Podcast appearances and mentions of baker heart

Professor Peter Kistler, cardiologist and world expert in heart rhythm disorders at the Baker Heart and Diabetes Institute, has busted the common misconception that coffee causes atrial fibrillation.See omnystudio.com/listener for privacy information.

Nightlife takes an in-depth look at Diabetes and its impact, with Philip Clark, joined by Professor Jonathan Shaw, Deputy Director at the Baker Heart and Diabetes Institute. 

What's the point of science if you can't communicate what you've discovered? This week Dr Shane spends time with four of Australia's FameLab finalists: early career scientists who present their original findings with just 3 minutes (and a prop)! Dr Clair Richards from the University of Technology Sydney expands on her work on preeclampsia and growing placental organoids, so that research can be conducted without further risk to mothers or their babies. Murdoch University animal production scientist, Georgia Welsh discusses her work on winter lambing management by providing different feed and shelter options. Auriane Drack, a PhD candidate at the University of Melbourne and Baker Heart and Diabetes Institute, shares her work navigating the complexities of treating heart disease.Finally, FameLab 2024 winner and PhD candidate Johannes Debler from Curtin University and the Centre for Crop and Disease Management discusses the arms-race between fungus and many of the legumes that are critical part of our agriculture.Program page: Einstein-A-Go-GoFacebook page: Einstein-A-Go-GoTwitter: Einstein-A-Go-Go

Anteris Technologies Ltd (ASX:AVR, OTC:AMEUF) CEO Wayne Paterson sits down with Jonathan Jackson in the Proactive studio to discuss how the company and its technology partner v2vmedtech, inc have reached the concept lock stage on the first phase of development for the next generation Transcatheter Edge to Edge Repair (TEER) system for mitral and tricuspid valve regurgitation. The two structural heart companies are developing the new TEER system for patients with mitral and tricuspid valve disease, where damaged valves cause blood to leak between the ventricles and atriums of the heart. TEER is becoming the primary intervention for this disease but current systems have limitations affecting procedural outcomes or patient eligibility. Anteris's new VClip™ aims to address these needs and provide better patient outcomes. Paterson noted how Dr Vinayak Bapat, v2vmedtech's chief medical officer, highlighted the importance of the concept lock as proof of concept data, noting rapid progress due to collaboration with engineers and leading interventional cardiologists. Approximately 2.5% of the US population has valvular heart disease, with significant mortality rates. The Baker Heart and Diabetes Research Institute estimates up to 600,000 Australians were living with heart valve disease in 2021, with many undiagnosed. This is a major milestone for advancing VClip™ towards a first-in-human study. Anteris is also developing DurAVR™, a transcatheter heart valve for treating aortic stenosis, designed with bioengineered tissue to mimic a healthy aortic valve's performance. #ProactiveInvestors #AnterisTechnologies #ASX #OTC #v2vmedtech, #TEER, #ValveRegurgitation, #MitralValve, #TricuspidValve, #HeartDisease, #VClip, #MedicalInnovation, #Cardiology, #HeartValveDisease, #Healthcare, #Bioengineering, #CardiacSurgery, #Transcatheter, #AorticStenosis, #DurAVR, #ValvularHeartDisease, #MedicalResearch, #InterventionalCardiology #invest #investing #investment #investor #stockmarket #stocks #stock #stockmarketnews

In this episode, we have Professor David Dunstan from the Baker Heart and Diabetes Institute in Melbourne. His research focuses on the role of physical activity and sedentary behaviour in relation to chronic diseases. ---- This podcast episode is sponsored by Fibion Inc. | Better Sleep, Sedentary Behaviour and Physical Activity Research with Less Hassle --- Learn more about Fibion Sleep and Circadian Rhythm Solutions: https://sleepmeasurements.fibion.com/ --- Collect, store and manage SB and PA data easily and remotely - Discover ground-breaking Fibion SENS: https://sens.fibion.com/ --- SB and PA measurements, analysis, and feedback made easy.  Learn more about Fibion Research : fibion.com/research --- Fibion Kids - Activity tracking designed for children. https://fibionkids.fibion.com/ --- Collect self-report physical activity data easily and cost-effectively https://mimove.fibion.com/ --- Follow the podcast on Twitter https://twitter.com/PA_Researcher Follow host Dr Olli Tikkanen on Twitter https://twitter.com/ollitikkanen Follow Fibion on Twitter https://twitter.com/fibion https://www.youtube.com/@PA_Researcher

The life-altering obstacles that come along with diabetes treatment may soon be a thing of the past, thanks to some groundbreaking research from the Baker Heart and Diabetes Institute. One of the biggest challenges in diabetes research is understanding why our immune systems target and destroy insulin-producing cells, an issue which has formed the cornerstone of the breakthrough.See omnystudio.com/listener for privacy information.

Professor Sam El-Osta from the Baker Heart and Diabetes Institute said the discovery could potentially "eliminate the need for round-the-clock insulin injections".See omnystudio.com/listener for privacy information.

Professor Peter Kistler, Cardiologist and Head of Clinical Electrophysiology Research at the Baker Heart and Diabetes Institute and Head of Electrophysiology at The Alfred hospital, discusses the latest developments in heart treatments including the role of artificial intelligence (AI) in assessing the risk of heart disease; Dr Kunal Verma, dual-accredited Clinical Geneticist and Cardiologist at Monash Health, unpacks the role of genetics in heart health; and the team canvass the health benefits of extra virgin olive oil. With Presenters Dr Mal Practice, Nurse Epipen, and Dr Kit Kat.Website: https://www.rrr.org.au/explore/programs/radiotherapyFacebook: https://www.facebook.com/RadiotherapyOnTripleR/Twitter: https://twitter.com/_radiotherapy_Instagram: https://instagram.com/radiotherapy_tripler

This week on the podcast Mikki chats to Prof David Dunstan about the dangers of sedentary behaviour and prolonged sitting. They discuss what sedentary behaviour actually is and how this differs from inactivity. They discuss the physiological changes that occur when we are sedentary and how it impacts our cardiovascular and respiratory health, how it impacts on fat deposition and at a population level, what is the % of people who could be considered sedentary. They discuss the physical activity guidelines and if these are enough to offset the risks associated with being sedentary, and also discuss recent research investigating the relationship between Quality of Life markers, psychological health and sedentary behaviour during Covid. Professor David Dunstan is the head of the Baker-Deakin Department of Lifestyle and Diabetes within the Institute for Physical Activity and Nutrition. He also holds the positions of Deputy Director and Laboratory Head (Physical Activity) at the Baker Heart and Diabetes Institute. His research focuses on understanding the adverse health consequences of too much sitting and the potential health benefits resulting from frequently breaking up sitting time with active countermeasures. In particular, he has developed effective strategies to reduce and break up sitting time in adults with or at risk of developing chronic diseases and to support office workers to reduce sedentary behaviour in workplace settings. He is also interested in how best to implement efficacious ‘sit less and move more' interventions at scale within healthcare settings for those living with or at risk of chronic disease. He was supported by external research fellowships for 16 years and has been a Chief Investigator on 18 nationally-funded studies worth approximately $17 million and 11 international studies from the UK, USA, Sweden and Finland worth more than US$20 million. Professor Dunstan was a Clarivate Highly Cited Cited Researcher in 2018, 2019, 2020 and 2021, placing him in the top 1% most cited for his subject field and year of publication. He has published over 340 peer-review papers and 5 book chapters and has a Scopus H-index of 79. Other highlights include: being an invited author on the 2016 Physical Activity/Exercise and Diabetes Position Statement of the American Diabetes Association; invited presentations at scientific meetings for the American Diabetes Association and European Society for the Study of Diabetes; and current Vice-President of the Asia-Pacific Society for Physical Activity (ASPA).Prof Dunstan: https://www.baker.edu.au/research/staff/david-dunstanReearch: https://www.researchgate.net/profile/D-Dunstan  Contact Mikki:https://mikkiwilliden.com/https://www.facebook.com/mikkiwillidennutritionhttps://www.instagram.com/mikkiwilliden/https://linktr.ee/mikkiwillidenSave 20% on all NuZest Products WORLDWIDE with the code MIKKI at www.nuzest.co.nz, www.nuzest.com.au or www.nuzest.comCurranz supplement: MIKKI saves you 25% at www.curranz.co.nz or www.curranz.co.uk ooff your first order

This week we were so lucky to have the opportunity to chat with Professor David Dunstan about being a research supervisor. David holds a joint appointment at the Baker Heart and Diabetes Institute and Deakin University in Melbourne, Australia with the positions of: Head – Baker/Deakin Department of Lifestyle and Diabetes and Chair, Lifestyle and Diabetes (Institute for Physical Activity and Nutrition, Deakin); and Deputy Director/Physical Activity Laboratory Head (Baker). His research focuses on understanding the adverse health consequences of too much sitting and the potential health benefits resulting from frequently breaking up sitting time. In particular, he has developed effective strategies to reduce and break up sitting time in adults with or at risk of developing chronic diseases and to support office workers to reduce sedentary behaviour in workplace settings. His current focus is directed at understanding how best to implement efficacious ‘sit less and move more' interventions at scale within the healthcare setting for those living with chronic diseases and elucidating the effects of sedentary behaviour on brain health. Relevant to our conversation, David has supervised many, many thriving and successful research students and has lots of excellent advice to share. You can follow David and learn more about his work here: https://baker.edu.au/research/staff/david-dunstan https://www.deakin.edu.au/about-deakin/people/david-dunstan https://www.linkedin.com/in/david-dunstan-07777a3/ https://twitter.com/DavidWDunstan Transcript: https://go.unimelb.edu.au/u24s

Rapha presents Life in the Peloton How does exercise affect the heart, and what does that mean for elite athletes when they stop training? Is it true that you need to 'de-train' the heart when you retire? I head into the lab with Dr. Andre La Gerche to put my heart through its paces and get some answers. If you're a regular listener to the pod, you might recall the episode around this time last year where I caught up with Sports Cardiologist Dr. Andre La Gerche, to learn more about how the heart functions in elite athletes. We went through the physiology of the changes that happen in elite athletes' hearts, and what some of the routine cardiac checks are looking for.   I first met Dr. Andre La Gerche while doing my UCI pre-season E.C.G testing with Team GreenEdge in 2013. Through his work as Head of Clinical Research at Baker Heart and Diabetes Institute in Melbourne, Dr. La Gerche has worked closely with numerous high-level athletes including many professional cyclists. He also has a 2h 29' marathon to his name, which I think you'll agree qualifies him as pretty athletically gifted himself! During our last chat, I brought up the idea of repeating the cardiac testing one year on from retirement. I was really keen to discover what happens to a trained heart when - like I did just over a year ago - you retire. Would my heart simply go back to normal? Or is it true that a pro athlete needs to ‘de-train' their heart? So here we are, one year on. I was a little apprehensive about lining up and putting myself through the pain of this testing now that I'm no longer pro. But, in the name of research, and a good pod, I put my heart through its paces with a host of tests including a fasting dexa scan, blood tests, a resting E.C.G electrocardiagram, a Vo2 Max test, and a supine cardiac MRI while pedalling, which checks for scarring of the heart. For the episode, we studies the test results, and had a fascinating chat that delved into the changes that have occurred in my heart since retiring, and drew some comparisons between myself and other pro cyclists, as well as the average healthy person of the same age, and other changes that have occured now that the intense stress of training has been removed from my body for the first time in 20 years. Dr. La Gerche's incredible knowledge of the workings of the heart in an athlete, and his insight as a keen athlete himself, made it a really fascinating chat for me, we covered many more topics around the heart and exercise which answered a lot of burning questions. So sit back and enjoy the listen, and I hope you learn a thing or two along the way (like me!) Cheers, Mitch  

Videos: Gravitas: Did the US help China cover-up Covid-19 outbreak? (10:57) Is Government the New God? – The Religion of Totalitarianis   Supplemental, dietary antioxidant intake linked with lower dementia risk Lishui University (China), December 12 2022. Results from a systematic review and meta-analysis published in the journal European Geriatric Medicine revealed a relationship between increased intake of antioxidant vitamins C and E and a lower risk of dementia. Futao Zhou and colleagues identified 75 studies from 19 articles that included a total of 28,257 participants for their review. The studies evaluated the association between intake from diet and/or supplements of beta-carotene, flavonoids, vitamin C and vitamin E with Alzheimer disease, all-cause dementia and cognitive impairment without dementia. The research included 2,557 participants with Alzheimer disease, 1,035 cases categorized as all-cause dementia and 6,197 cases of cognitive impairment without dementia. When high intake of vitamins C or E was compared to low intake, high dietary plus supplemental intake of either vitamin was associated with a “markedly” lower risk of Alzheimer disease. High vitamin C from diet plus supplementation was associated with 30% lower risk and high vitamin E with a 27% lower risk of the disease in comparison with low intake. Each 20 milligram per day increase in vitamin C from diet, diet plus supplements, or overall, was associated with a 2% reduction in the risk of Alzheimer disease. When dementia from all causes was examined, the authors reported that “It is supplemental, not dietary, use of vitamin E or vitamin C that can significantly reduce the risk.” High supplemental vitamin C intake was associated with a 19% lower risk of all-cause dementia and high supplemental vitamin E intake with a 20% lower risk compared with low intake. (NEXT) Antioxidant capacity of orange juice is multiplied tenfold University of Granada, December 5, 2022 The antioxidant activity of citrus juices and other foods is undervalued. A new technique developed by researchers from the University of Granada for measuring this property generates values that are ten times higher than those indicated by current analysis methods. The results suggest that tables on the antioxidant capacities of food products that dieticians and health authorities use must be revised. In order to study these compounds in the laboratory, techniques that simulate the digestion of food in the digestive tract are used, which analyse only the antioxidant capacities of those substances that can potentially be absorbed in the small intestine: the liquid fraction of what we eat. “The problem is that the antioxidant activity of the solid fraction (the fibre) isn't measured, as it's assumed that it isn't beneficial. However, this insoluble fraction arrives at the large intestine and the intestinal microbiota can also ferment it and extract even more antioxidant substances, which we can assess with our new methodology,” José Ángel Rufián Henares, professor at the University of Granada, explains. His team has developed a technique called ‘global antioxidant response' (GAR), which includes an in vitro simulation of the gastrointestinal digestion that occurs in our body, whilst taking into account the ‘forgotten' antioxidant capacity of the solid fraction. Upon applying the technique to commercial and natural orange, mandarin, lemon and grapefruit juices, it has been proved that their values greatly increase. For example, in the case of orange juice, the value ranges from 2.3 mmol Trolox/L (units for the antioxidant capacity) registered with a traditional technique to 23 mmol Trolox/L with the new GAR method. (NEXT) ‘Obesity can reduce life by up to 8 years' McGill University (Montreal), December 8, 2022 Life expectancy can be reduced by up to 8 years by obesity, which can also cause adults to lose as much as 19 years of healthy life if it leads to type 2 diabetes and cardiovascular disease. A study published in The Lancet Diabetes & Endocrinologyexamines the issue. The researchers behind the study analyzed data from the US National Health and Nutrition Examination Survey (NHANES), creating a disease-simulation model to estimate the risk of adults of different body weight developing diabetes and cardiovascular disease. From this, the researchers then calculated the extent to which overweight and obesity may contribute to both years of life lost and years of healthy life lost in American adults aged between 20 and 79 years old, in comparison to people of normal weight. They found that people who were overweight (BMI 25-30 kg/m2) were estimated to lose up to 3 years of life, depending on age and gender. Individuals classed as obese (BMI 30-35 kg/m2) were calculated to lose up to 6 years, and people classed as very obese (BMI 35 kg/m2 or more) could lose up to 8 years of life. According to the study, excess weight had the greatest impact on lost years of life among the young and dropped with increasing age. As well as reducing life expectancy, carrying extra weight was also found to reduce “healthy life-years,” which were defined in the study as years free of obesity-linked cardiovascular disease and diabetes. Young adults aged between 20 and 29 showed the highest losses of healthy life-years, adding up to around 19 lost years for very obese people. Among people who were overweight or obese, the researchers calculated that two to four times as many healthy life-years were lost than total years of life lost. The researchers behind that study found that infant mortality was “moderately increased” among overweight and mildly obese mothers (BMI 25-35 kg/m2) compared with mothers of a normal weight; but among more obese mothers (BMI over 35 kg/m2), the risk of infant mortality was more than doubled. (NEXT) The more TV you watch, the more bodily pain you have over time: Study Baker Heart and Diabetes Institute (Australia), December 12, 2022 Data from 4,099 participants of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab) has revealed that an increase in daily TV-watching time is significantly associated with an increase in bodily pain severity over time, according to a new study from the Baker Heart and Diabetes Institute. Bodily pain is common in aging adults and a common presentation in several chronic diseases, including people living with type 2 diabetes. “We found that increments in TV-viewing time over time predicted bodily pain severity,” Professor David Dunstan, principal researcher and Head of the Baker-Deakin Department of Lifestyle and Diabetes said. “Even a one-hour increase in daily TV time was significantly associated with an increase in pain severity. “And those findings were even more pronounced in those living with type 2 diabetes.” The study found that as average daily TV-viewing time increased, bodily pain worsened (score decreased). The mean bodily pain score for those aged 50 years at the start of the study, for example, was 76.9 and worsened by 0.3 units year-on-year. An increase of one hour in TV watching led to a worsening of bodily pain by 0.69 units (score further decreased), or the equivalent of more than two years of pain associated with natural aging. The study also found that the bodily pain scores for people living with type 2 diabetes were even more pronounced. The type 2 diabetes cohort had higher TV-viewing time and more severe bodily pain than those without the condition. People without type 2 diabetes watched on average 1.6 hours per day, compared to 2.2 hours for people with type 2 diabetes. When TV-watching time increased above 2.5 hours per day, the impact on bodily pain severity increased even more significantly. Long uninterrupted periods of time spent sitting (sedentary behavior), especially watching TV, can adversely impact blood glucose control, insulin and other aspects of metabolism in people with type 2 diabetes. Such alterations in metabolism increase levels of inflammation, which can act to precipitate bodily pain. These new findings highlight the benefits of reducing time spent in sedentary behaviors, for both the general population and those living with chronic disease. (NEXT) Study shows clear new evidence for mind-body connection University of Calgary (Canada), December 4, 2022 A group working out of the University of Calgary Department of Oncology has demonstrated that telomeres – protein complexes at the end of chromosomes – maintain their length in breast cancer survivors who practise meditation or are involved in support groups, while they shorten in a comparison group without any intervention. A total of 88 breast cancer survivors who had completed their treatments for at least three months were involved for the duration of the study. The average age was 55 and most participants had ended treatment two years prior. To be eligible, they also had to be experiencing significant levels of emotional distress. In the Mindfulness-Based Cancer Recovery group, participants attended eight weekly, 90-minute group sessions that provided instruction on mindfulness meditation and gentle Hatha yoga, with the goal of cultivating non-judgmental awareness of the present moment. Participants were also asked to practise meditation and yoga at home for 45 minutes daily. In the Supportive Expressive Therapy group, participants met for 90 minutes weekly for 12 weeks and were encouraged to talk openly about their concerns and their feelings. The objectives were to build mutual support and to guide women in expressing a wide range of both difficult and positive emotions, rather than suppressing or repressing them. All study participants had their blood analysed and telomere length measured before and after the interventions. Scientists have shown a short-term effect of these interventions on telomere length compared to a control group, but it's not known if the effects are lasting. Dr. Carlson says another avenue for further research is to see if the psychosocial interventions have a positive impact beyond the three months of the study period. (NEXT) Yoga reduces blood pressure in patients with prehypertension Sir Gangaram Hospital (India), December 8, 2022 Yoga reduces blood pressure in patients with prehypertension, according to a study. This study investigated the impact of hatha yoga on blood pressure in 60 patients with prehypertension who were otherwise healthy. Patients were randomised to two groups of 30 each to assess the effect of three months of yoga plus conventional lifestyle changes versus conventional lifestyle changes alone (control group) on 24 hour ambulatory blood pressure. Yoga included stretching exercises (asanas), breath control (pranayam) and meditation. Yoga practice was for one hour every day. Conventional lifestyle changes consisted of moderate aerobic exercise, diet, and smoking cessation. The investigators found that in the yoga group, both 24 hour diastolic BP and night diastolic BP significantly decreased by approximately 4.5 mmHg and 24 hour mean arterial pressure significantly decreased by around 4.9 mmHg. The control groupdid not show any significant change in blood pressure. Dr Angrish said: “Although the reduction in blood pressure was modest, it could be clinically very meaningful because even a 2 mmHg decrease in diastolic BP has the potential to decrease the risk of coronary heart disease by 6% and the risk of stroke and transient ischaemic attack by 15%.” He concluded: “Our research suggests that patients with prehypertension should be advised to practice hatha yoga (a combination of asanas, pranayam and meditation) for one hour daily. It may prevent the development of hypertension and in addition give a sense of well-being.”

