Podcasts about nos3

MTHFR is closely tied to heart disease, and nitric oxide (not to be confused with nitrous oxide, or laughing gas) is a big part of the reason why. In this episode we'll talk about: How nitric oxide is linked to heart attacks, strokes, alzheimers, sinus health, mouth breathing, and even some birth defects. Why humming matters How the NOS3 gene affects you and how it interacts with MTHFR How you can boost your nitric oxide production - with or without these genes. For the complete show notes, click here. If you want to be a Genetic Rockstar and join the MTHFR community, click here. If you heard be talk about the FREE MTHFR Basics course and want in, click here. --- Send in a voice message: https://anchor.fm/tohealthwiththat/message

@michaelsalzle. GST, NOS3, and PEMT

This week's episode features special Guest Host Mercedes Carnethon, as she interviews author Miriam Cortese-Krott and Associate Editor Charles Lowenstein as they discuss the article "Red Blood Cell and Endothelial eNOS Independently Regulate Circulating Nitric Oxide Metabolites and Blood Pressure." Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast, summary, and backstage pass to the journal and its editors. We're your co-host I'm Dr. Carolyn Lam, associate editor from The National Heart Center in Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, associate editor, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Carolyn Lam: Greg, today's feature paper is one of those really, really landmark papers that really advance our understanding of Nitric oxide signaling. And it's about red blood cell and Endothelial eNOS, and how they independently regulate circulating nitric oxide, metabolites, and blood pressure. A real, real must, but let's go on and look at the other papers in this issue first. Greg, you want to go first? Dr. Greg Hundley: You bet, Carolyn. Better grab a cup of coffee. And my first paper is from professor Nathan Mewton from Hôpital Louis Pradel Hospices Civils de Lyon. Carolyn, these authors hypothesized that Colchicine a potent anti-inflammatory agent may reduce infarct size in left ventricular remodeling at the acute phase of STEMI. And so to address this hypothesis, they performed a double-blind multi-center trial and randomly assigned patients admitted for a first episode of STEMI referred for primary PTCA to receive oral Colchicine two-milligram loading dose followed by 0.5 milligrams twice a day, or matching placebo from admission to day five and the primary efficacy outcome was infarct size determined by cardiovascular magnetic resonance imaging at five days. And the relative left ventricular end-diastolic volume change at three months and infarct size at three months was also assessed by cardiac MRI. And these were secondary outcomes. Dr. Carolyn Lam: Nice. Okay. So what were the results? Dr. Greg Hundley: Right, Carolyn. So 192 patients were enrolled. 101 in the Colchicine group and 91 in the controls. And as a result of this trial, the oral administration of high dose Colchicine at the time of Reperfusion. And for five days thereafter did not reduce infarct size assessed by cardiac MRI. And so Carolyn, the clinical implications of these results suggest that other studies exploring the timing, pharma kinetics, and dose-response of Colchicine, as well as other anti-inflammatory agents are needed to identify an effective method to reduce infarct size and limit remodeling in this group of patients. Dr. Carolyn Lam: Wow, it's just such a rich field done with all this about Colchicine. Well, our next paper is a pre-specified sub-analysis of the randomized EAST-AFNET 4 Trial and the sub-analysis assess the effect of systematic early rhythm control therapy that is using Antiarrhythmic drugs or catheter ablation compared to usual care, which means allowing rhythm control therapy to improve symptoms in patients with heart failure. And this was defined in the sub-analysis as the presence of heart failure symptoms of New York Heart Association status two to three or a left ventricular ejection fraction of less than 50%. Dr. Carolyn Lam: Now, the authors led by Dr. Kirchhof at University Heart and Vascular Center UKE in Hamburg, Germany included 798 patients in this sub-analysis of whom 442 had HFpEF, 211 had heart failure with mid-range ejection fraction and 132 had HF-rEF over a median of 5.1 years of follow-up the composite primary outcome of cardiovascular death stroke or hospitalization for worsening heart failure, or for acute coronary syndrome occurred less often in patients randomized to early rhythm control therapy compared with patients randomized to usual care. And this was not altered by heart failure status with an interaction P-value of 0.6. Left ventricular function, symptoms, and quality of life improved equally in both treatment strategies. Dr. Greg Hundley: Wow, Carolyn, a lot of information here. So what can we take away from this? Dr. Carolyn Lam: Well, let's remember that this is a sub-analysis, albeit pre-specified of that randomized trial of the EAST-AFNET 4 Trial, but nonetheless, the data supports a treatment strategy of rhythm control therapy with Antiarrhythmic drugs or ablation within a year of diagnosing atrial fibrillation in patients with signs and symptoms of heart failure to reduce cardiovascular outcomes. Dr. Greg Hundley: Very nice, Carolyn. So, Carolyn, my next paper pertains to Alarmin Interleukin-1 Alpha, and it comes to us from Dr. Thimoteus Speer at Saarland University. So, Carolyn, Alarmin Interleukin-1 Alpha is expressed in a variety of cell types, promoting sterile systemic inflammation. And the aim of the present study was to examine the role of Alarmin Interleukin-1 Alpha in mediating inflammation in the setting of acute myocardial infarction and chronic kidney disease. Dr. Carolyn Lam: Wow, sterile inflammation. It's a really hot topic now. So what did these authors find? Dr. Greg Hundley: Right, Carolyn. So we're going to call Alarmin Interleukin-1 Alpha. Let's just call it IL-1 Alpha and so increased IL-1 Alpha surface expression on monocytes from patients with acute myocardial infarction in patients with chronic kidney disease was found to be associated with cardiovascular events. Next, IL-1 Alphas itself served as an adhesion molecule, mediating leukocyte-endothelial adhesion, and finally, abrogation of IL-1 alpha prevented inflammation after myocardial infarction and ameliorated chronic kidney disease in Vivo. Dr. Carolyn Lam: Wow. So what does this mean clinically? Dr. Greg Hundley: Right, Carolyn, so perhaps targeted therapeutic inhibition of IL-1 Alpha might represent a novel anti-inflammatory treatment strategy in patients with myocardial infarction and in patients with chronic kidney disease. Dr. Carolyn Lam: Amazing. Thanks, Greg. Well, in today's issue, there's also an exchange of letters between doctors Lother and Filippatos on Finerenone and risk of hyperkalemia in CKD and type two diabetes. There's an On My Mind paper by Dr. Sattler on the single-cell immunology and cardiovascular METs in, do we know yet what we don't know? Dr. Greg Hundley: And then Carolyn, from the mailbag, a Research Letter from Professor Wehrens entitled “Atrial Specific LK Beta One Knockdown Represents a Novel Mouse Model of Atrial Cardiomyopathy with Spontaneous Atrial Fibrillation.” Well, Carolyn, how about we turn our attention to those red blood cells and endothelial nitric oxide synthase. Dr. Carolyn Lam: Yeah. Can't wait. Dr. Mercedes Carnethon: Well, welcome to this episode of Circulation on the Run. Our podcasts, where we have an opportunity to speak with authors of important papers that are appearing in the journal of circulation. I'm pleased to introduce myself. My name is Mercedes Carnethon, professor and vice-chair of preventive medicine at the Northwestern University Feinberg School of Medicine. And I'm pleased today to invite our guest author, Miriam Cortese-Krott, who is the faculty of the University of Duesseldorf, and a guest professor at the Karolinska Institute in Stockholm. And we have with us as well the other associate editor who handled the piece for circulation, Dr. Charlie