Podcasts about german cancer research center

On today's episode, meet Dr. Martin F. Dietrich, medical oncologist at Cancer Care Centers of Brevard. In his clinical practice, he addresses all aspects of hematologic and oncologic care, with a special research interest in the treatment of lung and breast cancer, and genetic evaluation and counseling of somatic and hereditary syndromes. He also holds a faculty appointment at the University of Central Florida in Orlando as an assistant professor of internal medicine. He also holds doctorates in cancer biology from the German Cancer Research Center and in molecular genetics from the University of Texas Southwestern Graduate School. He completed his fellowships in Hematology/Oncology in the physician-scientist training track at the University of Texas Southwestern Track as a T32 scholar of the National Cancer Institute. As a fellow of the American College of Physicians (FACP) and a Board-certified internist, Dr. Dietrich believes in a comprehensive approach to his patients' medical care.

Video: 1.Putin just EXPOSED the NATO nuclear plan and they are P*SSED | Redacted w Natali and Clayton Morris  2.Reaction To PayPal Threatening To Fine Users $2,500 Over ‘Misinformation' (4:20) 3.The Genius Behind PayPal's Bad Idea (7:36) 4.Clare Daly Latest Top 7 Contributions in the EU. (First 2 of 7 ) (start @ 1:56) 5. Tulsi Gabbard Speech LIVE | Tulsi Gabbard Accuses Joe Biden | US News Latest | English News LIVE   Polyphenol consumption in adolescents is associated with better cardiovascular health University of Barcelona (Spain), October 24, 2022 The consumption of polyphenols in adolescents is associated with a better cardiovascular health, according to a collaborative research study which includes the University of Barcelona. The study has been published in Scientific Reports. As part of the study, the researchers analyzed the amount of polyphenols in the urine of 1,326 adolescents that took part in the SI! Program (Integral Health) of 24 secondary education schools in Madrid and Barcelona. Polyphenols are bioactive compounds with antioxidant and anti-inflammatory properties found in several plant-based foods, mainly in fruit, vegetables, nuts and olive oil. To date, there were few studies on the intake of polyphenols in children and adolescents. “With the results of this study, we observed that a higher urinary polyphenol excretion is linearly associated with a higher cardiovascular health index in adolescents aged 11-14, specially in children. This cardiovascular health index is defined by the criteria established by the American Heart Association (AHA), which considers seven variables: body mass index, physical activity, smoking, diet, blood pressure, total cholesterol and blood glucose,” says Professor Rosa M Lamuela, director of the Institute for Research in Nutrition and Food Safety of the University of Barcelona NAC supplements may benefit cardiovascular health: Human data University of Marburg (Germany), October 16, 2022 Four weeks of supplementation with N-acetylcysteine (NAC) may reduce levels of homocysteine and improve blood pressure, says a new analysis of two randomized, double-blind, placebo-controlled trials. A daily dose of 1.8 grams of NAC could lower homocysteine levels by about 12%, and may improve systolic and diastolic blood pressure, according to findings published in the American Journal of Clinical Nutrition . Elevated levels of the amino acid homocysteine have been reported to increase the risk of cardiovascular disease. This has led some to point to the potential of the B-vitamins to reduce homocysteine levels and reduce the risk of CVD. B vitamins are cofactors for enzymes involved in homocysteine metabolism and therefore giving people vitamin B supplements is hypothesized to reduce homocysteine levels and therefore reduce cognitive impairment. However, clinical trials including participants at risk of, or already suffering from, cardiovascular disease have produced null results, with some experts arguing that short term B vitamin supplementation should not be expected to reverse the long-term development of heart disease. “Because recent analyses that controlled for confounders such as statins or folate fortification detected a benefit of folate/B-vitamins for stroke (22–24), homocysteine may conditionally be a therapeutic target,” wrote the authors of the new study, led by Prof Wulf Hildebrandt, formerly with the German Cancer Research Center and now at the University of Marburg (Germany). “Therefore, an alternative agent for (more) effective homocysteine lowering may be desirable, especially for conditions in which B-vitamins are ineffective [e.g., in renal disease] or if a reduction in homocysteine of >25% is intended.” There is a known link between homocysteine and NAC, and some studies have shown that NAC may reduce levels of the amino acid, but the data is somewhat mixed. Results showed that NAC supplementation significant decreased homocysteine levels by an average of 11.7% (versus 4.1% in the placebo groups), which cysteine levels increased by an average of 28.1% (versus 4% in the placebo groups). There were no significant differences between the hyperlipidemic and normolipidemic men, and the smoking status also did not affect the results. The researchers also found that NAC significantly decreased blood pressure in all the men. However, significant decreases in diastolic BP were observed only for the hyperlipidemic men, and not for the normolipidemic men. Study: Late afternoon exercise helps control blood sugar, cholesterol and triglyceride levels Huazhong University of Science and Technology (China), October 22, 2022 Results of a study published in the journal Front Endocrinol show that exercising at around 4 to 6 p.m. helps to control blood sugar, cholesterol and triglyceride levels better than exercising in the morning, or around 9 to 11 a.m. For the study, researchers observed 12 healthy young men. The volunteers were told to walk on a treadmill for one hour at 60 percent of their maximal oxygen uptake (VO2max) on Monday, Wednesday and Friday. The volunteers were all tested during and after a week of exercising only in the morning or just in the afternoon. After continuous 24-hour monitoring of their blood sugar levels, the total blood sugar levels of the men were lower when they exercised in the afternoon. Their blood sugar levels after meals were also lower following afternoon exercise. Most cell damage from high blood sugar is linked to a high rise in blood sugar at least one to two hours after eating a meal. The volunteers' triglyceride levels were also lower after afternoon exercise. This is crucial since your blood sugar level rises after you eat. If it rises too high, sugar sticks to cell membranes and damages them. That's why diabetes can damage every cell in your