Tim Gardner:                To go back to the original question, the significance of these, well, you were referring to as silent strokes. Can you comment on the clinical significance there? We hear of silent heart attack. What is a silent stroke and what are the implications of that long term for patients? Dr Anne Vedel:                 In other fields of research on the silent strokes, it's been shown that they correlate to both frequency of postoperative cognitive dysfunction and also later development of mild cognitive impairment and dementia. But these kinds of results, there isn't enough research in the field of cardiac study for us to say the same. But those are the implications from other research fields. Dr Tim Gardner:                But you can understand from the perspective of a cardiac surgeon, and this concern has been expressed and talked about in the literature for 20 years or more, the possibility that even what seems to be, with no injury apparent and no overt stroke, there may be some neurological consequence to cardiopulmonary bypass.                                                 So just to move on from that because I agree that we just don't have any reliable information that these silent strokes result in late or permanent injury, I think again the finding that manipulating the blood pressure, which seems to be intuitively beneficial in patients, especially elder patients, did not, in fact, show any benefit and, in fact, may have been associated with a slight increase in overt stroke. Is that a fair conclusion from your study? A summary of your study? Dr Anne Vedel:                 I would say it is a fair conclusion, and surprisingly so. The question is whether it is the blood pressure or the means that we apply to have this increase in blood pressure that is the point of interest here. Dr Tim Gardner:                You mean whether, in fact, using the norepinephrine, the vasoconstrictor, to increase the blood pressure whether that itself, it certainly didn't benefit, it may have been a problem. Dr Anne Vedel:                 Exactly. That's what I speculate might be the case. But I also think it's fair to say at this point that this is somewhat artificial physiological scenario, the cardiopulmonary bypass. Dr Tim Gardner:                I agree with that, that you're controlling blood flow and the patient is exposed to a lower hemoglobin and oxygen-carrying capacity and so on. But I think what struck me about your findings, or strikes me about your findings, is what appears to be in many of the patients, the low target patients, pretty effective autoregulation of the cerebral circulation, despite the artificiality of cardiopulmonary bypass.                                                 I think that's, again, something that has been not well known or well accepted by many people, thinking that if you lower body temperature, you lower hemoglobin, autoregulation may not be enough to maintain good cerebral perfusion. It looks like this study shows that in these patients, autoregulation worked fine. Is that fair? Dr Anne Vedel:                 Yes. Or sufficient blood flow was delivered. All in all, what's new in our study, I think, is that hypertension per se shouldn't necessarily be considered a proxy for hyperperfusion during bypass. Dr Tim Gardner:                Yeah, that's a very good qualification. So none of your patients, despite being in their mid to late 60s had evidence of carotid artery disease or whatever? Those patients were excluded from the trial, is that right? Dr Anne Vedel:                 No, that's not correct. We didn't screen for carotid artery disease because we don't routinely do that in our institution. As we describe in our discussion, we included quite a heterogeneous study sample by enrolling the patients that came to us. We didn't screen and we didn't exclude these patients that you mention. Dr Tim Gardner:                Do you know how does your group handle a patient that is known to have carotid artery disease, comes in with a known either prior endarterectomy or established disease? Do those patients, are they treated any differently either as a result of the study or just in general?                                                 