Dr Louise SeganDr Louise Segan is a PhD candidate and cardiologist at Alfred Health and the Baker Heart and Diabetes Institute. She is a passionate and effective advocate for gender equality in cardiology and medicine more broadly. She is also my wife of ten years the mother to my gorgeous son Marlo. Connect with Louise on LinkedIn.Our SponsorsWe are proudly sponsored by Neon Treehouse, the best digital agency on the planet earth. Delicious and healthy soda Kreol is the official drink of Humans of Purpose and you can get a 15% discount on purchases using promo code HUMANSOFPURPOSE. We would welcome your support and partnership to help us take the podcast forward. More about this below in Promotional Packages below.Promotional PackagesOur promotional packages amplify purpose-driven and socially impactful organisations and enable you to reach our global audience of over 10,000 episode listens per month and our growing social media community. Connect with our wonderful socially conscious audience who are based in major Australian cities, of whom 76% are 25-44 years old and 74% are senior professionals in their field. As part of our social enterprise model, we offer just a handful of opportunities per year. Click Here to learn more about collaborating on a custom campaign package.HoP MembershipLove Humans of Purpose? We are a social enterprise and we rely on your support to cover our costs of production. You can help sustain our work by Signing Up as a monthly or annual Humans of Purpose member like our rock star supporters Andrew 1, Andrew 2, Chris, Nikki, Margaret, Ben, Misha, Sarah and Geoff. You'll get the following awesome perks in return each and every week:Early access all episodesAd free all episodesFull transcripts all episodes5 Key Insights all episodesAudio notes all episodesBrokered intros all podcast guestsLinkedIn CommunityYou may not know this, but our highest and most engaged online community after Instagram is via our LinkedIn page. Join over 2,200 Humans of Purpose fans and followers and join in some great conversations, share your thoughts and see what other listeners from our community are saying about the podcast. Hosted on Acast. See acast.com/privacy for more information.

This week it was our huge pleasure to speak with Emily King, currently undertaking her PhD at the Baker Heart and Diabetes Institute in Melbourne. Her current project investigates whether insulin resistance develops as a result of mitochondrial dysfunction in skeletal muscle, using both mouse models and cell lines. The projected impact of these studies is to determine whether related conditions, such as Type 2 Diabetes, can be managed with novel, muscle-specific therapies. Emily is a passionate educator, holding sessional roles as a Graduate Teaching Associate within the Faculty of Science at Monash University. Emily also produces the podcast Voices of Academia (https://anchor.fm/academicvoices), a really important project that we discussed at length. Emily has won numerous awards & scholarships based on her communication and as you'll hear, she's a very gifted storyteller. She's also volunteered for various forms of science communication/educational writing including grant writing for The National Stroke Foundation, blog writing for Franklin women, and public speaking for a Women in Science forum. You can follow Emily and find out more about her work here: https://twitter.com/EKing_Sci http://www.lateralmag.com/articles/issue-30/a-partner-for-life https://www.linkedin.com/in/emily-king-8815a843/ https://baker.edu.au/research/staff/emily-jane-king Here are other accounts we mentioned in the podcast: Co-founder of Voices of Academia Dr Zoë Ayres: https://twitter.com/ZJAyres Voices of Academia Podcast: https://twitter.com/academicvoices https://twitter.com/PhD_Balance https://twitter.com/DragonflyMH Transcript: https://go.unimelb.edu.au/7c2e

Heart attack caused by rupture of unstable plaque in the coronary arteries is the number one cause of death worldwide. Melbourne-based medtech company Nirtek, is using laser technology discovered at the Baker Heart and Diabetes Institute, to develop the first intra-coronary guidewire device for the detection of unstable plaque to prevent heart attacks and save lives. Nirtek's device has been awarded funding through MTPConnect's Targeted Translation Research Accelerator program for Diabetes & Cardiovascular Disease, made possible by the Medical Research Future Fund.MTPConnect hosts Caroline Duell and Lauren Kelly, Senior Director of the TTRA Program are joined by Nirtek's CEO Matthew Hoskin, who shares the challenges of their medtech journey as the company prepares for a capital raise and works towards creating a prototype for clinical trials. Matthew also explains the value of the support provided by the Medical Device Partnering Program (MDPP), a TTRA venture partner, and MDPP's Olivia White joins the discussion.

Dr André La Gerche, Cardiologist at Alfred Health and Head of the Clinical Research Department at the Baker Heart and Diabetes Institute, canvasses how consistent exercise can reduce the impact of long COVID, and discusses the causes of sudden cardiac arrest and death; Dr Robert Gillies, Medical Doctor at the Alfred Hospital and co-founder of HoMie, talks about his work with HoMie and how the organisation supports young people affected by homelessness; and the team unpack recent research on zoom dysmorphia. With presenters Nurse Epipen, Dr G Spot, and Panel Beater.Website: https://www.rrr.org.au/explore/programs/radiotherapyFacebook: https://www.facebook.com/RadiotherapyOnTripleR/Twitter: https://twitter.com/_radiotherapy_Instagram: https://instagram.com/radiotherapy_tripler

We are joined today by the co-chairs of the IC-OS Exercise Working Group to discuss the role of exercise as a therapy for cardio-oncology patients. Dr. Erin Howden is the head of the Human Integrative Physiology Lab, co-lead of the Physical Activity Program at the Baker Heart and Diabetes Institute, Melbourne Australia. Dr. Scott Adams is an assistant Scientist at Toronto General Hospital Research Institute and exercise lead at the Ted Rogers Cardiotoxicity Prevention Program in Toronto, Canada. In this episode a reference was made to the following article: Florez Bedoya CA, Cardoso ACF, Parker N, et al: Exercise during preoperative therapy increases tumor vascularity in pancreatic tumor patients. Scientific Reports 9:13966, 2019

While high cholesterol and heart disease is said to be a man's illness, research from Baker Heart & Diabetes Institute shows more women have high cholesterol than men and account for more than half of heart disease events.  - Sinasabi na ang mataas na kolesterol at sakit sa puso ay kadalasang sakit ng mga lalaki, ngunit ayon sa ulat ng Baker Heart & Diabetes Institute marami sa mga kababaihan ang may mataas na kolesterol kumpara sa mga kalalakihan.

What do your genes say about your risk of disease? We want to know what types of diseases we, and our children, are susceptible to so we can to our best to mitigate them. When we hear about our own risk of genetic disease, it can be frightening, but it may not mean what it seems.In reality, genetic disease is highly complex, especially when multiple genes could contribute to any given trait. So, how do we collect this information and what does it mean?Today, Cosmos journalist Dr Deborah Devis talk to two experts. First up you will hear Professor Michael Inouye. He is Director of the Cambridge Baker Systems Genomics Initiative, Director of Research in the Dept Public Health & Primary Care at the University of Cambridge, Munz Chair of Cardiovascular Prediction & Prevention at the Baker Heart & Diabetes Institute, and a Turing Fellow at the Alan Turing Institute. Following the chat with Michael, Deborah talks to Dr Fayeza Khan, a Human Molecular Geneticist.Find the science of everything at the Cosmos Magazine website Subscribe to Cosmos Magazine (print) or the Cosmos WeeklyWatch and listen to all our Cosmos BriefingsSpecial 10% discount on Cosmos magazine print subscriptions (1 or 2 year), or 1 year Cosmos Weekly subscriptions for Cosmos Briefing podcast listeners!  Use coupon code COSMOSPOD in our shop.

Managing T1DM is extremely difficult Patients wearing insulin pumps should be asked if they have a current emergency plan in case the pump breaks down, and fresh supplies of insulin pens Continuous glucose monitoring tips: first fix the lows, help patients understand and identify causes for the highs and ensure the tube is not blocked and is re-sited every three days   Host: Dr David Lim | Total time: 35 mins Guests: A/Prof Neale Cohen, Endocrinologist; Director of Clinical Diabetes, the Baker Heart and Diabetes Institute, Melbourne Register for our fortnightly FREE WEBCASTS Every second Tuesday | 7:00pm-9:00pm AEST Click here to register for the next one See omnystudio.com/listener for privacy information.

Highlights of the podcast - this is republication of episode published earlier. --- In this episode, we have Professor David Dunstan from the Baker Heart and Diabetes Institute in Melbourne. His research focuses on the role of physical activity and sedentary behaviour in relation to chronic diseases. --- This podcast episode is sponsored by Fibion Inc. | The New Gold Standard for Sedentary Behaviour and Physical Activity Monitoring Learn more about Fibion: https://fibion.com/research ---

In this era of SGLT2 inhibitors and GLP1 agonists, we need to initiate these therapies early because of their cardioprotective and renoprotective (for SGLT2I) benefits The incidence of heart failure, silent ischaemia and arrhythmias are higher in patients with T2DM and GPs need a high index of suspicion to identify, diagnose and treat these   Host: Dr David Lim | Total time: 27 mins Guest: A/Prof Neale Cohen, Endocrinologist; Director of Clinical Diabetes, the Baker Heart and Diabetes Institute, Melbourne Register for our fortnightly FREE WEBCASTS Every second Tuesday | 7:00pm-9:00pm AEST Click here to register for the next one See omnystudio.com/listener for privacy information.

GLP1 agonists are a very important management option- GPs who have not yet used this class of medications should learn more and start They are potent in lowering blood glucose levels and weight. Given once a week and have non-glycaemic cardiovascular benefits There are few contraindications and can be used in patients with very low eGFR GLP1 agonists can be used as second-line after metformin, third line and some can also be used with insulin   Host: Dr David Lim | Total time: 38 mins Guest: A/Prof Neale Cohen, Endocrinologist; Director of Clinical Diabetes, the Baker Heart and Diabetes Institute, Melbourne   Register for our fortnightly FREE WEBCASTS Every second Tuesday | 7:00pm-9:00pm AEDT Click here to register for the next one See omnystudio.com/listener for privacy information.

There is no blame game when managing our indigenous patients with diabetes. Genetic factors make lifestyle changes less effective and some are at risk of a form of malignant, rapidly progressive T2DM in the setting of severe insulin resistance. Advocating for improved resources and staffing of remote clinics is essential.  Host: Dr David Lim | Total time: 31 mins Guest: A/Prof Neale Cohen, Endocrinologist; Director of Clinical Diabetes, the Baker Heart and Diabetes Institute, Melbourne   Register for our fortnightly FREE WEBCASTS Every second Tuesday | 7:00pm-9:00pm AEDT Click here to register for the next one See omnystudio.com/listener for privacy information.

