Podcasts about uk biobank

Pain, particularly chronic pain, is hard to research. New therapeutics are hard to screen for. Patients are not all the same. Sergui Pascu and colleagues at Stanford university have been growing brain samples from stem cells. Then they began connecting different samples, specialised to represent different brain regions. This week they announce their most complex “assembloid” yet, one that even reacts to hot chilli, passing a signal from the sensory neurons through to the thinking bits. The hope is that it can provide insights on how pain, and potential painkillers, work.Human brains are notoriously large, particularly infants. Whilst for primates the human pelvis is quite narrow, to allow us to walk and run on two legs. This notoriously makes childbirth, well, not as straightforward as most other species. This evolutionary “obstetric dilemma” has been debated for decades. Marianne Brasil, of West Washington University, and colleagues, have published this week a huge study of contemporary human genes and anatomies available from the UK Biobank to shed some more light on this ongoing compromise.Malta is an island in the Mediterranean no less than 80km from land. So how come Eleanor Scerri and colleagues have discovered archaeological evidence of hunter-gatherers living there from 8,500 years ago? And they didn't just visit and leave. They stayed for perhaps a millennium before farming arrived. Maybe a rethink of what nautical capabilities our ancestors had in the deep past is needed? A year ago, Science in Action gate-crashed a conference looking at plans for meeting the forthcoming arrival of asteroid Apophis in 2029. This year the meeting is in Tokyo, and Richard Binzel, emeritus professor of Astronomy at MIT, gives us an update on how the space agencies are hoping to collaborate to maximise the scientific value from what will be a global, visible, phenomenon in just 4 years. Is there enough time to get our collective wits together?(Image: 3D illustration of Interconnected neurons with electrical pulses. Credit: Getty Images)Presenter: Roland Pease Producer: Alex Mansfield Production Coordinator: Josie Hardy

Melissa E. Middeldorp, MPH, PhD, University Medical Centre, Groningen & University of Adelaide, is joined by So-Ryoung Lee, MD, PhD, Seoul National University Hospital, and Adrian D. Elliott, PhD, University of Adelaide/Royal, Adelaide Hospital, to discuss a study that compares atrial fibrillation (AF) epidemiology and risk factors between the UK Biobank (a predominantly European cohort) and the Korean NHIS-HEALS cohort to explore racial differences in AF incidence. Findings revealed that AF was more prevalent in the UK cohort than in the Korean cohort, with BMI and smoking showing stronger associations with AF risk in the UK population. Despite these differences, several risk factors, including hypertension and diabetes, were common predictors in both populations. The study highlights the complex interplay of lifestyle and healthcare system factors along with analysis of different large cohort studies in AF development and underscores the need for population-specific risk assessment and prevention strategies. https://www.hrsonline.org/education/TheLead https://www.heartrhythmjournal.com/article/S1547-5271(25)00128-6/fulltext Host Disclosure(s): M. Middeldorp: Nothing to disclose.   Contributor Disclosure(s): S. Lee: Nothing to disclose. A. Elliott: Nothing to disclose.   This episode has .25 ACE credits associated with it. If you want credit for listening to this episode, please visit the episode page on HRS365: https://www.heartrhythm365.org/URL/TheLeadEpisode96

Fitness trackers at the ready! Join James Gallagher at Cardiff Science Festival as he runs through the ways wearable tech is making an impact on health and how it might shape the future of medicines and care. With him are Dr Sanne Lugthart, Haematology consultant at the University Hospital of Bristol and Weston NHS Foundation Trust. She's pioneering using wearables and an app to track pain in people who suffer from sickle cell disease. Also on the panel is Professor Kathryn Peall who is Personal Chair, Division of Psychological Medicine and Clinical Neurosciences at Cardiff University. Kathryn tells James all about working with data from the UK Biobank to test if wearables could predict Parkinson's disease. She's also developing 80s-style headbands that could help take hospital grade sleep monitoring to the comfort of the bedroom. And, running experiments with the audience and on his skydiving assistant Danni, James is also joined by Damian Bailey, Professor of Physiology and Biochemistry from the University of South Wales.Presenter: James Gallagher Producers: Tom Bonnett and Hannah Robins Production Co-ordinator: Ishmael Soriano Editor: Colin Paterson

Mind Pump Fit Tip: Five SNEAKY and EASY ways to BOOST protein intake. (1:48) Three PROVEN movements to increase your push press. (19:37) Grip strength and its association with longevity. (29:04) Is AI making us dumber? (33:47) Four proven ingredients for a happy, lasting marriage. (36:00) An option when you can't get your veggies in. (43:39) Weird Science with Sal: Rupert's Drop. (44:57) Natural formations that look REAL. (49:37) #ListenerLive question #1 – Why can't I lean down and get better muscle definition? (55:18) #ListenerLive question #2 – Does metabolism adapt upwards? (1:07:41) #ListenerLive question #3 – What specific movements can I do with my client that can help her regain that ability to do hip flexion? (1:17:18) #ListenerLive question #4 – Any guidance on calorie targets for someone of my height and activity level? (1:29:05) Related Links/Products Mentioned Ask a question to Mind Pump, live! Email: live@mindpumpmedia.com Visit Butcher Box for this month's exclusive Mind Pump offer!  ** New users will receive their choice between chicken breast, ground beef, or top sirloin in every box for a year + use code MINDPUMP and get $20 off your first box. ** Visit Organifi for the exclusive offer for Mind Pump listeners! ** Code MINDPUMP at checkout for 20% off. ** Mind Pump Group Coaching February Promotion: MAPS Anabolic & No B.S. 6-Pack ** We are offering them both for the low price of $59.99, which is a savings of $114! ** Mind Pump #2450: The Smartest Way to Use Protein to Burn Fat & Build Muscle Visit Paleovalley for an exclusive offer for Mind Pump listeners! ** Discount is now automatically applied at checkout 15% off your first order! ** Mind Pump #2357: The 7 Overhead Presses Everyone Should Be Doing Handgrip strength and all-cause dementia incidence and mortality: findings from the UK Biobank prospective cohort study HANDGRIP DYNAMOMETER Study Finds That People Who Entrust Tasks to AI Are Losing Critical Thinking Skills Four Proven Ingredients of a Happy, Lasting Marriage Mind Pump #2325: Why Marriages Fail & What to Do About It With Dr. John Delony Prince Rupert's Drop vs Hydraulic Press [ 4K - Slow Motion ] ( S1 E9 ) Weird 'Square' Spotted On Mars Isn't As Mysterious As It Seems Visit NED for an exclusive offer for Mind Pump listeners! ** Code MINDPUMP at checkout for 20% off ** Train the Trainer Webinar Series Mind Pump #2385: Five Reasons Why You Should Hire a Trainer MAPS Prime Pro Webinar MAPS Prime Webinar Online Personal Training Course | Mind Pump Fitness Coaching Mind Pump #2360: What You Need to Know About GLP-1 With Dr. Tyna Moore Get your free Sample Pack with any “drink mix” purchase! Also try the new LMNT Sparkling — a bold, 16-ounce can of sparkling electrolyte water: Visit DrinkLMNT.com/MindPump Mind Pump Podcast – YouTube Mind Pump Free Resources People Mentioned Dr. John Delony (@johndelony) Instagram Dr. Stacy T. Sims (@drstacysims) Instagram Justin Brink DC (@dr.justinbrink) Instagram Dr. Tyna Moore (@drtyna) Instagram   

うつ病経験のある中高年は「高血圧」や「鼻炎」などを抱えがち？──英国で約17万人を調査。　英エディンバラ大学などに所属する研究者らが発表した論文「Depression and physical multimorbidity: A cohort study of physical health condition accrual in UK Biobank」は、うつ病の既往歴を持つ中高年は、そうでない人と比較して、より多くの長期的な身体疾患を抱え、新たな身体疾患も速いペースで蓄積することが明らかになった研究報告である。

Welcome to the Olink® Proteomics in Proximity podcast!  Below are some useful resources mentioned in this episode:  Olink® Reveal, accessible NGS-based proteomics for every lab: https://olink.com/products/olink-revealOlink tools and software·       Olink® Explore 3072, the platform utilized by the UK Biobank to measure ~3000 proteins in plasma: https://olink.com/products-services/explore/·       Olink® Explore HT, Olink's most advanced solution for high-throughput biomarker discovery, measuring 5400+ proteins simultaneously with a streamlined workflow and industry-leading specificity: https://olink.com/products-services/exploreht/  UK Biobank Pharma Proteomics Project (UKB-PPP), one of the world's largest scientific studies of blood protein biomarkers conducted to date, https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/news/uk-biobank-launches-one-of-the-largest-scientific-studies   Subscribe to the podcast on your favorite player or app:Apple Podcasts: https://apple.co/3T0YbSm   Spotify Podcasts: https://open.spotify.com/show/2sZ2wxO...   Google Podcasts: https://podcasts.google.com/feed/aHR0...   Amazon Music: https://music.amazon.com/podcasts/d97...   Podcast Addict: https://podcastaddict.com/podcast/409...   Deezer: https://www.deezer.com/show/5178787   Player FM: https://player.fm/series/series-3396598   In case you were wondering, Proteomics in Proximity refers to the principle underlying Olink technology called the Proximity Extension Assay (PEA). More information about the assay and how it works can be found here: https://bit.ly/3Rt7YiY  For any questions regarding information Olink Proteomics, please email us ...