Because that is a targeted group of patients, at least in my own experience, that we would be more concerned about allowing autoregulation to be the determinant, feeling that if there is a fixed stenosis in the carotid artery that we might need to increase the mean arterial pressure. Dr Anne Vedel:                 I can certainly understand your point and, of course, it is a concern in our center, as well. But having said that, there were no patients in the PPCI trial that came to us with a history of carotid artery disease, so it wasn't a concern for us in this study. Dr Tim Gardner:                That would be one point that I would make that we probably should pay attention to patients who do come for surgery and have known significant obstructive extracranial disease, but I understand that you didn't specifically have those patients or were aware of those patients.                                                 I think that this is a very useful study for us concerned about the possibility of inducing cerebral injury with cardiopulmonary bypass. To some people it's sort of counterintuitive that increasing perfusion pressure didn't improve the tolerance of patients to cardiopulmonary bypass but that's why you did the study. I think it's a very notable and important report that's going to be in circulation.                                                 The significance of these "silent infarcts" is merely something that we have to sort of sort out. I know you said that silent infarcts, as I agree, are associated with or presumed to be predictive of later cognitive dysfunction, dementia and so on. It really is a concerning message if that's the main message that comes out of these imaging studies. Because these are patients that, obviously, didn't have heart surgery for no reason, there was obviously a compelling indication for patients to have it.                                                 You would hate to re-ignite this concern as we had in and around year 2000 when the group at Duke was talking about writing about patients who had cognitive decline after cardiac surgery, were going to end up being demented five or 10 years down the line, so, that's from the perspective of a cardiac surgeon. Let's stick with the evidence but let's follow-up and see how predictive these silent infarcts are and what the consequences are long term. Do you think that's fair, Anne? Am I making a fair statement? Dr Anne Vedel:                 I absolutely do think it's fair. And for a cardiac surgeon as yourself, I would find it very interesting to see that these kind of studies are also conducted in TAVR patients where you have sometimes a 200% incidence of these silent strokes.                                                 I mean you have a good taste as a cardiac surgeon if you only see them in 50% of your patients, understand me correctly, but I don't necessarily think that this high incidence, it's high, yes, but compared to other patient groups, such as TAVR patients, it's not necessarily that bad. Dr Tim Gardner:                Right. Anne, I don't know whether you've seen the editorial that's going to accompany your paper, but it's very good. It's very supportive of your study and has some good comments. You'll be pleased with the editorial, I believe, if you haven't seen it. Dr Anne Vedel:                 Thank you very much. I'm happy to hear that. I know we do things a bit controversially over here in Copenhagen, compared to many centers in the U.S. Dr Tim Gardner:                That is not what the editorialists think. An anesthesiologist from Stanford and a neurologist from Penn, they have a very good commentary on your study and the whole field, so you'll be pleased. Anne Vedel:                       I'm very happy to hear that. Thank you. Carolyn Lam:      Well, listeners, I'm sure you learned a lot. Thank you for joining us today, and don't forget to tune in again next week.