Growing evidence fruit may lower type 2 diabetes risk Research has found eating at least two serves of fruit daily has been linked with 36% lower odds of developing type 2 diabetes Edith Cowan University (Australia), June 2, 2021 Eating at least two serves of fruit daily has been linked with 36 percent lower odds of developing type 2 diabetes, a new Edith Cowan University (ECU) study has found.  The study, published today in the Journal of Clinical Endocrinology and Metabolism, revealed that people who ate at least two serves of fruit per day had higher measures of insulin sensitivity than those who ate less than half a serve.  Type 2 diabetes is a growing public health concern with an estimated 451 million people worldwide living with the condition. A further 374 million people are at increased risk of developing type 2 diabetes. The study's lead author, Dr Nicola Bondonno from ECU's Institute for Nutrition Research, said the findings offer fresh evidence for the health benefits of fruit.  "We found an association between fruit intake and markers of insulin sensitivity, suggesting that people who consumed more fruit had to produce less insulin to lower their blood glucose levels," said Dr Bondonno.  "This is important because high levels of circulating insulin (hyperinsulinemia) can damage blood vessels and are related not only to diabetes, but also to high blood pressure, obesity, and heart disease. "A healthy diet and lifestyle, which includes the consumption of whole fruits, is a great strategy to lower your risk of developing type 2 diabetes." Fresh is best The study examined data from 7,675 Australians participating in the Baker Heart and Diabetes Institute's AusDiab Study and assessed fruit and fruit juice intake and the prevalence of diabetes after five years. Dr Bondonno said they did not observe the same beneficial relationship for fruit juice.  "Higher insulin sensitivity and a lower risk of diabetes was only observed for people who consumed whole fruit, not fruit juice," she said.  "This is likely because juice tends to be much higher in sugar and lower in fibre."  Dr Bondonno said that it's still unclear exactly how fruit contributes to insulin sensitivity, but it is likely to be multifaceted.  "As well as being high in vitamins and minerals, fruits are a great source of phytochemicals which may increase insulin sensitivity, and fibre which helps regulate the release of sugar into the blood and also helps people feel fuller for longer," she said. "Furthermore, most fruits typically have a low glycaemic index, which means the fruit's sugar is digested and absorbed into the body more slowly."  The study builds on Dr Bondonno's research into the health benefits of fruit and vegetables, particularly those that contain a key nutrient known as flavonoids. The research is part of ECU's Institute of Nutrition Research.     Ginkgo biloba leaves have multicomponent and multitarget synergistic effects on treatment of neurodegenerative diseases Jiangsu Kanion Pharmaceutical Co (China), June 1, 2021 According to news reporting out of Jiangsu, People's Republic of China, research stated, “Ginkgo biloba L. leaves (GBLs), as widely used plant extract sources, significantly improve cognitive, learning and memory function in patients with dementia. However, few studies have been conducted on the specific mechanism of Neurodegenerative diseases (NDs).” Our news journalists obtained a quote from the research from Jiangsu Kanion Pharmaceutical Co. Ltd., “In this study, network pharmacology was employed to elucidate potential mechanism of GBLs in the treatment of NDs. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to obtain the chemical components in accordance with the screening principles of oral availability and drug-like property. Potential targets of GBLs were integrated with disease targets, and intersection targets were exactly the potential action targets of GBLs for treating NDs; these key targets were enriched and analyzed by the protein protein interaction (PPI) analysis and molecular docking verification. Key genes were ultimately used to find the biological pathway and explain the therapeutic mechanism by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Twenty-seven active components of GBLs may affect biological processes such as oxidative reactions and activate transcription factor activities. These components may also affect 120 metabolic pathways, such as the PI3K/AKT pathway, by regulating 147 targets, including AKT1, ALB, HSP90AA1, PTGS2, MMP9, EGFR and APP. By using the software iGEMDOCK, the main target proteins were found to bind well to the main active components of GBLs.” According to the news editors, the research concluded: “GBLs have the characteristics of multi-component and multi-target synergistic effect on the treatment of NDs, which preliminarily predicted its possible molecular mechanism of action, and provided the basis for the follow-up study.” This research has been peer-reviewed.     Diets that promote inflammation could increase breast cancer risk Analysis of dietary patterns for over 350,000 women suggests eating more anti-inflammatory foods helps lower risk Catalan Institute of Oncology and Biomedical Research Institute (Spain) June 7, 2021  A new study of more than 350,000 women found that women with diets incorporating more foods that increase inflammation in the body had a 12% increase in their risk of breast cancer compared to women who consume more anti-inflammatory diets. The new findings are being presented at NUTRITION 2021 LIVE ONLINE.  The study authors found that moving from a more anti-inflammatory diet toward one that increases inflammation upped breast cancer risk in an almost linear manner. Foods that increase inflammation include red and processed meat; high-fat foods such as butter, margarines and frying fats; and sweets including sugar, honey and foods high in sugar. Fruits, vegetables, legumes, tea and coffee all have potentially anti-inflammatory properties. "Most studies examining diet and breast cancer risk have focused on single nutrients or foods rather than the whole diet," said the study's first author Carlota Castro-Espin, a predoctoral fellow at the Catalan Institute of Oncology and Bellvitge Biomedical Research Institute in Barcelona, Spain. "People consume food not nutrients, thus examining overall dietary patterns, rather than single components of diets can lead to more accurate conclusions when analysing associations with a health outcome such as breast cancer."  The new results are based on data from the European Investigation into Cancer and Nutrition (EPIC) study, a prospective study that recruited more than 500,000 participants across 10 European countries starting in the mid-1990s. The study included more than 13,000 breast cancer diagnoses during approximately 15 years of follow-up.  The typical diet for EPIC participants was measured for a year using food frequency or diet history questionnaires. The researchers used this information to calculate an inflammatory score for each study participant based on their intake of 27 foods.  The researchers examined dietary patterns linked with inflammation because long-term, low grade inflammation has been linked with the development of breast cancer. The large number of women in the study allowed the researchers to take a more nuanced look at the relationship between dietary patterns and breast cancer risk.  Their analysis showed that the increase in breast cancer risk due to pro-inflammatory diets appears to be more pronounced among premenopausal women. They also found that the association did not vary by breast cancer hormone receptor subtypes.  "Our results add more evidence of the role that dietary patterns play in the prevention of breast cancer," said Castro-Espin. "With further confirmation, these findings could help inform dietary recommendations aimed at lowering cancer risk."  As a next step, the researchers plan to evaluate the association of the inflammatory potential of diet and other dietary patterns with breast cancer survival using participants in the EPIC study.      Emerging impact of quercetin in the treatment of prostate cancer Shahid Beheshti University of Medical Sciences (Iran), June 3, 2021   According to news originating from Tehran, Iran, research stated, “Quercetin is a flavonoid agent detected in fruits and vegetables with anti-inflammatory, antioxidant, and anticancer effects. This flavonoid can suppress cell cycle transition and induce apoptosis in neoplastic cells.” Our news reporters obtained a quote from the research from Shahid Beheshti University of Medical Sciences: “Therapeutic effects of quercetin have been assessed in diverse cancers including prostate cancer through the establishment of in vitro and in vivo experiments. Moreover, this agent might prevent the initiation of this type of cancer as it indirectly blocks the activity of promoters of two important genes in the pathogenesis of prostate cancer i.e. androgen receptor (AR) and prostate specific antigen (PSA). Several in vitro investigations have identified the differential influence of quercetin on normal prostate cells versus neoplastic cells, emphasizing its specific cytotoxic effects on cancerous cells. The most appreciated route of quercetin effect on prostate cancer cells is the detachment of Bax from Bcl-xL and the stimulation of caspase families. Besides, quercetin might enhance the effects of other therapeutic options against prostate cancer. For instance, a combination of TNF-related apoptosis-inducing ligand (TRAIL) and quercetin has been recommended as a novel modality for the treatment of prostate cancer.” According to the news editors, the research concluded: “These kinds of strategies might overcome resistance to apoptosis in cancer cells. In the current paper, we summarize the recent data about the preventive and therapeutic influences of quercetin in prostate cancer.”     Breast microbiome modified by diet, fish oil Wake Forest School of Medicine, June 4 2021.    Findings reported on June 3, 2021 in Cancer Research add evidence to the effects of diet on the breast's microbiome, the community of microorganisms that exists in breast tissue.  “We have recently demonstrated that dietary patterns modulate mammary microbiota populations,” wrote David R. Soto-Pantoja and colleagues. “An important and largely open question is whether the microbiome of the gut and mammary gland mediates the dietary effects on breast cancer.” To help answer this question, the researchers fed a high fat or a control diet to mice that are susceptible to developing breast cancer. Animals that received the high fat diet had a greater number of tumors, more rapid tumor growth and larger tumor size than those that received the control diet.  Next, mice that were given high fat diets received fecal transplants from mice that received control diets, and control diet-fed animals received transplants from high fat diet-fed animals. The team found that animals that received the control diet developed as many tumors as mice that received the high fat diet.   In a double-blind trial, breast cancer patients were given fish oil supplements or a placebo for two to four weeks prior to surgical removal of their tumors. The researchers observed a change in the microbiota of tumor and normal breast tissue in participants who received fish oil, including an increase in Lactobacilli (which has been associated with reduce breast cancer tumor growth in animals) in normal tumor-adjacent breast tissue of participants who received fish oil for four weeks.  "Obesity, typically associated with a high-fat diet consumption, is a well-known risk factor in postmenopausal breast cancer," commented coauthor Katherine L. Cook, PhD, of Wake Forest University. "This study provides additional evidence that diet plays a critical role in shaping the gut and breast microbiome."     Self-administered aroma foot massage may reduce symptoms of anxiety   Okayama University (Japan), June 8, 2021  Researchers at Okayama University conduct the first community-based study on the effects of self-administered aromatherapy foot massage on stress and anxiety symptoms. The results suggest aromatherapy massages might provide an inexpensive, simple way of managing anxiety.   The continuing popularity of complementary therapies, such as aromatherapy and massage, has prompted scientists to investigate the effects of such therapies on the body in more detail. Complementary therapies are said to reduce the symptoms associated with stress and anxiety, and therefore may reduce the chances of severe illness, such as hypertension and heart disease. The precise effects on the body following such therapies is unclear, however.   Previous studies have focused on the effects of massage and aromatherapy treatments on blood pressure and mental state in hospitalized patients in Japan, but none have been conducted on individuals living in the community. Now, Eri Eguchi and co-workers at Okayama University, together with researchers across Japan, have conducted the first study into the effect of aromatherapy-based foot massage on blood pressure, anxiety and health-related quality of life in people living in the community.   57 participants took part in the study; 52 women and 5 men. Baseline blood pressure and heart rate values were taken at the start and end of the four-week trial period, as well as at a follow-up session 8 weeks later. Participants also completed questionnaires on anxiety status and health-related quality of life at each stage of the trial. The participants were divided into two groups, and one group were taught to perform a 45-minute aromatherapy-based foot massage on themselves three times a week for four weeks.   The results suggest that aroma foot massage decreased the participants' average blood pressure readings, and state of anxiety, and tended to increased mental health-related quality of life score. However the effect of massages was not significant with changes in other factors such as physical health-related quality of life scores and heart rate.   In their paper published in March 2016 in PLOS One, Eguchi's team are cautiously optimistic about the potential for self-administered massage to reduce anxiety in the population: "[although] it was difficult to differentiate the effects of the aromatherapy from the effects of the massage therapy... [the combination] may be an effective way to increase mental health and improve blood pressure."     Aromatherapy and massage Aromatherapy has long been used to relieve stress and anxiety in populations across the globe. Different aroma essential oils are said to have different properties, and are used to induce relaxation and promote well-being. Trials have indicated that certain essential oils, when inhaled, can reduce blood pressure levels and alleviate depression by stimulating the olfactory system. Massage (in its many forms) also has a long history in therapeutic medicine, and the practice of manipulating key pressure points in the body to induce relaxation has been shown to improve mental and physical health. However, detailed scientific studies of the effects of aromatherapy foot massage – an increasingly popular treatment in Japan – on blood pressure and perceived quality of life are limited.   Significance and further work While the trial carried out by Eguchi and her team is limited in some respects, their results provide an initial starting point from which to extend studies into the benefits of aroma foot massage for the general population. Their findings that massage, or the aromatherapy, or a combination of both, reduce blood pressurereadings (at least in the short term) warrants further investigation. Eguchi and her team acknowledge that their decision to advertise for participants may have encouraged more health-conscious and pro-active people to apply. They also received far more applications from women than men, although their age-range (from 27 to 72) was diverse. Further work is needed to determine the effect of aroma foot massage on specific age and sex categories, for example, before such interventions are encouraged in the wider population.     Proteomics reveals how exercise increases the efficiency of muscle energy production University of Copenhagen (Denmark), May 27, 2021 Mitochondria are the cell's power plants and produce the majority of a cell's energy needs through an electrochemical process called electron transport chain coupled to another process known as oxidative phosphorylation. A number of different proteins in mitochondria facilitate these processes, but it's not fully understood how these proteins are arranged inside mitochondria and the factors that can influence their arrangement. Now, scientists at the University of Copenhagen have used state-of-the-art proteomics technology to shine new light on how mitochondrial proteins gather into electron transport chain complexes, and further into so-called supercomplexes. The research, which is published in Cell Reports, also examined how this process is influenced by exercise training.  "This study has allowed for a comprehensive quantification of electron transport chain proteins within supercomplexes and how they respond to exercise training. These data have implications for how exercise improves the efficiency of energy production in muscle," says Associate Professor Atul S. Deshmukh from the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) at the University of Copenhagen.  Traditional methods provide too little detail It is already well established that exercise training stimulates mitochondrial mass and affects the formation of supercomplexes, which allows mitochondria in skeletal muscle to produce energy more efficiently. But questions remain about which complexes cluster into supercomplexes and how. To better understand supercomplex formation, particularly in response to exercise, the team of scientists studied two groups of mice. One group was active, and given an exercise wheel for 25 days, and the second group was sedentary, and was not provided the exercise wheel. After 25 days, they measured the mitochondrial proteins in skeletal muscle from both groups to see how the supercomplexes had changed over time.  When scientists typically analyze how supercomplexes form, they use antibodies to measure one or two proteins per electron transport chain complex. But as there can be up to 44 proteins in a complex, this method is both time consuming and provides limited information about what happens to the remainder of the proteins in each complex.  As a result, there is a lack of detailed knowledge in the field. Proteomics helps supercomplexes give up their secrets To generate much more detailed data, the team applied a proteomic technology called mass spectrometry to measure the mitochondrial proteins. By applying proteomics instead of antibodies, the scientists were able to measure nearly all of the proteins in each complex. This provided unprecedented detail of mitochondrial supercomplexes in skeletal muscle and how exercise training influences their formation. Their approach demonstrated that not all of the proteins in each complex or a supercomplex respond to exercise in the same manner.  "Mitochondrial protein content is known to increase with exercise, thus understanding how these proteins assemble into supercomplexes is crucial to decipher how they work. Our research represents a valuable and precious resource for the scientific community, especially for those studying how the mitochondrial proteins organize to be better at what they do best: produce energy under demand,", explains Postdoc Alba Gonzalez-Franquesa. The interdisciplinary project was a collaboration between the Deshmukh, Treebak and Zierath Groups at CBMR, and the Mann Group at the Novo Nordisk Foundation Center for Protein Research.

In this special episode of the podcast, we discuss the carbon emissions coming from computational biology with two experts: Loïc Lannelongue and Jason Grealey. What does ‘the cloud' or a server actually look like? How are IT use and computational science linked to carbon emissions? And does it make any difference if you reduce how much data you store or how many computations you run!? Join us on our mission towards more sustainable research as we discuss obstacles and solutions, talk to other caring scientists, and try to figure out how to make scientific research more sustainable. One thing is certain: Mission Sustainable isn't a Mission Impossible! Your hosts are: Adriana Wolf Perez, Ph.D., working as a scientist in a biomedical start-up company in Cambridge, UK Nikoline Borgermann, Ph.D., working as an independent green lab consultant at Ava Sustain in Copenhagen, Denmark ... and both are passionate about the planet and people! Reach out if you have questions or comments! podcast@avasustain.com Our guests are: Jason Grealey, Ph.D. student at Baker Heart and Diabetes Institute (Australia) Loic Lannelongue, Ph.D. student at Systems Genomic lab, University of Cambridge (UK) Useful links related to Episode 6: Jason's and Loïc's online tool: https://www.green-algorithms.org/ Jason's and Loïc's publications on the topic: https://onlinelibrary.wiley.com/doi/full/10.1002/advs.202100707 and https://www.biorxiv.org/content/biorxiv/early/2021/03/09/2021.03.08.434372.full.pdf The FAIR data concept: https://pubmed.ncbi.nlm.nih.gov/26978244/ and https://www.ukdataservice.ac.uk/manage-data/lifecycle Green Labs Netherlands: https://www.greenlabs-nl.eu/ Estel Collado Camps' blogpost on the topic here: https://www.radboudumc.nl/en/news/2021/green-intentions-april Twitter: @caringscientist Instagram: @thecaringscientist Our Linktree: www.linktr.ee/thecaringscientist Nikoline's website: www.avasustain.com You can find Nikoline's social media accounts under @avasustain (Twitter, LinkedIn, Instagram) Special thanks to: Estel Collado Camps (for reaching out, connecting us to Loïc and Jason, and helping to script) Joana Duro Fernandes (Podcast Cover) Laurie Pattison (Music)