body. When your blood sugar level increases, your pancreas releases insulin to keep blood sugar levels from rising too high. Insulin lowers blood sugar by then driving sugar from the bloodstream into the liver. But if your liver is full of sugar, the liver does not accept more sugar and all the extra sugar is converted to fatty triglycerides. Having a blood triglyceride level greater than 150 indicates that your blood sugar rises too high after meals and that you are already diabetic or prediabetic. Blood levels of the good high-density lipoprotein (HDL) cholesterol were also higher after afternoon exercise. When triglycerides rise too high, you are at increased risk for clots. To protect your body from a high rise in triglycerides, your HDL cholesterol carries the triglycerides from your bloodstream into your liver and a high rise in triglycerides causes a drop in blood levels of the HDL cholesterol. So the lower your HDL, the more likely you are to suffer a heart attack. Scientists reveal the relationship between sugar and cancer Flanders Institute for Biotechnology, October 16, 2022 A nine-year joint research project has led to a crucial breakthrough in cancer research. Scientists have clarified how the Warburg effect, a phenomenon in which cancer cells rapidly break down sugars, stimulates tumor growth. This discovery provides evidence for a positive correlation between sugar and cancer, which may have far-reaching impacts on tailor-made diets for cancer patients. The research has been published in the leading academic journal Nature Communications. This project main focus was the Warburg effect, or the observation that tumors convert significantly higher amounts of sugar into lactate compared to healthy tissues. As one of the most prominent features of cancer cells, this phenomenon has been extensively studied and even used to detect brain tumors, among other applications. But thus far, it has been unclear whether the effect is merely a symptom of cancer, or a cause. Prof. Johan Thevelein (VIB-KU Leuven): “Our research reveals how the hyperactive sugar consumption of cancerous cells leads to a vicious cycle of continued stimulation of cancer development and growth. Thus, it is able to explain the correlation between the strength of the Warburg effect and tumor aggressiveness. This link between sugar and cancer has sweeping consequences. Our results provide a foundation for future research in this domain, which can now be performed with a much more precise and relevant focus.” Living with others and community engagement are keys to reduced dementia risk University of New South Wales (Australia), October 24, 2022 Research published in The Lancet Healthy Longevity provides evidence to support that living with others, community group engagement and never feeling lonely are associated with slower cognitive decline. It is widely recognized that poor social connections such as small networks, infrequent interactions, and loneliness are modifiable risk factors for cognitive decline, with the 2020 Lancet Commission on dementia prevention estimating that tackling social isolation could prevent 4% of dementia cases worldwide. This research, led by UNSW Sydney's Centre for Healthy Brain Aging (CHeBA), investigated a range of measures of social connectedness to discover which had the most robust findings in relation to risk reduction of cognitive decline—and dementia. “We looked at a range of measures of social connections, in approximately 40,000 people across 13 international studies,” says lead author Dr. Suraj Samtani, Postdoctoral Fellow and social health expert at CHeBA. “Previous analyses of multiple international studies have many limitations. Co-author and CHeBA Co-Director Professor Henry Brodaty said that the findings have socio-economic significance. “We found that sharing a home with one or more person[s] and weekly community group engagement had the most robust results across studies, indicating these factors are fundamental components in the link with less cognitive decline,” says Professor Brodaty. “We also identified an association between never feeling lonely and a slower rate of cognitive decline.” Carrots Do Help Aging Eyes, Study Shows University of Utah School of Medicine, October 21, 2022 Your parents may have told you, “Eat your carrots, they're good for your eyes,” and a new study suggests they were on to something. Pigments called carotenoids — which give red or orange hues to carrots, sweet potatoes and orange peppers, or deep greens to produce like spinach, broccoli and kale — may help ward off the age-linked vision ailment known as macular degeneration, researchers said. “I tell my patients that fruit and vegetable consumption are very important for eye health — this study validates that notion,” said Dr. Paul Bernstein, a professor of ophthalmology and visual sciences at the University of Utah School of Medicine in Salt Lake City. Age-related macular degeneration (AMD) is one of the most common causes of vision loss, especially in the elderly. It affects the macula, the center part of the retina, and can lead to declines in sharp central vision and even blindness, experts say. Scientists have already linked a variety of factors to the condition including genetics, smoking and nutrition, said Bernstein, who was not involved in the new study. However, treatment for AMD may be limited depending on the type of macular degeneration that a person develops, he said. In the new study, Wu's team looked at data from health surveys that tracked people aged 50 and older — more than 63,000 women and almost 39,000 men -over a 25 year period. Participants were all nurses and other health professionals. Overall, about 2.5 percent of study participants developed either intermediate or advanced forms of the eye condition during the years of the study. Wu's team found that people who consumed the very highest levels of carotenoids known as lutein and zeaxanthin had a 40 percent lower risk of the advanced form of AMD compared to those who ate the very least. “Other carotenoids, including beta cryptoxanthin, alpha carotene and beta carotene, may also play protective roles,” Wu added. People who consumed the very highest amount of these carotenoids — found in foods such as carrots and sweet potato — had a 25 to 35 percent lower risk of the advanced form of the illness, the findings showed. Researchers did not find any link between the carotenoids and the intermediate form of macular degeneration, however. Lutein is found in eggs and dark leafy vegetables including broccoli, kale and spinach, Bernstein said. Zeaxanthin is harder to find in the diet, he said, but you can get it from corn, orange peppers and goji berries. Wu noted that both lutein and zeaxanthin concentrate in the macula, where they are thought to protect it from damage from oxygen and light.