In this episode, our guests discuss the potential of large-scale health datasets to transform research and improve patient outcomes and healthcare systems. Our guests also delve into the ethical, logistical, and technical challenges that come with these programmes. We hear how organisations such as UK Biobank, Our Future Health, and All of Us are collecting rich, diverse datasets, collaborating and actively working to ensure that these resources are accessible to researchers worldwide. Hosting this episode is Dr Natalie Banner, Director of Ethics at Genomics England. She is joined by Dr Raghib Ali, Chief Medical Officer and Chief Investigator at Our Future Health, Professor Naomi Allen, Professor of Epidemiology at the Nuffield Department of Population Health, University of Oxford, and Chief Scientist for UK Biobank, and Dr Andrea Ramírez, Chief Data Officer at the All of Us Research Program in the United States. "There are areas where academia and the NHS are very strong, and areas where industry is very strong, and by working together as we saw very good examples during the pandemic with the vaccine and diagnostic tests etc, that collaboration between the NHS and academia industry leads to much more rapid and wider benefits for our patients and hopefully in the future for the population as a whole in terms of early detection and prevention of disease." You can download the transcript or read it below.  Natalie: Welcome to Behind the Genes   Naomi: So, we talked to each other quite regularly. We have tried to learn from each other about the efficiencies of what to do and what not to do in how to run these large-scale studies efficiently. When you are trying to recruit and engage hundreds of thousands of participants, you need to do things very cost effectively. How to send out web-based questionnaires to individuals, how to collect biological samples, how the make the data easily accessible to researchers so they know exactly what data they are using.   All of that we are learning from each other. You know, it is a work in progress all the time. In particular you know, how can we standardise our data so that researchers who are using all of us can then try and replicate their findings in a different population in the UK by using UK Biobank or Our Future Health.    Natalie: My name is Natalie Banner, and I am Director of Ethics at Genomics England. On today's episode we will be discussing how we can unlock the potential of large health datasets. By that I mean bringing together data on a massive scale, including for example genomic, clinical, biometric, imaging, and other health information from hundreds and thousands of participants, and making it available in a secure way for a wide range of research purposes over a long time period.   Through collaboration and industry partnerships, these programmes have the potential to transform research and deliver real world benefits for patients and health systems. But they also come with challenges ranging from issues in equity and ethics through to logistics, funding, and considerable technical complexities. If you enjoy today's episode, we would love your support. Please like, share, and rate us on wherever you listen to your podcasts.     I'm delighted to be joined today by 3 fantastic experts to explore this topic. Dr Raghib Ali, Chief Medical Officer and Chief Investigator at Our Future Health. Professor Naomi Allen, Professor of Epidemiology at the Nuffield Department of Population Health, University of Oxford, and Chief Scientist for UK Biobank, and Dr Andrea Ramírez, Chief Data Officer at the All of Us Research Program in the United States.   Andrea, if I could start with you. It would be really great to hear about All of Us, an incredibly ambitious programme in the US, and maybe some of the successes it has achieved so far.   Andrea: Absolutely. Wonderful to be here with you and thank for you for the invitation. The All of Us Research Program started in 2016 from the Precision Medicine Initiative and was funded with the goal of recruiting 1 million or more participants into a health database. That includes information not only from things like biospecimens including their whole genome sequence, but also surveys that participants provide, and importantly linking electronic health record information and other public data that is available, to create a large database that researchers that access and use to study precision health.   We have recruited over 830,000 participants to date and are currently sharing available data on over 600,000. So, we're excited to be with your audience, and I hope we can learn more and contribute to educating people listening about precision medicine.   Natalie: Thank you, Andrea. And not that this is competitive at all, but Raghib, as we are recording this, I understand the Our Future Health programme is marking quite a phenomenal milestone of 1 million participants. Would you mind telling us a little bit about the programme and something that you see as the benefits of working at scale for health research.   Raghib: Thank you very much. So, Our Future Health is a relatively new project. It was launched in 2020 with the aim of understanding better ways to detect disease as early as possible, predict disease, and intervene early to prevent common chronic diseases. Similar to All of Us, we are creating a very large database of participants who contribute their questionnaire data, physical data, genetic data, and linkage to healthcare records, with the aim as I said, to really improve our understanding of how best to prevent common chronic diseases.   So, we launched recruitment in October 2022. Our aim is to recruit 5 million participants altogether, and in the last 2 years about 1.85 million people have now consented to join the project. But you are right, as of last week we have what we call 1 million full participants, so people that have donated a blood sample, completed the questionnaire, and consented to link to their healthcare records. In our trusted research environment, we now have data on over 1million people available for researchers to use.   Of course, we have learnt a lot from the approach of UK Biobank, which we are going to hear about shortly, but the resource is open to researchers across the world, from academia, from the NHS, from industry, so that will hopefully maximise the benefits of that data to researchers, but as I say with a particular focus on early detection, early intervention, and prevention research.   Natalie: Thank you Raghib. Great to have you with us. Naomi, Raghib mentioned that UK Biobank has been running for a long time, since 2006.  It is a real success story in terms of driving a huge range of valuable research efforts.  Could you talk to us a little bit about the study and its history and what you have learned so far about the sort of benefits and some of the challenges of being able to bring lots of different datatypes together for research purposes?   Naomi: Yeah, sure. So, UK Biobank started recruiting 0.5 million participants in 2006 to 2010 from all across the UK with a view to generating a very deep dataset. So, we have collected information on their lifestyle, a whole range of physical measures. We collected biological samples, so we have data on their genomics and other biomarkers. Crucially because they recruited 15+ years ago, we have been able to follow up their health over time to find out what happens to their health by linkage to electronic healthcare records. So, we already have 8,000 women with breast cancer in the resource, cardiovascular disease, diabetes, and so on.   But perhaps most importantly, not only does it have great data depth, and data breadth, and the longitudinal aspect, is the data is easily accessible to researchers both from academia and industry, and we already have 18,000 researchers actively using the data as we speak, and over 12,000 publications already generating scientific discoveries from the resource.      Natalie: So, we have got 3 quite different approaches. Recruiting in different ways, different scale, different depth of data collection and analysis, but all very much around this ethos of bringing lots of different datatypes together for research purposes. I wonder if you could talk a little bit about how you might be sort of working together, even though you have got slightly different approaches. Are there things that you are learning from one another, from these different data infrastructures, or how might you be looking in the future to work together to address some of the challenges that might come up from working at scale?      Naomi: So, we talk to each other quite regularly. We have tried to learn from each other about the efficiencies of what to do and what not to do in how to run these large-scale studies efficiently. When you are trying to recruit and engage hundreds of thousands of participants, you need to do things very cost effectively. How to send out web-based questionnaires to individuals, how to collect biological samples, how to make the data easily accessible to researchers so they know exactly what data they are using.   All of that we are learning from each other, and you know it is a work in progress all the time. In particular, how can we standardise our data so that researchers who say are using All of Us can then try and replicate their findings in a different population in the UK by using UK Biobank or Our Future Health. So, can we come up with common standards so that researchers can better directly compare the data that they are using? So, we are in close contact with each other.   Natalie: Fantastic, thank you. And Andrea, from your perspective obviously you are collecting data in the US. Are you finding ways of working internationally and with other infrastructures like Biobank and Our Future Health around things like data standards? It sounds like something simple, but I can imagine it is quite complex in practice.   Andrea: Absolutely, and that dialogue and understanding and learning from each other both informally in meetings and talking as well through the published literature. So, all of these datasets are actively widely used, and seeing what is coming out in publications helps us know what researchers are doing with the data. And when you see different researchers either generating hypotheses from our datasets in a different way, or testing hypotheses differently, that helps us understand where some benefit might be added to our dataset or where we really may need to grow in a different direction to meet some other research needs.   I think that every study design always struggles with that balance between knowing exactly what we want to study and therefore building very specific questions and very specific protocols, but also allowing for the knowledge that we don't really know all of the discovery we need to make and bringing in datapoints that will really generate those new hypotheses for the future.     I think for our study in particular, UK Biobank has been so remarkable in this way, helping structure All of Us to be able to contact our participants like UK Biobank and say, “Hey, we didn't really know what we were going to get, but we have put all this wonderful data together and now we need to do a deeper dive.”   So, the engagement and long-term return of those UK Biobank participants has really enriched our data, and we have learnt from UK Biobank a lot there, and hope through growing our partnerships programme that we can continue to create partnered research opportunities to strengthen that data as well. That is a new thing coming out of our group. You may have heard of it previously as ancillary studies, but we recognise the partnership that is important for those research opportunities. So, we are reporting here that we are hoping to rebrand it to reach a larger audience, and that is led by Dr. Shelley, as partnered research opportunities that will allow us to re-contact, bring our participants back, and really deepen that dataset.   Natalie: Thank you. And Raghib, I know that it is a really important part of the Our Future Health model about going back to participants, but you are in quite early stages of working out what those opportunities might look like.   Raghib: Yes, very much early stages. Just to reiterate the point for me personally, having started my research in the UK about 20 years ago, I have certainly learnt a lot personally, but we have all learnt a lot from the model that UK Biobank established in terms of collecting data and providing it to researchers, and I see these 3 studies as very much complimentary.   All of Us again have done a lot more work in terms of providing feedback to participants about their risk of disease and genetic information, and as you say Our Future Health was set up deliberately to not just be a purely observational study, but to give participants feedback about their risk of different chronic diseases as well as the opportunity to take part in not just studies to collect data, but also interventional studies to see if we can change the natural history of disease and prevent diseases in our participants.   So, that has never really been done at scale before, and that is certainly a big challenge for us to do, not just in the UK, but anywhere, including the US and working with health systems as to how best to do that. So, you know we have spent the last 2 years really trying to understand how best to recruit participants and to provide data to researchers for the next couple of years, and long beyond that we will be looking really as to how we can maximise the benefits of providing feedback to participants and taking part in interventional studies.   Naomi: I think one way in which we can all learn from each other actually, is we know how to recruit hundreds of thousands of people, the general population, into research study, and the next challenge is how do you keep engaging them, telling them what you are doing. You can't collect everything when they first join the study, or they would be with you for days. So, what UK Biobank has been doing is sending out web-based questionnaires, a couple a year, to find out extra information about health outcomes, lifestyle factors. Inviting them back to specific assessment centres.   So, we are inviting 100,000 participants back for imaging, and then again over the next few years for a second scan. So, I think the real challenge here is once you have recruited them, how to find that right cadence of engaging those participants to keep contributing their data and their biological samples to really maximise the value of the dataset for research. That is an ongoing challenge for all of us. But I have to say, the UK Biobank participants, they are an amazing group of individuals, very altruistic.   Our Future Health and All of Us, we don't give feedback, so there is nothing in it for our participants other than knowing that their data may help the future health of their children, and their grandchildren, and the rest of the world. So, that is very humbling, to know that the data that they have generated, and we have collected on them, is being used in that way.   Natalie: That's a really interesting point, Naomi, about the difference between a research study that is designed for answering a particular question. You gather specific data for a specific purpose, and when it comes to recruiting participants into that you can be very clear about what it is you are trying to do.   But of course, for all of these programmes, the whole nature of them is that you are collecting a lot of data over a long period of time, and it could be used for all sorts of different purposes. You can't say at the outset exactly what those purposes might be and what those outcomes might be. So, there is a really interesting question, and of course I would say this with my ethics hat on, a really interesting question around sort of participant trust and confidence in those programmes.   Naomi, you spoke just then about one way of retaining engagement and retaining people's interest, but I wonder Raghib and Andrea, if you have got thoughts on those sort of questions of how you can create that environment where participants can trust what you are doing with data over a long period of time, when you can't at the point at which they consent, say exactly how that data might be used? You have got a sense of the kinds of purposes, but you can't be too specific         Andrea: Sure. We know, and I have learnt from my own peers in this role, that enrolment in the study isn't the end point of engagement. All of Us's approach on engagement has been communicating with the entire community and really being there in the community, and that has been very powerful.   One effort over the last year we are proud of has been what we are dubbing participant driven enquiry, and that is where we say, “Thank you participants. We have gotten a ton of data out there for use, and funded researchers to use it all the time, but what do you, the participants, really want?” We were able to then take papers that researchers write and help tell participants and explain it in lay language, so the participants can say, “Hey, I have a question. Could you answer that for me?” Maybe we can, maybe we can't, but it has been very interesting to hear what participants want to know, and that participant driven enquiry project has turned out to be a big opportunity there.    The question they came to was not easy. Certainly, we didn't expect an easy question, but they came to us asking, “Why is my diabetes worse than someone else's? Is it the environment? Is it my genome? Is it my access to care? Why can't my diabetes be as well controlled as someone else's?”  So, that has been huge, to interact directly with our participants and help really close the loop by answering questions in the language of research and show them how their data is contributing back.    Natalie: Thank you. And Raghib, how are you sort of grappling with these questions, particularly because you are recruiting so very heavily at the moment?   Raghib: So, as you say it is a challenge, and people do join the programme primarily based on trust that we will use their data for public health benefit and for the benefit of the whole population, but they also join on the basis that they will get back information about their own health and their risk of disease. To do both of those is not straightforward. I mean, the first of those, it has been well established by UK Biobank, and about 80% of our participants also say they are doing it primarily for to altruistic reasons, which is great. But 80% also said they would like to receive feedback about their own health, which is also understandable, and so we need to find ways to provide that in a timely way, but also in a way that the health service can manage. That is going to be one of our key challenges going forward.    But to echo what Naomi and Andrea have said, I mean to maintain participant's engagement with the programme is not easy. We need to make sure that they are receiving information regularly, are kept up to date with what we are doing with their data, with the work that we are doing with academia, with the NHS, with industry etc. It is easier now than it was before because Our Future Health has been set up as a digital cohort, so we have means of communicating much more easily with our participants. But yeah, as you say we are at early stages. Over time that does get harder, to maintain that engagement. So, we know in the next one to 2 years we need to step up our work on feedback and recontact.   Natalie: Fantastic. I really love the idea of like the participant-led enquiry. That is something that I think our participant panel at Genomics England would really like to hear more about.   So, speaking about sort of ongoing engagement with participants, one of the challenges we know around recruiting into large-scale studies like this is that many research datasets don't have equal representation from all communities. That might have an impact on the quality, the representativeness of the scientific outputs that you can generate, and potentially the benefits back to patients and participants.   How are you addressing this challenge in recruitment where you may have some communities that are not as engaged with scientific research. You may have elements of distrust or people being marginalised, having difficulty accessing research and these sorts of opportunities. Do you have any examples of what has worked really well? Raghib, if I could come to you first.   Raghib: Sure. So, I mentioned I worked on UK Biobank about 20 years ago. One of the things I was looking at then was how we could maximise participation, particularly of people from ethnic minorities into the project. Because of the age group that was chosen by UK Biobank for very good reasons, age 40 to 69, the proportion of people from ethnic minorities was relatively small. So, although it was representative for that age group, I think it was about 6%, or 34,000 out of the 500,000, that were from non-white ethnic minorities.   So, when Our Future Health was set up, we knew that the population has changed anyway. You know, the UK has become a much more ethnically diverse society. But also, because it is a cohort from 18+ and I think minorities tend to be younger on average than the white population, we knew we had an opportunity to really have a big step change in the number of people that could take part in a study like this. So, our aim is actually to get 10% of the whole cohort from ethnic minorities, so 500,000 out of the 5 million from ethnic minorities. Actually, so far we are pretty much on track. So, of the 1.8 million that have consented, about 180,000 are from non-white ethnic minorities.   That is extremely important, particularly for genetic research where non-European populations are very much underrepresented in nearly all genetic databases. Secondly, from a UK context, although it applies of course in all countries, is that people from more deprived backgrounds are also less likely to take part in this type of research. So again, we have made a very deliberate attempt to try and ensure we have adequate numbers from the most deprived quintile. Again, about 10% of the cohort so far, nearly 200,000 are from that most deprived quintile who both are underrepresented in research, but also have the worst outcomes. So, this is really our first study that has been big enough in the UK to look at that group properly and understand some of the factors at an individual level that we haven't been able to in the past.   Finally, geographically, so the first time again because it is a digital cohort, we were able to recruit people from all over the UK. So, every single part of the UK is now represented in Our Future Health, particularly coastal communities and rural areas that haven't been able to take part in this type of study before, as well as Northern Ireland. You know, for the first time we have got that full geographical coverage.   Natalie: Fantastic. I suppose a lot of that recruitment approach has very much been about going to where people are, rather than expecting them to come to you. Is that right?     Raghib: That is right and thank you for reminding me. So yeah, we have had a different approach. So, we have opened up many, many more clinics than previous studies through a combination of mobile units, shopping centres, community pharmacy. Community pharmacy in particular has been very important. So, to date we have had about 400 different venues that we have been able to recruit. That is over 1 million people that have given blood samples, and that has really enabled people from every part of the country to take part. Secondly, we have kept clinics open in areas of greater deprivation and ethnic diversity much longer than in other areas, to maximise the opportunity for them to join. Thirdly, we do provide reimbursement for people with expenses to ensure they aren't excluded because of financial reasons, and again that has helped.    Natalie: So, really making those efforts is evidently paying off. Andrea, have you had similar experiences as All of Us? What has your approach been to try and ensure that you are getting a wider representation from different communities?    Andrea: It has really been a focus on the programme from the start to engage those who have not been included in research in the past and make sure the opportunity is there to participate. Our Engagement Division, led by Dr. Corrine Watson has really pioneered reaching those communities here in the US.   I think one other thing I will mention that we think about when we think about how to engage participants and reach people to return value back to those communities, is to make sure the people who are accessing the data also represent them, and we can build diversity within that researcher workforce. So, since our data was first released in 2020, we have recognised that the biomedical workforce also has a huge group of underrepresented individuals, and a lot of our researcher engagement and researcher outreach has focused on reaching those of diverse backgrounds and career paths.   To that end we have reached out and engaged historically black colleges as well as other minority serving institutions, really looking to make sure that their students and researchers can have the same access as more traditional research-based institutions in the US system.    That has been important because our system is built on cloud-based architecture and shared data that doesn't require a huge cluster on campus, and that helps remove a barrier that some of those institutions and researchers may have had. We also know they haven't been able to participate in the past, and we think that cloud architecture again can make the data much more feasible and be a huge support to diversifying the researcher workforce as we go forward. That circling back, helping them be the voices speaking to their community, helps build out that diverse participant community base as well.    Natalie: That's such an important point, because it is not just about the participants and the data you can collect, but also who is able to look at it? Who is actually able to undertake the research?    Naomi, can I bring you in here? I know that UK Biobank has been thinking a lot about researcher access to data and trying to ensure that the data that you hold, the really rich datasets you hold in UK Biobank, are more accessible to researchers from different backgrounds who may not have the same level of resources. Can you tell us a little bit about the work you have been doing on that?   Naomi: Yeah. So, just following on from what Andrea said, it is really important to get as diverse ideas as possible from across the global research community to really move public health forward.   So, what UK Biobank has done is we are putting mechanisms in place so that early career students, and career researchers, and researchers at all levels of their career from lower income countries, can access the data at a much lower fee. So, currently for most researchers it costs about £9,000 to access all of the data. So, that is 40 petabytes of genomic data, biomarkers, clinical outcomes, lifestyle factors and so on. So, early career researchers and those in lower income countries, it is about £500.   On top of that a group of big pharmaceutical companies have got together to create a global researcher access fund, which essentially covers this reduced fee so that all researchers no matter where they are from have exactly the same opportunity to access the data to advanced scientific discoveries. So, on top of that all our researchers now use our online secure research analysis platform. While there is no charge to access the platform, there are costs associated with compute needed to analyse and store the results.    So, AWS have donated research credits for early career researchers and those from lower income countries up to a total of about $500,000 per year, to use the research platform. So, researchers can apply to use these research credits to offset the costs of compute and storage. So, that means that we are trying to democratise access to researchers from all around the world.   I think actually our biggest challenge is not so much … we have largely dealt with you know subsidising the cost. It is actually making researchers from lower income countries aware that these resources exist, and that are applicable to them.   So, sometimes we hear from say researchers in Africa or South America, “Well, there is no point accessing UK Biobank because it is not relevant to our population.” You know, a third of our researchers are from China. So, even if UK Biobank hasn't got coverage of those racial ethnic populations, that doesn't mean that the associations that you find between risk factors and disease risk are not applicable to other different populations. And that is also why having different resources like UK Biobank, like Our Future Health, like All of Us, in different populations around the world, is so important in order to replicate those findings.    Natalie: Absolutely, and fantastic just to hear the attention that is being paid to trying to ensure that diversity of different types of researchers who will just bring different questions to the table, different perspectives on the data, different priorities, different types of questions.    So, speaking about that diversity of researchers, one really important part of his ecosystem that we haven't really touched on so far is around the role of industry. There are a lot of really important research questions being addressed by industry. Some that can only really come from, maybe it is pharmaceuticals, maybe it is tech.   From your perspectives, what kind of role can and should industry and commercial partners play in supporting the kinds of long-term research studies that you have set up, and ultimately trying to get to that point of sort of generating benefits back to patients and health systems. Naomi, can I start with you, for that sort of longer-term perspective for Biobank?   Naomi: So, industry are great partners for long-term studies like ours because they can bring additional funding, expertise, and technology. So, for UK Biobank, because it is so easily accessible to industry and academics alike on exactly the same terms, what it has meant is that industry, particularly big pharma and also now big tech, they can access the data, they see the value of the data for their own research purposes, and then they have invested into UK Biobank to do whole-exome sequencing, whole genome sequencing, proteomics at scale to increase the value of the dataset for their own drug discovery pipelines.   But of course, it means that the data that they have generated, which cost millions of dollars to generate, when you need deep pockets to do these kinds of study enhancements, then become available to all researchers. So, having access to these large-scale resources that have deep data on genomics, physical measures, other biomarkers, and clinical outcomes enables pharma to rapidly increase their drug discovery pipelines in generating new drugs and treatments for patients, and also those data are then shared with the rest of the global research community.     So, we found it to be a really exciting win/win in which industry get what they need to help move forward new drug targets and discovery, but also other researchers get what they need in order to make other scientific discoveries in different fields of research.        Natalie: Thank you. And Raghib, I know that for Our Future Health, that industry relationship is a really important part of the founding model. Will you tell us a little bit about how you are engaging and working with industry partners?   Raghib: Sure. So, as you said Our Future Health was set up in a different way, as a very public private partnership. Although the largest funder is the UK Government, more than half of our funding has come from a combination of life science companies, so pharmaceutical, diagnostic companies, as well as the medical charities, so the larger medical charities in the UK. That partnership is deliberate for all the reasons that Naomi has outlined. There are areas where academia and the NHS are very strong, and areas where industry is very strong, and by working together as we saw very good examples during the pandemic with the vaccine and diagnostic tests etc, that collaboration between the NHS and academia industry leads to much more rapid and wider benefits for our patients and hopefully in the future for the population as a whole in terms of early detection and prevention of disease. So, we have 16 life sciences companies that have joined as founding partners with Our Future Health who have contributed financially to the programme.    Equally importantly they have also contributed scientifically, so there is a huge amount of scientific expertise in industry, and they work with us with our Scientific Advisory Board with our scientists internally to think about the best use of the resource for drug discovery, diagnostics, new medical technologies, and new targets etc.    So, that is the vision, and so far, it is working well. It is a relatively new model to have set up a project like this in this way, but it has been a very collaborative approach, and we all recognise, all have similar aims, so recognise what we are working towards. You know, we meet regularly. We have a Joint Founders Board where as I say academia, NHS, industry, and the charities come together to decide on the priorities for the coming years.   Natalie: Fantastic. And Andrea, I suppose in the US it might be slightly different culturally from the UK, but the role of industry with All of Us, how are you engaging with those pharmaceutical, technology bodies, and partners as well?     Andrea: Absolutely, and maybe this goes back a bit to your first question. We at All of Us love learning from UK Biobank and have really seen them forge a lot of wonderful partnerships that have enriched and developed their dataset. We at All of Us have started with academia and working through partnership opportunities really intramurally at intramural centres that make up parts of the National Institute of Health. We believe that building on those close friends and family relationships we have both in the government and academia get us through our first step to be able to interface with commercial organisations. That really started with taking the first step this year to ensure broad availability of data that can maximise both use of the data available, as well as look forward to our partnership opportunities in the future.   So, commercial organisations as of 2024 have also been able to access the All of Us dataset that is that first step in thinking about what a partnership would be, and we are glad to build on the access that international organisations and academic organisations already have.   Natalie: A lot to look forward to here. We are going to have to wrap up in a moment, so I'd just like to leave you all with a final question before we have to end the podcast. There is huge ambition in all of the research programmes that you are leading and involved in, but what are you most excited about coming down the line in the next few years? What do you think is going to be feasible? What really gets you excited about the work that you are doing and where you see the potential benefits really landing in the next few years? Andrea, would you like to start?   Andrea: Thanks. There is a lot we are really excited about. I haven't had a chance yet to mention our paediatric cohort, and that in addition to expanding access for international research, in 2024 we were able to enrol our first paediatric participants. That really sets up the potential to observe participants across the lifespan. That is a huge advance for All of Us and we are excited about the paediatric work going forward.    Natalie: I love that, how do you come into the future with us? That is fantastic. Naomi.   Naomi: Yeah, if I had to choose one would be the possibility of being able to measure circulating proteins on all half a million participants. We have done this on about 55,000 participants, and just that subset alone is already generating fascinating insights for early biomarkers for disease through protein profiles and risk prediction of disease. I think having that on all half a million coupled with their genomics data and health outcomes, will bring a sea change in how we diagnose disease earlier. So, I think that is a really exciting avenue for us to go into over the next couple of years.   Natalie: Really enriching. That data sounds like a very exciting set of possibilities. Raghib.   Raghib: Thank you. There are so many opportunities here, but I will just maybe mention 3. So, the first, in terms of being able to combine the genetic data that we are collecting and all the other information about risk factors, and particularly the fact that we have this on a lot of young people, will enable us to identify people at high risk of diseases in the presymptomatic phase and then to be able to offer them both feedback about their risk of disease but also interventions that can change their natural incidences. That has never really been possible before. That is extremely important for all diseases for people, but also it is very important for our healthcare system.   So, those of you listening in the UK, I know the NHS is under a huge amount of pressure, and the current model of healthcare which has been in place really since the inception of the NHS, is to treat late-stage disease when people have already developed symptoms and signs. You know, it wasn't really possible to identify people earlier, but it is now, and Our Future Health will provide the evidence base to show that prevention really is better than cure, and to show that these approaches both lead to better clinical outcomes, but also are cost effective and a good use of resources. Of course, the new government is very much committed to this as well, you know moving from acute care to prevention, from hospitals to community, and from analogue to digital.     Finally, because our cohort has now become so large and does cover every part of the UK, and this wasn't something I necessarily thought about when we started Our Future Health, we are able to have unique insights into the health of the population across every age group, across every ethnic group, across every geographical area, and by deprivation, and to understand not just observationally in terms of risk factors, but also the impact of interventions on those different populations.   We can look at that, as I said at an individual level on millions of people to gain intelligence about what is going on in terms of public health, but also to see what will hopefully improve their health in the future. So, there are really, you know I have described transformational opportunities to improve health through both biomedical research and populational health insights now through the resource, and I look forward to working with colleagues across the UK and globally to deliver them.   Natalie: We will wrap up there. Thank you so much to our guests, Dr Raghib Ali, Professor Naomi Allen, and Dr Andrea Ramírez for joining me today as we discussed how collaboration, scale, ongoing engagement, can really unlock the potential of large-scale health datasets to drive brilliant new research and ultimately improve the lives of patients and the population.   If you would like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. I have been your host, Natalie Banner. This podcast was edited by Bill Griffin at Ventoux Digital and produced by Naimah Callachand.