Greater magnesium intake linked with lower risk of liver cancer Mt Sinai Hospital, March 22 2021.    A study of AARP members revealed a protective effect for increased intake of magnesium against the risk of developing liver cancer. The findings were published in the March 2021 issue of The American Journal of Clinical Nutrition.  For the current study, researchers at Vanderbilt University Medical Center in Nashvilleexamined data from 536,359 participants in the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study cohort, which is which is one of the largest and longest prospective cohorts that collected data concerning diet and cancer outcomes in the United States. Food frequency questionnaire responses provided by the participants during 1995 to 1996 were analyzed for total magnesium and total calcium intake from supplements and food. The subjects were followed up to December 31, 2011, during which 1,067 cases of primary liver cancer were diagnosed.  Among those whose total magnesium intake was among the top 25% of participants, there was a 35% lower adjusted risk of developing liver cancer in comparison with participants whose intake was among the lowest 25%. Heavy users of alcohol who had a high magnesium intake experienced an even greater protective effect.  As potential mechanisms for magnesium against liver cancer, authors Shalija C. Shah, MD, and colleagues observed that the mineral is a cofactor for enzymes involved in DNA replication and repair, gene expression, cell proliferation and differentiation, and other factors.  “Based on a prospective cohort analysis, we demonstrated that magnesium intake is associated with a lower risk of primary liver cancer, which was more pronounced among moderate and heavy alcohol users,” they concluded. “These findings add clinical value to the current expansive body of translational literature defining the mechanisms through which this essential micronutrient mediates inflammatory and antineoplastic pathways, particularly within the liver.”     Green leafy vegetables essential for muscle strength Eating just one cup of leafy green vegetables every day could boost muscle function, according to new research. Edith Cowan University (Australia), March 24, 2021   Eating just one cup of leafy green vegetables every day could boost muscle function, according to new Edith Cowan University (ECU) research. The study, published today in the Journal of Nutrition, found that people who consumed a nitrate-rich diet, predominantly from vegetables, had significantly better muscle function of their lower limb. Poor muscle function is linked to greater risk of falls and fractures and is considered a key indicator of general health and wellbeing. Researchers examined data from 3,759 Australians taking part in Melbourne's Baker Heart and Diabetes Institute AusDiab study over a 12-year period. They found those with the highest regular nitrate consumption had 11 per cent stronger lower limb strength than those with the lowest nitrate intake. Up to 4 per cent faster walking speeds were also recorded. Lead researcher Dr Marc Sim from ECU's Institute for Nutrition Research said the findings reveal important evidence for the role diet plays in overall health.  "Our study has shown that diets high in nitrate-rich vegetables may bolster your muscle strength independently of any physical activity," he said. "Nevertheless, to optimise muscle function we propose that a balanced diet rich in green leafy vegetables in combination with regular exercise, including weight training, is ideal." Muscle function is vital for maintaining good overall health, especially bone strength later in life. "With around one in three Australians aged over 65 suffering a fall each year, it's important to find ways of preventing these events and their potentially serious consequences," said Dr Sim. Go for green While leafy greens may be some of our least favourite vegetables, they could be the most important, according to Dr Sim. The research found nitrate-rich vegetables, such as lettuce, spinach, kale and even beetroot, provided the greatest health benefits. "Less than one in ten Australians eat the recommended five to six serves of vegetables per day," Dr Sim said. "We should be eating a variety of vegetables every day, with at least one of those serves being leafy greens to gain a range of positive health benefits for the musculoskeletal and cardiovascular system."  "It's also better to eat nitrate-rich vegetables as part of a healthy diet rather than taking supplements. Green leafy vegetables provide a whole range of essential vitamins and minerals critical for health." Building knowledge The study, a collaboration with Deakin University's Institute of Physical Activity and Nutrition and the Baker Heart and Diabetes Institute, builds on Dr Sim's previous research into nitrate and muscle function in older women.  It also adds to growing evidence linking vegetables with cardiovascular health, including a recent ECU study into cruciferous vegetables and blood vessel health. Dr Sim said the next step of his research will be exploring strategies to increase leafy green vegetable consumption in the general population.  "We are currently recruiting for the MODEL Study, which examines how knowledge of disease can be used to prompt people in making long-term improvements to their diet and exercise," said Dr Sim.     Preservative used in hundreds of popular foods may harm the immune system New science suggests the FDA should test all food chemicals for safety Environmental Working Group, March 25, 2021   A food preservative used to prolong the shelf life of Pop-Tarts, Rice Krispies Treats, Cheez-Its and almost 1,250 other popular processed foods may harm the immune system, according to a new peer-reviewed study by Environmental Working Group. For the study, published this week in the International Journal of Environmental Research and Public Health, EWG researchers used data from the Environmental Protection Agency's Toxicity Forecaster, or ToxCast, to assess the health hazards of the most common chemicals added to food, as well as the "forever chemicals" known as PFAS, which can migrate to food from packaging.  EWG's analysis of ToxCast data showed that the preservative tert-butylhydroquinone, or TBHQ, has been found to harm the immune system both in both animal tests and in non-animal tests known as high-throughput in vitro toxicology testing. This finding is of particular concern during the coronavirus pandemic. "The pandemic has focused public and scientific attention on environmental factors that can impact the immune system," said Olga Naidenko, Ph.D., EWG vice president for science investigations and lead author of the new study. "Before the pandemic, chemicals that may harm the immune system's defense against infection or cancer did not receive sufficient attention from public health agencies. To protect public health, this must change." TBHQ TBHQ is a preservative that is pervasive in processed foods. It has been used in foods for many decades and serves no function besides increasing a product's shelf life. Using new non-animal test results from ToxCast, EWG found that TBHQ affected immune cell proteins at doses similar to those that cause harm in traditional studies. Earlier studies have found that TBHQ might influence how well flu vaccines work and may be linked to a rise in food allergies.  PFAS Using ToxCast, EWG analyzed all publicly available studies that show how PFAS migrate to food from packaging materials or processing equipment. This is the first known compilation of available research on PFAS migration from packaging to food. In 2017, nationwide tests showed that many fast-food chains used food wrappers, bags and boxes coated with highly fluorinated chemicals. Human epidemiological studies show that PFAS suppresses immune function and decreases vaccine efficacy. Recently published research has also found a link between high levels of PFAS in the blood and the severity of Covid-19.  Surprisingly, for most PFAS, the ToxCast results did not match previous animal and human test data. This illustrates the limitations of this new chemical testing method. More research is needed to understand how PFAS harm the immune system. Food Chemicals Regulation The Food and Drug Administration's approach to the regulation of food additives does not consider the latest science on the health harms of additives that may be legally added to processed foods manufactured in the U.S. Last year, EWG published Food Additives State of the Science, which highlighted additives known to increase the risk of cancer, harm the nervous system and disrupt the body's hormonal balance.  Chemicals linked to health harms can be legally added to packaged foods because the FDA frequently allows food manufacturers to determine which chemicals are safe. Additives like TBHQ were approved by the FDA decades ago, and the agency does not consider new science to reassess the safety of food chemicals.  "Food manufacturers have no incentive to change their formulas," said Scott Faber, senior vice president for government affairs at EWG. "Too often, the FDA allows the food and chemical industry to determine which ingredients are safe for consumption. Our research shows how important it is that the FDA take a second look at these ingredients and test all food chemicals for safety." Less Toxic Food Preservatives Processed foods can be made without these potentially harmful ingredients, so shoppers should read labels carefully. TBHQ is often, though not always, listed on the ingredient label. It will be listed if it has been added to the product during manufacturing. But it can also be used in food packaging, particularly plastic packaging, in which case it may migrate to food.  EWG's Food Scores database helps consumers find products made with healthier alternatives, and our Healthy Living app allows shoppers to scan products while in stores to choose a better option.  EWG recommends that immunotoxicity testing be prioritized for chemicals in food and food contact materials in order to protect public health from their potential harm to the immune system.  EWG also calls on the FDA to close the regulatory loophole that allows potentially unsafe food additives to remain on the market. The FDA should also promptly review additives like TBHQ to reflect new science.     Transcendental Meditation effective in reducing PTSD, sleep problems, depression symptoms Maharishi International University, March 19, 2021   Veterans with PTSD who practiced the Transcendental Meditation technique showed significant reductions in PTSD symptom severity, according to a new study published today in Journal of Traumatic Stress. Fifty percent of the meditating veterans no longer met criteria for PTSD after three months compared to only 10 percent of controls. The randomized controlled study also showed significant reductions in veterans' symptoms of depression and anxiety, and sleep difficulties.  "Transcendental Meditation is a non-trauma-focused, easy-to-learn technique that was found in this study to improve PTSD symptoms, likely through the experience of physical rest," said Mayer Bellehsen, Ph.D., director of the Unified Behavioral Health Center for Military Veterans and their Families, Northwell Health, and study principal investigator. "In contrast to commonly administered therapies for PTSD that are trauma-focused and based on a patient's recall of past traumatic experiences, this intervention does not require extensive review of traumatic history, which some individuals find difficult to engage in. This intervention may therefore be more tolerable for some individuals struggling with PTSD." The randomized controlled trial, conducted at Northwell Health in Bay Shore, New York, assigned 40 veterans with documented PTSD to either the Transcendental Meditation (TM) group or treatment as usual control group. The TM treatment provided 16 sessions over 12 weeks, with twice-a-day daily home practice. PTSD symptom severity was assessed with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), and patient self-report with the PTSD Checklist for DSM -5 (PCL-5).  The results showed large effect sizes, indicating a strong TM treatment impact in reducing trauma symptoms for both PTSD measures. Other factors associated with trauma, such as depression and anxiety symptoms and sleep problems, also showed a strong impact of TM treatment. "This trial corroborates the findings of a large clinical trial published in The Lancet Psychiatry," said Sanford Nidich, Ed.D., Director of the Center for Social-Emotional Health at Maharishi International University Research Institute, and study co-investigator. "The current study further supports the effectiveness of Transcendental Meditation as a first-line treatment for PTSD in veterans. The availability of an additional evidence-based therapy will benefit veterans, both by offering them a greater range of options and by serving as an alternative treatment strategy for those who don't want to engage in trauma-focused treatment or who aren't responding to a previous PTSD intervention."  The authors point out in their research paper that TM may positively affect trauma symptom severity through the reduction of hyperarousal symptoms. Previous research has shown that TM practice decreases physiological responses to stressful stimuli. In addition, recent research indicates that TM may improve resilience and positive coping strategies, providing further benefit to both veterans and active military personnel.     Study: Eating White Bread & Bagels Can Be Worse Than Smoking – 49% Increase In Lung Cancer University of Texas, March 17, 2021 An alarming study has found eating foods high on the glycemic index (GI), such as bagels, white bread, and rice, increase the risk of developing lung cancer by 49 percent — particularly for non-smokers. In fact, when researchers studied the diets of 4,320 people, they were shocked to find non-smokers with diets high on the GI had nearly double the risk to develop the disease than those whose eating habits remained on the low end of the GI. Foods with high GI raise blood glucose and insulin, in turn causing increased insulin growth factors (IGFs), which are associated with greater risk for developing lung cancer. University of Texas MD Anderson Cancer Center conducted the study of 1,905 people who had cancer diagnoses and 2,415 healthy people, which was published this month in the journal Cancer, Epidemiology, Biomarkers & Prevention, RTreported. “The results from this study suggest that, besides maintaining healthy lifestyles, such as avoiding tobacco, limiting alcohol consumption, and being physically active, reducing the consumption of foods and beverages with high glycemic index may serve as a means to lower the risk of lung cancer,” explained Dr. Xifeng Wu, study senior author. Lung cancer is the number one cause of cancer deaths in the United States. More the 150,000 people will die from lung cancer in 2016 alone, according to the American Cancer Society. What’s more, a second study revealed Americans consume more than half their calories via “ultra-processed” foods, which directly contribute to health problems like obesity and heart disease. “Ultra-processed foods are products that contain several manufactured ingredients that are not generally used when cooking from scratch, including natural and artificial flavors or colors, artificial sweeteners, preservatives, and other additives,”CBS News explained. Obvious examples of ultra-processed foods include soft drinks; chicken and fish nuggets, as well as other reconstituted meat products; packaged snacks, both sweet and savory; packaged baked goods; and instant noodle products. Lead author of the study, Professor Carlos Augusto Monteiro at the University of São Paulo School of Public Health, Dept. of Nutrition, explained such highly-processed foods are designed to imitate natural foods, but often “disguise undesirable qualities of the final product.” Where a diet of fresh foods and minimally-processed products — like cheeses and simple breads — are healthiest, Monteiro told CBS News, ultra-processed products “are manufactured and marketed to replace those foods, drinks, dishes, and meals.” Such ‘foods’ are generally high in sugars, saturated fat, and sodium and contribute to a wide range of health issues, including diabetes, obesity, heart disease, and many more. Both studies ultimately suggest the need to cut out highly-processed products and return to a natural diet rich in fruits, vegetables, and whole grains. In other words, food — not products.   Move your body for five minutes every hour to counteract lockdown inactivity Kings College London, March 23, 2021 A study which looked at activity levels before and during the COVID-19 pandemic has found lockdown restrictions significantly reduced light activity associated with socialising and work. The study, published recently in BMJ Neurology and led by King's College London, examined how activity levels changed in study participants with muscular dystrophy and other inheritable myopathies. The sample included people with a range of physical abilities, from highly independent to assisted mobility, including 41 wheelchair users, who are often underrepresented in research. However, the authors say the findings are likely to be relevant to adults of various abilities and backgrounds because many people have lost their usual daily routine during lockdown. The study is unique because it used accelerometers to measure physical activity before and during lockdown as part of an ongoing longitudinal physical activity study from 2019 to 2020. The accelerometers measured activity intensity, frequency and time in vigorous, moderate, light and inactive categories. Researchers found there was a significant reduction in daily activity intensity during lockdown. Before lockdown, participants did a mean of 84.5 minutes per day of light activity and had a relatively low frequency of hourly movement. During lockdown, light activity reduced by a mean of 25 minutes per day and frequency of hourly movement reduced by a median of 11%. Moderate and vigorous activity did not change significantly during lockdown, but this might be explained by low baseline levels in this group.  In lockdown, the reduction in light activity time and frequency of movement was explained by restrictions on going to work, leisure pursuits and socialising. This light activity within daily routine is not exercise-focused so it can be difficult for individuals to detect these subtle light activity losses. However, light activity and regular movement throughout the day are associated with improved health outcomes for everyone, regardless of health conditions. Sarah Roberts-Lewis, the study lead and a Neurological Physiotherapist at King's College London, said; "Even people who don't do much exercise have been impacted by lockdown inactivity. During COVID-19 lockdown, our study detected an extra hour per day of inactivity in disabled and independent adults with neuromuscular diseases. Moving less is detrimental to health. Reduced activity can be especially harmful for those with neuromuscular conditions, disabilities or advanced age."  "The reduction in light activity measured in this study is likely to be similar for anybody whose daily routine has been restricted by lockdown. Based on our findings, we suggest people move their bodies for 5 minutes each hour during the day. Additionally, spend 30 minutes each day doing some extra light activity, like yoga or chair exercises. The World Health Organisation activity guidelines state 'every move counts'; they provide suggestions about light activites suitable for all abilities. Simple changes can help with reconditioning during and after lockdown."     Lifestyle program improves fertility for women with obesity, infertility University of Sherbrooke (Quebec) March 19, 2021 A lifestyle intervention targeting women with obesity and infertility is more effective in increasing the pregnancy rate compared with fertility treatments, according to a study presented virtually at ENDO 2021, the Endocrine Society's annual meeting. The lifestyle intervention, called the Fit-For-Fertility (FFF) program, is a cost-effective alternative to the usual standard of care for women with obesity seeking fertility treatments, according to lead researcher Matea Belan, Ph.D., of the University of Sherbrooke and the Research Center of the Centre Hospitalier Universitaire de Sherbrooke (RC-CHUS) in Quebec, Canada. "Our study shows that the FFF program can significantly improve the pregnancy rate, especially the spontaneous pregnancy rate when no fertility treatments are required, as well as the live-birth rate," she said. Obesity is a known risk factor for infertility in women of childbearing age. Lifestyle changes and a moderate weight loss of 5%-10% of a woman's initial weight have been shown to improve the odds of a pregnancy in women with obesity and infertility, Belan noted. "Lifestyle changes are recommended as the first-line treatment for these women," said study author Jean-Patrice Baillargeon, M.D., M.Sc., professor of the University of Sherbrooke and clinician investigator of the RC-CHUS. The new study tested Fit-For-Fertility, a multidisciplinary lifestyle intervention that includes a nutritionist and a kinesiologist, or human movement specialist. The researchers recruited 130 women receiving treatment at a fertility clinic, and randomly divided them into two groups. The first group had access to the Fit-For-Fertility program alone for the first six months of their participation, and in combination with fertility treatments if no pregnancy occurred after six months. The program included individual sessions with a nutritionist and a kinesiologist every six weeks. Women in the FFF group were also asked to follow at least once each one of the 12 group sessions, which included a 45-minute workshop on topics regarding nutrition, lifestyle changes and lifestyle habits, followed by a 45-minute session of initiation to different types of physical activity, including walking, circuit training, step workout and others. In the second group, the control group, women had access to the fertility treatments from the outset but did not take part in the FFF program. Data was collected for 18 months, or until the end of a pregnancy for women who became pregnant during those 18 months of participation. Of the 108 women who completed at least six months of the study, or became pregnant during the first six months, the FFF program generated a difference of 14.2 percentage points in the live-birth rate (51% for the FFF group and 36.8% for the control group). The spontaneous pregnancy rate (pregnancy without any fertility treatments) was 33.3% in the treatment group, compared with 12.3% in the control group. The researchers estimate the cost per additional newborn resulting from the FFF program at $12,633 (in 2019 Canadian dollars), somewhat similar to the willingness-to-pay for a newborn resulting from in vitro fertilization, which can cost up to $15,000. "We hope this research will give women with obesity and infertility affordable access to a tailored lifestyle intervention adapted to their condition and their specific needs in order to improve their chances of having a pregnancy and building a family," Belan said.     Vitamin B3 to stay younger? A global increase in antioxidant defenses of the body may delay aging and its diseases   Centro Nacional de Investigaciones Oncológicas (Spain), March 15, 2021   The gradual accumulation of cell damage plays a very important role in the origin of ageing. There are many sources of cellular damage, however, which ones are really responsible for ageing and which ones are inconsequential for ageing is a question that still lacks an answer. The Oxidative Hypothesis of Ageing -- also known as the Free Radicals Hypothesis -- was put forward in 1956 by Denham Harman. Since then, the large majority of attempts to prove that oxidative damage is relevant for ageing have failed, including multiple clinical trials in humans with antioxidant compounds. For this reason, although the accumulation of oxidative damage with ageing is undisputed, most scientists believe that it is a minor, almost irrelevant, cause of ageing. However, this may change in light of the recently published observations. A group of scientists from the Spanish National Cancer Research Centre (CNIO) headed by Manuel Serrano, in collaboration with a group from the University of Valencia, directed by José Viña, and researchers at IMDEA Food from Madrid, have tried to increase the global antioxidant capacity of the cells, rather than just one or a few antioxidant enzymes. To achieve this global improvement in the total antioxidant capacity, researches have focused on increasing the levels of NADPH, a relatively simple molecule that is of key importance in antioxidant reactions and that, however, had not been studied to date in relation to ageing. The researchers used a genetic approach to increase NADPH levels. In particular, they generated transgenic mice with an increased expression throughout their bodies of one of the most important enzymes for the production of NADPH, namely, glucose-6-phosphate dehydrogenase (or G6PD). The results, published today in the journal Nature Communications, indicate that an increase in G6PD and, therefore, in NADPH, increases the natural antioxidant defences of the organism, protecting it from oxidative damage, reducing ageing-related processes, such as insulin resistance, and increasing longevity. Antioxidants That Delay Ageing "As anticipated, the cells in these transgenic animals are more resistant to highly toxic artificial oxidative treatments, thus proving that an increase in G6PD really improves antioxidant defences," explains Sandrina Nóbrega-Pereira, first author of the study and currently a researcher at the Institute of Molecular Medicine of the University of Lisbon. Furthermore, when researchers analysed long-lived transgenic animals, they noted that their levels of oxidative damage were lower than in non-transgenic animals of the same age. They also studied the propensity of these animals to develop cancer and found no difference, suggesting that enhancing G6PD activity does not have an important effect on the development of cancer. The greatest surprise for the team was when they measured the ageing process in the transgenic mice: the animals with a high G6PD expression and, therefore, high levels of NADPH, delayed their ageing, metabolised sugar better and presented better movement coordination as they aged. In addition, transgenic females lived 14% longer than non-transgenic mice, while no significant effect on the longevity of males was observed. "This increased longevity, although modest, is striking taking into account that until now attempts to increase longevity by manipulating individual antioxidant enzymes had failed," said Pablo Fernández-Marcos, co-first author of the study and researcher at IMDEA Food. Overall Increase in the Antioxidant Capacity of Cells Perhaps the key is that the researchers involved in this paper enhanced all antioxidant enzymes in a comprehensive manner. "Compared to the traditional approach of administering antioxidants that react directly with oxygen, we have stimulated all the cell's natural antioxidant mechanisms by raising G6PD levels, and its by-product, NADPH," emphasizes Mari Carmen Gómez-Cabrera, co-author of the paper and researcher at the University of Valencia. Based on these results, the authors of the study point to the use of pharmacological agents or nutritional supplements that increase NADPH levels as potential tools for delaying the ageing process in humans and age-related diseases, such as diabetes, among others. More specifically, vitamin B3 and its derivatives are responsible for the synthesis of NADPH precursors and are suitable candidates for future studies.