Found My Fitness - Rhonda Patrick Podcast Notes Key Takeaways The way we respond to a diet is highly individualized – people uniquely respond to diet, even if fed the exact same foods“The dominant factor that determines the diurnal activity of microbes throughout the day is the timing of our feeding.” – Dr. Eran ElinavOur gut microbiome senses when we eat or don't eat and changes activity accordinglyChanges in health status, stress status, medication, the way we live, where we live, etc. reflect on our gut microbes and may impact the risk of developing diseasesA leaky gut is related to disease: diverse molecules secreted by the gut microbe are important in creating the normal state of leakiness which allows us to absorb food and block foreign molecules we don't want in our body – when disrupted, there's a strong link to disease (cancer, autoimmune & cardiovascular disease)The success of probiotic supplementation depends on whether the exogenous probiotic is welcomed by endogenous microbes in the gutThe complexity of taking antibiotics and probiotics: giving probiotics together with antibiotics may protect individuals from adverse effects of antibiotics – but the price may be a chronic disturbance in gut microbiome with probiotics taking over and reducing the diversity of the innate gut microbiomeAbout 80% of overweight people who diet will gain back the weight plus some – the microbiome seems to store a metabolic memory of past obesity which predisposes people to exaggerated weight gainBest practices for a healthy microbiome: (1) maintain a consistent, healthy sleep pattern; (2) stop smoking cigarettes; (3) eat during a regular window during the day (avoid night eating); (4) explore wearing a continuous glucose monitor for personalized data; (5) try a personalized nutrition approach (check out Day Two)Read the full notes @ podcastnotes.orgEran Elinav, MD, PhD, is a professor of immunology and principal investigator at the Weizmann Institute of Science in Tel Aviv, Israel, where he co-directs the Personalized Nutrition Project. Dr. Elinav is also a principal investigator at the German Cancer Research Center in Heidelberg, Germany. His research focuses on understanding the complex interactions between humans and the bacteria that reside in their gut and how these interactions shape human health and disease. In this episode, Dr. Elinav and I discuss... 00:06:38 - Circadian rhythm of the microbiome 00:17:17 - Lessons from Hunter-gatherers 00:24:44 - Nurturing the microbiome in children 00:35:16 - Triglycerides and cholesterol 00:38:58 - Saturated fat 00:40:25 - Effect of artificial sweeteners on the microbiome 00:56:10 - What causes recurrent obesity 00:58:17 - Impact of caloric restriction 00:59:26 - Intestinal permeability (gut leakiness) 01:19:54 - Bacteriophage therapy and precision probiotics 01:34:44 - Bacterial role in TMAO risk 01:40:33 - Weight gain from smoking cessation 01:41:53 - Tips for diet personalization Looking for more? Join over 300,000 people and get the latest distilled information on sleep, depression, and fasting straight to your inbox weekly: https://www.foundmyfitness.com/newsletter Try thirty days of our FoundMyFitness premium member to get access to exclusive episodes, emails, a live Q+A with Rhonda and more: https://www.foundmyfitness.com/trial

Eran Elinav, MD, PhD, is a professor of immunology and principal investigator at the Weizmann Institute of Science in Tel Aviv, Israel, where he co-directs the Personalized Nutrition Project. Dr. Elinav is also a principal investigator at the German Cancer Research Center in Heidelberg, Germany. His research focuses on understanding the complex interactions between humans and the bacteria that reside in their gut and how these interactions shape human health and disease. In this episode, Dr. Elinav and I discuss... 00:06:38 - Circadian rhythm of the microbiome 00:17:17 - Lessons from Hunter-gatherers 00:24:44 - Nurturing the microbiome in children 00:35:16 - Triglycerides and cholesterol 00:38:58 - Saturated fat 00:40:25 - Effect of artificial sweeteners on the microbiome 00:56:10 - What causes recurrent obesity 00:58:17 - Impact of caloric restriction 00:59:26 - Intestinal permeability (gut leakiness) 01:19:54 - Bacteriophage therapy and precision probiotics 01:34:44 - Bacterial role in TMAO risk 01:40:33 - Weight gain from smoking cessation 01:41:53 - Tips for diet personalization Looking for more? Join over 300,000 people and get the latest distilled information on sleep, depression, and fasting straight to your inbox weekly: https://www.foundmyfitness.com/newsletter Try thirty days of our FoundMyFitness premium member to get access to exclusive episodes, emails, a live Q+A with Rhonda and more: https://www.foundmyfitness.com/trial

Study of Prof Dr Karin Steindorf and Dr  Wiskeman of German Cancer Research Center, University of Heidelberg (DKFZ)

Et billigt, sikkert og tankevækkende enkelt middel ville kunne redde livet for tusindvis af af tyskere, skriver forskere fra German Cancer Research Center. Der er ikke tale om medicin, men derimod ganske almindelig D-vitamin i pilleform.