Lowenstein from Johns Hopkins University. So welcome to each of you this morning. Miriam Cortese-krott: Thank you. Dr. Charles Lowenstein : Thanks for having me. Dr. Mercedes Carnethon: Well, thank you. I'm really excited to jump right into this piece, Miriam, can you tell me a little bit about the rationale for carrying out the study, why you pursued it? Professor Miriam Cortese-Krott: The reason is because when I was working as a post-doc, I had to isolate an enzyme from red blood cells, which is a very, very difficult. And if you know, this enzyme is endothelial nitric oxide synthase, which produce nitric oxide, and actually, the red blood cell is full of the worst enemy of nitric oxide, which is hemoglobin. So actually, when I was talking about my project, everybody was asking, "Why are you doing that?" And I was actually able to isolate the enzyme and look at activity and be sure that the enzyme was fine, but the function of this enzyme was absolutely unknown. Professor Miriam Cortese-Krott: And the only way to study proteins in red blood cells is to make modification in the bone marrow of the mice. So in the Erythroid cells, because you can not, of course, if there are cells without nucleus you don't have any chance to modify them in culture, something like that. So the only way was to generate mice with modification specifically in the red blood cells. And I had the chance to create, to generate red cell-specific eNOS knockout mice. And of course, as a control endothelial-specific eNOS knockout mice by using the Cre-loxP technology. And with this technology, I could really understand what's happening to the physiology of the mouse if you remove this protein from the red blood cells. And so this was the whole idea. Dr. Mercedes Carnethon: Thank you so much. It was really exciting for me to read this piece. We are on opposite ends of the scientific inquiry spread as I'm an epidemiologist who does things at the population level, and you're identifying things at the basic science level. I thought the paper was extremely well-written and that encouraged people to dig in, even if you're unfamiliar, and in part that's because you provided such a great explanation of how your findings are used and how they're relevant to the process. Do you mind sharing a little bit about your findings and how you expect that they will be used by our scientific community? Professor Miriam Cortese-Krott: I think the main finding of this paper is that if you remove eNOS from the red blood cells if the mice are hypertensive, have hypertension, and this is completely something that you actually will not expect, as I told you that indeed red cells are full of the enemy of nitric oxide that remove it immediately. So you can ask yourself how it is possible. But I think the key finding here in this paper was that I also generated the opposite model. So I created the model a conditional eNOS Knockout model where you can decide in which tissue you want to have your enzyme. And of course, I applied for red blood cells. And what you see in this model is that you start from a global knockout mouse with hypertension, you reintroduce the eNOS just in the red blood cells, you have normal tension. So this means, this is the main finding. You have a switch in the red blood cells, which is the enzyme eNOS, which it's behaving in a completely different way clearly as compared to the vessel wall eNOS and still regulating blood pressure. Dr. Mercedes Carnethon: Well, thank you so much. I think this is the point at which I like to turn to the associate editor who handled the piece. Charlie, you and I don't get to talk as often given the diversity of work that we each pursue, but Charlie, tell me a little bit about what excited you about this piece? Dr. Charles Lowenstein: Thanks, Mercedes. So I love this piece. I thought Miriam, your article is so great. So a couple of thoughts. One is nitric oxide and nitric oxide synthase are so important in biology and medicine, nitric oxide regulates blood pressure. It regulates neurotransmission. It regulates inflammation. And this is true, not only in the lab, looking at cells in mice, but also in the human. So genetic variance in the endothelial nitric oxide synthase gene or NOS3 are associated with risks for diseases like coronary artery disease. So eNOS is just so important in biology and medicine. And now some ancient history. When I was a cardiology fellow, about a hundred years ago, I worked in the lab that first purified nitric oxide synthase proteins, and we cloned two of the nitric oxide synthase genes that was in the lab of Dr. Solomon Snyder at Johns Hopkins back in the 1700s. Dr. Charles Lowenstein: So when we cloned the nitric oxide synthase genes, when we and others did, we made a huge mistake. We chose the names for these isoforms from the tissue where they were first isolated. So we called the brain nitric oxide synthase nNOS, because it's a neurons, macrophages MCnos we called it MCnos and in endothelial cells, we called it the nitric oxide synthase eNOS or endothelial NOS. But in the last 20 years, lots of investigators have found these isoforms are in other cells, not just the original cells at discovery. And so Miriam's question is just so important, which cells make endothelial NOS also called NOS3. That's the history. Now what Miriam has discovered is just so important. I was so fascinated by her work because as she just said, she made two amazing discoveries. One, red blood cells make endothelial nitric oxide synthase. Dr. Charles Lowenstein: And that's been a controversy for a long time. Some people have said, "Yes." Some, "No." And Miriam made the definitive answer. Yes, red blood cells make eNOS, and secondly, she has discovered so much about the physiology of ENO coming from red blood cells, the nitric oxide that's made inside red blood cells regulates blood pressure. What a magical, interesting, and important finding. That's a little bit about the history. Nitric oxide and NOS are important in medicine. The people who originally cloned and purified the nitric oxide synthase isoforms named them after the tissue in which they discovered. And Miriam has made a major discovery that it's not only endothelial cells that make nitric oxide but also red blood cells. Dr. Mercedes Carnethon: Thank you so much for that summary. And I guess, I would have thought perhaps this was something of an Elixir of youth because if you've been working in this area for 200 plus years and Miriam, you started working on this as part of your dissertation work, you both have a lot of insight and background on where we've been and what the advances are. Miriam, can you tell me a little bit about how you'd like to see these findings used by the scientific community? Professor Miriam Cortese-Krott: I think I would like that the scientific community would use my mice first because I think, as Charles has said, it's not only red cells that express eNOS and it's not only endothelial cells. There are other cells producing eNOS and the function in the other cells is not known even in leukocytes, even when they have iNOS of course, but also have eNOS. So you can use my mice since it's a flux model. You can choose whatever you want, what cell you want, and then knock it in and knock it out. So this is one thing that I think the community could really do. I cannot do everything. So I'm happy to give my mice away. Professor Miriam Cortese-Krott: And the second thing is I would like too that in particular, the clinical community would see this link between Emathology and cardiovascular disease. This is something that was started, of course, there are studies looking at anemia and cardiovascular disease, but these studies have sometimes some issues I of course cannot speak as a basic scientist. I cannot speak about huge clinical trials, but I think this link exists and exists at the molecular level and it can be a target for pharmacological therapy. So I think this is what I would like to transport with this study to the clinical community and the basic science community. Dr. Mercedes Carnethon: Yeah. I think this is the point at which Charlie, I turn it