Professor Tom Marwick, director of the Baker Heart and Diabetes Institute, explained more about the trial on 3AW Breakfast. See omnystudio.com/listener for privacy information.

Head of the Physical Activity Laboratory at the Baker Heart and Diabetes Institute, David Dunstan, says the recommendations acknowledge, for the first time, that any movement is beneficial. See omnystudio.com/listener for privacy information.

This week’s episode includes author Mark Chan, editorialist Thomas Wang, and Associate Editor Wendy Post as they discuss the prioritization of candidates of post-myocardial infarction heart failure using plasma proteomics and single-cell transcriptomics. TRANSCRIPT BELOW: Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr Greg Hundley: And I'm Greg Hundley, associate editor, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Well, Carolyn, this week's feature, really interesting, involving proteomics and single-cell transcriptomics, trying to identify how we could prioritize individuals after they've sustained myocardial infarction as to whether or not they'll develop heart failure. Lots to go over in that feature. But before we get to that, how about we grab a cup of coffee and start in with some of the other interesting papers in this issue? Dr Carolyn Lam: Absolutely. I've got my coffee and I have to tell you though, I am so excited about this feature, it comes from Singapore, but my first paper too is about transcriptomic profiling. But Greg, I have to ask you first, have you heard of the cardiac cellulome? Dr Greg Hundley: Oh my goodness, Carolyn. So you're starting the reverse-quiz strategy to help me. I have not heard of the cellulome. Help enlighten me. Dr Carolyn Lam: I just love that word. We've heard of all kinds of other omes, but this cellulome is something I've learned through today's paper. So the authors today who are Alexander Pinto from Baker Heart and Diabetes Institute and colleagues, they developed a novel cardiac single-cell transcriptomic strategy to characterize the cardiac cellulome. And that refers to the network of cells that forms the heart. The method was utilized to profile the cardiac cellular ecosystem in response to two weeks of angiotensin II as a pro-fibrotic stimulus. So what did they find? Well, they identified two previously undescribed cardiac fibroblasts populations that are the key drivers of fibrosis. Their names were Fibroblast-Cilp and Fibroblast-THBS4. Now, these do not correspond to smooth muscle actin-expressing myofibroblasts, which have been widely viewed as the primary drivers of fibrosis. So this is really novel. The cardiac cellular landscape was sexually dimorphic at the cell abundance and gene expression level, including cellular responses to angiotensin II induced tissue remodeling. So these data really provide insights into the cellular and molecular mechanisms that promote pathologic remodeling in the mammalian heart, and really highlight that early transcriptional changes precede chronic cardiac fibrosis. Dr Greg Hundley: Very nice, Carolyn. Well, let me switch to the clinical realm. And my first paper comes from Professor Holger Thiele from the Heart Center Leipzig at the University of Leipzig, and it's involving general versus local anesthesia with conscious sedation for patients undergoing TAVI procedures. So the study comes from the SOLVE-TAVI study, and it's a multi-center open-label 2x2 factorial randomized trial of 447 patients with aortic stenosis undergoing transfemoral TAVR, comparing conscious sedation versus general anesthesia. And the primary efficacy endpoint was powered for equivalence, and consisted of the composite of all-cause mortality, stroke, myocardial infarction, infection requiring antibiotic treatments, and acute kidney injury at 30 days. Dr Carolyn Lam: Wow, Greg, as I understand it, about half of patients today receive TAVI or TAVR with conscious sedation. So it's really an important question. So what did they find? Dr Greg Hundley: You're exactly right. So the composite end point occurred in 27% of the conscious sedation patients and 26% of the general anesthesia patients. Really equivalent. And this held true for each of those composite endpoints. In addition, there was a lower need for inotropes or vasopressors with conscious sedation, versus general anesthesia. Thus, these findings suggest that conscious sedation can safely be used for patients undergoing TAVR procedures. Dr Carolyn Lam: Very important clinical one, Greg. Well, I've got a clinical paper for you too. And this one, trying to answer the question, what's the optimal duration of dual anti-platelet therapy, or DAPT, after PCI with drug-eluting stents. A very familiar, perhaps, an important question. So these authors, led by Dr Deepak Bhatt from Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, performed a systematic review and network meta-analysis of 24 randomized controlled trials comparing short-term DAPT, or less than six months, followed by aspirin or P2Y12 inhibitor monotherapy, versus mid-term DAPT, which was six months, versus 12 months DAPT, as well as an extended-term DAPT, which was more than a year after PCI with a drug-eluting stent. Dr Greg Hundley: So Dr Carolyn, three groups, what did they find? Dr Carolyn Lam: Compared to 12 months DAPT, short-term DAPT followed by P2Y12 inhibitor monotherapy reduced major bleeding after PCI with a drug-eluting stent, whereas extended-term DAPT reduce myocardial infarction at the expense of more bleeding events. Overall, the extended-term DAPT was associated with a higher risk of major bleeding compared with all other DAPT groups, except in patients with acute coronary syndrome. Dr Greg Hundley: So extended, more bleeding complications. So take me home on this, Carolyn, what is the final message here? Dr Carolyn Lam: Here's the message. Compared with 12-month DAPT, the net clinical benefit appears to favor short-term DAPT followed by P2Y12 inhibitor monotherapy instead of aspirin in select patients. Although, extended term DAPT has a role for patients who have a low bleeding risk, but a higher ischemic risk, such as those with acute coronary syndrome, thus a personalized approach appears to be warranted. Dr Greg Hundley: Very good. Well, I'm going to turn back to the world of basic science and discuss a paper related to pulmonary hypertension. And it comes from Dr Sébastien Bonnet from the University Laval. So Carolyn, the subcellular mechanisms that govern the transition from a compensated to a de-compensated right ventricle in patients with pulmonary hypertension remain poorly understood, and as a consequence, there are no clinically established treatments for RV failure and a paucity of clinically useful biomarkers. So this study investigated the long non-encoding RNAs, powerful regulators of cardiac development disease, in relation to adverse RV remodeling in pulmonary artery hypertension. Dr Carolyn Lam: So these LNK RNAs, I think that's what they're called, right? Long non-coding RNAs, what did they find? Dr Greg Hundley: This was another one of our really nice translational articles, because they combined results from both animals and human subjects. The authors demonstrated that the long non-coding RNA H19 is upregulated in decompensated right ventricles due to pulmonary hypertension, and the finding correlated with RV hypertrophy and fibrosis. Now, similar findings were observed in monocrotaline and pulmonary artery banded rats. The authors found that silencing H19 limits pathological RV hypertrophy, fibrosis, and capillary rarefaction, thus preserving RV function in those two models of pulmonary hypertension, both the monocrotaline and the pulmonary artery banded rats, without effecting pulmonary vascular remodeling. And finally, Carolyn, the authors found that circulating H19 levels in plasma of patients, discriminate pulmonary arterial hypertension patients from controls correlated with RV function and predicted long-term survival in two independent idiopathic pulmonary artery hypertension cohorts. Moreover, H19 levels delineated subgroups of patients with differential prognosis, when combined with NT-proBNP levels or the risk score proposed by both the Reveal and the 2015 European Pulmonary Hypertension Guidelines. So, in summary, these authors findings identify H19 as a potentially new therapeutic target to impede the development of maladaptive RV remodeling, and thus a promising biomarker as well of pulmonary arterial hypertension severity and prognosis. Dr Carolyn Lam: Oh, Greg, I love that. Not just the paper, but the way you explained it. Thanks so much. Well, let's dip into what else there is in today's issue, shall we? First, there's Global Rounds by Dr Yacoub entitled, Towards Meeting the Challenges of Improving Cardiovascular Health in Egypt. There's a research letter by Dr Cheng on imaging the sarcoplasmic reticulum calcium signaling in intact cardiac myocytes. There's another Research Letter by Dr Angiolillo on the pharmacodynamic and pharmacokinetic effects of a low maintenance dose ticagrelor regimen, versus standard dose clopidogrel, in patients with diabetes without prior major cardiovascular events, undergoing elective PCI. And this is the OPTIMUS-6 study. There's an On my Mind paper by Dr Santos on coronary artery calcification and familial hypercholesterolemia, and an ECG Challenge by Dr Liu, which is not your uncommon electrocardiographic findings, and really looking at Q waves with post-QRS deflections. I'll let you take a look. Dr Greg Hundley: Oh, wow, Carolyn. This issue is just jammed with really nice articles. I've got a research letter entitled, Long-Term Outcomes After Infective Endocarditis, Following Transcatheter Aortic Valve Replacement, and it's from Dr Josep Rodés-Cabau from Quebec Heart and Lung Institute. And then finally, a nice exchange of letters by Drs Rozenbaum, Kemner, and Parasuraman regarding the article Cost-Effectiveness of Tafamidis Therapy for Transthyretin Amyloid Cardiomyopathy, and there's a very nice response by Dr Kazi. Now we get to proceed on to that feature article. Dr Carolyn Lam: Yay! Let's go, Greg. Dr Greg Hundley: Well listeners, we are to our feature discussion. And today we have Dr Mark Chan from the National University of Singapore, our own associate editor, Dr Wendy Post from Johns Hopkins, and Dr Thomas Wang from the University of Texas Southwestern Medical Center. Well, Mark, we'll start with you. Could you explain to us some of your thinking behind how you formulated this study and what was the hypothesis that you wanted to address? Dr Mark Chan: The background, really, was to try to prioritize protein candidates in post myocardial infarction heart failure. We do know that there are several hundred candidates out there in the literature, but really, what we wanted to do was to try to enrich and select out what we thought would be the most biologically relevant proteins. And really, the hypothesis was that, by combining two very powerful unbiased discovery tools that have been developed in the last few years, we would be able to achieve this goal. The two tools, I think, Tommy would be very familiar with, because he's used plasma proteomics as well in a lot of his work. That's one of the unbiased discovery tools that we used. Measuring 1300 proteins in blast mine. Second two was a single-cell transcriptomics where we're able to look at RNA sequences, genome RNA sequences, at the individual cell level. So we first started off with cohorts of patients with acute myocardial infarction that were followed up for about five years for heart failure events, and we obtained plasma from these patients at about 30 days after myocardial infarction. So with the initial plasma proteomics, and found more than 200 candidates, actually very similar to what we actually see in the literature in terms of protein candidates predicting heart failure, in particular, post-MI heart failure. We then thought that what we really want to do is prioritize the most important proteins, and that's when we went onto single-cell transcriptomics. And we found a total of 83 protein candidates, which were directionally similar across the human plasma proteomics and the single-cell transcriptomic data across different models of ischemic heart failure. And six candidates are the ones that we are hoping to discuss a bit more about, the top six candidates, today, which I'm sure you'll ask me about very soon. Dr Greg Hundley: You've really led us into the next question. Tell us a little bit about the six candidates. Dr Mark Chan: The top six candidates to all of us are really familiar with NT-proB natriuretic peptide that's been around for decades, cardiac troponin, that's the second well-known, well-established candidate, and four other candidates that seem to be really emerging as potential targets in heart failure and ischemic cardiomyopathy. Angiopoietin-2, thrombospondin-2, latent-transforming growth factor binding protein 4, and a less commonly investigated protein, FSLT3, or follistatin-like related protein 2. The two candidates that are particularly interesting to me are angiopoietin-2 and thrombospondin-2 , and looking at a lot of Tommy Wang's work as well, we can see that these two candidates looking to be important future targets for biomarker discovery, validation, and maybe, potentially, druggable candidates to manage patients with post-MI heart failure and ischemic cardiomyopathy. Dr Greg Hundley: Wendy, coming to you as an associate editor and really an expert in genetic epidemiology, what intrigued you about this article? Especially I heard Mark discuss differentially expressed genetics and transcriptomics. What brought you to this article and what increased its relevance to you? Dr Wendy Post: We were very intrigued by both the importance of the problem that was being addressed, in that ischemic cardiomyopathy is a very common and major challenge that we all encounter as cardiologists, but also the unique approach that was used to handle a large amount of data. So with the plasma proteomic approach, which Mark described as the first step, you take thousands of data points and try to narrow it down, which he did, but still needed to narrow it down even more. And then use a complimentary, but different, approach to try to understand which of these hits, so to speak, maybe the ones that are important. And so using the single-cell transcriptomic approach, was able to narrow down to these six candidates. And then it was very reassuring that two of the six were what we would have hypothesized. So if you didn't find those, we'd worry that maybe something was wrong with your approach. So on the one hand, you'd say, "Well, we already knew that. So what are you telling us?" But it actually was proof, so to speak, that your approach was working, and that these other four novel candidates might turn out to be the next BNP. So that was really a few of the things that intrigued us about this paper. Dr Greg Hundley: So Tommy, as a practicing clinical cardiologist, and then also, really, as a clinician researcher, what do you see as relevant with Mark's work and also Wendy's description here for all of us that are seeing patients that has sustained myocardial infarction? Dr Thomas Wang: I think as Mark and Wendy have both nicely summarized, but I'll revisit, they're really two areas in which knowledge of these biomarkers could impact patient care down the road. One is an informative set of biomarkers to tell us which among the large number of patients with myocardial infarction might be destined to develop heart failure so that we can, as clinicians, ramp up our therapies, increase our vigilance, increase our monitoring, so that we might be able to intervene on that at a very early stage, or even before the heart failures develop. The second, which is potentially even more exciting, is the possibility that some of these biomarkers might be so informative of pathways leading to heart failure, that we could actually directly intervene on the pathways that are reflected by these biomarkers. So in other words, biomarkers would tell us not just biology, but about therapeutically effective strategies. And I think, as Mark has nicely emphasized, there are scores, if not hundreds, of biomarkers that have been looked at in this context, and there's no amount of resource in the world that allows investigators to pursue, in prospective clinical studies or experimental studies, all of these biomarkers. And so the real value of their study is to illustrate an approach for winnowing down this large number of biomarkers down to a smaller set, a much smaller set, that seem really worth pursuing in further study. Dr Greg Hundley: Well, with that lead in, Tommy and Mark and Wendy, maybe start with you, Mark, what do you see as the next step and this area of research moving forward? Dr Mark Chan: I think I need to sound a word of caution first with respect to the study itself. It is, at the end of the day, still a very descriptive study. Heavy in bioinformatic elucidation of targets. So careful mechanistic validation and further understanding of these highly prioritized targets will still be important. In terms of how we can potentially get these results closer to the post-MI heart failure patients, closer to the bedside, one concept that I think it's becoming increasingly apparent is that a lot of these bioactive proteins in circulating plasma are likely a part of the secretome. Part of what we call exosomes or micro-bubbles that are secreted by cells. And we do see the origin big cells in the single-cell studies as part of this paper. We do get an idea. A lot of these cells really are within the extracellular matrix, which is the substrate in which your cardiomyocytes are embedded. We think that enriching the plasma for the exosome fraction, which one of my colleagues is now working on, could be the best way to derive a more powerful tool for prognostication. To really determine with a high level of specificity, not just sensitivity, but highly specific to determine which patients end up with post-myocardial infarction heart failure. So enriching plasma for exosomes and potentially looking at the proteins within these exosomes, we've already started work on that. And so far, the results, compared to the proteins just measured in free plasma, seem to predict heart failure events a lot better when we come down to the exosome fraction. The other project, this is using exosomes to treat post-MI large animal models. So we have injected mesenchymal cell stem cell derived exosomes, and we've shown that they can reduce infarct size in large animal models, and also prevent some of the hemodynamic complications that result in heart failure. But really, trying to find which are the proteins actually are meaningfully preventing heart failure and reducing infarct size, I think that is also going to be part of the next steps. Dr Greg Hundley: Mark, thank you for that summary. Tommy, do you have anything to add to that? Dr Thomas Wang: I certainly agree with all that's been said. I would also emphasize that understanding the biology of some of these newer biomarkers and how they might link heart failure or active MI is going to be really important when we consider potential clinical applications. And so, further along the experimental line, I think animal models, mouse models, and other types of models, being which the biology and pathways we would manipulate it so that we can see whether these biomarkers truly do reflect etiologic pathways in heart failure would be valuable. Dr Greg Hundley: Thank you, Tommy. Well, listeners, we've had a great presentation from Dr Mark Chan, an excellent review by both Wendy Post and Tommy Wang, emphasizing how we are discovering new protein biomarkers using plasma proteomics for identification of those that may develop heart failure after myocardial infarction. And more to come in this area. We feel very privileged to have the opportunity to work with bright young investigators like this and present this work in Circulation For both Carolyn and myself, we wish you a great week and look forward to catching you next week on the Run. This program is copyright American Heart Association, 2020.