Another interview with a leading global scientists and authority Prof Henning Walczak.This is the citiesbac series of interviews with leading international thought leaders, influencers, academics and change makers by Dinis Guarda for citiesabc.com global platform for uniting and creating solutions for cities and a 4IR Magna Carta for humanity!citiesabc founder Dinis Guarda, Professor Yu Xiong and Professor Henning Walczak talk about the Covid-19 pandemic is affecting every single aspect of the society and how healthcare systems all around the world struggle before this novel coronavirus. Prof. Walczak also highlights the importance of staying at home and the work done by health experts in searching for treatments and a vaccine.Henning Walczak is Professor of Cancer Biology at University College London (UCL), United Kingdom, and Scientific Director of the Cancer Research UK-UCL Centre. Born in Germany, Professor Walczak previously conducted research at the German Cancer Research Center in Heidelberg and also worked for the biotech company Immunex Corportation in Seattle, United States. Together with the Heidelberg immune geneticist Peter Krammer he founded the biotech firm Apogenix, which he still advises. In 2007, Walczak transferred to London, initially to Imperial College and then to UCL. He has received numerous major awards, including an ERC Advanced Grant and the Wellcome Trust Senior Investigator Award.After being awarded the Humboldt Professorship in 2019, he is to join the University of Cologne to expand his research there.Professor Yu Xiong is an academic, researcher and serial entrepreneur. He was trained as a computer scientist, then became a professor in various business schools across the UK. He is active in doing research, growing start-ups, creating his own companies. During his career, he has wide publications in top academic journals, and created business impact in multiple industries.Dinis Guarda is an author, academic, influencer, serial entrepreneur and leader in 4IR, AI, Fintech, digital transformation and Blockchain. With over two decades of experience in international business, C level positions and digital transformation, Dinis has worked with new tech, cryptocurrencies, drive ICOs, regulation, compliance, legal international processes, and has created a bank, and been involved in the inception of some of the top 100 digital currencies. Dinis has created various companies such as Ztudium tech platform and citiesabc, among others.https://www.citiesabc.com/TWITTER: https://twitter.com/citiesabc_INSTAGRAM: https://www.instagram.com/citiesabc/FACEBOOK: https://www.facebook.com/citiesabc/

In this episode, Dr. Erin Stair interviews renowned cancer epidemiologist, Dr. Anthony Miller, on why he believes our widespread use of cell phones and exposure to wireless technology are fueling a future cancer epidemic, especially in young people. He talks about the data, mechanisms of action, why folks don't seem to take this threat seriously and why technology companies don't feel the need to mitigate risk. Dr. Miller is a trained medical doctor and Professor Emeritus at the University of Toronto's Dall Lana School of Public Health. He is a longtime advisor to the World Health Organization and was the Senior Epidemiologist for the International Agency for Research on Cancer. He also served as the Head of Epidemiology at the German Cancer Research Center and as a consultant to the Division of Cancer Prevention of the U.S. National Cancer Institute. He's published numerous studies on the epidemiology of breast cancer; cancer evaluation and screening tools; environmental causes of cancer, and cancer control measures. Dr. Miller has served as the director of the epidemiology unit for the National Cancer Institute of Canada, a clinical professor for the Department of Clinical Epidemiology and Biostatistics at McMaster University, and was the Chairman for the Department of Preventive Medicine and Biostatistics at the University of Toronto. He's received numerous awards for his work, including: The Medal of Honour from the International Agency for Research on Cancer; The Distinguished Achievement Award from the American Society for Preventive Oncology; and The Distinguished Contributions Award from the Canadian Society of Epidemiology and Biostatistics. To contact Erin, visit bloomingwellness.com Read Erin's new parody on the Sleazy Side of the Wellness Industry here!Follow Erin on Instagram here

Isaiah has a Ph.D. in Anatomy & Cell Biology and is an internationally recognized Fortune 500 consultant. He is an expert in the biotechnology industry and specializes in helping people transition into cutting-edge career tracks.Isaiah believes that if you feel stuck somewhere in your life right now, you should make a change. Don’t sit still and wait for the world to tell you what to do. Start a new project. Build your own business. Take action. Experimentation is the best teacher.Isaiah did his undergraduate work at Franklin & Marshall College in Pennsylvania and received his Ph.D. in Anatomy and Cell Biology from the University of Iowa. Since graduating, he has been advancing his career in cell biology and business coaching. In the last two years, Isaiah has given over 250 seminars in 20 different countries throughout Europe, New Zealand, Australia and North America.Isaiah has worked with numerous leaders in the biotechnology industry, including Lilly Pharmaceuticals, Leinco Technologies, Orflo Technologies, Bio-Rad Laboratories, Cellerant Therapeutics, Miltenyi Biotec, McCord Research, Expert Cytometry, Tree Star, Amgen, Celgene, Ambrx, BD Biosciences, Baxter Bioscience, Pfizer, Roche, and Genentech. He has also presented at Harvard University, Stanford University, Oxford University, Cambridge University, Cancer Research UK, University of Amsterdam, German Cancer Research Center, Pasteur Institute, Curie Institute, St. Jude Children’s Research Hospital, University of Tasmania, University of Sydney, University of Western Australia, and many other prestigious institutions.Check out what Isaiah is up to at: https://cheekyscientist.com/