to you because you really stand at the intersection of both of those communities. What questions do you have for Miriam going forward, as you think about spreading the word on this important work? Dr. Charles Lowenstein: So Miriam's discovery is just so important and she now has the tools to help answer really, really important questions. How is nitric oxide made in red blood cells? How is it stored in red blood cells? How is it transported throughout the body in red blood cells? What is the chemistry of nitric oxide, when it is stored, when it combines with oxygen when it forms nitrite and nitrate, how is it released from red blood cells? How is it targeted from a red blood cell to the vasculature? So there're these great basic science questions that Miriam and her colleagues are now poised to answer. So there's the science part of it. Then there's the medicine part of it because Miriam's mice and her great discovery have really huge implications for medicine. And so the question is, how can we use ENO? How can we deliver it? How can we target ENO to human tissues? Dr. Charles Lowenstein: How can we turn on erythrocyte, nitric oxide synthase? How can we turn it off? Because there are all these medical diseases where too much nitric oxide is bad, like in sepsis or inadequate amounts, don't protect the vasculature like atherosclerosis. Then there are all these other interesting questions. When we transfuse red blood cells, sometimes if you transfuse aged red blood cells, it's not good. You can harm people. Maybe we can load up or activate eNOS in stored red blood cells and then help deliver more ENO to patients who need red blood cells. So there are all these fascinating medical questions that we can look at based on Miriam's really important discovery. Dr. Mercedes Carnethon: Well, thank you so much. We're coming to the end of this wonderful and informative podcast. And I guess, I'd just ask Miriam, do you have anything else you'd like our listeners to know about your work and about the findings from this study? Professor Miriam Cortese-Krott: I would like people know that hard work help a lot, and that you have to believe in what you are doing and the quality of your science at the end would bring their true discoveries. So I think it's important specifically, for the young women in science that having this message too. So the science per se must be excellent and to proceed, you need a lot of work, but then the work goes to a good end. Dr. Mercedes Carnethon: Miriam, thank you so much for that inspirational note. The hard work that scientists need, the persistence across one's career and building from earlier discoveries, and bringing those forward through one's career are always critically important. And so I hope everyone has really enjoyed this episode and this opportunity to hear from Dr. Cortese-Krott. Miriam, you've done such wonderful work, and thank you as well, Charlie, for your insights about the intersection of this work with clinical care and basic science. Professor Miriam Cortese-Krott: Thank you. Dr. Charles Lowenstein: Thank you. Dr. Mercedes Carnethon: Thank you all very much for joining us today in this episode of Circulation on the Run. Dr. Greg Hundley: This program is copyright of the American Heart Association, 2021. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, visit ahajournals.org.  

We're a very sick population and if we keep thinking that we need to kill and hunt down these sicknesses, viruses, and bacteria, that will forever put us at the mercy of the government or other organizations claiming to try and save us vs. us putting the actual work and effort in to become the healthiest versions of ourselves. It's all about choices vs being manipulated and basically lied to in my opinion. - Dr. Ben Lynch   Do you have symptoms of Dirty Genes?   Get 15% off your CURED Nutrition order with the code WELLNESSFORCE   ---> Get The Morning 21 System: A simple and powerful 21 minute system designed to give you more energy to let go of old weight and live life well.   JOIN THE FACEBOOK GROUP | *REVIEW THE PODCAST*   Wellness Force Radio Episode 353 Best-selling Author of Dirty Genes, Naturopathic Physician, and President of Seeking Health, Dr. Ben Lynch, explains how to overcome genetic dysfunction, the difference between making our own health choices vs. being manipulated by the system, why any face mask that isn't N95 certified is useless, what the Super 7 Genes are and how they can be supplemented with products from Seeking Health.   Discover the connection between dirty genes, how to clean them, and how to protect yourself from COVID-19 as well as all viruses out there.     Listen To Episode 353 As Dr. Ben Lynch Uncovers:   [1:30] Making Our Own Health Choices vs Being Manipulated By The System Dr. Ben Lynch Seeking Health Dirty Genes by Dr. Ben Lynch 297 Mike Mutzel His statement and medical perspective on May 22nd, 2020 of where we were at with COVID-19. The negative impact of relying on external things compared to taking action on our own health. How suppressing with antibiotics, antacids, antidepressants, and focusing on "killing" the coronavirus, cancer, disease etc. is the mentality that keeps us digging a hole for humanity. What steps we can take to make our own health choices that support our wellbeing vs relying on the systems of the government or the healthcare industry to "fix us." Fear-mongering platforms that the mass media and government are creating around face masks and hand sanitizer. Judy Mikovits Dr. Ben Lynch & Judy Mikovits Facebook Live "People Are Brainwashed by The Big Pharma" - Judy Mikovits Leave You Speechless Why lifestyle change should be considered first before giving a patient a new medication.   [11:00] Questions We Should Be Asking Now About COVID-19 Questions we should be asking ourselves about COVID-19 before creating so much pandemonium around it. Asking the question, Why are we making a big deal about the coronavirus now and not with influenza, H1N1, or measles? Unpacking why there are specific times in history when people with agendas are pushing for vaccines. Comparing control through COVID-19 to looking closely at how Nazi Germany took meticulous records and statistics of all of their prisoners to keep their soldiers busy which then encouraged them to forget how awful their actions were towards people and hijack their conscious thinking. 345 Dr. Zach Bush 350 Greg Anderson Why educating people about the truth doesn't mean we have to keep them in constant fear and busywork. Miseducation about COVID-19 testing, what it actually is, what it does for us, and how it "keeps us safe" or not. What he can tell us about COVID-19 antibodies, vaccines, PCR, and the actual testing that matters for us right now. Why the influenza vaccine, according to one study, will not prevent the spread of it, the severity of it, nor prevent infecting other people; all it did was just shorten the duration of the sickness. Testing for Coronavirus Antibodies and Coronavirus Vaccine Status Report   [20:30] Becoming A True Seeker Of Health Why a true health seeker is someone who just wants to explore it with an unbiased lens. His approach to looking at health with a Socratic lens, taking his time, and really dig into the paperwork. Dr. Ben Lynch's Facebook page Exploring what is it about our microbiome and disconnection to it that are driving more people to be susceptible to any virus let alone COVID-19. Why illness like chronic sinusitis has a higher chance of occurring when there is less diversity in the nasal microbiome. What it actually takes to have a good, diverse microbiome beyond eating fermented foods like kefir, kimchi, and sauerkraut. Different forms of good bacteria that can be found all of the body - our eyes, nose, cheeks, armpits, etc. and why they're so important for our overall health The devastation we are creating for good bacteria, our food, and our own health as we are blasting COVID-19 with sprays, chemicals, disinfectants, sanitizers, and UVs Why antibiotics and antacids are not the first solutions we should go to when we get sick as our healthy bacteria will fight them off on their own. How swollen tonsils actually work as a line of defense to let us know if we're intolerant to certain foods.   [27:00] Why Any Face Mask That Isn't N95 Is Useless Why Mother Nature is very resilient as she has backup systems for backup systems to repair what we're trying to do to this planet with pesticides, pollution, COVID-19, and natural resource drilling. How to tell whether or not our soil is actually healthy. Why we're actually destroying ourselves when we destroy the environment. His views as face masks and why he's 100% confident that it's actually hurting us as it's used as a governmental tool to maintain the fear and submission. Why face masks are useless unless they're N95 because the size of the holes are not sufficient, they're not properly sealed, and you're just exhaling and inhaling the old, toxic air. Unpacking the fact that people with respiratory symptoms such as COPD cannot wear a face mask as it will kill them. The Model Health Show - Can A Mask Really Keep Us Safe? How the coronavirus is proving that we are a sick population and a vaccine is not going to fix that.   [34:00] Making Our Own Conscious Health Decisions How we can use our time in quarantine to pause, start thinking about things and look at what's really going on with COVID-19. Taking a close look at people's personal agendas that are out in plain sight for us all to see including Bill Gates with the WHO as he funds and controls it. Unpacking Washington state governor Jay Inslee's agenda as his daughter works for Gates and he is supported by Big Pharma and the Bill And Melinda Gates Foundation. The new awakening as we pause and actually take a look around us to see what is truly going on in the world and who's ruling it with their wealth power. Exploring the narrative of true health freedom during COVID-19 and beyond. What vitamins such as A, B, C, D, K as well as iron and zinc we should be adding to our diet. Standing by what you know is right for your health and the health of your family rather than allowing the government to control your decisions. Is a vaccine truly the answer to the coronavirus pandemic? With Dr. Ben Lynch and Dr. Paul Saladino on Fundamental Health Podcast Why it's natural that you will have a much more severe reaction to an infection or a virus like a coronavirus if your primary body's antioxidant, glutathione, is low. What the coronavirus actually is: A whole-body hypoxia of the blood vessels as they break and are unable to transport oxygen everywhere. Why putting people on ventilators is not working to help patients with COVID-19 as it increases oxygenated stress and kills 90% of the people.   [20:30] Taking Back Control Of Your Health From The Government How to take back the responsibility of your health rather than the government control it for you. What the government should actually be focusing on instead of what we can and can't do about our health. Why he feels that former President Obama's choice for Minister of Agriculture, the former head of Monsanto, was the wrong choice. Unpacking what he knows about campaign finance reform. The story behind Seeking Health and their hummingbird logo plus what they stand for especially during COVID-19.   [53:00] How To Clean Your Dirty Genes What steps you can take today to get back to the root of your personal health practices. Exploring the concept of Dirty Genes and how to get well again by making good choices focused on living our healthiest lives. How to make your genes clean with a good diet, movement, sleep, and even your wellness tribe. What steps you can take to bring in the stress you feel each day or in specific situations and let them go as you clean your genes. Why you are not your anxiety, depression, or mental health disorder but your own person and that condition is a dirty gene that can be washed depending on what it is. Type 1 Diabetes Expert Dr. Jody Stanislaw How to use the Dirty Genes book as a guide and refer to it when you need it during your wellness journey. Leaders Eat Last by Simon Sinek The power of starting small when working towards implementing change in your life.   [1:06:00 ] The Super Seven Genes Unpacking what methylation defects are, how we can notice them, and where the process of healing begins. The impacts of certain genes being methylated at various times and their impact on our health. Breaking down how methylation can be a good way for our body to expel toxins from the body. Why he chooses not to consume rice, rice drinks, and rice-based supplements due to them being very high in arsenic. How he chose the Super 7 Genes when there are 19,000 genes in the human body including MTHFR, COMT Fast, COMT Slow, DAO, MAOA Fast, MAOA Slow, GST/GPX, NOS3, and PEMT. The map provided in Dirty Genes to help you along your wellness journey. The Millionaire Messenger by Brendon Burchard The power of giving people what they really need to help them without any expectations. Defining what success actually is: the happiness and gratefulness that you feel. Gary Vaynerchuk How reducing the things you don't need from useless belongings to toxic people to junk food will optimize your life. Why you actually need electrolytes to stay properly hydrated. BREATHE M21 Wellness Guide Wellness Force Community   Power Quotes From The Show   Are Face Masks Hurting Us? "I'm 100% confident that being enforced to wear face masks is hurting us. Face masks are a tool used by the government to maintain the fear and submission. In addition, if a face mask isn't N95 qualified, then when you speak or cough, they will do nothing for the person that is standing next to you. The size of the holes and seal in non-N95 masks are insufficient." - Dr. Ben Lynch     Cleaning Our Dirty Genes "For me, Dirty Genes is a culmination of all of the things that I have learned; how our genes function, what makes them function the best, what prevents them from functioning, and how to optimize their functioning through other outlets than nutrition, lifestyle, and behavior but targeted supplementation and genetic variations." - Dr. Ben Lynch     Unlocking Our Health Freedom "It's great that we can take this moment in quarantine and have time to start thinking about things and really start to look at what is actually going on. Just like prey when facing their predator, they will give it their all to fight back. So, this moment is really a blessing because it is pissing off the world; not just the American public, this quarantine is making the world fight back for its health freedom. It's causing a lot of people to really stop, look, listen, think, and really start understanding what's going on in a big way and none of this is hidden. The government and people with money who have an agenda like Bill Gates who funds WHO are in plain sight." - Dr. Ben Lynch       Links From Today's Show  Dirty Genes by Dr. Ben Lynch 297 Mike Mutzel Judy Mikovits Dr. Ben Lynch & Judy Mikovits Facebook Live "People Are Brainwashed by The Big Pharma" - Judy Mikovits Leave You Speechless 345 Dr. Zach Bush 350 Greg Anderson The Model Health Show - Can A Mask Really Keep Us Safe? Dr. Ben Lynch - We're NOT fighting a virus.  Is a vaccine truly the answer to the coronavirus pandemic? With Dr. Ben Lynch and Dr. Paul Saladino on Fundamental Health Podcast Dr. Ben Lynch on Air Filtration Fear Unmasked: Discover The Truth About The Coronavirus Shutdown by Clay Clark Type 1 Diabetes Expert Dr. Jody Stanislaw Leaders Eat Last by Simon Sinek The Millionaire Messenger by Brendon Burchard Dr. Ben Lynch - Protests are increasing. Here are my thoughts about how to protest in a safe and respectful manner. Gary Vaynerchuk Testing for Coronavirus Antibodies and Coronavirus Vaccine Status Report Dr. Ben Lynch - Scientists are baffled. They don’t know why coronavirus (or any virus) greatly impacts the elderly population. Leave Wellness Force a review on iTunes BREATHE M21 Wellness Guide Wellness Force Community Dr. Ben Lynch Facebook Instagram Twitter YouTube Seeking Health Facebook Instagram Twitter YouTube   About Dr. Ben Lynch Dr. Ben Lynch is the best-selling author of Dirty Genes and President of Seeking Health, a company that helps educate both the public and health professionals on how to overcome genetic dysfunction. He received his doctorate in naturopathic medicine from Bastyr University. He lives in Seattle, WA with his wife and three sons.   