In this episode, Dr. Alexander Glaser (US) explores the relationship between genetic predisposition and lifestyle in benign prostatic hyperplasia (BPH).Drawing on data from a UK Biobank cohort study, he investigates whether varying levels of physical activity can modulate genetic risk factors for BPH. Dr. Glaser provides a detailed overview of the study's methodology, key findings, and potential implications for preventive and personalised approaches to managing prostate health. This episode sheds light on the critical intersection of genetics and lifestyle in addressing urological conditions.For more EAU podcasts, please go to your favourite podcast app and subscribe to our podcast channel for regular updates: Apple Podcasts, Spotify, EAU YouTube channel.

¿Deberías dejar el café? ☕ Descubre si esta popular bebida está ayudando o perjudicando tu salud. En este video, exploramos los beneficios y riesgos del café respaldados por la ciencia, y al final te damos recomendaciones prácticas para saber si deberías reducir su consumo o dejarlo por completo. Hablaremos de: ✅ Cómo el café afecta tu rendimiento físico y mental. ✅ Los beneficios antioxidantes y sus posibles riesgos ocultos. ✅ Ansiedad, insomnio y otros efectos de la cafeína en exceso. ✅ Alternativas saludables al café para quienes quieren reducirlo. Mira hasta el final para descubrir todo lo que necesitas saber sobre esta bebida tan popular. ¡Este video podría cambiar tu forma de consumir café para siempre!

Today's episode has been a long time coming. For years, more scientists and health influencers have claimed that even moderate drinking does serious damage to one's health. As someone who likes being healthy and also loves a glass of wine (or scotch), Derek really wanted to understand this issue more deeply. This week, he published a long article in The Atlantic about his research on the health effects of moderate drinking—meaning one or two drinks a night. In today's episode, he breaks down his research process and conclusions, sharing audio from his interview with Canadian health researcher Tim Stockwell, who is one of the most prominent skeptics of the supposed benefits of moderate drinking. If you have questions, observations, or ideas for future episodes, email us at PlainEnglish@Spotify.com. Host: Derek Thompson Guest: Tim Stockwell Producer: Devon Baroldi Links Derek's original article in The Atlantic (free gift link!): https://www.theatlantic.com/ideas/archive/2025/01/moderate-drinking-warning-labels-cancer/681322/?gift=o6MjJQpusU9ebnFuymVdsD7vJ9S6Vd2LMCE-zROPKQs&utm_source=copy-link&utm_medium=social&utm_campaign=share "The Battle Over What to Tell Americans About Drinking" in the NYT: https://www.nytimes.com/2025/01/01/health/alcohol-dietary-guidelines.html "Alcohol and Cancer Risk 2025" The U.S. Surgeon General's Advisory https://www.hhs.gov/sites/default/files/oash-alcohol-cancer-risk.pdf A meta-analysis in The Lancet on alcohol use and burden for 195 countries and territories https://www.thelancet.com/article/S0140-6736(18)31310-2/fulltext Vinay Prasad on alcohol and the meta-analysis https://www.drvinayprasad.com/p/what-is-the-truth-about-alcohol-consumption Emily Oster on alcohol and health https://parentdata.org/alcohol-and-health/ Tim Stockwell, et al, meta-analysis on alcohol, 2023 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2802963 "Associations between alcohol consumption and gray and white matter volumes in the UK Biobank" https://www.nature.com/articles/s41467-022-28735-5 Learn more about your ad choices. Visit podcastchoices.com/adchoices

Welcome to the Olink® Proteomics in Proximity podcast!   Below are some useful resources mentioned in this episode:  Olink tools and software·       Olink® Explore 3072, the platform utilized by the UK Biobank to measure ~3000 proteins in plasma: https://olink.com/products-services/explore/·       Olink® Explore HT, Olink's most advanced solution for high-throughput biomarker discovery, measuring 5400+ proteins simultaneously with a streamlined workflow and industry-leading specificity: https://olink.com/products-services/exploreht/  UK Biobank Pharma Proteomics Project (UKB-PPP), one of the world's largest scientific studies of blood protein biomarkers conducted to date, https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/news/uk-biobank-launches-one-of-the-largest-scientific-studies  Press release and news story from UK Biobank:https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/news/launch-of-world-s-most-significant-protein-study-set-to-usher-in-new-understanding-for-medicine https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/news/dataset-of-thousands-of-proteins-marks-landmark-step-for-research-into-human-health https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/news/uk-biobank-launches-one-of-the-largest-scientific-studies News stories:Today Programme – Professor Rory Collins live on programme, timestamp 02:36:37   Times – ‘Game-changing' study of blood proteins will help fight disease Independent – World's largest proteins study ‘invaluable' for understanding disease – experts Daily Mail – How Alzheimer's could be diagnosed a DECADE earlier following huge study of blood proteins Mirror – New blood test reveals risk of developing different diseases in 'new frontier of science' Science – Seeking disease insights, UK Biobank launches largest study of human proteinsTechnology Networks – UK Biobank Launches Largest Proteomics Study for Disease Research Chemical and Engineering News – Pharma firms team up to study UK proteomics data  Links to referred episodes:  • Evan – Episode 20:     https://share.transistor.fm/s/f795811e    https://open.spotify.com/episode/6lv5GA8hZCgDvujlBltS9f?si=36a29e6cfa4b4fae     https://podcasts.apple.com/us/podcast/how-proteomics-is-shaping-pharma-strategies/id1645900688?i=1000635040581 • Chris – Episode 16:     https://share.transistor.fm/s/255ad207     https://open.spotify.com/episode/0oe0S6zI8cryUtgZTjGlRq?si=8a7b0323b1364b96     https://podcasts.apple.com/us/podcast/interview-about-the-uk-biobank-with-dr-christopher-whelan/id1645900688?i=1000622521524  Subscribe to the podcast on your favorite player or app:Apple Podcasts: https://apple.co/3T0YbSm   Spotify Podcasts: https://open.spotify.com/show/2sZ2wxO...   Google Podcasts: https://podcasts.google.com/feed/aHR0...   Amazon Music:

Lange, Michael www.deutschlandfunk.de, Forschung aktuell

Topics this week: Meat Substitutes Linked to 42% Higher Depression Risk in Vegetarians - Big Dru talks about the recent research that indicates vegetarians who consume plant-based meat alternatives (PBMAs) may face a 42% higher risk of depression compared to those who avoid these products. Study Overview: Participants: The study analyzed data from over 3,300 vegetarians, including vegans, from the UK Biobank. HEALTHLINE Findings: Vegetarians consuming PBMAs exhibited: -A 42% increased risk of depression. -Higher levels of C-reactive protein (CRP), indicating increased inflammation. -Slightly elevated blood pressure. -Lower levels of apolipoprotein A, associated with HDL ("good") cholesterol. -Conversely, a 40% reduced risk of irritable bowel syndrome (IBS). Therapy of the Week: 10% OFF ALL #TitanMedical Center Weight Loss Therapies Special! DON'T MISS THIS AMAZING SPECIAL!!! Let our #TitanMedical weight loss therapies help you lose weight & feel great! You get to choose from any of our great weight loss therapies and get 10% off each one! All of our therapies come from U.S. licensed pharmacies straight to you! Semaglutide ECA Stack Plus Titan Trim (Tesofensine) Tirzepatide AOD 9604 L-Carnitine Titan Complete Prometheus Fat Burning Cream *********** This special ends 1/3/2024!!! -------------- Get On Email List! Text: titanmedical To: 22828 About Titan Medical Center: We offer Hormone Replacement Therapy, Medical Weight Loss, Injectable Vitamin & Amino Therapies, Relationship, Bedroom Enhancing Therapies, On-Site or Nationwide Blood Work Testing, Peptide Therapies, In-House IV Therapy, & Primary Care. We are based in Tampa, Florida but YES we service NATIONWIDE! We can help you enhance your life and performance while operating at optimal health levels. We have medical doctors and start with blood work testing to get you on the right track! Some of our therapies are available without blood work testing. Call Titan Medical Center to learn how you can have a healthier, stronger life. We offer telemedicine (via FaceTime or Skype) from the comfort of your own home where you will see a licensed medical provider. Our Titan therapies are doctor prescribed & shipped directly to your doorstep from a licensed US pharmacy!

The impact of schizophrenia genetic load and heavy cannabis use on the risk of psychotic disorder in the EU-GEI case-control and UK Biobank studies Psychological Medicine Using data from the EU-GEI case-control study and UK Biobank, researchers examined the independent and combined effect of heavy cannabis use and schizophrenia polygenic risk score (PRS), on risk for psychosis. Schizophrenia PRS and cannabis use independently increased risk of psychosis. Schizophrenia PRS was not associated with patterns of cannabis use. It was associated with lifetime and daily cannabis use without psychosis, but the effect was substantially reduced when cannabis use disorder (CUD) PRS was included in the model. Regular users of high-potency cannabis had the highest odds of being a case independently of schizophrenia PRS. Regular use of high-potency cannabis remains a strong predictor of psychotic disorder, independent of schizophrenia PRS. Schizophrenia PRS does not seem to be associated with heavy cannabis use. These are important findings, at a time of increasing use and potency of cannabis worldwide.    Read this issue of the ASAM Weekly Subscribe to the ASAM Weekly Visit ASAM

Send us a textLink to Health Type Quiz Link to Living Well, Aging Strong 6-month group experience As the holiday season approaches, the question of how much alcohol is too much becomes ever more pressing. What if the festive cheer of a drink or two could be clouded by the potential for long-term health risks? Dr. Bobby unpacks the complex and often contradictory research around alcohol, helping listeners navigate the decision: is it best to have none, or is a little okay? By exploring the impacts of alcohol on weight/appetite, heart disease, cancer, sleep, and cognitive health, and by considering personal health types, listeners can make more informed choices about their drinking habits. Key Topics Covered:Conflicting Headlines and Research: Discussing the confusion around alcohol's health effects, from Gallup poll insights to studies highlighting both potential benefits and risks.Health Risks Explored: Weight Gain: Alcohol adds calories and increases appetite, contributing to potential weight gain (study on caloric intake). Heart Disease: Early studies suggested moderate benefits for small amounts of alcohol, but advanced analyses, like Mendelian randomization, challenge this assumption, not showing a protective effect (study on genetic analysis). Cancer Risks: Alcohol consumption has been linked to several cancers, including breast and colon cancer.  (WHO fact sheet).Sleep Impacts: Alcohol disrupts sleep quality, even if consumed earlier in the day (small study on sleep effects).Cognitive Decline: Even mild drinking shows potential risks for brain health, with larger consumption exacerbating damage (UK Biobank study).Defining Drinking Levels: Categories from non-drinker to heavy drinking were clarified, helping listeners identify where they stand (National Survey on Drug Use and Health).Personal Stories and Practical Decisions: Dr. Bobby shares his personal experience with holiday indulgence and offers practical strategies for mindful drinking.Role of Health Types: Leveraging your health archetype (e.g., Purposeful Path Planner or Contentment Creator) to guide decisions about alcohol consumption.Takeaways:  Know Your Limits: For most, keeping alcohol under seven drinks per week minimizes risks without eliminating enjoyment.As we navigate the complexities of alcohol's impact on health, I share my personal approach of allowing myself up to seven drinks a week, accepting some level of risk for the sake of balance. With the Living Well Aging Strong program, we provide tools to create personalized health plans, empowering you to make choices that align with your lifestyle. Let's embark on this journey together, equipped with knowledge and support, as we strive for imp

Oxford Nanopore y UK Biobank desarrollan el mayor mapa epigenético para combatir cáncer y demencia  Oxford Nanopore Technologies y UK Biobank están creando el mapa epigenético más completo del mundo. Este mapa va a registrar cómo factores externos, como el estilo de vida y el ambiente, modifican el ADN humano sin alterar su estructura.Déjanos tu comentario y escucha más en Flash Diario en Spotify.La epigenética, clave en este proyecto, estudia estos cambios y su impacto en enfermedades como el cáncer y la demencia. Utilizando tecnología de vanguardia, analizarán 50.000 muestras para identificar hasta el 98 % de los marcadores epigenéticos. Este conocimiento permitirá comprender mejor cómo se desarrollan estas enfermedades y diseñar tratamientos más precisos y personalizados. ¿Qué implica este avance para el futuro de la medicina y nuestra salud?  Este mapa puede redefinir el diagnóstico y tratamiento de enfermedades  Un mapa epigenético es una representación detallada de los cambios químicos que afectan cómo se expresan los genes, sin modificar el ADN. En este caso, el proyecto analizará cómo los estilos de vida, como la dieta o el tabaquismo, influyen en la activación o desactivación de ciertos genes. Oxford Nanopore, con su tecnología avanzada, permitirá mapear el 98 % de estas modificaciones, un salto gigantesco frente al 3 % que los métodos actuales lograban. Este análisis detallado se combinará con información genética, imágenes y datos médicos de los participantes para ofrecer una visión completa de cómo se desarrollan enfermedades en la mediana y tercera edad.  El cáncer y la demencia afectan a millones de personas cada año, y aunque los avances genéticos han ayudado, no siempre explican por qué surgen estas enfermedades. Ahí es donde entra la epigenética, que estudia los factores externos que alteran cómo funcionan los genes. Sin embargo, los datos disponibles hasta ahora han sido limitados y fragmentados. Esto ha dificultado la creación de herramientas efectivas para diagnóstico temprano o tratamiento personalizado. El nuevo proyecto promete resolver este problema al ofrecer un nivel de detalle sin precedentes, permitiendo identificar patrones de riesgo y comprender mejor la resistencia de tumores a los tratamientos actuales.  El impacto de este mapa epigenético puede ser transformador. Por un lado, permitirá a los médicos diseñar tratamientos personalizados basados en el perfil epigenético de cada paciente, lo que mejorará la eficacia de los tratamientos y reducirá efectos secundarios. Además, podría usarse para diagnosticar enfermedades como el cáncer o la demencia en sus primeras etapas, mucho antes de que aparezcan síntomas evidentes. Este proyecto también refuerza el liderazgo del Reino Unido en ciencias de la vida, posicionando al país como un referente en investigación y tecnología de vanguardia. Al integrar los hallazgos epigenéticos con datos genéticos y médicos, este avance representa un paso gigante hacia una medicina más preventiva y personalizada.  La epigenética permite entender por qué, a pesar de tener el mismo ADN, algunas personas desarrollan enfermedades y otras no. Este mapa, creado con muestras de participantes predominantemente sanos, servirá como referencia para identificar los primeros signos de enfermedades relacionadas con la edad. Además, las herramientas desarrolladas con este proyecto podrían usarse globalmente para mejorar la atención médica y reducir costos. Gordon Sanghera, CEO de Oxford Nanopore, destacó que el objetivo final es traducir estos avances científicos en beneficios reales para los pacientes.  El mapa epigenético que desarrollan Oxford Nanopore y UK Biobank promete revolucionar la medicina al ofrecer un análisis detallado de cómo el ambiente y el estilo de vida influyen en el desarrollo de enfermedades como el cáncer y la demencia. Este proyecto no solo avanza hacia la medicina personalizada, sino también hacia la prevención. ¿Qué opinas sobre este tipo de avances? Déjanos tu comentario y escucha más en Flash Diario en Spotify.Bibliografía:technologynetworks.comdevdiscourse.comindiatoday.inConviértete en un seguidor de este podcast: https://www.spreaker.com/podcast/flash-diario-de-el-siglo-21-es-hoy--5835407/support.