Host: Jennifer Caudle, DO Guest: Karol Watson, MD, PhD Under the 2017 Hypertension Guidelines, 46 percent of U.S. adults have high blood pressure which is up from 32 percent under the old benchmark. This interview covers the key information physicians need to know from the new guidelines in order to improve blood pressure control rates. Host Dr. Jennifer Caudle is joined by Dr. Karol Watson, an attending cardiologist and a Professor of Medicine/Cardiology at the David Geffen School of Medicine at UCLA. Dr. Watson is a principal investigator for several large National Institutes of Health research studies, including the Diabetes Prevention Program Outcomes Study and the Multi-Ethnic Study of Atherosclerosis. She reacts to the new guidelines and reflects on what these changes could mean to patients. The American Medical Association's M.A.P. framework and blood pressure improvement program is dedicated to helping health care providers improve blood pressure control in their adult patient populations, and a new AMA resource can help you succeed in Medicare's Merit-Based Incentive Payment System (MIPS) while you manage and treat high blood pressure. This resource outlines the different measures that relate to hypertension management in each MIPS performance category, potential MIPS score results, and related AMA resources that can help you improve the health of …

Host: Jennifer Caudle, DO Guest: Karol Watson, MD, PhD Under the 2017 Hypertension Guidelines, 46 percent of U.S. adults have high blood pressure which is up from 32 percent under the old benchmark. This interview covers the key information physicians need to know from the new guidelines in order to improve blood pressure control rates. Host Dr. Jennifer Caudle is joined by Dr. Karol Watson, an attending cardiologist and a Professor of Medicine/Cardiology at the David Geffen School of Medicine at UCLA. Dr. Watson is a principal investigator for several large National Institutes of Health research studies, including the Diabetes Prevention Program Outcomes Study and the Multi-Ethnic Study of Atherosclerosis. She reacts to the new guidelines and reflects on what these changes could mean to patients. The American Medical Association's M.A.P. framework and blood pressure improvement program is dedicated to helping health care providers improve blood pressure control in their adult patient populations, and a new AMA resource can help you succeed in Medicare’s Merit-Based Incentive Payment System (MIPS) while you manage and treat high blood pressure. This resource outlines the different measures that relate to hypertension management in each MIPS performance category, potential MIPS score results, and related AMA resources that can help you improve the health of ...

Host: Jennifer Caudle, DO Guest: Karol Watson, MD, PhD Under the 2017 Hypertension Guidelines, 46 percent of U.S. adults have high blood pressure which is up from 32 percent under the old benchmark. This interview covers the key information physicians need to know from the new guidelines in order to improve blood pressure control rates. Host Dr. Jennifer Caudle is joined by Dr. Karol Watson, an attending cardiologist and a Professor of Medicine/Cardiology at the David Geffen School of Medicine at UCLA. Dr. Watson is a principal investigator for several large National Institutes of Health research studies, including the Diabetes Prevention Program Outcomes Study and the Multi-Ethnic Study of Atherosclerosis. She reacts to the new guidelines and reflects on what these changes could mean to patients. The American Medical Association's M.A.P. framework and blood pressure improvement program is dedicated to helping health care providers improve blood pressure control in their adult patient populations, and a new AMA resource can help you succeed in Medicare’s Merit-Based Incentive Payment System (MIPS) while you manage and treat high blood pressure. This resource outlines the different measures that relate to hypertension management in each MIPS performance category, potential MIPS score results, and related AMA resources that can help you improve the health of ...

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

On this week's show, we discuss some of the latest research and findings in our News & Views segment. Our stories are about how the soda industry plays politics to advance its agenda, whether salt is good or bad in the human diet, and whether calcium supplements pose a heart-health risk. The Moment of Paleo segment offers ideas about how we can think about areas of our lives, by analogy, based on what we know about whole foods vs. processed foods and supplements. In the After the Bell segment a truly thought-provoking talk about how we create ourselves with our thoughts. Links for this episode:This Episode's Homepage on latestinpaleo.comLatest in Paleo on Facebook — Leave a Comment About this Episode or Post a News LinkThe Latest in Paleo Health News TickerFood & Product RecommendationsThe Paleo Answer - Loren CordainThe End of Dieting - Dr. Joel FuhrmanMore Book & Audiobook RecommendationsSponsorship of National Health Organizations by Two Major Soda Companies - American Journal of Preventive MedicineCoke and Pepsi Give Millions to Public Health, Then Lobby Against It - The New York TimesBig soda is buying off big health orgs to keep profits and Americans fat | Ars TechnicaPepsi gets aggressive on cutting sugar from its drinks - Oct. 17, 2016Sodium Intake and All-Cause Mortality Over 20 Years in the Trials of Hypertension Prevention. - PubMed - NCBIHold the salt this Thanksgiving for a longer life: study | CTV NewsLowering Salt Intake Reduces Mortality, Study Confirms - Renal and Urology NewsMore Research Cites Salt's Potential Health RisksCalcium Intake From Diet and Supplements and the Risk of Coronary Artery Calcification and its Progression Among Older Adults: 10?Year Follow?up of the Multi?Ethnic Study of Atherosclerosis (MESA)Calcium Supplements May Damage the Heart - 10/11/2016Calcium supplements could increase risk of heart disease, new study finds - The Washington PostStudy: Calcium Supplements Actually Increases Risk of Heart Disease - NBC NewsIsaac Lidsky: What reality are you creating for yourself? | TED Talk | TED.com