This month on Episode 16 of the Discover CircRes podcast, host Cindy St. Hilaire highlights four featured articles from the August 28 and September 11 issues of Circulation Research. This episode features an in-depth conversation with Drs Andrew Murphy and Michelle Flynn from The Baker Heart and Diabetes Institute at Monash University in Melbourne, Australia regarding their study Transient Intermittent Hyperglycemia Accelerates Atherosclerosis By Promoting Myelopoiesis.   Article highlights:   Fish, et al. KRAS Mutations Cause Arteriovenous Malformations   Ehling, et al. B55a in Vascular Biology   Barrett, et al.  Platelet Activity and Vascular Health in COVID-19   Furmanik, et al. Nox5 in VSMC Phenotype and Calcification     Cindy St. Hilaire:  Hi. Welcome to Discover CircRes, the podcast to the American Heart Association's journal, Circulation Research. I'm your host, Dr Cindy St. Hilaire, from the Vascular Medicine Institute at the University of Pittsburgh. And today I'm going to share with you four articles selected from our late August and early September issues of Circulation Research. I'm also going to speak with Drs Andrew Murphy and Michelle Flynn from The Baker Heart and Diabetes Institute at Monash University in Melbourne, Australia regarding their study Transient Intermittent Hyperglycemia Accelerates Atherosclerosis By Promoting Myelopoiesis. So first, the highlights. The first article I'm sharing with you is titled Somatic Gain of KRAS Function in the Endothelium is Sufficient to Cause Vascular Malformations that Require MEK but not PI 3-Kinase Signaling. First authors are Jason Fish, Carlos Perfecto Flores-Suarez, and Emily Boudreau. And the corresponding authors are Jason Fish and Joshua Wythe, and they're from University of Toronto and Baylor College of Medicine. Arterial venous malformations, or AVMs, are tangles of blood vessels in which the arteries are directly connected to the veins without going through the capillary bed. These are thought to be present from birth and when they occur in the brain, they can cause an array of symptoms such as headaches or seizures, but they are also the leading cause of hemorrhagic stroke in children and young adults. This is because the venous system is not muscularized to respond to the pressure forces that are exerted on arteries. These pressure forces cause distension and eventual leakage at the site of AVMs. Vessel tissue recovered from patients undergoing AVM repair has been shown to contain sematic gain of function mutations in the protein RAS GTPase, which is encoded by the gene, KRAS. However, whether these gain of function mutations directly cause AVMs has not been established. This study now shows that endothelial cells with constitutive expression of gain of function KRAS mutants in mice and zebra fish causes vascular malformations and cranial hemorrhages. Inhibiting a MEK kinase, which is a downstream mediator of RAS signaling, prevented hemorrhages in the mutant KRAS carrying fish. In vitro studies also showed that overactive RAS GTPase protein caused excessive angiogenic behavior of endothelial cells. Together, this work confirms the link between gain of function KRAS mutations and brain AVMs, and suggests that MEK inhibition could be a potential strategy for nonsurgical treatment. The second article I want to share with you is titled B55a/PP2A Limits Endothelial Cell Apoptosis During Vascular Remodeling: A Complimentary Approach To Kill Pathological Vessels. The first author is Manuel Ehling and the corresponding author is Massimiliano Mazzone. And the work was completed at Leuven Center for Cancer Biology in Belgium. Building a mammalian vascular system is a dynamic process that is dependent on both growth of new vessels, as well as the pruning of unwanted ones. But while much is known about molecular mechanisms underlying angiogenesis, comparatively little is understood about the mechanisms regulating vascular pruning. This study discovered that suppression of the protein phosphatase 2 subunit, B55A, is a key protein regulating the pruning process. They found that in mouse vascular development, B55a is widely expressed. However, in adult mice expression is restricted only to sites of active angiogenesis. Deletion of B55a in mice caused death in mid to late stages of embryogenesis as a result of vascular problems that appeared to be due to excessive vessel pruning. Switching off B55a in adult mice when the vascular development is for the most part complete did not cause any apparent problems. They did find though, that inhibition of B55a significantly delayed growth of tumors that form from the injection of cancerous cells. Inhibition of B55a produced tumors with less dense vasculature and reduced metastatic potential. Thus, the author suggests that ramping up blood vessel pruning, be it inhibition of B55a, could be a novel strategy for limiting tumor growth. The next article I want to share is titled Platelet and Vascular Biomarkers Associated With Thrombosis and Death in COVID-19. The first author is Tessa Barrett and the corresponding author is Jeffrey Berger, and they're from New York University. Our knowledge of the complications of COVID-19 is evolving every day. Laboratory testing done to date suggests that approximately 30% of hospitalized COVID-19 patients go on to develop thrombotic events. Platelets are central characters in both arterial and venous thrombosis, and it is known that virus platelet interactions can stimulate a pro-coagulant and inflammatory state during a viral infection. Further, recent studies have reported COVID-19 patients have hyperactive platelets and autopsies of COVID-19 patients exhibit micro and macro thrombi across vascular beds, even in patients without clinical thrombosis. This group then hypothesized that biomarkers of platelet activation are associated with incident thrombosis or death in COVID-19 patients. To test this, they randomly selected 100 COVID-19 positive patients and analyzed banked samples collected on the day of the COVID-19 diagnosis to investigate in vivo platelet activity, as well as vascular health biomarkers. They show for the first time that biomarkers of platelet activation at the time of diagnosis are associated with thrombosis or death in patients hospitalized with COVID-19. Their findings suggest platelet activation mechanisms may contribute to adverse events and highlight the potential role of antiplatelet therapy in this disease. The last article I want to share with you before we switch to our interview is titled Reactive Oxygen-Forming Nox5 Links Vascular Smooth Muscle Cell Phenotypic Switching and Extracellular Vesicle-Mediated Vascular Calcification. The first authors are Malgorzata Furmanik and Martijn Chatrou. And the corresponding author is Leon Schurgers from Maastricht University in The Netherlands. Vascular calcification is an active process regulated by several mechanisms, including vascular smooth muscle cell apoptosis, osteochondral genic transdifferentiation, extracellular vesicle release, and cellular senescence. In healthy adult arteries, smooth muscle cells maintain a contractile phenotype. However, various insults such as oxidative or mechanical stress, can induce smooth muscle cells to lose their contractility and this process of de-differentiation is termed phenotypic switching. And phenotypic switching is thought to precede the development of vascular disease. Patients with conditions such as chronic kidney disease have mineral imbalances in their circulation and also exhibit higher levels of vascular calcification. However, the mechanisms behind these observations are not well defined. This group found that extracellular calcium can enter the smooth muscle cells via extracellular vesicles and this increased cytosolic calcium concentration. Increased calcium induces expression and activity of Nox5 in NADPH oxidase. Activation of Nox5 increased production of reactive oxygen species, which in turn decreased contractile marker expression, and also promoted calcification in vitro. Intracellular calcium signaling also further enhanced extracellular vesicle secretion, and decreased extracellular vesicle uptake. This then promoted the accumulation of extracellular vesicles in the extracellular matrix, which is a mechanism that promotes calcification. Together, these data suggest that mineral imbalances, such as those seen in chronic kidney disease patients, contribute to loss of smooth muscle cell contractility, which promotes osteochondral genic transdifferentiation. For the interview portion today, I have with me Drs Andrew Murphy and Michelle Flynn from the Baker Heart and Diabetes Institute and Monash University in Melbourne Australia. And we're going to be discussing their manuscript titled Transient Intermittent Hyperglycemia Accelerates Atherosclerosis by Promoting Myelopoiesis. But really I like the running title, which is Hyperglycemic Spikes Accelerate Atherosclerosis. So thank you both very much for joining me today. Michelle Flynn: Thanks for having us. Cindy St. Hilaire: So before we start to ‘stalk a bit about what the details of this study is, could you maybe give us a little primer on what you've done that led up to this study? Andrew Murphy: Yeah, so this really was a continuation of a study that began actually when I was in my postdoc in Allan Tall lab and working with Ira Goldberg’s lab with the postdoc  Prabhakara R Nagareddy there. We've shown along with Ed Fisher’s group at NYU, that mice that had established atherosclerotic lesions that were then made diabetic, failed to have lesion regression compared to those that were non-diabetic with normalized plasma cholesterol levels. We showed that if we gave an SGLT-2 inhibitor to normalize glucose that regression then started to occur. And then we found that this was primarily driven by myelopoiesis, suddenly increased production of monocytes, which through that entered the plaque. And so from that, that was in the hyperglycemic model which is sort of a very rare patient group these days, because most people are on well-controlled glucosteroid drugs. And really the SGLT-2 inhibitors have been a game changer in that scenario. And what we were trying to do with this study was bring it into a more clinically relevant setting that might show the potential importance of glucose on a much larger population. Cindy St. Hilaire: Excellent. Maybe you could give us an introduction to the link between what's known about diabetes and cardiovascular disease and the interplay? Michelle Flynn: So diabetic and pre-diabetic patients actually account for 65% of all cardiovascular deaths, which really indicates that diabetes itself plays a major factor alongside other things like obesity and hypercholesterolemia. And so we've previously shown that hyperglycemia was actually driving atherosclerosis in a chronic hyperglycemic setting. So given that kind of vascular disease actually affects both diabetic and pre-diabetic patients, we suspected that it may not just be chronic hyperglycemia or really intense hyperglycemia that could be driving this issue. And so what we were actually looking at in this paper was how more transient levels of hyperglycemia, which actually occur quite often in both diabetic patients and pre-diabetic patients, how much this can contribute to cardiovascular disease. Andrew Murphy: I guess this link between poor glucose control and cardiovascular disease is obviously very well established. The interesting part is that HbA1c only predicts part of the risk. If you look at fasting blood glucose, again, that's only partially responsible, but if you look at postprandial or two hour glucose loads, you'll see that that is more predictive of cardiovascular events than the other two measures. And it seems to be a continuum. So even if you are a healthy or non-diabetic individual, you obviously still have those postprandial events and depending how high that goes up is thought to be a predictive of future cardiovascular outcomes. And so obviously that's worse than people with pre-diabetes and then again worse with people that have actual, full blown diabetes. Cindy St. Hilaire: And what is a transient hyperglycemic event? What would do that in maybe you and me who don't have diabetes versus someone who has diabetes or is pre-diabetic? Michelle Flynn: So essentially what we're modeling with this transient hyperglycemia is that postprandial increase in glucose after you have a meal, which in people who have impaired glucose tolerance is going to be more pronounced than in someone who has a normal glucose tolerance. Cindy St. Hilaire: Got it. And so how did you test this in the mice? Michelle Flynn: We did this by developing a novel model of transient hyperglycemia. So we used ordinary wild type mice that weren't diabetic, and we injected them with glucose intraperitoneally, which then increased blood glucose levels in the plasma after about 15 minutes up to about 15 to 20 millimolar. And then after about two hours, this decreased back down to baseline levels. So this was very similar to what you actually see in a postprandial event. And by doing this four times throughout the day, we were able to mimic what you might see in a patient who has had several meals across the day who has impaired glucose tolerance. Andrew Murphy: One other advantage with the model that we used was that we were trying to really isolate the effects of glucose. And so by injecting glucose intraperitoneally in otherwise healthy mice, it bypasses the incretin response, which we know loses efficacy, I guess, in people that are diabetic. And so we were just really mimicking acute glucose rises that would occur after a meal. And then obviously in this wild type mouse the insulin response would then kick in to clear the glucose so it really tests that glucose hypothesis. Cindy St. Hilaire: So it's really digging in deeply on the actual sugar component, not just eating in general or other aspects. So in some of your experiments, or I guess in actually most of them, you show that the injection of glucose, it increased the plaque size in these mice, but it didn't alter the cholesterol levels. So can you explain a bit what's going on there? A little bit about the mechanism you discovered and kind of specifically introducing RAGE and the S100A8 and A9 axis? Michelle Flynn: Yeah, so what we showed was that regardless of cholesterol levels, we were seeing an increase in clot plaque size, and this was actually driven by the monocytes and neutrophils which were increased in the circulation of these mice. And then these are able to infiltrate into the plaque where they promote plaque progression. And what we found was that the increase in monocytes and neutrophils was due to an increase in their production within the bone marrow. And this was in turn due to the signaling by a protein heterodimer of S100A8 and A9, which signals via the receptor RAGE in the bone marrow on the progenitors of these cells, which induces their proliferation and differentiation. And then that produces an increase in the production of those immune cells, which promote plaque progression. Cindy St. Hilaire: Interesting. So it's really independent of kind of the basic thing that everyone thinks about, or I guess as non-scientists think about, is cholesterol. The public really focus on cholesterol, but what your study's showing is there's this whole other glucose mediated immune arm to it. What else does this S100A8-A9 regulate? Andrew Murphy: So S100A8 and A9 has some intracellular roles, which may direct the development of the model itself, but really a lot of its extracellular roles and so on is promoting sterile inflammation, chemotaxis, so activation of local immune cells. And in the context of diabetes and obesity, many of other diseases, it can signal via RAGE, as Michelle said, but it can also signal by TLR4. And so it seems as though in those diseases driven mainly by glucose, such as the modeling of postprandial hyperglycemia or all kinase in general, it will signal via RAGE, but we've also shown in the setting of obesity that it will signal via TLR4 to stimulate things like interleukin 1 beta. We've also had a paper just recently in Circulation  with Prabhakara Nagareddy’s group where we've shown post myocardial infarction that prime neutrophils in the heart to eventually release IL1-beta and cause myelopoiesis in that way. Cindy St. Hilaire: Wow, so this is really kind of an early activator of a much bigger immune response, whether it's in atherosclerosis or MI or probably, I don't know, a handful other things, I guess, right? Andrew Murphy: It seems to be really important when neutrophils are involved. So in a setting of an MI, we know that they come into the heart very early and become activated and it really makes them about 40% of the cytosol proteins of the cells. So when it degranulates or lyses, they are kind of neutral, at least in the predominant protein. Cindy St. Hilaire: Okay. So this is released in NETs in NETosis then? Andrew Murphy: That's what we're sort of discovering so far. So I guess all I can say is, stay tuned, this is a story for another day. Cindy St. Hilaire: Okay. That's really interesting though. Andrew Murphy: We haven’t looked in gglucose driven events yet. Cindy St. Hilaire: Yeah and actually one of the interesting things I've learned from your study, I had known about GLUT1 and that GLUT1 was I guess the constituently active of the glucose transporters, but I didn't realize it was so high on neutrophils and that neutrophils were so dependent metabolically on glucose. Can you maybe tell a little bit more about that story? Michelle Flynn: Yes. So the neutrophil itself is actually very highly dependent on glycolysis because it doesn't actually have many mitochondria. So compared to most cells, they have very few mitochondria so they can't really rely upon the oxidative phosphorylation for their general metabolism. And so they predominantly rely on glucose coming into the cell and then being shuttled through glycolysis to generate their energy. And yeah this does seem to be predominantly due to uptake of glucose through GLUT1. Cindy St. Hilaire: And then that excess glucose, the byproduct, is reactive oxygen species and upregulation and this cascade of- Michelle Flynn: Yes, yes that's correct. Cindy St. Hilaire: Okay, great. So currently we use HbA1c as a biomarker for overall kind of glucose regulation in diabetic patients. And based on your studies and perhaps the studies of others, would neutrophil numbers or even S100A8 or A9 be a better metric to figure out where a pre-diabetic or even a healthy patient is in terms of their glucose tolerability? Michelle Flynn: Yeah. That could actually be an interesting marker to look at. Given that neutrophils and S100 are also associated with obesity and diabetes in general, and as well as the risk for cardiovascular disease. So with the progression of diabetes, you could expect that the levels of these would increase as well. Andrew Murphy: We've shown previously when we first discovered that the S100 was important in diabetes, that in the Pittsburgh study with Trevor Orchard's group, he had followed people with type one diabetes for 20 years, that those that did develop a cardiovascular event had a higher S100A8 and A9 levels and that correlated with neutrophils. And so it certainly seems to be a marker of predictive outcomes. And so those that do have poorer glycemic control will have higher neutrophils. That's well known. And so perhaps you're right that probably in combination with HbA1c or things like two hour post glucose challenges, S100A8 and A9 and perhaps neutrophil counts would also be a nice predictive measure of potential cardiovascular outcomes of that person. Cindy St. Hilaire: Wow. That'd be really great because you could then maybe kind of more fine tune and predict which patients might be more or less susceptible to cardiovascular events. Andrew Murphy: That's right. Yeah. I think one other important aspect would be if HbA1c is deemed to be relatively well under control, yet you still have a high level of S100A8 and A9, that perhaps those transient spikes are contributing. You're not picking that up in the HbA1c, which looks like the average over approximately a month. And so that could be a nice way to add value onto that score. Cindy St. Hilaire: Interesting. I didn't realize it was that stable about over a month. All right. So I'm relatively healthy. I'm not pre-diabetic, but if I eat a whole bunch of cake or a whole bunch of ice cream or drink a lot of beer, does that create un me a transient hyperglycemic event that is of the same range we're talking about and what do your findings suggest for people who are relatively healthy and things we should be aware about regarding eating habits and things like that? Andrew Murphy: Yeah. I think it's a really good question. And it's sort of hard to give you an exact answer to that right now. We need to look at that in people, model these sort of same spikes in people, but what we I guess don't know yet, even in the preclinical models is how high and how long does that glucose have to be? And I think that's one of the most important questions first. So is there a danger zone where these neutrophils start be the innate senses of hyperglycemia that start to then release S100A8 and A9 to cause these downstream events? But what our data does show is that if you're doing this, having a binge night or a binge day once a week for your life, then that's probably not going to be a great thing. Cindy St. Hilaire: Yeah. All right. So you need to figure out is one scoop of ice cream okay, but two not so great. Andrew Murphy: Maybe if it's two different flavors it'll be okay. Cindy St. Hilaire: Maybe, right? That's great. So, I mean, is there a way we could potentially therapeutically target this signaling axis or is it too ubiquitous in terms of what it regulates? Is there a way to harness what you've found potentially in the clinic? Michelle Flynn: Yeah, so there's an inhibitor of S100A8 and A9 that prevents its binding to RAGE. It's currently approved as an Orphan Drug for systemic sclerosis in both the US and the UK. And that drug itself, we tested in our preclinical mouse model, and we found that it was in fact able to prevent their production of these immune cells, as well as prevent the accelerated atherosclerosis in response to these transient hypoglycemic spikes. Andrew Murphy: So another sort of line of thinking that we're exploring is that we could actually target neutrophil metabolism itself. And so now we're sort of understanding, are there certain proteins that are more abundantly expressed in neutrophils and not other cells in the body that would regulate glycolysis? I know that might sound a bit of a pie in the sky sort of idea, because glycolytic pathway's quite regulated, but there we have found some proteins that are rich in neutrophils and not other cells that may be responsible for the early steps of glycolysis. And so whether that can be harnessed or not, we'll have to see in the future, but it might be a way of more directly targeting neutrophils rather than approaching that's important in sterile inflammation. Cindy St. Hilaire: That makes sense. That is such a cool idea and this is really such a beautiful story. It's one of those papers that you just read it and it's just such a logical progression, but it's also really interesting and I really appreciated all those bone marrow transplants. I did those in grad school, so well done. It's a beautiful story. And then I'm just really happy that you published it with us. So thank you so much for joining me today. Andrew Murphy: Yeah thanks for having us. Michelle Flynn: Thank you. Cindy St. Hilaire: That's it for highlights from the late August and early September issues of Circulation Research. Thank you so much for listening. Please check out the Circulation Research Facebook page and follow us on Twitter and Instagram with the handle @CircRes and #DiscoverCircRes. Thank you to our guests, Drs Andrew Murphy and Michelle Flynn. This podcast is produced by Rebecca McTavish and Ashara Ratnayaka, edited by Melissa Stoner, and supported by the Editorial Team of Circulation Research. Some of the copy text for the highlighted articles is provided by Ruth Williams. I'm your host, Dr Cindy St. Hilaire, and this is Discover CircRes, your on-the-go source for the most exciting discoveries in basic cardiovascular research.  