Try Seeking Health Today Get 10% off all Seeking Health products throughout July 2020 with the code: JOSH10 At Seeking Health, we believe there is a fundamental step missing, almost 100% of the time, in today’s healthcare system. A consistent focus on treating symptoms, rather than building health, can mean that you cycle in and out of symptoms and “treatment” over and over, sometimes for years. The root cause for many health conditions and symptoms stems from ineffective digestion and poor diet, along with other issues like environmental exposures, sleep issues and even a lack of community. Supporting you to optimize your digestion, reduce environmental exposure and toxic burden, and optimize your diet so nutrients can flood in, is our path to increasing energy and helping your immune system and overall health.     About Seeking Health Supplements Seeking Health provides supplements out of the belief that in order to remain healthy in our toxic, high stress environment, with our nutrient-depleted soils, one must supplement with pure, scientifically-formulated nutrients. Most of our products are GMO-free Most of our products are free of common allergens such as milk, eggs, fish, shellfish, tree nuts, peanuts, gluten, corn, yeast, and soy Most of our products are free of magnesium stearate Certificates of Analysis on our products are available by request   Build Immunity. 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Podcast Notes Key Takeaways Bone broths and organ meats are an excellent source of glycine, an amino acid important for opposing the adverse effects of a meat-based protein-rich dietAll things considered, animal-based proteins > vegetable proteinsIf you’re active, you don’t necessarily have to limit your carbs to 30-50 grams/day to maintain a state of ketosisSleep & exercise:Research has shown that ~20-30 minutes of aerobic activity prior to breakfast can enhance deep sleep levels later on at nightTaking a cold shower after a late-night workout improves sleep by lowering your body temperatureThe seven most crucial genes to focus on when examining your genome analysis: MTHFR, GST, COMT, DAO, MAO, NOS3, and PEMTRead the full notes @ podcastnotes.orgIn my new book  I reveal a never-before-seen, systematized approach to increasing healthspan and lifespan using a potent combination of ancestral wisdom and modern science. Three years in the making and complete with over 600 pages of inspiring stories, workout plans, nutrition protocols, and much more, Boundless is the first step-by-step guide for optimizing every element of your life force and obtain true, lasting, boundless energy. You’ll discover how to get smarter, sleep better, build muscle, burn fat, fix your gut, have mind-blowing sex, defy aging and much more. Fact is, you are far more than average. The power to operate at your full human capacity already exists inside you, just waiting to be unleashed. This book will teach you exactly how. And I've received plenty of questions about Boundless, including who it's for, what kind of routines and plans are included in it, more specifics on chapter content, and much more. So in this special solosode, I'm not only digging into some of the latest longevity, ketone, caffeine, creatine, sleep and protein research I've discovered lately, but also answering all your burning questions about Boundless, which you can now ! During this discussion, you'll discover: -News Flashes mentioned in this podcast…4:30 The launch of Boundless is upon us. Check out the for information on events related to the launch! There is SO MUCH wrong in and I’ll address it in my next podcast This just in… Even though it can be beneficial, Interesting… Sleep latency (how long it takes you to fall asleep) Yet another use for creatine… Cool summary of Yep, you can still be in ketosis without severe carbohydrate restriction (actually you can do it at 25% carb intake)…check out Wow! . (Just goes to show that the “30-50g carbs a day” for nutritional ketosis is not applicable to most athletes!) -Q&A related to … -Are there training routines or training plans specifically for losing fat and/or putting on muscle?…35:25 Physiological parameters I follow: Mitochondrial density Lactic acid tolerance Fat burning and metabolic efficiency Strength (w/ an eye on longevity) Mobility Refer to Chs. 8, 9, 11 -What type of nutrition plans are discussed in the book?…40:56 No one-size-fits-all approach (teaching you to fish rather than handing you a fish) , , , , , , , Carnivore Diet, , Recommended starting points, markers to progress to eventually Eating choices w/ specific gene variations, blood and stool markers, etc. Refer to Ch 21 -Does the book have info related to gut/intestinal health?…45:15 Refer to Chapter 13 Yeast and parasites are addressed How to deal w/ insufficient stomach acid Food intolerances (malabsorption) Best tests to use Huge section on mold and mycotoxins -Is there info on how women can rebalance their hormones?…49:45 Ch. 19 is on longevity and anti-aging Recommended doctors and specialists are mentioned Maintaining DHEA levels, use of peptides, etc. -Does Boundless include recipes?…52:16 and Psychedelics and nootropics (proper use) cooking podcast -Which chapter is a must for a reader to implement in their lifestyle immediately?…54:06 Chapter 20: Invisible: Hidden Variables that Make or Break Your Mind, Body and Spirit How to hire a building biologist () , etc. Biohacks for home and office Using light for circadian rhythm; what light to use and when How to photosynthesize the body Book: My own routines: productivity, software, office hacks, etc. Using effectively Natural household cleaners (, , , , etc.) Also recommend Ch 21 on routines and lifestyle -Rapid fire questions…58:08 Will it be available on Kindle? Yes, but I highly encourage you to get the hard copy. Why is it so expensive? Because it's freaking big, comprehensive, and a work of art. When will the pre-order copy ship? Book launches and orders will ship on 21 Jan. Will it be available in Australia? Yes. Go to find out how. -A few insider tips from Boundless…1:02:00 Gene repair by Dr. Ben Lynch Little-discussed oils How do fish gain the nutrients which make fish oil efficacious? Plant-based oil Sleep optimization Connection between exercise and sleep 20-30 minutes of aerobic exercise prior to breakfast (especially in the sunshine) can enhance deep sleep levels Training hard in the morning can damage sleep patterns Mid-day 20-40 minutes naps timed 5-7 hours after you wake can negate effects of hard workout in the morning, using devices like , , Finish your workout at least 3 hours before bedtime A few intense 10 minute bouts of exercise can alleviate sleepiness during periods of sleep deprivation can relax the joints quickly hydrogen tablets -And much more… Resources mentioned in this episode: – – – – – – – – – made by Dr. John Lieurance of – cooking podcast – Book: by Dr. Ben Lynch – hydrogen tablets – device – BGF podcasts you might like: Episode sponsors: –: Nature’s “first food” that supports immunity, GI function, athletic recovery, and more. BGF listeners, receive a 10% discount off your entire order at Kion when you use discount code: BGF10 –: After using the Joovv for close to 2 years, it's the only light therapy device I'd ever recommend. Give it a try: you won't be disappointed. Order using and receive a month's supply of Kion Berry Aminos absolutely free. –: It's the Navy SEAL of probiotics, and right now you can get a bottle of BiOptimizers P3-OM absolutely free (plus shipping) when you use my link. No gimmicks, no strings attached. Pick it up –: Organic brands you love, for less. Your favorite organic food and products. Fast and free shipping to your doorstep. Receive a gift card up to $20 when you begin a new membership using . Got questions for me about the articles I discussed in today's podcast? How about my new book, Boundless? Leave a comment below and I'll answer!