Dr Carolyn Lam:                Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Today's feature discussion revolves around important hemodynamic and echo data from the reprise three trial, comparing the lotus and core valve transcatheter aortic valves in patients with high surgical risk. Can't wait? Well it's coming right up after these summaries.                                                 The first original paper this week provide experimental data showing that the endothelium controls cardiomyocyte metabolism and function via notch signaling. Corresponding author, Dr. Fischer, from German Cancer Research Center in Heidelberg, Germany, and colleagues, studied fatty acid transport in cultured endothelial cells and transgenic mice with endothelial specific notch inhibition, or wild type mice treated with neutralizing antibodies against the Notch ligand. They showed that notch signaling in the endothelium controlled blood vessel formation and fatty acid transport in the adult mouse heart. Inhibition of Notch signaling in the vasculature led to expansion of the cardiac vasculature and impairment of fatty acid transport to cardiomyocytes. This resulted in metabolic reprogramming and heart failure.                                                 Together, these data provide compelling evidence for a central role of Notch signaling at the coordination of nutrient transport processes in the heart. These findings help to explain how pharmacological inhibition of Notch signaling, for example, in oncology could lead to heart failure. The findings also help to identify the signals and molecules involved in endothelial transport capacity and show how these could offer new targets for the treatment of heart failure.                                                 The next paper raises the prospect of new treatment options to combat ischemic heart disease and its progression to heart failure. Ischemic injury to the myocardium is known to trigger a robust, inflammatory response, which is an integral part of the healing process, although much effort has been directed at tempering the inflammatory response in hopes of achieving clinical gain. Major efforts have focused on individual cytokines, the complement cascade, and antibodies to adhesion molecules preventing leukocyte invasion.                                                 In contrast, relatively little effort has focused on macrophages. Although macrophage transformation is known to be crucial to myocardial repair, the events governing this transformation are poorly understood. In today's paper, co-corresponding authors of the trial in Hill, from UT Southwestern Medical Center, performed an elegant series of experiments and showed that release of DNA from necrotic tissue during myocardial infarction, triggered in macrophages a recently described innate immune response known as the GMP-AMP synthase-stimulator of interferon genes pathway or cGAS-STING pathway.                                                 This response in turn promoted an inflammatory macrophage phenotype. Suppression of the pathway promoted emergence of reparative macrophages, thereby mitigating pathological ventricular remodeling. These results therefore reveal for the first time, that the cytosolic DNA receptor, GMP-AMP synthase, functions during cardio ischemia as a pattern recognition receptor in the sterile immune response.                                                 Furthermore, this pathway governs macrophage transformation, thereby regulating post injury cardiac repair. As modulators of this pathway are currently in clinical use, these findings raise the prospect of new treatment options to combat ischemic heart disease and its progression to heart failure.                                                 Cigarette smoking is a well-known risk factor for atherosclerotic cardiovascular disease. However, less is known about the risk for heart failure. First author, Dr. Kamimura, corresponding author, Dr. Hall, from University of Mississippi Medical Center, and their colleagues investigated 4129 black participants without a history of heart failure or coronary heart disease at baseline in the Jackson Heart Study.                                                 They examined the relationship between cigarette smoking and left ventricular strength and function by using cardiac magnetic resonance imaging. They found that current cigarette smoking status, smoking intensity in terms of cigarettes per day, and smoking burden in pack-years, were independently associated with higher left ventricular mass, lower left ventricular strain, higher brain natriuretic peptides, higher BNP levels and higher risk of incident heart failure hospitalization in blacks.                                                 These relationships were significant after adjustment for coronary heart disease, suggesting mechanisms beyond atherosclerosis may contribute myocardial dysfunction and increased risk of heart failure in smokers. In summary, these findings suggest that smoking is associated with structural and functional left ventricular abnormalities that lead to heart failure in blacks and that smoking cessation should be encouraged in those with risk factors for heart failure.                                                 What happens to the risk modifying effects of exercise in individuals with increased genetic risk of cardiovascular disease. Drs. Tikkanen, Gustafsson, and Ingelsson from Stanford University School of Medicine performed the study in about 500,000 individuals from the UK Biobank and reported and compared the association's objective and subjective measures of fitness and physical activity with prospective cardiovascular disease events and all-cause death.                                                 They found consistent and robust inverse association, particularly between objective measures of fitness and physical activity and six cardiovascular outcomes and total mortality. Using genetic risk scores for coronary heart disease and atrial fibrillation, they showed that these inverse associations were present in each genetic risk category, suggesting that elevated genetic risk for these diseases can be compensated for by exercise.                                                 