Harlan Krumholz, editor-in-chief of JACC, provides a wrap-up of the JACC papers at the AHA Scientific Sessions in Chicago in 2024. JACC's Obesity Revolution page features various trials to provide perspectives on obesity, including SUMMIT, LookAHEAD, and SELECT. Other studies featured include the DANGER trial; REALIZE-K; AMPLATZER; HELIOS-B; a study on sedentary behaviors from the UK Biobank; systolic pressure and blood pressure in patients with HFpEF; rural and urban differences in cardiovascular mortality from 2010-2022; and the association of hospital cardiologist integration with patient outcomes

We're bringing back a favorite—nutrition headlines! And this version just might be our best! In today's episode, we are sharing four new nutrition studies. There's new research on bright light treatment and using it for more than just seasonal depression. Are night owls smarter than early risers? Or is being a “morning lark” better? You might not be to blame for your kids' fussy eating tendencies. And does having a sweet tooth predispose you to some health conditions?  Sources referenced include:   Bright Light Therapy for Nonseasonal Depressive Disorders: A Systematic Review and Meta-Analysis Sleep duration, chronotype, health and lifestyle factors affect cognition: a UK Biobank cross-sectional study Nature and nurture in fussy eating from toddlerhood to early adolescence: findings from the Gemini twin cohort Artificial intelligence driven definition of food preference endotypes in UK Biobank volunteers is associated with distinctive health outcomes and blood based metabolomic and proteomic profiles   Thank you for listening to The Happy Eating Podcast. Tune in weekly on Thursdays for new episodes! For even more Happy Eating, head to our website!  https://www.happyeatingpodcast.com Learn More About Our Hosts:  Carolyn Williams PhD, RD: Instagram: https://www.instagram.com/realfoodreallife_rd/ Website: https://www.carolynwilliamsrd.com Facebook: https://www.facebook.com/RealFoodRealLifeRD/ Brierley Horton, MS, RD Instagram: https://www.instagram.com/brierleyhorton/ Got a question or comment for the pod? Please shoot us a message!  happyeatingpodcast@gmail.com Produced by Lester Nuby OE Productions

Welcome to the Olink® Proteomics in Proximity podcast! Below are some useful resources mentioned in this episode:  Olink tools and softwareOlink® Explore 3072, the platform utilized by the UK Biobank to measure ~3000 proteins in plasma: https://olink.com/products-services/explore/Olink® Explore HT, Olink's most advanced solution for high-throughput biomarker discovery, measuring 5400+ proteins simultaneously with a streamlined workflow and industry-leading specificity: https://olink.com/products-services/exploreht/  UK Biobank Pharma Proteomics Project (UKB-PPP), one of the world's largest scientific studies of blood protein biomarkers conducted to date, https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/news/uk-biobank-launches-one-of-the-largest-scientific-studies  Research articlesThe support of human genetic evidence for approved drug indicationsMatthew R Nelson et al,  Nature Genetics 2015https://www.nature.com/articles/ng.3314 Proteomic aging clock predicts mortality and risk of common age-related diseases in diverse populationsM. Austin Argentieri et al,  Nature Medicine 2024https://www.nature.com/articles/s41591-024-03164-7 Plasma protein-based organ-specific aging and mortality models unveil diseases as accelerated aging of organismal systemsLudger J.E. Goeminne et al, Cell Metabolism 2024, in presshttps://www.sciencedirect.com/science/article/abs/pii/S1550413124004017?via%3Dihub Plasma proteomic associations with genetics and health in the UK BiobankBenjamin B. Sun et, Nature 2023https://www.nature.com/articles/s41586-023-06592-6 Rare variant associations with plasma protein levels in the UK BiobankRyan S. Dhindsa; Nature 2023https://www.nature.com/articles/s41586-023-06547-x Disease prediction with multi-omics and biomarkers empowers case–control genetic discoveries in the UK BiobankManik Garg, Nature Genetics, 2024https://www.nature.com/articles/s41588-024-01898-1 China Kadoorie Biobank: https://www.ckbiobank.org/publicationsPublications: https://www.ckbiobank.org/publications Subscribe to the podcast on your favorite player or app:Apple Podcasts: https://apple.co/3T0YbSm  Spotify Podcasts: https://open.spotify.com/show/2sZ2wxO...  Google Podcasts: https://podcasts.google.com/feed/aHR0...   Amazon Music: https://music.amazon.com/podcasts/d97...   Podcast Addict:

Pelle Lindqvist, PhD, is a Swedish obstetrician and epidemiologist with particular interest in the role of sun exposure habits in health outcomes. He has become more well-known particularly because of his publications in the last decade on how sun exposure impacts disease incidence and mortality. In 2014 and 2016, Pelle and colleagues used data from the Melanoma in Southern Sweden Cohort of 30,000 women over 20 years. The published results demonstrated that those with the greatest sun-seeking habits had lower all-cause mortality when compared with those with the lowest sun-seeking habits. These results have since been replicated using data from the UK Biobank, making it crystal clear that our disconnection from sunlight is affecting health in a foundational manner.References for the papers discussed in this podcast are shown in the youtube version.Please consider subscribing to my Substack to support the podcast and get deeper insights into these topics. https://ricciflow.substack.com/Follow Me:WebsiteSubstackConsultationInstagramYoutubeTwitter/XSpotifyAppleLinktree

This episode went live on World Menopause Day.Menopause is an inevitable aspect of life for half of the global population, but one that requires far more study. New genomic insights could empower women with better reproductive choices and insights into likely future health.In this episode, I talk with Dr Stasa Stankovic. She has a PhD in Genomic Medicine from Cambridge University, and is on a mission to reshape the future of women's health by developing, and eventually commercialising, prediction tools and next generation therapeutics for female reproductive disorders.We discuss the complexities of female reproductive health, particularly focusing on ovarian ageing and menopause. We also explore the genetic factors influencing menopause timing, and the importance of understanding reproductive health beyond fertility.Stasa shares her collaborative work on large-scale genomics, using samples from the UK Biobank to conduct genome-wide association studies (GWAS). These have highlighted many genes associated with menopause and thus pave the way for potential new diagnostic techniques and therapeutic interventions to give women greater control of their reproductive health.Menopause affects every woman, but also indirectly impacts husbands, partners, colleagues and friends. The work Stasa and her colleagues are doing will have implications not just for women but for all of us.“We need to empower women with knowledge.” – Stasa Stankovic You'll hear about:01:37 - Stasa's area of research04:14 - Why the science behind menopause is so important07:36 - The ovarian reserve and what that means12:26 - Contributing factors to menopause17:24 - The key findings of the genome-wide association (GWAS) study21:21 - Getting the right targets for intervention27:05 - The challenge of finding animal models for menopause28:22 - Turning lab science into commercial science31:40 - Stasa on the choices that women have38:38 - Is gene intervention possible? Connect with Stasa:LinkedIn - https://www.linkedin.com/in/stasa-stankovic-93723a137/ OvartiX - https://ovartix.com/  Connect with me:LinkedIn: https://www.linkedin.com/in/markdavison100/  If you need any lab equipment:Grant Instruments: https://www.grantinstruments.com/  Grant Instruments on LinkedIn: https://www.linkedin.com/company/grant-instruments-cambridge-ltd/ 

Subscribe to our channel: https://www.youtube.com/@optispan We recently came across a study published in the European Journal of Nutrition that examined the relationship between plant and animal protein intake and measures of biological aging. The study, which uses data from the UK Biobank, a long-term database of biological data from half a million participants in the United Kingdom, found that a higher plant protein intake correlates inversely with biological aging. Matt takes us through the study and gives us his take on the results and potential explanations for them as well as on the validity of the biological age measures used, the complexities of nutrition research, and core principles of healthy eating. Producers: Tara Mei, Nicholas Arapis Video Editor: Jacob Keliikoa DISCLAIMER: The information provided on the Optispan podcast is intended solely for general educational purposes and is not meant to be, nor should it be construed as, personalized medical advice. No doctor-patient relationship is established by your use of this channel. The information and materials presented are for informational purposes only and are not a substitute for professional medical advice, diagnosis, or treatment. We strongly advise that you consult with a licensed healthcare professional for all matters concerning your health, especially before undertaking any changes based on content provided by this channel. The hosts and guests on this channel are not liable for any direct, indirect, or other damages or adverse effects that may arise from the application of the information discussed. Medical knowledge is constantly evolving; therefore, the information provided should be verified against current medical standards and practices. More places to find us: Twitter: https://twitter.com/optispanpodcast Twitter: https://twitter.com/optispan Twitter: https://twitter.com/mkaeberlein Linkedin: https://www.linkedin.com/company/optispan https://www.optispan.life/ Hi, I'm Matt Kaeberlein. I spent the first few decades of my career doing scientific research into the biology of aging, trying to understand the finer details of how humans age in order to facilitate translational interventions that promote healthspan and improve quality of life. Now I want to take some of that knowledge out of the lab and into the hands of people who can really use it. On this podcast I talk about all things aging and healthspan, from supplements and nutrition to the latest discoveries in longevity research. My goal is to lift the veil on the geroscience and longevity world and help you apply what we know to your own personal health trajectory. I care about quality science and will always be honest about what I don't know. I hope you'll find these episodes helpful!

Darshan H. Brahmbhatt, Podcast Editor of JACC: Advances discusses a recently published original research paper on improving cardiovascular disease prediction with machine learning using UK Biobank mental health data.

In a episode of *Your Health Matters*, host Karl Sterling, co-host Elizabeth Bruce, and guest expert Dr. Sherie Viencek explored the connection between hormones and brain health, especially in relation to aging and cognitive conditions like Alzheimer's disease. Dr. Viencek, with over 30 years of experience in integrative health, shared insights into how hormonal changes impact brain function and overall well-being. Hormonal Therapy and Brain Health Dr. Viencek explained the optimal timing for starting hormone replacement therapy (HRT), emphasizing that starting at 55 or older significantly reduces biological aging. Research from Stanford shows that continued HRT use enhances metabolic activity and brain function. She pointed out that the old recommendation to stop HRT at 60-65 is now considered outdated. Recent guidelines suggest discontinuing HRT based on personal health needs rather than age. Key points: - HRT at 55 or older: Reduces biological aging and supports brain function. - Ongoing HRT: Benefits metabolism and cognition. - New guidelines: Routine discontinuation at 60-65 is no longer necessary. Thyroid Health Dr. Viencek noted that around 20 million Americans have hypothyroidism, with many undiagnosed due to inadequate thyroid testing. She stressed the importance of comprehensive thyroid panels, including antibody testing, as low T3 hormone levels are linked to depression and cognitive issues. This highlights the importance of thorough thyroid evaluations, especially for patients with depression. Key points: - Hypothyroidism prevalence: 20 million Americans, with many undiagnosed. - T3 hormone: Critical for brain function, low levels linked to depression. - Comprehensive thyroid panels: Necessary for accurate diagnosis. Lifestyle Factors for Brain Health Dr. Viencek shared findings from the UK Biobank that regular napping is associated with larger brain volume, suggesting potential protection against cognitive decline. Additionally, she discussed a study showing that inhaling pleasant aromas during sleep can significantly improve memory, revealing the impact of sensory experiences on cognitive health. Key points: - Napping: Linked to larger brain volumes and potential cognitive protection. - Pleasant aromas during sleep: Can enhance memory. Meditation and Cognitive Function Dr. Viencek recommended a daily 12-minute meditation practice called *Chi Pre Yoga*, which has been shown to reduce the risk of Alzheimer's, improve memory, sleep quality, and boost immune function. Meditation, she emphasized, is a simple yet powerful tool for brain health. Key points: - Chi Pre Yoga: A daily 12-minute meditation that helps reduce Alzheimer's risk. - Benefits: Improves memory, sleep, and immunity. Conclusion and Call to Action Karl Sterling encouraged listeners to take proactive steps in their health, particularly by seeking comprehensive hormonal and thyroid evaluations. Dr. Viencek emphasized the importance of understanding how hormonal balance impacts brain health and urged listeners to address these issues early for better cognitive function as they age. Listeners were reminded to consult healthcare providers for personalized advice and to stay informed through Dr. Viencek's resources at Sage Functional Health, which includes upcoming webinars on hormone testing and management. This episode offered valuable insights into how hormones, lifestyle choices, and practices like meditation can significantly influence brain health, providing actionable steps to maintain cognitive function and well-being as we age. Be sure to visit http://www/sagefunctionalhealth.com

英国生物数据库UK Biobank公布了迄今为止世界上最大的全基因组序列数据集，包含近50万人的基因数据。这些数据将通过UK Biobank的云平台向全世界的申请者开放。

It's In the News! A look at the top diabetes stories and headlines happening now. Top stories this week: The FDA approved Omnipod 5 for people with type 2 who use insulin, Dexcom's Stelo, the first over the counter CGM, is now on sale. more evidence that bright light at night may increase the risk of diabetes, a price cut for Zepbound, and more! Find out more about Moms' Night Out  Please visit our Sponsors & Partners - they help make the show possible! Learn more about Gvoke Glucagon Gvoke HypoPen® (glucagon injection): Glucagon Injection For Very Low Blood Sugar (gvokeglucagon.com) Omnipod - Simplify Life Learn about Dexcom  Edgepark Medical Supplies Check out VIVI Cap to protect your insulin from extreme temperatures Learn more about AG1 from Athletic Greens  Drive research that matters through the T1D Exchange The best way to keep up with Stacey and the show is by signing up for our weekly newsletter: Sign up for our newsletter here Here's where to find us: Facebook (Group) Facebook (Page) Instagram Twitter Check out Stacey's books! Learn more about everything at our home page www.diabetes-connections.com  Reach out with questions or comments: info@diabetes-connections.com Episode transcription with links:   Hello and welcome to Diabetes Connections In the News! I'm Stacey Simms and every other Friday I bring you a short episode with the top diabetes stories and headlines happening now. XX In a first for any automated insulin delivery system, The FDA clears Omnipod 5 for people with type 2 diabetes. The new indication is based on data from the real-world multicenter SECURE-T2D trial of a racially diverse group of 305 adults with type 2 diabetes who were taking insulin. About half were also taking a glucagon-like peptide-1 (GLP-1) receptor agonist. Use of the Omnipod 5 resulted in a significant A1c reduction from 8.2% at baseline to 7.4% at 13 weeks (P < .001), with no differences in outcome by GLP-1 receptor agonist use. Some doctors are already prescribing the Omnipod 5 off-label to some of their patients with type 2 and other types of diabetes. Private insurance will typically cover it, although prior authorization is often required. Medicare Part B requires certification of C-peptide deficiency for coverage of insulin pumps. This new indication is likely to increase uptake of the Omnipod 5 into primary care, where the vast majority of people with type 2 diabetes are managed. https://www.medscape.com/viewarticle/fda-clears-omnipod-5-system-type-2-diabetes-2024a1000fld XX For the first time, you can get a CGM over the counter, with no prescription. Dexcom began selling Stelo this week.. intended for people with Type 2 diabetes who don't take insulin, although it can be used by people without diabetes. It costs 99 dollars for a one-time order of two sensors or $89 dollars for a monthly prescription. Stelo is a 15-day sensor based on Dexcom's other glucose monitors. The main difference from prescription products is in what information users get through the app. Stelo flags glucose spikes, provides information on time-in-range goals, and includes meal and activity logging. The intent is to reveal how food, exercise and sleep can affect a person's glucose levels. Competitor Abbott plans to launch two over-the-counter CGMs: one called Lingo, for people without diabetes, and one called Libre Rio, for people with diabetes who don't use insulin. It has not yet priced either sensor. Abbott said it plans to debut its competing Lingo device this summer. The company has not said when it will launch its Rio CGM. https://www.medtechdive.com/news/dexcom-sells-stelo-over-the-counter-cgm/725310/ XX You'll soon be able to get vials of Lilly's popular weight loss drug, Zepbound, from a direct to consumer website, at a lower cost. This is still nearly 400 dollars a month for the lowest dose $550 for the next lowest and it will come in vials, not pens. Lilly and Novo have been struggling to make enough of their obesity medications to meet soaring demand, especially keeping up the pen supply. Lilly's medicines are now listed as available by the U.S. Food and Drug Administration, though they are not yet off the FDA's official shortage list where they have been most of the year. I haven't seen this mentioned in any of the reporting but.. if it's coming in a vial, you have to use a syringe to inject. Not much of a barrier to this group listening.. but pens have made using drugs like this much easier for a lot of people and I worry that going back to syringes is better for these companies than the patients. Zepbound is terzepatide, the same mediation as in Mounjaro. The latter is approved for people with type 2 diabetes, so this could be a way for some people to better access Mounjaro which is very hard to come by. https://www.reuters.com/business/healthcare-pharmaceuticals/lilly-launches-single-dose-vials-zepbound-weight-loss-expand-us-supply-2024-08-27/ XX In a few months the US govermet will announce the list of 15 moe drugs they'll negotiate Medicare prices for.. and Ozempic is a top candidate. This is speculation from Wall Street analysts but I think worth watching. All the drugs on their prediction list have been on the market since at least 2017 and are among those that the Medicare health program spends the most on. Under President Joe Biden's signature Inflation Reduction Act (IRA), prices for 10 highly popular prescription drugs used by Medicare will be cut by 38% to 79% in 2026. The industry has fought the negotiation program, saying it will stifle innovation. Government researchers predict that the use of diabetes drug Ozempic for weight loss would raise the U.S. deficit over the next 10 years at its current price. Medicare spent over $4.6 billion on the drug in 2022. https://www.reuters.com/business/healthcare-pharmaceuticals/ozempic-wall-streets-list-2027-medicare-drug-negotiations-2024-08-23/ XX Type 2 diabetes and prediabetes are associated with accelerated brain aging, according to a new study from Karolinska Institutet in Sweden published in the journal Diabetes Care. The good news is that this may be counteracted by a healthy lifestyle. Type 2 diabetes is a known risk factor for dementia, but it is unclear how diabetes and its early stages, known as prediabetes, affect brain aging in people without dementia. Now, a comprehensive brain imaging study shows that both diabetes and prediabetes can be linked to accelerated brain aging. The study included more than 31,000 people between 40 and 70 years of age from the UK Biobank who had undergone a brain MRI scan (magnetic resonance imaging). The researchers used a machine learning approach to estimate brain age in relation to the person's chronological age.   Prediabetes and diabetes were associated with brains that were 0.5 and 2.3 years older than chronological age, respectively. In people with poorly controlled diabetes, the brain appeared more than four years older than chronological age. The researchers also noted that the gap between brain age and chronological age increased slightly over time in people with diabetes. These associations were attenuated among people with high physical activity who abstained from smoking and heavy alcohol consumption. https://medicalxpress.com/news/2024-08-healthy-lifestyle-counteract-diabetes-brain.html XX   Edgepark Commercial XX Another study showing the link between bright light at night and a higher risk of developing type 2. This study in the journet Lancet In the large modeling study, the research team investigated whether personal light exposure patterns predicted the risk of diabetes using data from approximately 85,000 people and around 13 million hours of light sensor data. The participants – who did not have type 2 diabetes – wore devices on their wrists for one week to track their light levels throughout the day and night. They were then tracked over the following nine years to observe whether they went on to develop type 2 diabetes. “Light exposure at night can disrupt our circadian rhythms, leading to changes in insulin secretion and glucose metabolism,” he says. Having more exposure to light at night (between 12:30 am and 6:00 am) was linked to a higher risk of developing type 2 diabetes, and this was true regardless of how much light people were exposed to during the day. The research accounted for other factors associated with type 2 diabetes, such as lifestyle habits, sleep patterns, shift work, diet, and mental health.   Even after taking these factors into account, the findings showed that getting more light at night was still a strong predictor of developing diabetes. https://scitechdaily.com/scientists-discover-simple-and-cheap-way-to-reduce-your-risk-of-diabetes/ XX Is there a link between voice pitch and glucose levels? And is it strong enough to one day perhaps lead to non-invasive glucose monitronig? Klick Labs published a new study in Scientific Reports today—confirming the link In "Linear Effects of Glucose Levels on Voice Fundamental Frequency in type 2 diabetes and Individuals with Normoglycemia," researchers investigated how blood glucose levels influence the frequency of the voice in 505 participants across three glycemic statuses—non-diabetic, prediabetic, and type-2 diabetic. Participants were fitted with continuous glucose monitors (CGMs) and recorded their voices multiple times daily for two weeks. The analysis revealed a linear relationship where an increase in CGM glucose levels corresponded to an increase in the fundamental frequency in the voice. The lead author says, "Whereas current glucose monitoring methods are often invasive and inconvenient, voice-based glucose monitoring could be as easy as talking into a smartphone, which could change the game for the estimated 463 million people around the world living with type 2 diabetes."   Klick Labs' latest research marks another step forward in its ongoing commitment to advancing the detection and management of diabetes using voice tech and machine learning. Their October 2023 study in Mayo Clinic Proceedings: Digital Health demonstrated that voice and AI can screen for type 2 diabetes with high accuracy.   https://medicalxpress.com/news/2024-08-diabetes-links-blood-glucose-voice.html#google_vignette XX Earlier this year we talked to the teenager behind a free bolus calculator. The FDA took T1D1 down, when they and Apple started cracking down on health tools without regulatory approval. Drew Mendalow has been working to bring it back and we have an update: He says, “Over the last two years, we have been tirelessly working to complete our FDA premarket submission. Thanks to contributions by the T1D community, we were able to complete the preparations needed for the Human Factors Study. The trial itself is the last, vital piece needed before we can submit the app to the FDA. Now, we're thrilled to announce that the team at Dexcom has graciously offered to run the study for us!” It's a big deal – kudos to Dexcom and to Drew. We'll let you know when T1D1 is back in the app store. XX Join us again soon!