Podcast Notes Key Takeaways Bone broths and organ meats are an excellent source of glycine, an amino acid important for opposing the adverse effects of a meat-based protein-rich dietAll things considered, animal-based proteins > vegetable proteinsIf you’re active, you don’t necessarily have to limit your carbs to 30-50 grams/day to maintain a state of ketosisSleep & exercise:Research has shown that ~20-30 minutes of aerobic activity prior to breakfast can enhance deep sleep levels later on at nightTaking a cold shower after a late-night workout improves sleep by lowering your body temperatureThe seven most crucial genes to focus on when examining your genome analysis: MTHFR, GST, COMT, DAO, MAO, NOS3, and PEMTRead the full notes @ podcastnotes.orgIn my new book  I reveal a never-before-seen, systematized approach to increasing healthspan and lifespan using a potent combination of ancestral wisdom and modern science. Three years in the making and complete with over 600 pages of inspiring stories, workout plans, nutrition protocols, and much more, Boundless is the first step-by-step guide for optimizing every element of your life force and obtain true, lasting, boundless energy. You’ll discover how to get smarter, sleep better, build muscle, burn fat, fix your gut, have mind-blowing sex, defy aging and much more. Fact is, you are far more than average. The power to operate at your full human capacity already exists inside you, just waiting to be unleashed. This book will teach you exactly how. And I've received plenty of questions about Boundless, including who it's for, what kind of routines and plans are included in it, more specifics on chapter content, and much more. So in this special solosode, I'm not only digging into some of the latest longevity, ketone, caffeine, creatine, sleep and protein research I've discovered lately, but also answering all your burning questions about Boundless, which you can now ! During this discussion, you'll discover: -News Flashes mentioned in this podcast…4:30 The launch of Boundless is upon us. Check out the for information on events related to the launch! There is SO MUCH wrong in and I’ll address it in my next podcast This just in… Even though it can be beneficial, Interesting… Sleep latency (how long it takes you to fall asleep) Yet another use for creatine… Cool summary of Yep, you can still be in ketosis without severe carbohydrate restriction (actually you can do it at 25% carb intake)…check out Wow! . (Just goes to show that the “30-50g carbs a day” for nutritional ketosis is not applicable to most athletes!) -Q&A related to … -Are there training routines or training plans specifically for losing fat and/or putting on muscle?…35:25 Physiological parameters I follow: Mitochondrial density Lactic acid tolerance Fat burning and metabolic efficiency Strength (w/ an eye on longevity) Mobility Refer to Chs. 8, 9, 11 -What type of nutrition plans are discussed in the book?…40:56 No one-size-fits-all approach (teaching you to fish rather than handing you a fish) , , , , , , , Carnivore Diet, , Recommended starting points, markers to progress to eventually Eating choices w/ specific gene variations, blood and stool markers, etc. Refer to Ch 21 -Does the book have info related to gut/intestinal health?…45:15 Refer to Chapter 13 Yeast and parasites are addressed How to deal w/ insufficient stomach acid Food intolerances (malabsorption) Best tests to use Huge section on mold and mycotoxins -Is there info on how women can rebalance their hormones?…49:45 Ch. 19 is on longevity and anti-aging Recommended doctors and specialists are mentioned Maintaining DHEA levels, use of peptides, etc. -Does Boundless include recipes?…52:16 and Psychedelics and nootropics (proper use) cooking podcast -Which chapter is a must for a reader to implement in their lifestyle immediately?…54:06 Chapter 20: Invisible: Hidden Variables that Make or Break Your Mind, Body and Spirit How to hire a building biologist () , etc. Biohacks for home and office Using light for circadian rhythm; what light to use and when How to photosynthesize the body Book: My own routines: productivity, software, office hacks, etc. Using effectively Natural household cleaners (, , , , etc.) Also recommend Ch 21 on routines and lifestyle -Rapid fire questions…58:08 Will it be available on Kindle? Yes, but I highly encourage you to get the hard copy. Why is it so expensive? Because it's freaking big, comprehensive, and a work of art. When will the pre-order copy ship? Book launches and orders will ship on 21 Jan. Will it be available in Australia? Yes. Go to find out how. -A few insider tips from Boundless…1:02:00 Gene repair by Dr. Ben Lynch Little-discussed oils How do fish gain the nutrients which make fish oil efficacious? Plant-based oil Sleep optimization Connection between exercise and sleep 20-30 minutes of aerobic exercise prior to breakfast (especially in the sunshine) can enhance deep sleep levels Training hard in the morning can damage sleep patterns Mid-day 20-40 minutes naps timed 5-7 hours after you wake can negate effects of hard workout in the morning, using devices like , , Finish your workout at least 3 hours before bedtime A few intense 10 minute bouts of exercise can alleviate sleepiness during periods of sleep deprivation can relax the joints quickly hydrogen tablets -And much more… Resources mentioned in this episode: – – – – – – – – – made by Dr. John Lieurance of – cooking podcast – Book: by Dr. Ben Lynch – hydrogen tablets – device – BGF podcasts you might like: Episode sponsors: –: Nature’s “first food” that supports immunity, GI function, athletic recovery, and more. BGF listeners, receive a 10% discount off your entire order at Kion when you use discount code: BGF10 –: After using the Joovv for close to 2 years, it's the only light therapy device I'd ever recommend. Give it a try: you won't be disappointed. Order using and receive a month's supply of Kion Berry Aminos absolutely free. –: It's the Navy SEAL of probiotics, and right now you can get a bottle of BiOptimizers P3-OM absolutely free (plus shipping) when you use my link. No gimmicks, no strings attached. Pick it up –: Organic brands you love, for less. Your favorite organic food and products. Fast and free shipping to your doorstep. Receive a gift card up to $20 when you begin a new membership using . Got questions for me about the articles I discussed in today's podcast? How about my new book, Boundless? Leave a comment below and I'll answer!