The knowledge that lifestyle choices have substantial effects on disease risk could encourage individuals to initiate a healthier lifestyle to reduce their overall risk. In the longer term, identifying subgroup space on genetic risk that benefit most from lifestyle interventions, could help personalize preventive strategies for chronic diseases.                                                 Well, that wraps it up for our summaries, now for our feature discussion.                                                 Today's featured paper deals with transcatheter aortic valve replacement, which we are all going to recognize has rapidly emerged as a treatment of choice in inoperable patients and, it's a reasonable alternative to surgical aortic valve replacement in high- and intermediate-surgical-risk patients. However, the success of this technology is in large part due to the rigor with which quantitative echocardiography by core laboratories has been used to assess the native and prosthetic aortic valve function.                                                 Today's feature paper gives us such important data from the REPRISE III trial, which compares the Lotus and the CoreValve transcatheter aortic valve in patients with high and extreme surgical risk. I'm so pleased to have the corresponding author, Dr. Federico Asch, from MedStar Washington Hospital Center, as well as our associate editor, Dr. Dharam Kumbhani from UT Southwestern. All right Federico, please help me here, so as a noninterventionist and a person who doesn't deal with all these different types of valves every day, please tell us what was the motivation of looking so closely at the echocardiographic data from REPRISE, because the REPRISE III trial results were already published? Dr Federico Asch:             The most interesting aspect of this analysis is really that there is a very methodic, blinded comparison of two different valves. The valve that is being tested and that the reason why Boston Scientific has sponsored the study, is the Lotus valve, the Lotus System is, if you want, a new valve that is not clinically approved in the United States yet, that basically, it's a completely repositionable bovine pericardial valve that comes in different sizes.                                                 The three sizes that were tested in here are what we would call the small, or 23 millimeters, the medium, 25 millimeters, and the large, 27 millimeters. Each patient, at the moment of randomization, or at the moment of inclusion, were randomized to the small, medium, or large Lotus valve vs the clinically approved CoreValve, which is a Medtronic product. Obviously, this is taken as the control group because this is one of the valves that is widely clinically available nowadays in the United States and worldwide.                                                 This is exactly the motivation here. On one side, to prove whether this valve was as good as CoreValve or not and whether it was as safe as the CoreValve as well, and that, the study was about. Every three patients that were randomized, two were randomized to the new valve, the Lotus, and one was randomized to the CoreValve.                                                 An important note to make here is because the control arm included clinically available valves at the beginning of the study, the previous generation of CoreValve was used and then about halfway through the trial, the Evolut valve was the one being used, so there's two different valves on the CoreValve system that were tested in this trial while Lotus was a single earlier generation valve. We focus here on the hemodynamic implications, that meaning, the gradients and the degree, if you want, of obstruction that these valves could have over time, and the amount of regurgitation that these two valves and how they compare to each other. Dr Carolyn Lam:                That's great. Could I ask if you had any hypothesis going in, because as I recall, the Lotus valve actually met the non-inferiority comparison, but it did have significantly higher rates of new pacemaker implantation and valve thrombosis, right? So, was that perhaps a hypothesis going in and what did you find? Dr Federico Asch:             So, the initial hypothesis of the trial overall was that this new valve was one that was designed to have less paravalvular regurgitation, which is something as you probably know, has been of significant concern in the cardiology world ever since the initial clinical trials for Tyler with Partner and CoreValves.                                                 Patients with more significant paravalvular leak did have worse outcome over time, so, one of the main goals of this valve itself, was to prevent that paravalvular regurgitation. So, that was the initial idea behind this product I would say, not just the clinical trial and obviously, this clinical trial tried to prove that, indeed, as I mentioned before, the primary effectiveness end point was mortality, disabling stroke, and paravalvular leak, the main driver on the difference between the two valves there was indeed a much lower paravalvular regurgitation on the Lotus valve compared to CoreValve.                                                 There was also lower stroke rate, but the most important difference was on the paravalvular aortic regurgitation. Of course, when you think of any of these devices, for them to be able to prevent paravalvular leak, they have to have some kind of skirt or cushioning around the valve, an adaptive seal, which in the case of the Lotus valve, that would prevent any flow around the stent, but one of the risks of that of course is that by trying to seal the valve, you're actually, you may be decreasing a little bit the effective orifice area, so it was actually very important to understand whether gradients with this valve were higher and whether the potential differences in the gradients did turn into any difference in clinical outcomes. Dr Carolyn Lam:                That is super clear now. What did you find? Dr Federico Asch:             I would say, the findings from a hemodynamic standpoint, we can briefly summarize them in two aspects of it. No surprise, the paravalvular leak was significantly lower for Lotus compared to CoreValve, and that was true for any of the three sizes, for the small, medium, and large size in all of them, the rate was significantly lower for Lotus. It was actually under 1% of the patients with moderate or higher paravalvular leak, as opposed to an average of 6.7% on the CoreValve, but on the other side of the spectrum, the gradients and the effective orifice area, and the dimensional index were all significantly better on the CoreValve compared to the Lotus.                                                 