In this podcast, Dr. Katrina Poppe reviews a study by Celeste McCracken and Dr. Zahra Raisi-Estabragh that evaluates the effectiveness of cardiovascular risk scores in cancer survivors using UK Biobank data. The research reveals that standard risk scores often underestimate cardiovascular risk in cancer survivors, particularly those with Hodgkin's lymphoma, hematological cancers, and brain malignancies, highlighting the need for tailored risk assessment tools for this population.

A new study just published says that perimenopausal women are more likely to experience bipolar and major depressive disorder. Cardiff University academics worked with charity Bipolar UK and the UK Biobank, a large-scale biomedical database, to look at nearly 130,000 UK women and focused on the four years around the last menstrual period. Dr Clare Dolman, an ambassador for Bipolar UK and patient and public involvement lead on the project, joins Jessica Creighton.We Might Regret This is a brand new BBC comedy that has been pegged by reviews as ‘the next Fleabag'. It centres on Freya, who is an artist and tetraplegic, as she moves in with her partner and hires her best friend to be her personal assistant. The series is partly based on the experiences of Kyla Harris, the co-creator who stars as Freya. She joins Jessica to talk about everything from having a third person in a relationship to misconceptions around disability.What do you think of maternity clothes? For mums-to-be in 2024, it's apparently all about low-cut jeans and crop tops, moving away from traditional maternity wear. Retailers are recording a decrease of maternity clothes searches with women instead opting for regular clothes, perhaps in a bigger size. So why the shift? Jessica is joined by Assistant Fashion Editor at The Times, Hannah Rogers and influencer and author Alex Light to discuss.A brand new documentary film called Daughters follows four girls whose fathers are in prison in the US. They are all preparing for a special prison visit – a father-daughter dance that sees some of them meeting for the first time. Co-director of the film and CEO of Girls for a Change Angela Patton joins Jessica to talk about her work with black girls and their fathers, along with a father and daughter from the UK who have personal experience of the challenges of a father being in prison.