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. This week's feature paper takes a deep dive into nitric oxide signaling, that extremely important pathway in cardiovascular health and disease. This time, taking a novel look at genetic predisposition, phenotypic consequences, and therapeutic implications. All that coming right up after these summaries.                                                 The first original paper describes the derivation and validation of a novel model to stratify the risk of death due to circulatory etiology in patients resuscitated from cardiac arrest without an ST elevation MI.                                                 First author, Dr. Bascom, corresponding author Dr. Setter from Maine Medical Center in Portland and their colleagues use the International Cardiac Arrest Registry to derive a novel model termed the CREST Model, which describes an incrementally high risk of circulatory etiology death with an increasing score.                                                 Now, CREST is a simple score with components of C for prior coronary artery disease. R for non-shockable rhythm. E for ejection fraction less than 30% on admission. S for shock at the time of admission. T for ischemic time more than 25 minutes. The authors showed that this CREST tool may allow for estimation of circulatory risk and improve triage of cardiac arrest survivors without STEMI at the point of care.                                                 The next study reports associations between usual sodium, potassium and blood pressure using gold standard 24-hour urinary data collected for the first time among a nationally representative sample of adults in the United States.                                                 First and corresponding author Dr. Jackson from Centers for Disease Control and Prevention used cross-sectional data from 766 participants aged 20 to 69 years with complete blood pressure and 24-hour urine collections in the 2014 national health and nutrition examination survey.                                                 They found that there was a strong direct relationship between higher sodium excretion and higher blood pressure and hypertension. In addition, there was an inverse relationship between potassium excretion and blood pressure and hypertension. When added to the evidence based from longitudinal and interventional studies, these results support clinicians dietary advise to lower sodium intake and increase consumption of potassium containing foods.                                                 The next two studies in this week's journal examine the utility of circulating biomarkers to aid in the diagnosis of acute aortic dissection. As a reminder, the AHA/ACC guidelines published in 2010, proposed using the aortic dissection detection risk score or ADD risk score as a primary screening tool based on scoring the presence of three categorical risks.                                                 Number one, high risk conditions such as Marfan Syndrome, a family history of aortic disease, known aortic valve disease, known thoracic aortic aneurysm or previous aortic manipulation. Number two, The pain features such as chest, back or abdominal pain described as being of abrupt onset severe intensity or ripping, tearing. Number three, the examination features such as evidence of profusion deficit, systolic blood pressure difference, spoken neurological deficit or aortic diastolic murmur and hypertension or shock.                                                 The presence of one or more markers within each of these categorical features is given an ADD score of one with a maximum cumulative score of three if all three categorical features are present. In the first of these two papers in this week's journal, first author Dr. Nazareen, corresponding author Dr. Morello and colleagues from Molinette Hospital in Italy performed the advised International Multi Centers Study, which prospectively assessed the diagnostic performance of standardized strategies integrating pre-test probability assessment and D-dimer in 1,850 patients from the emergency department.                                                 They found that in patients with an ADD risk score above one and D-dimer less than 500 nanograms per milliliter, the rate of acute aortic syndromes was significant at one in 22 cases. Rule out strategies for acute aortic syndromes integrating an ADD risk score of zero or one with D-dimer less than 500 were found to miss only around 1 in 300 cases of acute aortic syndrome.                                                 Integrating the ADD risk score with D-dimer could help to standardize diagnostic decisions on advanced imaging for suspected acute aortic syndrome balancing the risks of misdiagnosis and over testing. The authors concluded that patients at high probability of acute aortic syndrome such as with an ADD risk score above one should proceed to computer tomography and geography or other conclusive imaging irrespective of D-dimer levels.  However, in those with an ADD risk score of zero or one, with a D-dimer of less than 500 were possible rule out diagnostic strategies for acute aortic syndrome.                                                 The second manuscript in the present issue suggests that soluble ST2 might be an even better biomarker than D-dimer to rule out aortic dissection. In this paper by first author, Dr. Wang, co-corresponding authors, Dr. Du and Guo from Beijing Anzhen Hospital and Peking University respectively, the authors measured plasma concentrations of soluble ST2 using the R&D Systems assay in 1,360 patients including 1,027 participants in the retrospective discovery set and 330 patients with an initial suspicion of acute aortic dissection and ruled in a prospective validation cohort.                                                 The proportion of acute aortic dissection, this acute chest pain cohort was high at more than 40%. The authors found that soluble ST2 measured using this research grade assay showed higher levels in acute aortic dissection than in acute myocardial infarction or in acute pulmonary embolism. The result suggested that soluble ST2 levels could be useful as a rule out marker possibly even to an extent moderately superior to D-dimer.                                                 A cut-off level of around 35 nanograms per milliliters using the research grade soluble ST2 assay appeared to reliably rule out acute aortic dissection if used within 24 hours after symptom onset with a negative likelihood ratio of 0.01 and a negative predictive value of more than 99%. These intriguing findings are discussed in an accompanying editorial by Dr. Toru Suzuki from University of Leicester and Dr. Kim Eagle from University of Michigan. Well, that wraps it up for our summaries. Now, for our future discussion.                                                 Nitric oxide signaling plays a key role in the regulation of vascular tone and platelet activation. In fact, the pharmacologic stimulation of nitric oxide pathway is emerging as a therapeutic strategy in cardiovascular medicine in many areas including in heart failure preserved dejection fraction.                                                 Today's paper is therefore all the more intriguing because it seeks to understand the impact of a genetic predisposition to enhanced nitric oxide signaling on the risk for cardiovascular disease as a way of informing of the potential utility of pharmacologic stimulation of the nitric oxide pathway.                                                 Intrigued? Well, I certainly and I'm so glad to have with us the corresponding author, Dr. Sekar Kathiresan from Massachusetts General Hospital as well as a familiar voice, Dr. Peipei Ping, associate editor from UCLA here to discuss this paper.                                                 Sekar, could I ask you as an introduction to tell us a little bit more of the general approach of looking at genetic predisposition as a way of perhaps forecasting potential utility of pharmacologic stimulation? Could you tell us a little bit more about that? Dr. Sekar Kathiresan:      Yes. I'm delighted to speak a little bit more about this idea of using naturally occurring genetic variation to understand if a medicine developed against a target is going to work in terms of efficacy and also potentially lead to on target side effect.                                                 As you know, there are lots of variants for mutations in genes that eventually become targets for medicines. Over the last 10, 15 years, there's been an explosion in our understanding of human genetic variation, specifically in genes targeted by medicines.                                                 The idea here is that if there's a naturally occurring mutation in that target gene, you can simply ask what are the phenotypic consequences of carrying that mutation. Also use that information to predict, as I said, the efficacy of pharmacologic manipulation and potentially on-target side effects. This approach has become a very powerful approach.                                                 A famous recent example of gene, PCSK9, where mutation in this gene occur naturally. A lower function of PCSK9 and individuals who carry this mutations have lower LDL levels and lower risk of heart attack. This information has led to the development of medicine that mimic those mutations and those medicines have been proven now to lower LDL as well as lower risk of heart attack, a phenomenon anticipated by the genetics. Dr. Carolyn Lam:               If I understand it right then, with regards to today's paper, the idea is that if a genetic predisposition to enhanced nitric oxide signaling associates with reduced risk of cardiovascular disease, then that would support the hypothesis that pharmacologic stimulation of the nitric oxide pathway would prevent or treat the cardiovascular disease, right? Could you further expand? Because you also did a meditation analysis. How would we understand that? Dr. Sekar Kathiresan:      Let me walk you through the basics of this paper. Our hypothesis initially was a genetic predisposition to enhance nitric oxide signaling would actually affect a range of cardiovascular diseases. Nitric oxide is a well-known molecule, a regulator of a number of important processes; vascular tone, blood pressure, platelet aggregation.                                                 