The bottom line is, we have two valves that each of them has a specific strength. On one side, Lotus has less paravalvular leak. On the other hand, CoreValve has a better gradient profile than Lotus. I would say in two lines, that's the findings of this study. We did take these findings further and compared among different valve sizes and we saw that these differences were consistent at each of the valve size, so if we would compare the small Lotus with the small CoreValve or the large Lotus with CoreValve, the findings were very similar.                                                 They were always significant, and what is important is that while there was a difference, both for paravalvular leak and for gradients and other hemodynamic parameters, the reality is that when it came to clinical outcomes, there was no significant difference among the two. Dr Carolyn Lam:                Dharam, you have to weigh in now as an interventional cardiologist, what does this mean to you. Dr Dharam Kumbhani:   First of all, Federico, congrats to you and Ted and the rest of the group. I think this is obviously a very important trial and I think this hemodynamics paper, I think definitely moves, helps understand the differences a little bit better, so I think this is a very valuable contribution. I think you said it exactly right. I think what is really interesting is that you have a significant introduction into the paravalvular leak, but yet you have, because of difference in valve design, one being annular vs the other being super annular, you have higher gradients with the Lotus valve compared with the CoreValve, so you wonder if the two differences can cancel themselves out in some way, because you don't see any difference in clinical end points at one year, and also, I guess, what we've learned from the Partner data and other CoreValve data is it would be really helpful to see how this evolves over time, whether there will be any late separation of the curves or just a long-term follow-up, whether that will still be important.                                                 I think that is the really interesting insight that we glean from this analysis. I want to make two other points. I think the other interesting thing about the design of the Lotus valve, and probably having such a great seal for the paravalvular leak reduction and having higher radial strength, I would think, at the annulus, I suspect that that's probably also the reason why the pacemaker rate is higher with this, compared with CoreValve, so it's almost 30% in this trial. About 20%, 18% already had an existing pacemaker, so particularly I guess, as we move to lower-risk population, I think that will certainly, balancing the two and deciding probably one valve doesn't fit everybody and we may have to have strategies to figure out which may be the best valve for a given patient based on this.                                                 The other point I'd like to make is the question about stents or valve thrombosis and I know that your group has been heavily invested in that research, because I know in the JAMA paper, there was a report of few valve thrombosis events and you also bring that home here in this hemodynamics paper. Is there anything you want to elaborate on that or any insights that you feel would be helpful for the next set of trials and next generation of the Lotus valve? Dr Federico Asch:             Yeah, you're bringing two very, very important points. Let me address the thrombosis one first. As you very well described, we have been working a lot on multiple different valves and understanding why this is happening. It's clearly something of concern. In this study in particular, we did not have data collected to detect subclinical thrombosis, which is what most of us have been talking mostly about over the last few years. The diagnosis of thrombosis here was not so clinical. These were patients that mostly, because gradients were going up, were detected. They were image ... there was one or two cases with TE and the other ones with CTs and then they were given anticoagulation and those results, and based on that is that the diagnosis of thrombosis was made. All those cases, nine cases, indeed, happen on the Lotus group. The CoreValve is one in that overall has shown to have lower rates of thrombosis in general and I'm not just talking about our own report. Our report was consistent with that.                                                 That may be something related to the fact that it's a super annular valve and the flow through the valve may be better, if you want, but we don't know that. The rate of thrombosis, again, clinical thrombosis, in this case, for the Lotus valve was 1.5%, which is still low, but it's impossible to compare to all those new reports that are coming out because those are mostly subclinical, which is not the case here.                                                 