Pradeep is a brilliant geneticist and Director of Preventive Cardiology, holds the Paul & Phyllis Fireman Endowed Chair in Vascular Medicine at Mass General Hospital and on faculty at Harvard Medical School and the Broad Institute. His prolific research has been illuminating for the field of improving our approach to reduce the risk of heart disease. That's especially important because heart disease is the global (and US) #1 killer and is on the increase. We didn't get into lifestyle factors here since there was so much ground to cover on new tests. drugs, and strategies.A video snippet of our conversation on ApoB. Full videos of all Ground Truths podcasts can be seen on YouTube here. The audios are also available on Apple and Spotify.Transcript with links to key publications and audioEric Topol (00:06):Well, welcome to Ground Truths. I'm Eric Topol and with me is Pradeep Natarajan from Harvard. He's Director of Preventative Cardiology at the Mass General Brigham Health System and he has been lighting it up on the field of cardiovascular. We're going to get to lots of different parts of that story and so, Pradeep welcome.Pradeep Natarajan (00:31):Thanks Eric, really delighted and honored to be with you and have this discussion.Eric Topol (00:36):Well, for years I've been admiring your work and it's just accelerating and so there's so many things to get to. I thought maybe what we'd start off with is you recently wrote a New England Journal piece about two trials, two different drugs that could change the landscape of cardiovascular prevention in the future. I mean, that's one of the themes we're going to get to today is all these different markers and drugs that will change cardiology as we know it now. So maybe you could just give us a skinny on that New England Journal piece.Two New Lipid Targets With RNA DrugsPradeep Natarajan (01:16):Yeah, yeah, so these two agents, the trials were published at the same time. These phase two clinical trials for plozasiran, which is an siRNA against APOC3 and zodasiran, which is an siRNA against ANGPTL3. The reason why we have medicines against those targets are based on human genetics observations, that individuals with loss of function mutations and either of those genes have reduced lipids. For APOC3, it's reduced triglycerides for ANGPTL3 reduced LDL cholesterol and reduced triglycerides and also individuals that have those loss of function mutations also have lower risk for coronary artery disease. Now that's a very similar parallel to PCSK9. We have successful medicines that treat that target because people have found that carriers of loss of function mutations in PCSK9 lead to lower LDL cholesterol and lower coronary artery disease.(02:11):Now that suggests that therapeutic manipulation without significant side effects from the agents themselves for APOC3 and ANGPTL3 would be anticipated to also lower coronary artery disease risk potentially in complementary pathways to PCSK9. The interesting thing with those observations is that they all came from rare loss of function mutations that are enriched in populations of individuals. However, at least for PCSK9, has been demonstrated to have efficacy in large groups of individuals across different communities. So the theme of that piece was really just the need to study diverse populations because those insights are not always predictable about which communities are going to have those loss of function mutations and when you find them, they often have profound insights across much larger groups of individuals.Eric Topol (03:02):Well, there's a lot there that we can unpack a bit of it. One of them is the use of small interfering RNAs (siRNA) as drugs. We saw in the field of PCSK9, as you mentioned. First there were monoclonal antibodies directed against this target and then more recently, there's inclisiran which isn't an RNA play if you will, where you only have to take it twice a year and supposedly it's less expensive and I'm still having trouble in my practice getting patients covered on their insurance even though it's cheaper and much more convenient. But nonetheless, now we're seeing these RNA drugs and maybe you could comment about that part and then also the surprise that perhaps is unexplained is the glucose elevation.Pradeep Natarajan (03:53):Yeah, so for medicines and targets that have been discovered through human genetics, those I think are attractive for genetic-based therapies and longer interval dosing for the therapies, which is what siRNAs allow you to do because the individuals that have these perturbations, basically the naturally occurring loss of function mutations, they have these lifelong, so basically have had a one-time therapy and have lived, and so far, at least for these targets, have not had untoward side effects or untoward phenotypic consequences and only reduce lipids and reduce coronary artery disease. And so, instead of taking a pill daily, if we have conviction that that long amount of suppression may be beneficial, then longer interval dosing and not worrying about the pill burden is very attractive specifically for those specific therapeutics. And as you know, people continue to innovate on further prolonging as it relates to PCSK9.(04:57):Separately, some folks are also developing pills because many people do feel that there's still a market and comfort for daily pills. Now interestingly for the siRNA for zodasiran at the highest dose, actually for both of them at the highest doses, but particularly for zodasiran, there was an increase in insulin resistance parameters actually as it relates to hyperglycemia and less so as it relates to insulin resistance, that is not predicted based on the human genetics. Individuals with loss of function mutations do not have increased risks in hyperglycemia or type 2 diabetes, so that isolates it related to that specific platform or that specific technology. Now inclisiran, as you'd mentioned, Eric is out there. That's an siRNA against PCSK9 that's made by a different manufacturer. So far, the clinical trials have not shown hyperglycemia or type 2 diabetes as it relates inclisiran, so it may be related to the specific siRNAs that are used for those targets. That does merit further consideration. Now, the doses that the manufacturers do plan to use in the phase three clinical trials are at lower doses where there was not an increase in hyperglycemia, but that does merit further investigation to really understand why that's the case. Is that an expected generalized effect for siRNAs? Is it related to siRNAs for this specific target or is it just related to the platform used for these two agents which are made by the same manufacturer?Eric Topol (06:27):Right, and I think the fact that it's a mystery is intriguing at the least, and it may not come up at the doses that are used in the trials, but the fact that it did crop up at high doses is unexpected. Now that is part of a much bigger story is that up until now our armamentarium has been statins and ezetimibe to treat lipids, but it's rapidly expanding Lp(a), which for decades as a cardiologist we had nothing to offer. There may even be drugs to be able to lower people who are at high risk with high Lp(a). Maybe you could discuss that.What About Lp(a)?Pradeep Natarajan (07:13):Yeah, I mean, Eric, as you know, Lp(a) has been described as a cardiovascular disease risk factors for quite so many years and there are assays to detect lipoprotein(a) elevation and have been in widespread clinical practice increasing widespread clinical practice, but we don't yet have approved therapies. However, there is an abundance of literature preclinical data that suggests that it likely is a causal factor, meaning that if you lower lipoprotein(a) when elevated, you would reduce the risk related to lipoprotein(a). And a lot of this comes from similar human genetic studies. The major challenge of just relating a biomarker to an outcome is there are many different reasons why a biomarker might be elevated, and so if you detect a signal that correlates a biomarker, a concentration to a clinical outcome, it could be related to that biomarker, but it could be to the other reasons that the biomarker is elevated and sometimes it relates to the outcome itself.(08:10):Now human genetics is very attractive because if you find alleles that strongly relate to that exposure, you can test those alleles themselves with the clinical outcome. Now the allele assignment is established at birth. No other factor is going to change that assignment after conception, and so that provides a robust, strong causal test for that potential exposure in clinical outcome. Now, lipoprotein(a) is unique in that it is highly heritable and so there are lots of different alleles that relate to lipoprotein(a) and so in a well powered analysis can actually test the lipoprotein(a) SNPs with the clinical outcomes and similar to how there is a biomarker association with incident myocardial infarction and incident stroke, the SNPs related to lipoprotein(a) show the same. That is among the evidence that strongly supports that this might be causal. Now, fast forward to many years later, we have at least three phase three randomized clinical trials testing agents that have been shown to be very potent at lowering lipoprotein(a) that in the coming years we will know if that hypothesis is true. Importantly, we will have to understand what are the potential side effects of these medicines. There are antisense oligonucleotides and siRNAs that are primarily in investigation. Again, this is an example where there's a strong genetic observation, and so these genetic based longer interval dosing therapies may be attractive, but side effects will be a key thing as well too. Those things hard to anticipate really can anticipate based on the human genetics for off target effects, for example.(09:52):It's clearly a risk signal and hopefully in the near future we're going to have specific therapies.Eric Topol (09:57):Yeah, you did a great job of explaining Mendelian randomization and the fact the power of genetics, which we're going to get into deeper shortly, but the other point is that do you expect now that there's these multiple drugs that lower Lp(a) efficiently, would that be enough to get approval or will it have to be trials to demonstrate improved cardiovascular outcomes?Pradeep Natarajan (10:24):There is a great regulatory path at FDA for approval just for LDL cholesterol lowering and inclisiran is on the market and the phase three outcomes data has not yet been reported because there is a wide appreciation that LDL cholesterol lowering is a pretty good surrogate for cardiovascular disease risk lowering. The label will be restricted to LDL cholesterol lowering and then if demonstrated to have clinical outcomes, the label could be expanded. For other biomarkers including lipoprotein(a), even though we have strong conviction that it is likely a causal factor there hasn't met the bar yet to get approval just based on lipoprotein(a) lowering, and so we would need to see the outcomes effects and then we would also need to understand side effects. There is a body of literature of side effects for other therapies that have targeted using antisense oligonucleotides. We talked about potential side effects from some siRNA platforms and sometimes those effects could overtake potential benefits, so that really needs to be assessed and there is a literature and other examples.(11:31):The other thing I do want to note related to lipoprotein(a) is that the human genetics are modeled based on lifelong perturbations, really hard to understand what the effects are, how great of an effect there might be in different contexts, particularly when introduced in middle age. There's a lot of discussion about how high lipoprotein(a) should be to deliver these therapies because the conventional teaching is that one in five individuals has high lipoprotein(a), and that's basically greater than 75 nanomoles per liter. However, some studies some human genetic studies to say if you want to get an effect that is similar to the LDL cholesterol lowering medicines on the market, you need to start with actually higher lipoprotein(a) because you need larger amounts of lipoprotein(a) lowering. Those are studies and approaches that haven't been well validated. We don't know if that's a valid approach because that's modeling based on this sort of lifelong effect. So I'm very curious to see what the overall effect will be because to get approval, I think you need to demonstrate safety and efficacy, but most importantly, these manufacturers and we as clinicians are trying to find viable therapies in the market that it won't be hard for us to get approval because hopefully the clinical trial will have said this is the context where it works. It works really well and it works really well on top of the existing therapies, so there are multiple hurdles to actually getting it directly to our patients.How Low Do You Go with LDL Cholesterol?Eric Topol (13:02):Yeah, no question about that. I'm glad you've emphasized that. Just as you've emphasized the incredible lessons from the genetics of people that have helped guide this renaissance to better drugs to prevent cardiovascular disease. LDL, which is perhaps the most impressive surrogate in medicine, a lab test that you already touched on, one of the biggest questions is how low do you go? That is Eugene Braunwald, who we all know and love. They're in Boston. The last time I got together with him, he was getting his LDL down to close to zero with various tactics that might be extreme. But before we leave these markers, you're running preventive cardiology at man's greatest hospital. Could you tell us what is your recipe for how aggressive do you go with LDL?Pradeep Natarajan (14:04):Yeah, so when I talk to patients where we're newly getting lipid lowering therapies on, especially because many people don't have a readout of abnormal LDL cholesterol when we're prescribing these medicines, it's just giving them a sense of what we think an optimal LDL cholesterol might be. And a lot of this is based on just empirical observations. So one, the average LDL cholesterol in the modern human is about 100 to 110 mg/dL. However, if you look at contemporary hunter gatherers and non-human primates, their average LDL is about 40 to 50 and newborn babies have an LDL cholesterol of about 30. And the reason why people keep making LDL cholesterol lowering medicines because as you stack on therapies, cardiovascular disease events continue to reduce including down to these very low LDL cholesterol values. So the population mean for LDL cholesterol is high and everybody likely has hypercholesterolemia, and that's because over the last 10,000 years how we live our lives is so dramatically different and there has not been substantial evolution over that time to change many of these features related to metabolism.(15:16):And so, to achieve those really low LDL cholesterol values in today's society is almost impossible without pharmacotherapies. You could say, okay, maybe everybody should be on pharmacotherapies, and I think if you did that, you probably would reduce a lot of events. You'll also be treating a lot of individuals who likely would not get events. Cardiovascular disease is the leading killer, but there are many things that people suffer from and most of the times it still is not cardiovascular disease. So our practice is still rooted in better identifying the individuals who are at risk for cardiovascular disease. And so, far we target our therapies primarily in those who have already developed cardiovascular disease. Maybe we'll talk about better identifying those at risk, but for those individuals it makes lots of sense to get it as low as possible. And the field has continued to move to lower targets.(16:07):One, because we've all recognized, at least based on these empirical observations that lower is better. But now increasingly we have a lot of therapies to actually get there, and my hope is that with more and more options and the market forces that influence that the cost perspective will make sense as we continue to develop more. As an aside, related aside is if you look at the last cholesterol guidelines, this is 2018 in the US this is the first time PCSK9 inhibitors were introduced in the guidelines and all throughout that there was discussions of cost. There are a lot of concerns from the field that PCSK9 inhibitors would bankrupt the system because so many people were on statins. And you look at the prior one that was in 2013 and cost was mentioned once it's just the cost effectiveness of statins. So I think the field has that overall concern.(17:01):However, over time we've gotten comfortable with lower targets, there are more medicines and I think some of this competition hopefully will drive down some of the costs, but also the overall appreciation of the science related to LDL. So long-winded way of saying this is kind of the things that we discussed just to give reassurance that we can go to low LDL cholesterol values and that it's safe and then we think also very effective. Nobody knows what the lower limit is, whether zero is appropriate or not. We know that glucose can get too low. We know that blood pressure can be too low. We don't know yet that limit for LDL cholesterol. I mean increasingly with these trials we'll see it going down really low and then we'll better appreciate and understand, so we'll see 40 is probably the right range.Eric Topol (17:49):40, you said? Yeah, okay, I'll buy that. Of course, the other thing that we do know is that if you push to the highest dose statins to get there, you might in some people start to see the hyperglycemia issue, which is still not fully understood and whether that is, I mean it's not desirable, but whether or not it is an issue, I guess it's still out there dangling. Now the other thing that since we're on LDL, we covered Lp(a), PCSK9, the siRNA, is ApoB. Do you measure ApoB in all your patients? Should that be the norm?Measuring ApoBPradeep Natarajan (18:32):Yeah, so ApoB is another blood test. In the standard lipid panel, you get four things. What's measured is cholesterol and triglycerides, they're the lipids insoluble in blood to get to the different tissues that get packaged in lipoprotein molecules which will have the cholesterol, triglycerides and some other lipids and proteins. And so, they all have different names as you know, right? Low density lipoprotein, high density lipoprotein and some others. But also in the lipid panel you get the HDL cholesterol, the amount of cholesterol in an HDL particle, and then most labs will calculate LDL cholesterol and LDL cholesterol has a nice relationship with cardiovascular disease. You lower it with statins and others. Lower risk for cardiovascular disease, turns out a unifying feature of all of these atherogenic lipoproteins, all these lipoproteins that are measured and unmeasured that relate to cardiovascular disease, including lipoprotein(a), they all have an additional protein called ApoB. And ApoB, at least as it relates to LDL is a pretty good surrogate of the number of LDL particles.(19:37):Turns out that that is a bit better at the population level at predicting cardiovascular disease beyond LDL cholesterol itself. And where it can be particularly helpful is that there are some patients out there that have an unexpected ratio between ApoB and LDL. In general, the ratio between LDL cholesterol and ApoB is about 1.1 and most people will have that rough ratio. I verify that that is the expected, and then if that is the expected, then really there is no role to follow ApoB. However, primarily the patients that have features related to insulin resistance have obesity. They may often have adequate looking LDL cholesterols, but their ApoB is higher. They have more circulating LDL particles relative to the total amount of LDL cholesterol, so smaller particles themselves. However, the total number of particles may actually be too high for them.(20:34):And so, even if the LDL cholesterol is at target, if the ApoB is higher, then you need to reduce. So usually the times that I just kind of verify that I'm at appropriate target is I check the LDL cholesterol, if that looks good, verify with the ApoB because of this ratio, the ApoB target should be about 10% lower. So if we're aiming for about 40, that's like 36, so relatively similar, and if it's there, I'm good. If it's not and it's higher, then obviously increase the LDL cholesterol lowering medicines because lower the ApoB and then follow the ApoB with the lipids going forward. The European Society of Cardiology has more emphasis on measuring ApoB, that is not as strong in the US guidelines, but there are many folks in the field, preventive cardiologists and others that are advocating for the increasing use of ApoB because I think there are many folks that are not getting to the appropriate targets because we are not measuring ApoB.Why Aren't We Measuring and Treating Inflammation?Eric Topol (21:37):Yeah, I think you reviewed it so well. The problem here is it could be part of the standard lipid panel, it would make this easy, but what you've done is a prudent way of selecting out people who it becomes more important to measure and moderate subsequently. Now this gets us to the fact that we're lipid centric and we don't pay homage to inflammation. So I wrote a recent Substack on the big miss on inflammation, and here you get into things like the monoclonal antibody to interleukin-6, the trial that CANTOS that showed significant reduction in cardiovascular events and fatal cancers by the way. And then you get into these colchicine trials two pretty good size randomized trials, and here the entry was coronary disease with a high C-reactive protein. Now somehow or other we abandon measuring CRP or other inflammatory markers, and both of us have had patients who have low LDLs but have heart attacks or significant coronary disease. So why don't we embrace inflammation? Why don't we measure it? Why don't we have better markers? Why is this just sitting there where we could do so much better? Even agents that are basically cost pennies like colchicine at low doses, not having to use a proprietary version could be helpful. What are your thoughts about us upgrading our prevention with inflammation markers?Pradeep Natarajan (23:22):Yeah, I mean, Eric, there is an urgent need to address these other pathways. I say urgent need because heart disease has the dubious distinction of being the leading killer in the US and then over the last 20 years, the leading killer in the world as it takes over non-communicable diseases. And really since the early 1900s, there has been a focus on developing pharmacotherapies and approaches to address the traditional modifiable cardiovascular disease risk factors. That has done tremendous good, but still the curves are largely flattening out. But in the US and in many parts of the world, the deaths attributable to cardiovascular disease are starting to tick up, and that means there are many additional pathways, many of them that we have well recognized including inflammation. More recently, Lp(a) that are likely important for cardiovascular disease, for inflammation, as you have highlighted, has been validated in randomized controlled trials.(24:18):Really the key trial that has been more most specific is one on Canakinumab in the CANTOS trial IL-1β monoclonal antibody secondary prevention, so cardiovascular disease plus high C-reactive protein, about a 15% reduction in cardiovascular disease and also improvement in cancer related outcomes. Major issues, a couple of issues. One was increased risk for severe infections, and the other one is almost pragmatic or practical is that that medicine was on the market at a very high price point for rare autoinflammatory conditions. It still is. And so, to have for a broader indication like cardiovascular disease prevention would not make sense at that price point. And the manufacturer tried to go to the FDA and focus on the group that only had C-reactive protein lowering, but that's obviously like a backwards endpoint. How would you know that before you release the medicine? So that never made it to a broader indication.(25:14):However, that stuck a flag in the broader validation of that specific pathway in cardiovascular disease. That pathway has direct relevance to C-reactive protein. C-reactive protein is kind of a readout of that pathway that starts from the NLRP3 inflammasome, which then activates IL-1β and IL-6. C-reactive protein we think is just a non causal readout, but is a reliable test of many of these features and that's debatable. There may be other things like measuring IL-6, for example. So given that there is actually substantial ongoing drug development in that pathway, there are a handful of companies with NLRP3 inflammasome inhibitors, but small molecules that you can take as pills. There is a monoclonal antibody against IL-6 that's in development ziltivekimab that's directed at patients with chronic kidney disease who have lots of cardiovascular disease events despite addressing modifiable risk factors where inflammatory markers are through the roof.(26:16):But then you would also highlighted one anti-inflammatory that's out there that's pennies on the dollar, that's colchicine. Colchicine is believed to influence cardiovascular disease by inhibiting NLRP3, I say believed to. It does a lot of things. It is an old medicine, but empirically has been shown in at least two randomized controlled trials patients with coronary artery disease, actually they didn't measure C-reactive protein in the inclusion for these, but in those populations we did reduce major adverse cardiovascular disease events. The one thing that does give me pause with colchicine is that there is this odd signal for increased non-cardiovascular death. Nobody understands if that's real, if that's a fluke. The FDA just approved last year low dose colchicine, colchicine at 0.5 milligrams for secondary prevention given the overwhelming efficacy. Hasn't yet made it into prevention guidelines, but I think that's one part that does give me a little bit pause. I do really think about it particularly for patients who have had recurrent events. The people who market the medicine and do research do remind us that C-reactive protein was not required in the inclusion, but nobody has done that secondary assessment to see if measuring C-reactive protein would be helpful in identifying the beneficial patients. But I think there still could be more work done on better identifying who would benefit from colchicine because it's an available and cheap medicine. But I'm excited that there is a lot of development in this inflammation area.Eric Topol (27:48):Yeah, well, the development sounds great. It's probably some years away. Do you use colchicine in your practice?Pradeep Natarajan (27:56):I do. Again, for those folks who have had recurrent events, even though C-reactive protein isn't there, it does make me feel like I'm treating inflammation. If C-reactive protein is elevated and then I use it for those patients, if it's not elevated, it's a much harder sell from my standpoint, from the patient standpoint. At the lower dose for colchicine, people generally are okay as far as side effects. The manufacturer has it at 0.5 milligrams, which is technically not pennies on the dollar. That's not generic. The 0.6 milligrams is generic and they claim that there is less side effects at the 0.5 milligrams. So technically 0.6 milligrams is off label. So it is what it is.CHIP and Defining High Risk People for CV DiseaseEric Topol (28:40):It's a lot more practical, that's for sure. Now, before I leave that, I just want to mention when I reviewed the IL-1β trial, you mentioned the CANTOS trial and also the colchicine data. The numbers of absolute increases for infection with the antibody or the cancers with the colchicine are really small. So I mean the benefit was overriding, but I certainly agree with your concern that there's some things we don't understand there that need to be probed more. Now, one of the other themes, well before one other marker that before we get to polygenic risk scores, which is center stage here, defining high risk people. We've talked a lot about the conventional things and some of the newer ways, but you've been one of the leaders of study of clonal hematopoiesis of indeterminate potential known as CHIP. CHIP, not the chips set in your computer, but CHIP. And basically this is stem cell mutations that increase in people as we age and become exceptionally common with different mutations that account in these clones. So maybe you can tell us about CHIP and what I don't understand is that it has tremendous correlation association with cardiovascular outcomes adverse as well as other system outcomes, and we don't measure it and we could measure it. So please take us through what the hell is wrong there.Pradeep Natarajan (30:14):Yeah, I mean this is really exciting. I mean I'm a little bit biased, but this is observations that have been made only really over the last decade, but accelerating research. And this has been enabled by advances in genomic technologies. So about 10 years or plus ago, really getting into the early days of population-based next generation sequencing, primarily whole exome sequencing. And most of the DNA that we collect to do these population-based analyses come from the blood, red blood cells are anucleate, so they're coming from white blood cells. And so, at that time, primarily interrogating what is the germline genetic basis for coronary artery disease and early onset myocardial infarction. At the same time, colleagues at the Broad Institute were noticing that there are many additional features that you can get from the blood-based DNA that was being processed by the whole exome data. And there were actually three different groups that converged on that all in Boston that converged on the same observation that many well-established cancer causing mutations.(31:19):So mutations that are observed in cancers that have been described to drive the cancers themselves were being observed in these large population-based data sets that we were all generating to understand the relationship between loss of function mutations in cardiovascular disease. That's basically the intention of those data sets for being generated for other things. Strong correlation with age, but it was very common among individuals greater than 70; 10% of them would have these mutations and is very common because blood cancer is extremely, it's still pretty rare in the population. So to say 10% of people had cancer causing driver mutations but didn't have cancer, was much higher than anyone would've otherwise expected. In 2014, there were basically three main papers that described that, and they also observed that there is a greater risk of death. You'd say, okay, this is a precancerous lesion, so they're probably dying of cancer.(32:17):But as I said, the absolute incidence rate for blood cancer is really low and there's a relative increase for about tenfold, but pretty small as it relates to what could be related to death. And in one of the studies we did some exploratory analysis that suggested maybe it's actually the most common cause of death and that was cardiovascular disease. And so, a few years later we published a study that really in depth really looked at a bunch of different data sets that were ascertained to really understand the relationship between these mutations, these cancer causing mutations in cardiovascular disease, so observed it in enrichment and older individuals that had these mutations, CHIP mutations, younger individuals who had early onset MI as well too, and then also look prospectively and showed that it related to incident coronary artery disease. Now the major challenge for this kind of analysis as it relates to the germline genetic analysis is prevalence changes over time.(33:15):There are many things that could influence the presence of clonal hematopoiesis. Age is a key enriching factor and age is the best predictor for cardiovascular disease. So really important. So then we modeled it in mice. It was actually a parallel effort at Boston University (BU) that was doing the same thing really based on the 2014 studies. And so, at the same time we also observed when you modeled this in mice, you basically perturb introduce loss of function mutations in the bone marrow for these mice to recapitulate these driver mutations and those mice also have a greater burden of atherosclerosis. And Eric, you highlighted inflammation because basically the phenotype of these cells are hyper inflamed cells. Interestingly, C-reactive protein is only modestly elevated. So C-reactive protein is not fully capturing this, but many of the cytokines IL-1β, IL-6, they're all upregulated in mice and in humans when measured as well.(34:11):Now there've been a few key studies that have been really exciting about using anti-inflammatories in this pathway to address CHIP associated cardiovascular disease. So one that effort that I said in BU because they saw these cytokines increased, we already know that these cytokines have relationship with atherosclerosis. So they gave an NLRP3 inflammasome inhibitor to the mice and they showed that the mice with or without CHIP had a reduction in atherosclerosis, but there was a substantial delta among the mice that are modeled as having CHIP. Now, the investigators in CANTOS, the manufacturers, they actually went back and they survey where they had DNA in the CANTOS trial. They measured CHIP and particularly TET2 CHIP, which is the one that has the strongest signal for atherosclerosis. As I said, overall about 15% reduction in the primary outcome in CANTOS. Among the individuals who had TET2 CHIP, it was a 64% reduction in event.(35:08):I mean you don't see those in atherosclerosis related trials. Now this has the caveat of it being secondary post hoc exploratory, the two levels of evidence. And so, then we took a Mendelian randomization approach. Serendipitously, just so happens there is a coding mutation in the IL-6 receptor, a missense mutation that in 2012 was described that if you had this mutation, about 40% of people have it, you have a 5%, but statistically significant reduction in coronary artery disease. So we very simply said, if the pathway of this NLRP3 inflammasome, which includes IL-6, if you have decreased signaling in that pathway, might you have an even greater benefit from having that mutation if you had CHIP versus those who didn't have CHIP. So we looked in the UK Biobank, those who didn't have CHIP 5% reduction, who had that IL-6 receptor mutation, and then those who did have CHIP, if they had that mutation, it was about a 60% reduction in cardiovascular disease.(36:12):Again, three different lines of evidence that really show that this pathway has relevance in the general population, but the people who actually might benefit the most are those with CHIP. And I think as we get more and more data sets, we find that not all of the CHIP mutations are the same as it relates to cardiovascular disease risk. It does hone in on these key subsets like TET2 and JAK2, but this is pretty cool as a preventive cardiologist, new potential modifiable risk factor, but now it's almost like an oncologic paradigm that is being applied to coronary artery disease where we have specific driver mutations and then we're tailoring our therapies to those specific biological drivers for coronary artery disease. Hopefully, I did that justice. There's a lot there.Why Don't We Measure CHIP?Eric Topol (36:57):Well, actually, it's phenomenal how you've explained that, but I do want to review for our listeners or readers that prior to this point in our conversation, we were talking about germline mutations, the ones you're born with. With CHIP, we're talking about acquired somatic mutations, and these are our blood stem cells. And what is befuddling to me is that with all the data that you and others, you especially have been publishing and how easy it would be to measure this. I mean, we've seen that you can get it from sequencing no less other means. Why we don't measure this? I mean, why are we turning a blind eye to CHIP? I just don't get it. And we keep calling it of indeterminate potential, not indeterminate. It's definite potential.Pradeep Natarajan (37:51):Yeah, no, I think these are just overly cautious terms from the scientists. Lots of people have CHIP, a lot of people don't have clinical outcomes. And so, I think from the lens of a practicing hematologists that provide some reassurance on the spectrum for acquired mutation all the way over to leukemia, that is where it comes from. I don't love the acronym as well because every subfield in biomedicine has its own CHIP, so there's obviously lots of confusion there. CH or clinical hematopoiesis is often what I go, but I think continuing to be specific on these mutations. Now the question is why measure? Why aren't we measuring it? So there are some clinical assays out there. Now when patients get evaluated for cytopenias [low cell counts], there are next generation sequencing tests that look for these mutations in the process for evaluation. Now, technically by definition, CHIP means the presence of these driver mutations that have expanded because it's detectable by these assays, not a one-off cell because it can only be detected if it's in a number of cells.(38:55):So there has been some expansion, but there are no CBC abnormalities. Now, if there's a CBC abnormality and you see a CHIP mutation that's technically considered CCUS or clonal cytopenia of unknown significance, sometimes what is detected is myelodysplastic syndrome. In those scenarios still there is a cardiovascular disease signal, and so many of our patients who are seen in the cancer center who are being evaluated for these CBC abnormalities will be detected to have these mutations. They will have undergone some risk stratification to see what the malignancy potential is. Still pretty low for many of those individuals. And so, the major driver of health outcomes for this finding may be cardiovascular. So those patients then get referred to our program. Dana-Farber also has a similar program, and then my colleague Peter Libby at the Brigham often sees those patients as well. Now for prospective screening, so far, an insurance basically is who's going to pay for it.(39:51):So an insurance provider is not deemed that appropriate yet. You do need the prospective clinical trials because the medicines that we're talking about may have side effects as well too. And what is the yield? What is the diagnostic yield? Will there actually be a large effect estimate? But there has been more and more innovation, at least on the assay and the cost part of the assay because these initial studies, we've been using whole exome sequencing, which is continuing to come down, but is not a widely routine clinical test yet. And also because as you highlighted, these are acquired mutations. A single test is not necessarily one and done. This may be something that does require surveillance for particular high risk individuals. And we've described some risk factors for the prevalence of CHIP. So surveillance may be required, but because there are about 10 genes that are primarily implicated in CHIP, that can substantially decrease the cost of it. The cost for DNA extraction is going down, and so there are research tests that are kind of in the $10 to $20 range right now for CHIP. And if flipped over to the clinical side will also be reasonably low cost. And so, for the paradigm for clinical implementation, that cost part is necessary.Eric Topol (41:10):I don't know the $10 or $20 ones. Are there any I could order on patients that I'm worried about?Pradeep Natarajan (41:17):Not yet clinical. However, there is a company that makes the reagents for at least the cores that are developing this. They are commercializing that test so that many other cores, research cores can develop it. I think it's in short order that clinical labs will adopt it as well too.Eric Topol (41:36):That's great.Pradeep Natarajan (41:37):I will keep you apprised.What About Polygenic Risk Scores?Eric Topol (41:39):I think that's really good news because like I said, we're so darn lipid centric and we have to start to respect the body of data, the knowledge that you and others have built about CHIP. Now speaking of another one that drives me nuts is polygenic risk score (PRS) for about a decade, I've been saying we have coronary disease for most people is a polygenic trait. It's not just a familial hypercholesterolemia. And we progressively have gotten better and better of the hundreds of single variants that collectively without a parental history will be and independently predict who is at double, triple or whatever risk of getting heart disease, whereby you could then guide your statins at higher aggressive or pick a statin, use one or even go beyond that as we've been talking about. But we don't use that in practice, which is just incredible because it's can be done cheap.(42:45):You can get it through whether it's 23andMe or now many other entities. We have an app, MyGeneRank where we can process that Scripss does for free. And only recently, Mass General was the first to implement that in your patient population, and I'm sure you were a driver of that. What is the reluctance about using this as an orthogonal, if you will, separate way to assess a person's risk for heart disease? And we know validated very solidly about being aggressive about lipid lowering when you know this person's in the highest 5% polygenic risk score. Are we just deadheads in this field or what?Pradeep Natarajan (43:30):Yeah, I mean Eric, as you know, lots of inertia in medicine, but this one I think has a potential to make a large impact. Like CHIP mutations, I said news is about 10% in individuals greater than 70. The prospect here is to identify the risk much earlier in life because I think there is a very good argument that we're undertreating high risk individuals early on because we don't know how to identify them. As you highlighted, Dr. Braunwald about LDL cholesterol. The other part of that paradigm is LDL cholesterol lowering and the duration. And as we said, everybody would benefit from really low LDL cholesterol, but again, you might overtreat that if you just give that to everybody. But if you can better identify the folks very early in life, there is a low cost, low risk therapy, at least related to statins that you could have a profound benefit from the ones who have a greater conviction will have future risk for cardiovascular disease.(44:21):You highlighted the family history, and the family history has given the field of clues that genetics play a role. But as the genome-wide association studies have gotten larger, the polygenic risk scores have gotten better. We know that family history is imperfect. There are many reasons why a family member who is at risk may or may not have developed cardiovascular disease. A polygenic risk score will give a single number that will estimate the contribution of genetics to cardiovascular disease. And the thing that is really fascinating to me, which is I think some of a clinical implementation challenge is that the alleles for an individual are fixed. The genotyping is very cheap. That continues to be extremely cheap to do this test. But the weights and the interpretation of what the effects should be for each of the SNPs are continually being refined over time.(45:18):And so, given the exact same SNPs in the population, the ability to better predict cardiovascular diseases getting better. And so, you have things that get reported in the literature, but literally three years later that gets outdated and those hypotheses need to be reassessed. Today, I'll say we have a great relative to other things, but we have a great polygenic risk score was just reported last year that if you compare it to familial hypercholesterolemia, which has a diagnostic yield of about 1 in 300 individuals, but readily detectable by severe hypercholesterolemia that has about threefold risk for cardiovascular disease. By polygenic risk score, you can find 1 in 5 individuals with that same risk. Obviously you go higher than that, it'll be even higher risk related to that. And that is noble information very early in life. And most people develop risk factors later in life. It is happening earlier, but generally not in the 30s, 40s where there's an opportunity to make a substantial impact on the curve related to cardiovascular disease.(46:25):But there is a lot of momentum there. Lots of interest from NIH and others. The major challenge is though the US healthcare system is really not well set up to prevention, as you know, we practice healthcare after patient's developed disease and prevent the complications related to progression. The stakeholder incentives beyond the patient themselves are less well aligned. We've talked a lot here today about payers, but we don't have a single payer healthcare system. And patients at different times of their lives will have different insurers. They'll start early in life with their parents, their first employer, they'll move on to the next job and then ultimately Medicare. There's no entity beyond yourself that really cares about your longevity basically from the beginning and your overall wellness. That tension has been a major challenge in just driving the incentives and the push towards polygenic risk scores. But there are some innovative approaches like MassMutual Life Insurance actually did a pilot on polygenic risk scoring.(47:33):They're in the business of better understanding longevity. They get that this is important data. Major challenges, there are federal protections against non-discrimination in the workplace, health insurance, not necessarily life insurance. So I think that there are lots of things that have to be worked out. Everybody recognizes that this is important, but we really have to have all the incentives aligned for this to happen at a system-wide level in the US. So there's actually lots of investment in countries that have more nationalized healthcare systems, lots of development in clinical trials in the UK, for example. So it's possible that we in the US will not be the lead in that kind of evidence generation, but maybe we'll get there.The GLP-1 DrugsEric Topol (48:16):Yeah, it's frustrating though, Pradeep, because this has been incubating for some time and now we have multi ancestry, polygenic risk scores, particularly for heart disease and we're not using it, and it's not in my view, in the patient's best interest just because of these obstacles that you're mentioning, particularly here in the US. Well, the other thing I want to just get at with you today is the drugs that we were using for diabetes now blossoming for lots of other indications, particularly the glucagon-like peptide 1 (GLP-1) drugs. This has come onto the scene in recent years, not just obviously for obesity, but it's anti-inflammatory effects as we're learning, mediated not just through the brain but also T cells and having extraordinary impact in heart disease for people with obesity and also with those who have heart failure, about half of heart failure for preserved ejection fraction. So recently you and your colleagues recently published a paper with this signal of optic neuropathy. It was almost seven eightfold increase in a population. First, I wanted to get your sense about GLP-1. We're also going to get into the SGLT2 for a moment as well, but how do you use GLP-1? What's your prognosis for this drug class going forward?Pradeep Natarajan (49:55):As it relates to the paper, I can't claim credit as one of my former students who is now Mass Eye and Ear resident who participated, but we can talk about that. There's obviously some challenges for mining real world data, but this was related to anecdotes that they were observing at Mass Eye and Ear and then studied and observed an enrichment. In general though, I feel like every week I'm reading a new clinical trial about a new clinical outcome benefit as it relates to GLP-1 receptor agonists. This is kind of one thing that stands out that could be interrogated in these other clinical trials. So I would have that caveat before being cautious about ocular complications. But the data has been overwhelmingly beneficial, I think, because at minimum, obesity and inflammation are relayed to myriad of consequences, and I'm really excited that we have therapies that can address obesity that are safe.(50:52):There's a legacy of unsafe medicines for obesity, especially related to cardiovascular disease. So the fact that we have medicines that are safe and effective for lowering weight that also have real strong effects on clinical outcomes is tremendous. We in cardiology are increasingly using a range of diabetes medicines, including GLP-1 receptor agonists and SGLT2 inhibitors. I think that is also the secular changes of what influences cardiovascular disease over time. I talked about over the last 10 years or so with this increase in deaths attributable to cardiovascular disease. If you look at the influences of traditional clinical risk factors today, many of them have decreased in importance because when abnormal, we recognize them, in general we modify them when recognized. And so, many of the things that are unaddressed, especially the features related to insulin resistance, obesity, they start rising in importance. And so, there is a dramatic potential for these kinds of therapies in reducing the residual risks that we see related to cardiovascular disease. So I'm enthusiastic and excited. I think a lot more biology that needs to be understood of how much of this is being influenced specifically through this pathway versus a very effective weight loss medicine. But also interesting to see the insights on how the effect centrally on appetite suppression has profound influences on weight loss as well too. And hopefully that will lead to more innovations in weight management.The SGLT-2 DrugsEric Topol (52:25):And likewise, perhaps not getting near as much play, but when it came on the cardiovascular scene that an anti-diabetic drug SGLT2 was improving survival, that was big, and we still don't know why. I mean, there's some ideas that it might be a senolytic drug unknowingly, but this has become a big part of practice of cardiology in patients with diabetes or with preserved ejection fraction heart failure. Is that a fair summary for that drug?Pradeep Natarajan (53:00):Yeah, I totally agree. I mean, as there has been increased recognition for heart failure preserved ejection fraction, it has been almost disheartening over the last several years that we have not had very specific effective therapies to treat that condition. Now, it is a tremendous boon that we do have medicines interestingly focused on metabolism that are very helpful in that condition for heart failure with preserved ejection fraction. But there is still much more to be understood as far as that condition. I mean, the major challenge with heart failure, as you know, especially with heart failure preserved ejection fraction, it likely is a mix of a wide variety of different etiologies. So in parallel with developing effective therapies that get at some aspect is really understanding what are the individual drivers and then targeting those specific individual drivers. That requires a lot of unbiased discovery work and further profiling to be done. So lot more innovation, but relative to heart failure itself, it is not had widespread recognition as heart failure reduced ejection fraction. So much more to innovate on, for sure.Eric Topol (54:07):Right, right. Yeah, I am stunned by the recent progress in cardiovascular medicine. You have been center stage with a lot of it, and we've had a chance to review so much. And speaking of genetics, I wanted to just get a little insight because I recently came across the fact that your mother here at the City of Hope in Southern California is another famous researcher. And is that, I don't know what chromosome that is on regarding parental transmission of leading research. Maybe you can tell me about that.Pradeep Natarajan (54:41):Yeah, I mean, I guess it is a heritable trait when a parent has one profession that there is a higher likelihood that the offspring will have something similar. So both of my parents are PhDs, nonphysicians. There is a diabetes department at the City of Hope, so she's the chair of that department. So very active. We do overlap in some circles because she does investigate both vascular complications and renal complications. And then sometimes will ask my advice on some visualization. But she herself has just had a science translational medicine paper, for example, just a couple of months ago. So it's fun to talk about these things. To be honest, because my parents are researchers, I was not totally sure that I would be a researcher and kind of wanted to do something different in medicine. But many of my early observations and just how common cardiovascular disease is around me and in my community and wanting to do something useful is what got me specifically into cardiology.(55:45):But obviously there are numerous outstanding, important questions. And as I went through my career, really focused on more basic investigations of atherosclerosis and lipids. What got me excited sort of after my clinical training was the ability to ask many of these questions now in human populations with many new biological data sets, at least first centered on genetics. And the capabilities continue to expand, so now I teach first year Harvard medical students in their genetics curriculum. And when I talk to them just about my career arc, I do remind them they're all doing millions of things and they're exploring lots of things, but when they get to my shoes, the capabilities will be tremendously different. And so, I really advise them to take the different experiences, mainly in an exercise for asking questions, thoughtfully addressing questions, connecting it back to important clinical problems. And then once they start to understand that with a few different approaches, then they'll totally take off with what the opportunities are down the road.Eric Topol (56:51):No, it's great. I mean, how lucky somebody could be in the first year of med school with you as their teacher and model. Wow. Pradeep, we've really gone deep on this and it's been fun. I mean, if there's one person I'm going to talk to you about cardiovascular risk factors and the things that we've been into today, you would be the one. So thank you for taking the time and running through a lot of material here today, and all your work with great interest.Pradeep Natarajan (57:24):Thanks, Eric. I really appreciate it. It's tremendous honor. I'm a big fan, so I would be glad to talk about any of these things and more anytime.***************Thanks for listening, reading or watching!The Ground Truths newsletters and podcasts are all free, open-access, without ads.Please share this post/podcast with your friends and network if you found it informative!Voluntary paid subscriptions all go to support Scripps Research. Many thanks for that—they greatly helped fund our summer internship programs for 2023 and 2024.Thanks to my producer Jessica Nguyen and Sinjun Balabanoff for audio and video support at Scripps Research.Note: you can select preferences to receive emails about newsletters, podcasts, or all I don't want to bother you with an email for content that you're not interested in. Get full access to Ground Truths at erictopol.substack.com/subscribe