A couple of important genes in the nitric oxide pathway are, one, nitric oxide synthase, the key enzyme that generates NO. Second is a soluble guanylyl cyclase that is a regulatory molecule involved in NO biology. One of the genes that is part of that pathway is called GUCY183, which is basically a subunit of the soluble guanylyl cyclase.                                                 What we did was we looked at those two genes and asked, "Are there naturally occurring variations in those two genes that actually give us a sense that they gain function that they actually activate nitric oxide signaling. It turned out there are two polymorphisms. One in nitric oxide synthase and the other is in the soluble guanylyl cyclase subunit that are essentially gain of function. They're common polymorphisms.                                                 We know their gain of function because the carriers of these DNA variants have lower blood pressure. An indicator that there's enhanced NO signaling. We use these two polymorphisms as an instrument to understand the phenotypic consequences of having lifelong enhanced nitric oxide signaling.                                                 What we looked at was the relationship of individuals who carried both of the gene variants or gained a function and asked whether these individuals what the relationship of carrying the variant was to a range of cardiovascular diseases as well as a range of quantitative traits like blood pressure or kidney function.                                                 We looked at this in extremely large human population samples where genotype and phenotype had been collated. Most important of these samples is a recent study of a population-based cohort study called the UK Biobank, which has involved about a half million people where genotype and have phenotype have been assembled.                                                 What we found was that genetic predisposition to enhance nitric oxide signaling was associated with reduced risk of several important cardiovascular diseases. First, coronary heart disease. Second, peripheral arterial disease, and third, ischemic stroke.                                                 That provide a very compelling evidence that atherosclerotic cardiovascular disease would be lower based on enhanced nitric oxide signaling. What was surprising to us is we also found a couple of other diseases where it seemed to benefit from enhanced nitric oxide signaling namely kidney function and pulmonary function. These were a little surprising to us, but I think it really suggest that NO plays an important role in a range of diseases.                                                 In terms of your question about what aspect of NO biology is leading to be relationship to these diseases, is it simply the blood pressure effect for example or could you actually infer a mechanisms beyond the blood pressure? We looked at that specifically in the context of cardiovascular disease and we're able to show that the protection afforded by the enhanced nitric oxide signaling gene variants, that protection exceeded the amount predicted by the blood pressure change. In fact, by quite a bit suggesting that there are probably non-blood pressure mechanisms that are at play in terms of the protection afforded by enhanced nitric oxide signaling gene variants. Dr. Carolyn Lam:               Peipei, I have to invite your thoughts now. This is such an amazing paper. We had great discussions as an editor team. Tell us your thoughts. Dr. Peipei Ping:                 The editorial team as well as the reviewers have been very impressed with the quality of the datasets and the value and detail, the metadata analysis together with the appropriate analytical approach. The study is done in our view in a very careful manner and the analysis was performed through the highest standards.                                                 What we also recognized is the potential impact that this particular study may have on multiple areas of studies, in particularly with their findings, the spectrum of individuals, how they carry nitric oxide signaling trends. You could appreciate that the individual score or genetic score paired with the analysis of the genetic variance that they have done, they see from the mental idea that examine both genetic as well as phenotype of each individual is critically important for medicine to be prescribed in the next step of therapies. Dr. Carolyn Lam:               Building on that thought, Sekar, could I ask you? You found some rare inactivating variance. Are these the patients then you think should be targeted for NO enhancing therapies? What's the clinical implications of your findings? Dr. Sekar Kathiresan:      I think there are two ways to think about the implications of these findings. One is there's just a simple biologic insight, the pharmacologic activation of NO signaling maybe protective beyond pulmonary hypertension. As you know, there are actually compounds in the clinic right now that are pharmacologic activators of soluble guanylate cyclase. Those medicines work in the rare condition of pulmonary hypertension.                                                 our work suggest that those medicines are likely to work in a broader range of indications including atherosclerotic cardiovascular disease, kidney disease and pulmonary function. At a simple level, those experiments, I think, should be looked at. Those indications should be looked at.                                                 Whether we've identified a subset of a population that particularly will respond versus it will be a general phenomenon across a range of different individuals that have impaired nitric oxide signaling, I think time will tell. Certainly, one group to think about would be those who are indigenously deficient in nitric oxide signaling and we did find that there are small subset of patients who have inactivating mutations in these two genes and they have higher blood pressure and increased risk for cardiovascular disease.                                                 It was a pretty rare phenomenon, so very small number of individuals would be relevant there. I'm not sure actually that you necessarily want to limit the potential benefit of NO signaling, enhanced NO signaling to just that subgroup. In fact, my prediction would be that the medicine would be relevant for a very large percentage of the population. That you do not need to limit the potential application of this therapy to just those who carry the inactivating mutations. Dr. Peipei Ping:                 I agree largely of what Sekar has discussed. I would add that in situations where genetic information are available with the patients, what the study has offered is fairly clear in the patients where rare variance that inactivate the NOS3 or the guanylyl cyclase off the genes. Maybe a failure it is with a higher systolic blood pressure risk. I'm entirely supportive with the general conclusion that we have come to a time point where NOS outside signaling activation is a critical new element of therapy in cardiovascular health and disease. Dr. Sekar Kathiresan:      Thank you Peipei. Thank you Sekar for taking the time to share your thoughts with us. We are so proud to be publishing paper in circulation. So proud and happy to be chatting about this on this podcast. You've been listening to Circulation on the Run. Thank you for joining us and please tune in again next week.

Suicide, one of the leading causes of death among young adults, seems to be plausibly modulated by both genetic and personality factors. The aim of this study was to dissect the potential association between genetics and temperament in a sample of 111 suicide attempters and 289 healthy controls. We focused on 4 genes previously investigated in association with suicide on the same sample: the nitric oxide synthase 1 and 3 (NOS1 and NOS3), the neuronal cell adhesion molecule 1 (NCAM1), and the tachykinin receptor 1 (TACR1) genes. In particular, we investigated whether a set of genetic variants in these genes (NOS1 : rs2682826, rs1353939, rs693534; NOS3 : rs2070744, rs1799983, rs891512; NCAM1 : rs2301228, rs1884, rs1245113, rs1369816, rs2196456, rs584427; TACR1 : rs3771810, rs3771825, rs726506, rs1477157) were associated with temperamental traits at the Temperament and Character Inventory (TCI). No strong evidence was found for the association between TCI personality traits and the polymorphisms considered in the 4 genes, with the exception of an association between reward dependence trait and the rs2682826 SNP in NOS1 in the healthy sample. However, this result could be plausibly interpreted as a false-positive finding. In conclusion, our study did not support the thesis of a direct modulation of these genes on temperament; however, further studies on larger samples are clearly required in order to confirm our preliminary findings and to exclude any possible minor influence. Copyright (C) 2011 S. Karger AG, Basel

Introduction: Coronary artery disease progression after primary coronary artery bypass grafting may, beside classical atherosclerosis risk factors, be depending on genetic predisposition. Methods: We investigated 192 CABG patients (18% female, age: 60.9 +/- 7.4 years). Clinically cardiac adverse events were defined as need for reoperation (n = 88; 46%), reintervention (n = 58; 30%), or angina (n = 89; 46%). Mean follow-up time measured 10.1 +/- 5.1 years. Gene polymorphisms (ApoE, NOS3, LIPC, CETP, SERPINE-1, Prothrombin) were investigated separately and combined (gene risk profile). Results: Among classical risk factors, arterial hypertension and hypercholesterinemia significantly influenced CAD progression. Single ApoE, NOS3 and LIPC polymorphisms provided limited information. Patients missing the most common ApoE epsilon 3 allele (5,2%), showed recurrent symptoms (p = 0,077) and had more frequently reintervention (p = 0,001). NOS3 a allele was associated with a significant increase for reintervention (p = 0,041) and recurrent symptoms (p = 0,042). Homozygous LIPC patients had a higher reoperation rate (p = 0.049). A gene risk profile enabled us to discriminate between faster and slower occurrence of cardiac adverse events (p = 0.0012). Conclusion: Single APOE, LIPC and NOS3 polymorphisms permitted limited prognosis of cardiac adverse events in patients after CABG. Risk profile, in contrast, allowed for risk stratification.