One could argue that if would have done CTs on every patient here at 30, 45 days, we would have found much higher rates in both valves, but we don't know that. We don't have the data to address that. Dr Dharam Kumbhani:   As I remember, almost all of them, I think seven out of eight of those reported, were in the 23 valve, right? They were not ... I think the larger valves ... Dr Federico Asch:             Exactly. There were nine cases overall, eight of them were on the small valve, on the 23 millimeters, and one was in the middle size, on the 25 millimeters. You are completely right. Dr Dharam Kumbhani:   I don't know what to make of that, but that was an interesting observation as well. Dr Federico Asch:             Yeah. It's interesting because when you look at reports of subclinical thrombosis, actually some of the reports suggest that this is more common in bigger valves than in smaller valves. Registries, I'm talking about, but that didn't seem to be the case here, but again, we need to understand the limitations. This was not a study geared towards detecting sub clinical thrombosis or thrombosis overall. These are just clinically reported cases that were analyzed thoroughly but they were triggered by some kind of clinical event, what's mostly an increase in the gradient.                                                 That's all that I would make out of the thrombosis. I think there is definitely more that we need to learn about it. We know that both CoreValve and Lotus have been reported to have cases of thrombosis, but in general, CoreValve seems to be of all the type of devices, the one with the lowest incidents. Dr Dharam Kumbhani:   Maybe your studies will help in understanding the influence of hemodynamic profile, patient-prosthesis mismatch, to the risk of thrombosis. I think the interactions are not well understood. I think that will be very interesting going forward. Dr Federico Asch:             Exactly. And the other comment that I wanted to make, Dharam, regarding your first impression about the pacemakers and the gradients, a couple of observations that I want to make out of that, one is that the difference in gradients between Lotus and CoreValve seem to be the highest early and then over months, that difference seemed to get smaller and smaller, still significant though, even at one year, but one could argue that if, as we continue following up these patients, maybe the difference starts getting smaller and smaller to the point that to become irrelevant, but we don't know that. That is just the impression that we get at looking at the curves over time.                                                 The pacemaker, obviously, as you can imagine, this is something that is of concern for everybody. It's a high rate, the newer Lotus generations are geared towards having lower paravalvular leak, like the head Lotus Edge and so we would expect that in the future that would be the case, but we don't know. The same way that it is important to mention that CoreValve has been addressing their initial concern, which was paravalvular leak.                                                 I mentioned before that the control arm in this clinical trial included CoreValve classic, earlier generations from roughly half of the patients, and the paravalvular leak in that group was a little bit over 10%, while the second group, which was the Evolut R had already a much lower rate of paravalvular leak, but was still significantly higher than Lotus, but was definitely better.                                                 I think what this points out to, is that all these devices are so early in their life, in their history, that all the efforts that each of these companies are making into fixing the specific problems that each of them have, really turn into a next generation that addresses more aggressively all these things. In the case of CoreValve, definitely the paravalvular leak is one and they are making very good progress in the care of Lotus, the permanent pacemaker is one and we expect in subsequent generations to improve as well. Dr Carolyn Lam:                It's been very enlightening for me and I'm sure for all our listeners. Thank you for joining us today listeners. Don't forget to tune in again next week.

Cancer has become one of the most dangerous diseases of the aging population of industrialized countries. Finding tools to fight cancer is hard, because Cancer presents itself as highly heterogeneous, with over 100 types of cancers described. Not only does Cancer affect aged humans, it has been observed in children in the form of e.g. Medulloblastoma. In the third episode of Active Motif's Epigenetics Podcast, our host Dr. Stefan Dillinger sits down with Dr. David Jones, group leader at the German Cancer Research Center in Heidelberg, to talk about his research on Medulloblastoma and also the emerging role of epigenetic factors in Cancer. References for this episode Alioto, Ivo Buchhalter, … Ivo G. Gut. A comprehensive assessment of somatic mutation detection in cancer using whole-genome sequencing. Nature Communications. 2015 Dec 9; 6, Article number: 10001 doi:10.1038/ncomms10001 David TW Jones, Natalie Jäger, … Peter Lichter. ICGC PedBrain: Dissecting the genomic complexity underlying medulloblastoma. Nature. 2012 Aug 2; 488(7409): 100–105. doi:10.1038/nature11284 Jeremy Schwartzentruber, Andrey Korshunov, … Nada Jabado. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature. 2012 Feb 9; 482, 226–231 doi:10.1038/nature10833 Active Motif Contact Details Follow Active Motif on Twitter Follow our Epigenetics Podcast on Twitter Join us on LinkedIn Like us on Facebook Email us @Active Motif Europe or Active Motif North America.

Extensive research has established that physical activity is inversely associated with the risk of developing cardiovascular disease in healthy adults. In patients with manifest cardiovascular disease, current clinical practice guidelines recommend encouraging patients to undertake daily moderate intensity physical exercise for secondary prevention. While such recommendations are based on numerous clinical trials clearly showing that exercise-based cardiac rehabilitation improves prognosis in heart disease patients, only a few prospective studies have examined the potential benefit of physical activity in clinical practice under real-life conditions.A recent Heart paper investigates the association of leisure time physical activity level with prognosis in a cohort of patients with coronary heart disease. Lead author Ute Mons, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, discusses what they found.Read the full paper:http://goo.gl/gDHlH2