Are night owls cognitively superior to early risers? A new study suggests that may be the case. The periodic table could be expanding soon, with scientists on the verge of creating a new element. And, on This Day in History, the Statue of Liberty's cornerstone is laid on Bedloe's Island Night owls are 'cognitively superior' to early risers. Here's why STUDY: Sleep duration, chronotype, health and lifestyle factors affect cognition: a UK Biobank cross-sectional study A new element on the periodic table might be within reach (sciencenews.org) Nuclear Structure 2024 (21-July 26, 2024): Pursuing New Superheavy Elements: Progress Update from Berkeley Lab · Indico (anl.gov) Creating the Statue of Liberty Liberty Island Chronology Cornerstone of the Statue of Liberty Pedestal Contact the show - coolstuffcommute@gmail.com Learn more about your ad choices. Visit megaphone.fm/adchoices

Components of social connection are associated with mortality, but research examining their independent and combined effects in the same dataset is lacking. That has now changed thanks to a recent study published in BMC Medicine. We're joined by the primary author of that study to discuss the results and to get his perspective on social connectivity, loneliness and isolation and the impact on mortality. Discussed:Subjective and objective types of social connectionAnalysis of more than 458,000 participants with full data from the UK Biobank cohort linked to mortality registersWhat types of loneliness and social isolation are linked to a higher risk of death Potential implications for screeningGuest: study author and Clinical Research Fellow at the University of Glasgow Dr. Hamish Foster References: Study: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-023-03055-7 Surgeon General Advisory: https://www.hhs.gov/sites/default/files/surgeon-general-social-connection-advisory.pdfSurgeon General Report on Social Connection: www.hhs.gov/sites/default/files/sg-social-connection-general.pdf

Professor Danny Altmann is a Professor of Immunology at Imperial College London in the UK. In this interview, Professor Altmann will describe the functional changes in the body that occur with Long COVID.1. Altmann DM, Whettlock EM, Liu S, Arachchillage DJ, Boyton RJ. The immunology of long COVID. Nature Reviews Immunology. 2023 Oct;23(10):618-34.2.Elneima O, McAuley HJ, Leavy OC, Chalmers JD, Horsley A, Ho LP, Marks M, Poinasamy K, Raman B, Shikotra A, Singapuri A. Cohort profile: post-hospitalisation COVID-19 (PHOSP-COVID) study. International Journal of Epidemiology. 2024 Feb 1;53(1):dyad165.3.Douaud G, Lee S, Alfaro-Almagro F, Arthofer C, Wang C, McCarthy P, Lange F, Andersson JL, Griffanti L, Duff E, Jbabdi S. SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature. 2022 Apr 28;604(7907):697-707.4.Stein SR, Ramelli SC, Grazioli A, Chung JY, Singh M, Yinda CK, Winkler CW, Sun J, Dickey JM, Ylaya K, Ko SH. SARS-CoV-2 infection and persistence in the human body and brain at autopsy. Nature. 2022 Dec 22;612(7941):758-63.5.Hany M, Sheta E, Talha A, Anwar M, Selima M, Gaballah M, Zidan A, Ibrahim M, Agayby AS, Abouelnasr AA, Samir M. Incidence of persistent SARS-CoV-2 gut infection in patients with a history of COVID-19: Insights from endoscopic examination. Endoscopy International Open. 2024 Jan;12(01):E11-22.6.

Darby Saxbe is a professor at USC and holds a PhD in Clinical Psychology. Her research includes studying the effects of stress hormones in couples and most importantly the changes that the male brain undergoes after becoming a parent. She has scientifically discovered slight gray matter loss in men following fatherhood and termed it Dad Brain. She is currently writing a book about her research. She's also a wife, musician in a Mom Band and mother of two kids! In our conversation today we discussed:* Early influences on her scientific research* What it was like having two kids while getting your post doc* The neuroplasticity of the brain* Stress hormones in couples* How fatherhood reshapes men's brains to make them more efficient* Changes in the ‘default mode network' and the visual network in new Dads* How brain changes are different in new Dads vs. new Moms* The implications of her research for public policy, paid family leave and the support for new parents—Where to find Darby Saxbe* Linkedin: https://www.linkedin.com/in/darbysaxbe/* X: https://twitter.com/Darbysaxbe* USC: https://dornsife.usc.edu/nestlab/Where to find Adam Fishman* FishmanAF Newsletter: www.FishmanAFNewsletter.com* LinkedIn: https://www.linkedin.com/in/adamjfishman/* Instagram: https://www.instagram.com/startupdadpod/—In this episode, we cover:[1:52] Welcome[2:25] Professional background[5:18] What was the spark for the research?[8:26] Did having children during postdoc help shape research?[10:08] Cortisol[13:57] Dad brain[25:55] Should we worry about brain shrinkage after becoming a parent?[29:55] Brain efficiency in parenting[31:33] Default mode and visual network for Dads[35:43] Enhancement in social cognition[38:06] Indifference[40:35] Parental leave[44:48] Darby's book/ future research[48:35] Advice to new parents/dads[51:10] Follow along[52:05] Darby's Mom band[54:55] Rapid fire—Show references:Darby's Research: https://dornsife.usc.edu/nestlab/publications/Prenatal prolactin predicts postnatal parenting attitudes and brain structure remodeling in first-time fathers: https://www.sciencedirect.com/science/article/abs/pii/S0306453023003104Darby on Google Scholar: https://scholar.google.com/citations?hl=en&user=q676bXMAAAAJDad Brain is Real: https://www.nytimes.com/2024/06/16/opinion/dad-brain-fatherhood-parenting.html?unlocked_article_code=1.0E0.biCq.04uwT7G2QN-x&smid=url-shareMore on Dad Brain: https://theconversation.com/brain-study-identifies-a-cost-of-caregiving-for-new-fathers-227319Cortical volume reductions in men transitioning to first-time fatherhood: https://academic.oup.com/cercor/article-abstract/34/4/bhae126/7645338?redirectedFrom=fulltext&login=falseUSC: https://www.usc.edu/Fulbright: https://us.fulbrightonline.org/UK Biobank: https://www.ukbiobank.ac.uk/Scrooge McDuck: https://en.wikipedia.org/wiki/Scrooge_McDuckSuper Why: https://pbskids.org/superwhy/Inside Out: https://www.imdb.com/title/tt2096673/Inside Out 2: https://www.imdb.com/title/tt22022452/?ref_=fn_al_tt_1Beetlejuice: https://www.imdb.com/title/tt0094721/Throwing Muses: https://throwingmuses.com/The Killers: https://www.thekillersmusic.com/Breeders: https://www.thebreedersmusic.com/Seven Up!: https://www.imdb.com/title/tt0058578/Rushmore: https://www.imdb.com/title/tt0128445/A Hard Day's Night: https://www.imdb.com/title/tt0058182/—For sponsorship inquiries email: podcast@fishmana.com.For Startup Dad Merch: www.startupdadshop.com Production support for Startup Dad is provided by Tommy Harron at http://www.armaziproductions.com/ This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit startupdadpod.substack.com

Se coucher tard a des effets significatifs sur le cerveau, comme le démontrent plusieurs études scientifiques. Une étude publiée dans Nature en 2017 a montré que les individus qui dorment moins de six heures par nuit ont une performance cognitive réduite, notamment en termes de mémoire, d'attention et de prise de décision. Les chercheurs ont observé une diminution de la matière grise dans les régions du cerveau associées à ces fonctions chez les personnes chroniquement privées de sommeil.En 2019, une étude dans JAMA Psychiatry a révélé que les adolescents qui se couchaient après minuit avaient un risque accru de développer des symptômes dépressifs. L'étude, portant sur 4 175 adolescents, a trouvé que chaque heure de coucher tardive augmentait de 38% le risque de symptômes dépressifs et de 23% celui de pensées suicidaires.De plus, une étude de l'université de Stanford a souligné que se coucher tard perturbe le rythme circadien, provoquant un désalignement entre l'horloge interne et les cycles naturels de lumière et d'obscurité. Cela peut entraîner une dysrégulation de la sécrétion de mélatonine, une hormone cruciale pour le sommeil. Un mauvais alignement du rythme circadien a été associé à des troubles de l'humeur, notamment la dépression et l'anxiété.Des données de la UK Biobank, portant sur 91 000 participants, ont montré que les individus qui se couchaient après 23 heures avaient un risque 25% plus élevé de développer des troubles cognitifs et de l'humeur par rapport à ceux qui se couchaient plus tôt. Ces effets sont exacerbés par la lumière bleue des écrans, qui inhibe la production de mélatonine et perturbe le sommeil.Une autre recherche publiée dans Sleep en 2020 a révélé que les personnes qui se couchent tard sont plus susceptibles de souffrir de troubles de la régulation émotionnelle, ce qui peut entraîner une augmentation des comportements impulsifs et des difficultés à gérer le stress.Mais alors quelle est l'heure maximale à laquelle faut-il aller au lit pour préserver sa santé mentale ?Les chercheurs ont analysé les données de 73 888 adultes, âgés en moyenne de 63,5 ans, issus de la UK Biobank. Les participants ont fourni des informations sur leurs habitudes de sommeil et ont porté un moniteur d'activité pendant une semaine. Les résultats montrent que plus de 19 000 participants étaient des "couche-tôt", plus de 6 800 des "couche-tard", et près de 48 000 se situaient entre les deux.Les données de sommeil ont été comparées aux dossiers médicaux des participants, révélant que se coucher tard est associé à des taux plus élevés de troubles mentaux et comportementaux. Ceux qui se couchaient tard, qu'ils soient du matin ou du soir, avaient des taux plus élevés de dépression et d'anxiété.Les conclusions de l'étude indiquent qu'il convient de se coucher avant une heure du matin pour préserver la santé mentale, soulignant que les comportements nuisibles, comme les pensées suicidaires, la consommation d'alcool et de drogues, et la suralimentation, sont plus fréquents la nuit. Hébergé par Acast. Visitez acast.com/privacy pour plus d'informations.