What are the most interesting things in sedentary behaviour research at the moment?Professor David Dunstan from the Baker Heart and Diabetes Institute in Melbourne. His research focuses on the role of physical activity and sedentary behaviour in relation to chronic diseases.Dr Amanda Rebar is senior lecturer at Central Queensland University, Australia and director of the Motivation of Health Behaviours (MoHB) Lab. She has experience providing evidence-based guidance for community-based programs with a focus on mental health and safety outcomes.Dr Arto Pesola is working as research manager at Active Life Lab in South-Eastern University of Applied Sciences. He is researching health effects of sedentary behaviour and developing health technologies aiming at making life healthier - with less sitting. ---This podcast episode is sponsored by Fibion Inc. | The New Gold Standard for Sedentary Behaviour and Physical Activity MonitoringLearn more about Fibion: fibion.com/research---

Vol 213, Issue 3: 3 August. Professor Tom Marwick is Director of the Baker Heart and Diabetes Institute. Dr Prasanna Venkataraman is a cardiologist. They discuss the use of coronary artery calcium scoring as a risk assessment tool for cardiovascular disease. With MJA news and online editor, Cate Swannell.

Dr Carolyn Lam: Welcome to Circulation On The Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr Greg Hundley: And I'm Dr Greg Hundley, Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Well, Carolyn, our feature article today looks at the use of Apixaban versus Warfarin, so a trial between the two in patients with atrial fibrillation and advanced kidney disease. But before we get to that, how about if we break away, grab a cup of coffee and go through some of the other important papers in this issue? Dr Carolyn Lam: Yeah, and why not start with talking about our gut and fiber in the diet. Now, we know that a diet poor in fiber is associated with the prevalence of hypertension, but what are the underlying mechanisms? Well, this first paper I want to talk about is from Dr Marques from Baker Heart and Diabetes Institute in Australia and colleagues who basically performed a nice series of mouse experiments and found that a diet lacking prebiotic fiber led to a gut microbiome that was pro hypertenenogenic facilitated the development of cardiac hypertrophy in germ free mice. Even in the absence of fiber, gut metabolites called short chain fatty acids usually produce from the fermentation of prebiotic fiber by the gut microbiota, but they were able to protect against the development of hypertension, cardiac hypertrophy and fibrosis in a preclinical model. This cardioprotection involved short chain fatty acid receptors, and a decrease in the ratio of sodium to potassium excretion and changes in genome white methylation that supported higher levels of T regulatory cells. Dr Greg Hundley: Oh my goodness, Carolyn. So I need to know what I eat for lunch? What's the take home message here? Dr Carolyn Lam: Lots of fiber and definitely not the low fiber westernized diet, which may underlie hypertension. And how? Through deficient short chain fatty acid production and thus the take home is maintaining a healthy, short chain fatty acid producing microbiome is important for the cardiovascular health. Dr Greg Hundley: Wow, Carolyn. I love that article because it really helps provide some perspective on all the diet information that we've been receiving lately. Well, my paper is from doctor ... another Carolyn, but this is Carolyn Ho from Brigham and Women's Hospital- Dr Carolyn Lam: I love her. Dr Greg Hundley: ... And it involves hypertrophic cardiomyopathy and left ventricular systolic dysfunction. So Carolyn, the term end-stage has been used to describe hypertrophic cardiomyopathy with left ventricular systolic dysfunction. And that's defined when someone has hypertrophic cardiomyopathy and the LVEF is less than 50%. The prognosis of patients with this condition has been reportedly poor, but it's very rare in occurrence and therefore, the natural history really remains incompletely characterized. So what did the authors do in this study? They evaluated more than 500 patients from 11 high volume hypertrophic cardiomyopathy specialty centers comprising the international Sarcomeric Human Cardiomyopathy Registry or SHaRe registry. And they were used to describe the natural history of patients with hypertrophic cardiomyopathy and left ventricular systolic dysfunction. Dr Carolyn Lam: Interesting. So what did they find, Greg? Dr Greg Hundley: Number one, first overall, this group of patients, hypertrophic cardiomyopathy with left ventricular systolic dysfunction occurs in about 8% of those with hypertrophic cardiomyopathy. Although the natural history of left ventricular systolic function and hypertrophic cardiomyopathy is variable, 75% of those that have this condition experience adverse events including 35% experiencing a death equivalent at a medium of 8.4 years after developing their systolic dysfunction. In addition to clinical features, the genetic substrate appears to play a role in both prognosis, so there are multiple sarcomeric variants, and in the risk for incident development of left ventricular systolic function with hypertrophic cardiomyopathy due to variance in the thin filaments within those myocytes. Dr Carolyn Lam: Nice. Thanks for that Greg. My next paper is a really interesting secondary analysis if you may, of the EXSCEL study. As a reminder, the Exenatide Study of Cardiovascular Event Lowering or EXSCEL assessed the impact of once weekly exenatide versus placebo in patients with type two diabetes and showed non-inferiority but not superiority for the primary MACE outcome. Now, during this trial, while aiming for glycemic echo-poise, a greater drop-in of open label glucose lowering medications occurred in the placebo group, thus prompting the current authors, which is Dr Rury Holman from University of Oxford and their colleagues to really explore the possible impact of unbalanced open labeled drop-in of glucose lowering medication on EXSCEL outcomes. To our modern diabetes trial, they used three methodologies. One, drop-in visit, right censoring. Two, inverse probability for treatment waiting. And three, applying drug class risk reductions. Now, Greg, I could either quiz you on these methods or summarize the results, which would you prefer? Dr Greg Hundley: Well, Carolyn, this calls for the infamous phone a friend. So one of the nice things we have at Circulation is a wonderful group of statisticians that really help us go through all the papers. But I sure would like to pick up the phone and call one of those folks now. But I think what I'm going to do ... maybe just give me the results of this study. That's what I prefer. Dr Carolyn Lam: I thought you might say that. So the EXSCEL observed has its ratios for MACE remained robust after right censoring or application of the literature derived risk reductions, but the exenatide versus placebo MACE effect size and statistical significance were increased by the inverse probability treatment waiting approach. So I think the take home is that effects of open label drop in cardioprotective medications do need to be considered carefully when designing, conducting and analyzing cardiovascular outcome trials of glucose lowering agents. Do we have the perfect solution? Perhaps not, but this was a really important paper to just look at and study. So Greg, I can see that you are stats out, so I'm going to tell you a little bit more about other papers in this week's issue. There's a research letter by Dr Zhang on transcription factor Kruppel-like factor 15 and how it regulates the circadian susceptibility to ischemia-reperfusion injury in the heart. Dr Greg Hundley: Very good, Carolyn. Well, I've got a couple of other papers. There's a nice in-depth piece from Dr Gregory Marcus from the University of California, San Francisco on how we evaluate and manage patients that have premature ventricular contractions. Dr Mori Krantz from Denver Health and Hospital Authority gives us an EKG challenge in someone that's had a needle stick. And then finally, there's a nice perspective piece from Dr Paul Armstrong from the Canadian VIGOUR Centre, department of medicine cardiology at the University of Alberta. And he really goes over nicely how we're going to do global collaboration to enhance cardiovascular care. What a great issue. And now onto that feature where we're going to hear a little bit about Apixaban and Warfarin in those individuals with atrial fibrillation and chronic kidney disease. Dr Carolyn Lam: Let's go, Greg. Today's feature paper really represents the first randomized data on NOAC versus warfarin in a very important group of patients, that is those with atrial fibrillation and advanced chronic kidney disease. So happy to have with us the corresponding author, Dr John Stanifer from Munson Healthcare, Traverse, Michigan. As well as our associate editor, Dr Chang-Sheng Ma from Beijing Anzhen Hospital in China. Welcome, welcome. So John, could you tell us the inspiration if you may, or the rationale, for doing this study? Dr John Stanifer: This is a population that's near and dear to my heart as a practicing nephrologist. We care for so many patients with atrial fibrillation, particularly those on dialysis or those with advanced kidney disease. And as other practitioners and people taking care of this population will tell you, this is just such a confusing and challenging clinical problem to try to deal with. And then really this stems from that important clinical need that we recognize almost on a daily basis. Dr Carolyn Lam: I just love that you shared that John, because coming from a nephrologist, and we're usually talking to cardiologists where we think about this all the time and have no idea what to do. So tell us about your study and what you found. Dr John Stanifer: As you know, these were data that were taken from the Aristotle trial that was finished in 2011, that was really a landmark study that established the real superiority of Apixaban compared with Warfarin and the general population. And it happened that within the study, there were several patients, 269 that had a creatinine clearance of between 25 and 30 milliliters per minute. We then took those data from those patients and compared really in this study, the safety of Apixaban compared with Warfarin within that subpopulation, and then compared that as an interaction with the safety of Apixaban versus Warfarin in patients with creatinine clearance of greater than 30. Dr Carolyn Lam: And what did you find? Dr John Stanifer: Well, in conclusion, we really found that among these patients with a creatine clearance of 25 to 30 MLs per minute in atrial fibrillation that Apixaban did cause less bleeding than Warfarin. And it appeared to be an even greater relative risk reduction when you compare that with the safety of Apixaban versus Warfarin and those with a less severe kidney disease. Dr Carolyn Lam: It's truly the first time I've seen data like this. So congratulations John and thank you so much for publishing this paper with us at Circulation. Chang-Sheng, Circulation seems to be publishing a lot in the space of combined renal and cardiac disease, which is very interesting. Why was this paper so important to us as well? Dr Changsheng Ma: It's a very important question for a clinical practice. The anticoagulation therapy in patient with advanced CKD. And observation or analysis have demonstrated inconsistent of findings regarding the net clinical benefit of warfarin in reducing the risk for stroke in patients with advanced CKD. The problem of Warfarin treatments in this patient group is dramatically higher bleeding risk. The current study also show that the bleeding risk was three- to four-fold higher in patient with advanced CKD compared to that in patient with creatinine clearance more than 30 milliliters per minute when treated with a Warfarin. So these studies are our first randomized data for NOAC compared with warfarin in patients with advanced CKD. The results provide important information as to the safety of Apixaban in this special patient group with high risk of bleeding. With reduced risk of bleeding, we may expect net clinical benefits of Apixaban in preventing stroke in patients with advanced CKD. Dr Carolyn Lam: Indeed. John, did you demonstrate that net clinical benefit or could you perhaps explain if future steps are needed to look at that a bit better? Dr John Stanifer: Well, I think absolutely future studies are needed. You have to keep in mind that these were pre-specified groups within Aristotle. These are still post-trial data from this study and that absolutely we need studies that are powered to really compare the safety. I would add not just apixaban with warfarin, but I would also add placebo to that. Dr Carolyn Lam: Interesting. Changsheng, you had some questions for John as well. Dr Changsheng Ma: Yes. John, I had questions for you. If you take a randomized trial for the answer for this question, how many cases do you think? Dr Carolyn Lam: How many cases of? Dr Changsheng Ma: How many cases should there be for a sample size for a trial? Dr John Stanifer: Well, you're really putting me on the spot here. I'll have to go back to my statistical days. Well, I think the easy part in the design of a trial for a question like this is that the event rates are so high. Whether that be for both safety outcomes related to hemorrhage and bleeding risks or primary benefit outcomes. So that would be very beneficial with that respect. But I think the key to designing a study ... and I know that there are several ongoing RENAL-AF and several others that are trying to examine this very question, but I think as a nephrologist, what we would kind of push back on a little bit is that there's no placebo arm to these trials. And I actually think that that would be a step forward even though that would be a very challenging thing, I think at this point to push for ... I think the nephrologist has kind of continued to push for that a little bit. Dr Carolyn Lam: So John, that was beautifully answered. If I could ask you then, have these results influenced your practice even now? Dr John Stanifer: Well, prior to this, we've been a little bit nervous with Apixaban, even though observational data may suggest that it would be safer or potentially usable in patients with advanced kidney disease. But part of the real conundrum and some of the challenges that come up are really around dosing of Apixaban. And they say, "Well, gosh, if they're in stage renal disease, yeah, maybe it's too bad. Maybe the kidney function is way too low and we need to kind of reduce it based just on that one criterion as opposed to the three criteria laid out in Aristotle." So I think that was some of the challenges. but I think after seeing these data and seeing the safety relative to Warfarin was really there in this patient group, yeah, it has influenced me a little bit. I am a little more adamant about switching patients. Dr Carolyn Lam: Yep. Chang-Sheng, do you agree with that? What do you think are next steps here? Dr Changsheng Ma: Because clinical practice is different, apparently, more evidence is badly needed to guide the future clinical practice because the patients with creatinine clearance even less than 25 milliliters per minute. And those in dialysis were not included in any of the pivotal studies of NOAC. Dr John Stanifer: Absolutely. Dr Changsheng Ma: It is still uncertain whether this patient will benefit from Apixaban or other NOACs. So in this study, even the significant less measured bleeding events were observed. I think the all-cause mortality was not different between the two groups. So the next step we should design a new trial to confirm whether Apixaban will really improve the prognosis of the patient with advanced CKD and AF. Dr John Stanifer: I will second that. For sure we want to answer that very important efficacy question related to this class of medications. Dr Carolyn Lam: Efficacy and patients on hemodialysis. Wow. This really just opens up a lot, but you're right. It's such tantalizing information that you see in ... so thank you so much John, for publishing this paper with us. Chang-Sheng, it's such a great paper. I remember the discussions we had during our editors’ discussions and it's so nice to see it out in print. I'm telling you, audience, you have to get hold of this paper. It will change this field I think and will lead to further trials exactly like you've heard here, and that we've put John on the spot to describe. Dr Carolyn Lam: Thank you very much gentlemen for a wonderful discussion. Thank you, audience, for joining us. You've been listening to Circulation On The Run. Join us again next week. Dr Greg Hundley: This program is copyright the American Heart Association, 2020.  

[Apologies for the sound quality. We had problems during the recording, that we were not able to solve in the limited time frame.]Professor Neville Owen  works at the Physical Activity and Behavioural Epidemiology Research Group, Baker Heart and Diabetes Institute. His research relates to the primary prevention of diabetes, heart disease and cancer, through identifying the health consequences and environmental determinants of physical inactivity and sedentary behaviour — too little exercise and too much sitting. This involves laboratory-based experimental work, large-scale prospective observational studies and real-world intervention trials. He has published some 500 peer-reviewed papers and chapters.---This podcast episode is sponsored by Fibion Inc. | The New Gold Standard for Sedentary Behaviour and Physical Activity MonitoringLearn more about Fibion: fibion.com/research---Physical Activity Researcher Podcast have created a ‘Purchase Guide for Researchers: Accelerometer-based Activity Trackers’. You can download it from here.---

In this episode, we have Professor David Dunstan from the Baker Heart and Diabetes Institute in Melbourne. His research focuses on the role of physical activity and sedentary behaviour in relation to chronic diseases.---This podcast episode is sponsored by Fibion Inc. | The New Gold Standard for Sedentary Behaviour and Physical Activity MonitoringLearn more about Fibion: https://fibion.com/research---Physical Activity Researcher Podcast have created a ‘Purchase Guide for Researchers: Accelerometer-based Activity Trackers’. You can download it from here.---

Interview with Teisha Archer (AUS) - Fundraising and Philanthropy Director, Coach and Consultant After 10 years leading philanthropic & corporate partnerships in the medical research and education sectors, Teisha now provides strategic fundraising and philanthropic advice to a range of not-for-profit clients, as well as running training workshops for staff, executive and Boards. Included in this episode: Teisha's early years working in fundraising and key lessons learnt Philanthropy & Corporate Partnerships for Baker Heart and Diabetes Improving your Major Gifts strategies Fundraising Leadership Consulting for fundraising teams What's been key to the fundraising success of the Brave Foundation Fundraising trends to be aware of for the future Teisha's final piece of advice --- Send in a voice message: https://anchor.fm/fulfilled-fundraisers/message

Dr Harry Nespolon talks to Prof John Dixon from the Baker Heart & Diabetes Institute about the management of obese patients – including the use of very low calorie diets, pharmacotherapy, and the latest surgical options.

Guest: Dr. Andrew Murphy is an Associate Professor at the Baker Heart and Diabetes Institute and Monash University in Melbourne, Australia. He seeks to understand the processes by which hematopoietic stem cells and the bone…

Louise Segan Louise is Cardiology Registrar at Barwon Health, Key Contributor and Member of the Women in Cardiology ("WIC") Working Group and a Research Fellow at Baker Heart and Diabetes Institute   WIC are working towards better representation of female cardiologists in senior positions and greater numbers of women in cardiology. Learn more at womenincardiology.com.au The Purpose Sign up to our monthly email (called 'The Purpose') for details of our months podcasts, upcoming events, discounts and opportunities Podcast Review Do you love the pod? Vote with your feet (or fingers in this case) by leaving us a review and comments here via the iTunes Store! Support the show.

Dr Shane, Dr Linden, Dr Laura, Dr Ray bring you this week's hottest science, including ice dunes on Pluto, cockroach milk, and the recent weather's tracking with the current climate models. The team chat with Dr Aya Mousa (Monash University, Monash Centre for Health Research and Implementation) about Vitamin D, how it works and what it does in various organs of the body. They interview Dr Tan Nguyen (WEHI) about his work with a relatively unknown protein called SIDT2, which he found was important for the immune response during viral infection, warning uninfected cells of incoming infection so they are better prepared to fight off infection. Their final guest is Dr Francine Marques, a National Heart Foundation Future Leader Fellow at the Baker Heart and Diabetes Institute, about her investigation into the molecular genomics of hypertension - a major risk factor for cardiovascular morbidity and mortality. Remember, Science is everywhere, including:Website, Facebook, Twitter, Podcasts

A drug based on a form of cholesterol might be able to reduce the damage done by heart attacks. Working with experimental mice, scientists in Australia have found that so-called good cholesterol, also known as "HDL", if injected into the bloodstream shortly after a heart attack can prevent heart cells from dying. The experiments suggest that the HDL temporarily alters the way heart cells burn glucose, giving them more energy and improving their survival. Chris Smith spoke to Sarah Heywood, who carried out the work at the Baker Heart and Diabetes Institute in Melbourne, Australia Like this podcast? Please help us by supporting the Naked Scientists

A drug based on a form of cholesterol might be able to reduce the damage done by heart attacks. Working with experimental mice, scientists in Australia have found that so-called good cholesterol, also known as "HDL", if injected into the bloodstream shortly after a heart attack can prevent heart cells from dying. The experiments suggest that the HDL temporarily alters the way heart cells burn glucose, giving them more energy and improving their survival. Chris Smith spoke to Sarah Heywood, who carried out the work at the Baker Heart and Diabetes Institute in Melbourne, Australia Like this podcast? Please help us by supporting the Naked Scientists

June 12-18 is Men's Health Week. Men make up 49% of the population, and we're determined to reduce the number of men dying prematurely. Sadly, more than four men die every hour in Australia from conditions that might have been prevented, this is a catastrophic situation for the family left fatherless! In this episode we discuss men's health with Associate Professor Gary Richardson. Gary is the Director of the Szalmuk Family Department of Medical Oncology in the Cabrini Institute. He is a past-chairman of the Medical Oncology Group of Australia and immediate past-president of the Private Cancer Physicians of Australia. He established the Oncology clinical research program at Cabrini, the Cabrini Family Cancer Clinic, the Oncology Service at Cabrini Brighton, and the apheresis service. He is Chairman of Foundation 49. Foundation 49 is a not-for-profit men’s health promotion initiative of Baker Heart and Diabetes Institute. They encourage men to take better care of their own health and wellbeing and have regular health checks.They produce great resources including the highly valued Men’s Health Toolkit Booklet, the Whole New Ball Game Magazine and a monthly EDM with information on events and activities. Foundation 49 - http://www.49.com.au/ The Foundation 49 Business Breakfast on 14th June 2016 is the main fundraiser of the year and is the largest Men’s Health event in Victoria during International Men’s Health Week. Get involved and support the fundraising breakfast here: F49 Business Breakfast

Dr. Carolyn Lam:               Welcome to Circulation on the Run. Your weekly podcast summary and [inaudible 00:00:06] of the journal and its editors. I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. In just a moment we will be discussing really fascinating preclinical data to suggest that high fiber diet and acetate supplementation may change the gut microbiota and thereby prevent the development of hypertension and heart failure. But first here's your summary of this week's issue.                                                 The first paper describes the impact of heart transplantation on the functional status of children with end stage heart failure in the United States. First author, Dr. Peng, corresponding author Dr. Almond and colleagues from Stanford University, use the organ procurement and transplantation network to identify 1,633 US children age less than 21 years, and surviving one year or more post-heart transplant, from 2005 to 2014, with a functional status score available at three time points. Namely at listing, at transplant, and one year or more post-heart transplant. They found that at the one year assessment 64% were fully active with no limitations, or a functional status score of 10. 21% had minor limitations with strenuous activity, or a functional status score of 9. And 15% scored a functional status score lower than 9. Compared to the listing functional status, functional status at one year post-transplant increased in 91%, and declined or remain unchanged in 9%. Early rejection, older age, African-American race, chronic steroid use, hemodynamic support at heart transplantation, and being hospitalized at transplantation, were all associated with abnormal functional status post-transplant.                                                 These findings may be helpful to patients, families, and referring providers by providing a contemporary picture of the post-heart transplant life in children as they weigh the risks and benefits of transplantation.                                                 The next paper brings cardiac reprogramming one step closer to clinical translation. In this paper by first author Dr. Mohamed, corresponding author Dr. Srivastava, and colleagues from Gladstone Institute of Cardiovascular Disease in San Francisco, the authors used a high throughput chemical screen in post-natal mouse cardiac fibroblasts, and found that transforming growth factor beta, or TGF beta, and WNT, or wint inhibition, enhanced transcription factor based direct reprogramming of cardiac fibroblasts to induce cardiomyocyte like cells in vitro and in vivo. A combination of TGF beta and wint chemical inhibitors increased the quality, quantity, and speed of direct reprogramming, resulting in improved cardiac function after injury as early as one week after treatment. These chemical inhibitors enhanced human cardiac reprogramming and reduced the number of transcription factors needed for human cardiac reprogramming to just four factors. These findings if validated in large animals could facilitate a combined gene therapy and small molecule approach to heart failure.                                                 The next study is the first report of the risks of cardiac mortality among five year survivors of childhood cancer beyond 50 years of age. First author Dr. Fidler, corresponding author Dr. Hawkins, and colleagues from University of Birmingham in United Kingdom, looked at the British childhood cancer survivors study, a population based cohort of 34,489 five year survivors of childhood cancer that was diagnosed from 1940 to 2006 and followed up until February 28th in 2014. The authors quantify the cardiac mortality access risk. Overall 181 cardiac deaths were observed, which was 3.4 times that expected. Survivors were two and half times more at risk of ischemic heart disease, and almost six times more at risk of cardiomyopathy or heart failure at death than expected. Among those aged over 60 years, subsequent primary neoplasms, cardiac disease, and other circulatory conditions accounted for 31%, 22%, 15% of all deaths. Specifically for cardiomyopathy or heart failure deaths, survivors diagnosed between 1980 and 1989 had 29 times the excess number of deaths observed per survivors diagnosed either before 1970 or from 1990 onwards. Thus the authors concluded that excess cardio mortality among five year survivors of childhood cancer remains increased beyond 50 years of age, and has clear messages in terms of preventative strategies. However, the fact that the risk was greatest in those diagnosed in 1980 to 1989, suggests that initiatives to reduce cardio toxicity among those treated more recently may be have a measurable impact.                                                 The last study describes the 30 day results of the Source 3 Registry, that is the European Post Approval Registry of the latest generation of the Sapien 3 trans-catheter heart valve. Dr. Wendler and colleagues from King's Health Partners in London, describe that these 30 day results of the Source 3 Registry demonstrate that trans-catheter uratic valve implantation, or TAVI, using the Sapien 3 resulted in high procedural success with low procedural complications, and excellent post-implant hemodynamics. Moderate to severe paravalvular leakage appeared to be lower with the Sapien 3 than reported with prior versions of this trans-catheter heart valve. Rates of pacemaker implantation were higher with the Sapien 3 than in earlier generations of the valve. This, in combination with the growing experience of patient selection, procedure planning, execution, and post-operative care has led to one of the best short-term outcomes ever reported after TAVI. These results are discussed in an accompanying editorial by Dr. [Altassi 00:06:58], and Dr. [Urani 00:06:58], from the Emery Midtown Hospital in Atlanta, Georgia, where they say that these early results from Source 3 Registry are a source of encouragement with some caveats.                                                 Well, those were your summaries. Now for our feature discussion.                                                 I am so honored to have two lovely ladies join me today on the show. And they are the first author of a feature paper, Dr. Francine Marques from Baker Heart and Diabetes Institute in Melbourne, Australia, as well as Dr. Peipei Ping, associate editor from the David Geffen UCLA School of Medicine. Welcome ladies. Dr. Peipei Ping:                 Hi, hello. Dr. Francine Marques:   Hi, thank you for having us. Dr. Carolyn Lam:               As a clinician, I have very very often advised my hypertensive patients to go on the dash diet. And you know, I have no had any trouble explaining the low salt bit, right? I understand it. But then I realize that I've always advocated as well the high fiber bit, not actually really understanding how high fiber directly impacts blood pressure. And I'm so excited because your paper, Francine, shed some light on this and it actually has something to do with the gut. So could you please explain what you did and what you found? Dr. Francine Marques:   So we fed a mouse model called [adoca 00:08:25] model of habitation, that also developed heart failure, we fed them a high fiber diet for three weeks, and then after that we did a surgery to make them become [habitant 00:08:36] safe and we followed them up for six weeks. And what we observed through that trajectory is that mice that were fed a high fiber diet had significantly lower systolic and diastolic blood pressure, and also an improvement in the heart function, and also a decrease in both heart and brainal fibrosis. And the reason why the fiber is so important is because although we usually don't digest the fiber, the bacteria in our gut absolutely love it. And that allows the bacteria, good bacteria to grow. And with that growth we have release of the fermentation of the fiber, releases in short chain fatty acid. So these specific molecules can then be put back into our body and can help us in our health. So we also fed these mice acetate, which is one of the short chain fatty acids, directly and we also observed very good improvements in blood pressure and cardiovascular health. Dr. Carolyn Lam:               It's just fascinating. So these are studies in mice. What do you think of clinical translational aspects of this? Dr. Francine Marques:   Large epidemialogical studies have shown that there is an inverse correlation between fiber consumption and blood pressure. And they have seen this through very small clinical trials looking into the intake of fiber lowering blood pressure. But our study opens the possibility of new interventions using maybe short chain fatty acids specifically, but are also looking into a different type of fiber. So most studies would look into either soluble or insoluble fiber directly. Our study, the diet that we used, is mostly resistant starches. So these are their preferred type of fiber for bacteria growth in our gut. And maybe they use a [inaudible 00:10:32] type of fibers as well could be a new [inaudible 00:10:36] opportunity. Dr. Carolyn Lam:               Peipei, I remember you discussing this paper at our editorial meetings and you so beautifully highlighted the novelty of this paper. Could you share this with our listeners? Dr. Peipei Ping:                 Often within many complex studies trying to understand cellular pathways and mechanisms of cardio protection, it's a very important topic as we have had our research focus on in the pas t 25 years. What's very unique and provocative of this particular study is that it simply identified critical metabolic pathways that actually is underlying the protective effects. Many of us have wondered about with eating, for example vegetables or high fiber diet, it is examined specific molecules that have both a direct as well as an endocryne path that would circulate things back to the cardiac muscles, and having the muscles becoming more protective because of regulation of certain transcriptomic pathways to support cardiac muscle contraction. So we were very impressed by both the new concept as well as the state of the art technologies employed in this investigation. Dr. Francine Marques:   Thank you, that's very nice. Dr. Carolyn Lam:               I couldn't agree more, you put it so beautifully Peipei. I thought that it was really nice also linking pathways as well as linking several organ systems. Is there anything you might want to highlight about the renal effects, not just cardiac? Dr. Francine Marques:   Yes. Many times investigations been focusing on if something went wrong how do we cure it? More precious is when we find novel results telling us the healthy individuals, what are the things we should be doing so our blood pressure would stay at the normal level, or our cardiac function is being protected if there's an insult or injury. And so in this situation, the examination of the entire renal transcriptomic do give us very valuable information on how the blood pressure regulation system that maybe actually protected by the short chain fatty acid acetate. Dr. Carolyn Lam:               So true Francine. Anything else to add? Dr. Francine Marques:   Just to say circulation, for giving the opportunity to submit this paper, and share it with the world. We're very very excited about the data. Dr. Carolyn Lam:               Yeah we should be the ones to thank you. It's a beautiful paper. We're very privileged to publish it in circulation. May I ask what are next steps for you? What do you think needs to be done from here? Dr. Francine Marques:   We're validating this in other models now. And we're also looking into the [inaudible 00:13:57] microbiome and how that's related to habitation. So trying to really pinpoint mechanisms and how we can move this forward into the clinic. Dr. Carolyn Lam:               That's so great. And Peipei, do you think that there's certain gaps that urgently need to be addressed now? Dr. Peipei Ping:                 Yes, I think one of the most beautiful thing that ... Concept, illustrated this investigation is we really couldn't be just focusing on one organ, our primary interest organ, heart, alone. What's demonstrated here is a beautiful link of both mechanism as well as governed by transforming parbolytes with endocryne effects. How the gut, the kidney, and the heart are all connected together in this process, achieving a better protective condition in the environment for the cardiac muscle. Dr. Carolyn Lam:               Thank you listeners. You've been listening to Circulation on the Run. Tune in next week for even more news.