Recently, a series of papers were published in Nature and Nature journals illuminating the physiologic effects of exercise from an NIH initiative called MoTrPAC. To understand the wealth of new findings, I spoke with Professor Euan Ashley, who, along with Matt Wheeler, heads up the bioinformatics center.Earlier this week, Stanford announced Evan Ashley will be the new Chair of the Department of Medicine. He has done groundbreaking work in human genomics, including rapid whole genome sequencing for critically ill patients and applying the technology for people with unknown diseases. A few years ago he published The Genome Odyssey book. As you'll see from our conversation, he has also done extensive work on the science of exercise.Video snippet from our conversation. Full videos of all Ground Truths podcasts can be seen on YouTube here. The audios are also available on Apple and Spotify.Transcript with audio and external linksEric Topol (00:06):Well, hello, it's Eric Topol with Ground Truths, and I'm really delighted today to welcome my friend, Euan Ashley. He is the Roger and Joelle Burnell Chair of Genomics and Precision Health at Stanford. He's done pioneering work in genomics, but today we're going to talk about something very different, which he also is working in exercise. Exercise the cover of a Nature paper in May regarding this MoTrPAC, which we're going to talk about this big initiative to understand the benefits of exercise. But before I hand it over to Euan, and I just want to mention his description of the paper that he posted to summarize started with, “Exercise may be the single most potent medical intervention ever known.” So Euan welcome.Euan Ashley (01:01):Yeah, well, great. It's wonderful to be here, Eric, and so nice to see you.Eric Topol (01:06):Yeah. Well, we have a lot to talk about because exercise is a fascinating topic. And I guess maybe we'd start with the MoTrPAC, which is an interesting acronym that you all came up with. Maybe tell us a bit about that with the 800 rats and the 2,400 people and the 17,000 molecules, there's a lot there.Euan Ashley (01:24):Right, right. Yeah. Well, first of all, of course, before you do any scientific study, especially with a large number of people in a consortium, you need a good acronym. So that was where we started with the idea was to focus on the molecular transducers of physical activity. As you pointed out there at the beginning, we really don't have a more potent medical intervention, especially for prevention of disease. I mean, it's just such a powerful thing that we have, and yet we don't really understand how it works. And so, the MoTrPAC Consortium was designed to really work together, bring groups of people across the US together who all have some interest in exercise and some ability to measure molecules and really put together the world's largest study of exercise to try and start answering some of the questions about where the potency of this intervention come from.Eric Topol (02:20):So the first crop of papers, and there were several of them that came out all on the same day in Nature publications, was about the rats. The people part is incubating, but can you give us a skinny on, there was a lot there, but maybe you could just summarize what you thought were the main findings.Key MoTrPAC FindingsEuan Ashley (02:43):Yeah, of course, of course. And the MoTrPAC Consortium, I'll say first of all, yeah, large group is probably I think 36 principal investigators funded by the Common Fund. And so, it brings together large numbers of people, some of whom who spend most of their time thinking about let's say animal exercise. Some have spent a lot of time thinking about humans in exercise and many of whom think about measuring technologies. And as you say, these first group of papers were focused on the rat study, but actually the study goes much more broadly than that. But of course, there are some advantages to the animal protocols. We can look at tissue and we'll talk about that in a moment. But the humans, of course, are where we're most interested in the end. And we do have tissues coming from humans blood and adipose tissue and skeletal muscle, but those are obviously the only organs we can really access.(03:31):So there's a rat study, which is this one we'll talk about, and that's aerobic exercise and training. There's human studies that include aerobic exercise, strengths studies as well. There's a study in kids, pediatric study and then also a study of people who are very fit because here we're focusing on the change from sedentary to fit. And so that gives us the key exercise signal. So this first crop of papers was really our first look, cross-tissue, cross multi-omics, so multiple different modalities of measurement. And I think, yeah, we were like about nine and a half thousand assays, 19 tissues, 25 different measurement platforms, and then four training points for these rats. So let's talk about the rats for a minute. What do they do? So they normally live at night. They're active at night. In this study, we reverse that so that we can actually do the studies during the day.(04:25):So we reverse their at night cycle and they do their treadmill exercise over the course of several weeks. They start with about 20 minutes, and they do more every day. There's a control group of rats that just get placed on the treadmill and then don't do any exercise. And so, this is a controlled study as well. And over the course of time, we work more, it's about eight weeks in total and then two days after each of those bouts of exercise. So it's not an acute study, we measure to see where we are. So we also have this time trajectory of exercise. So what did we find? I mean, I think the first thing I would say, we talked about just how potent exercise is. It's very, very clear from looking at all these tissues that when you exercise regularly, you are just a different person, or in this case a different rat.(05:15):Like literally every tissue is changed dramatically and some in quite surprising ways. So I give you a couple of the things that surprised me or that I thought were most interesting. The first thing was this question of how does exercise actually work? Because exercise is a stress. You go out and you pound the pavement or you're on the bike or whatever, and then your body recovers. And so, there's been this idea, it's referred to as hormesis, this idea that some of the benefit of exercise might come from this recurrent stress. So your body learns how to deal with stress. And so given that we were very interested that this heat shock response was so prominent across multiple tissues. So heat shock proteins are molecular chaperones and they take care of protein folding to make sure it's appropriately done and they prevent protein aggregation. And when proteins need degraded because they're damaged, the heat shock system jumps in.(06:10):So perhaps not surprising, but pretty interesting that the heat shock proteins were very prominent part of the stress response to exercise. And remember, this is not acute exercise, so these are benefits that are built up over time, so that was one. A surprising one to me, the adrenal gland. So we're used to thinking of adrenaline as an epinephrine, as a stress hormone, but actually we saw dramatic changes in the adrenal gland and we don't necessarily think too much. You think about the exercising muscles, you think about the heart, we think about the lungs, when we think about exercise, you don't necessarily think that you're changing your adrenal gland, but it was one of the most changed tissues. The immune system was a common upregulated system. We saw that. And in fact, some of the tissues in which the immune genes were most changed were somewhat surprising.(07:02):So the small intestine, for example, was a place where there was a highest enrichment of immune mediated pathways. And then some tissues changed pretty early, like the small intestine changed after just one or two weeks of training other tissues like the brown adipose tissue. It was more like seven or eight weeks of training before we saw the real changes in there. So just one or two little things that struck out, but I think this really the first molecular map of exercise. So we're looking across the whole system across multiple modalities of measurement across multiple tissues.Simulating StressEric Topol (07:34):So as far as understanding the benefits of exercise, does this tell us that it really does simulate stress that it's conditioning the body to deal with stress as reflected by the various points you just summarized?Euan Ashley (07:51):Yeah, I think that is exactly right. I mean, part of what we were trying to understand was in what way are you changed after you do exercise regularly? And I think if we think about things that are positive, then the ability to deal with stress at a cellular level, quite literally repair mechanisms seems to be a big part of it. The other aspect that was interesting is that when you're measuring this many analytes, you can also compare that with disease. And so, we understand that exercises is preventive benefit against disease. So in some cases, and this was work highlighted by my colleague Maléne Lindholm in the mitochondrial paper that came along with the main paper and she looked with a team across all mitochondrial changes across all of the tissues of the cell. So these are the workhorses of the individual cells that like the batteries inside the cells of the mitochondria.(08:54):And we saw big changes across, it's not surprisingly, but it's the energy source for cells, big changes across many tissues. But interestingly for two specific really important diseases, a liver disease in one case and type 2 diabetes on the other, it was very clear that the training upregulated a network that was exactly the opposite of that of the disease. And so, it really was intervening in a way that was very specifically opposite to the way we know disease mechanisms go. So it does seem like, I mean people talk about an exercise pill. I think this shows that that is just not going to be possible. There may be ways we could mimic some elements of exercise, but there's no pill. This is a multisystem, multi-tissue, multidimensional response to exercise.Eric Topol (09:44):Yeah, I think it's really important. That was one of the questions I was going to ask you is whether this would ever be simulated by a drug. And I think you already answered that, and the fact that it's so comprehensively sweeping across every organ and all these different signals, tens thousand plus signals across them, it's really striking. We never really understood the benefits of exercise and not that it's all resolved by any means. Some of the things that were interesting too was the sex specific findings. Maybe you want to comment about that because we don't spend enough time thinking about how sex does have a big effect on physiology.Sex-Specific FindingsEuan Ashley (10:24):Yeah, I mean that's a really good point and one that I think was really underlined for us at every corner, every turn of the analysis here. So really no matter which measurement modality, no matter which tissue, no matter which point of training, if we just asked these computer models to sort of separate the data according to the prominent signals without giving it a clue of what to do, the so-called unsupervised models, then sex basically came out every single time. So I think you say you're absolutely right that we so often overlook the difference. For years we've said, oh, it's too expensive to do animal studies in both sexes, so we'll just pick one. And males were picked more often. But there are plenty of studies that were just females, and I mean that clearly is wrong, and we are really, sometimes it appeared like we're almost dealing with two different species.(11:18):They were so different. But I think we can also learn from what those differences were. Interestingly, some of them were most profound in adipose tissue, so in fat, and that was the case both at rest, sedentary and amplified by exercise. So we saw big difference between females and males in relation to the kinds of signals that were prominent in the white adipose tissue. So this fat storage tissue, for example, in sedentary females, insulin signaling and the trigger to make fat and store fat was very prominent. But whereas in the males, even before any exercise, the fat signals were more related to metabolism, and we could have wild speculation about in evolutionary terms why that might be. Obviously, males and females have different biological many differences in their biology and obviously thinking about hormone systems and specifically pregnancy of course. And so, we could probably come up with some theories. In reality, all we know now are these observations were found and they're pretty interesting and they show us that we really always need to think separately about both sexes and look at both independently.Eric Topol (12:39):Well, and the other thing that you already pointed out, but I just want to underscore, you can't do this stuff in people. You can't just do fat biopsies and whatnot. So I mean, the fact that you can do this multi-omic, multi-organ type assessment is just really an extraordinary opportunity for learning. And while we're on the white fat story just briefly, we would rather have a lot more brown fat, but as we age, and I assume it's the same in rats, they don't have much as they get older brown fat. Does exercise help us get more brown fat or are we just stuck with the white adipose tissue?Brown vs White FatEuan Ashley (13:21):Yeah, well, it certainly allows us to have less of a white adipose tissue, and I think it's potential that our brown adipose tissue maybe more functional, and for those who are listening who are not familiar, I mean these really are different colors that relate to the actual color of the tissue, but the color is different because the brown adipose tissue contains lots of mitochondria and lipid droplets, and the brown adipose is there to help essentially generate heat. It has a very different function in a way, but even white adipose tissue that we think of as just being about storing energy, people think of fat as a very metabolically neutral or inert tissue, but in reality it's not. It's signaling. It's constantly, it's a tissue that's as alive as any other and not just a storage for excess energy, but exercise definitely appears to alter both in this sexually dimorphic way as we noted already and clearly both in a positive health way where I think the makeup of the brown tissue is different. The white tissue, there is less of it obviously with exercise, which is something that is well known, but not new here for the first time. But still important to have seen that even in the rats.Eric Topol (14:49):And there's even, we talked a moment go about drugs, but there are some molecules that are thought to be able to help convert white to brown fat that are understudy and we'll see if they get anywhere that's interesting. But also, you talked about aerobic exercise and with us both being cardiologists, and I know throughout my earlier part of my career, we only talked about aerobic exercise. There was no such thing as strength training, and we even discouraged that or we never talked about it. Now we know how important strength training is and not just strength and resistance training, but balance and posture and all these other things. I assume you can't study that in the rats.Euan Ashley (15:32):Well, it's not impossible. This study of course is about endurance, but as you say, and there are some models, I mean I've even seen models in trying to trigger flies to do strength training.Eric Topol (15:46):Wow, I didn't know that.Intensity of ExerciseEuan Ashley (15:46):That somewhere, yeah, we'll have something, there are various methods of making animals hang off things, and this was treadmill. So it's a fairly routine and standard I think part of a rat's life to run. So this was not so different. As we mentioned at the beginning in the human study, we do have a strength portion and the endurance portion, which I think is very important because as you say, the benefits of exercise are found really across both of those. And indeed, as you say, flexibility and other often neglected element of physical activity. But yeah, those benefits are there for both aerobic exercise and endurance. And in fact, they are perhaps even higher for higher intensity exercise. Although I think we don't necessarily recommend everybody do higher intensity exercise. I don't think it's necessary to get most of the benefits of exercise, but there is some additional benefit.(16:42):One of my favorite facts, I think I first saw it probably on a presentation a few years ago, but I looked up the original and recalculated it. But if you look at this very big study of half a million people and look at their physical activity over the course of years and correlate it with their likelihood of being alive or being dead, then it was clear that one minute of exercise bought you five minutes of extra life. And I just thought that was just a really interesting way of putting it essentially. And actually it's a little more, if you did high intensity exercise, one minute would give you seven or eight minutes of extra life. So I tell this to my patients when they come in and tell me they don't have enough time to exercise. I said, oh, well, one minute of exercise. I'm not very popular when I tell them that, but anyway.Eric Topol (17:30):You think it's true. Do you think it's based on good data?Euan Ashley (17:34):Well, the data is large, I mean half a million people. I think we've also seen it currently since the early fifties when we were first doing the London bus conductor study that Jerry Morris did that you will know well, where he compared bus conductors on the London to the bus drivers and found a significantly reduced cardiovascular mortality among the conductors because they were on their feet all day up and down stairs and the driver otherwise in the same environment the drivers were sitting. So I think we have a wealth of epidemiologic correlative evidence that exercise leads to a greater length of life, greater longevity, maybe more than for anything else. The causal evidence is less of course, but we do have causal evidence too. There are enough randomized trials and now increasingly some genetic causal evidence that helps us understand that this is really a causal link and that we actually can change our outcome if we do additional exercise.Mental Health BenefitEric Topol (18:32):Oh, and I don't question at all what you said about the enhancing healthy aging health span and even possibly lifespan. I just wondered about the one to five ratio if we could assert that. I mean that's really interesting and it's a good motivating factor because as you well know by that WHO criteria, one out of four people aren't even close to the modest exercise recommendation. So we got ways to go to get people to spruce up exercise. Now speaking of people, I do want to come back to MoTrPAC and the people plan, but I do want to before that get your sense about a couple of really fascinating studies. So earlier this year there was a study of every exercise study that's been looking at mental health along with SSRIs that name drugs that are used for mental health. And it was a pretty fascinating study. I think I'm just going to pull it up. They looked at everything that this is for depression, walking, jogging, yoga, strength training, SSRIs. And what was fascinating is that dancing, walking, jogging, it made the drugs look like a joke. They didn't seem to work at all. So this was 218 studies with over 14,000 people. And so, I don't know that enough people recognize this fact that this Prozac nation and all this stuff about the SSRIs, but exercise seems to do wonders for people who are depressed, anxious, stressed. What do you think about that?Euan Ashley (20:26):Yeah, I mean it's exactly right. I mean I think that it's very clear from the data and as you mentioned, you and I tend to focus first on the cardiovascular benefit, which is very significant, potentially 50% reduction in risk, but there are similar sorts of numbers when you look at mental health and exercise as an intervention for mental health has been very well studied and has these really dramatic benefits. And I think even if we go in the more general population and think about the fact people talk about a runner's high or an exercise high, and many, many of us, myself included, feel that. And a few years ago, I started exercising every morning and now if I don't do that, I really feel like I'm missing something, there's something in the chemistry of my brain is not quite right. And so, I think that benefit for those who have mental health issues is also very much felt and is real at the brain chemical signaling level and with this few adverse effects as exercise has, I do think we need to think of it earlier and more prominently for almost every disease.Eric Topol (21:40):Yeah, you're I think alluding to the opioids that are released with exercise and addiction to exercise, which is what ideally if everybody could be addicted to exercise, that might help a lot of things. As you mentioned in your post that I started with, “its benefits in prevention outstrip any known drugs: 50% reduction in the cardiovascular disease, 50% reduction in risk of many cancers, positive effects on mental health that we just discussed, pulmonary health, GI health, bone health, muscle function. You name it.” So you said it really well there, and that was just one recent report that substantiated the mental health. I want to also mention another report that's fascinating on cancer that is a publication again recently was looking at both mice and people with pancreatic cancer. And what was fascinating about it is the more exercise of the mice and in the people, the more survival that is from pancreatic cancer, which as we both know and all the listeners will know, is that one of the worst cancers of humankind. So the affecting cancer is fascinating. Now can you dial up your immune system response with exercise?Euan Ashley (23:02):Yeah, I think you can. And I think we were at some level expecting to see it because it's certainly a known thing, but I think again, this is able, our ability to measure it in this study is just much deeper than we've ever had in any study before. And so, I think when we think about mechanisms that might relate to reduced risk of cancer, as you say, we think first of the immune system and that signal was there in many places. As we mentioned at the very beginning, sometimes to me in some slightly surprising places like the small intestine, we don't think of that necessarily as the seat of immune activation, but I think what we were doing, what we were seeing is those signals really across all the tissues and ultimately the immune system is a distributed system. It senses in multiple places and then obviously has implementation.(23:53):Now exactly in what way we've turned up our T or B cells, for example, to be able to attack those cancers or support the therapy that's been given. I don't think we understand that yet. But actually, you bring up another great point, which is part of MoTrPAC was to create this molecular map and analyze it and put the first analysis out there. So that's what we've done, but just as big and maybe even a bigger reason is that to release the data and to make it accessible for everyone and anyone in the world as of the moment this paper came out can go to our data portal at https://motrpac-data.org/ and download the data and then use that in their own work. They can do their own analysis just of this data, but also what we're hoping is that they'll start to use the data, let's say as control data for a cancer study or for a diabetes study or for others. So we really hope it'll fuel many, many more studies over many years from now.Eric Topol (24:52):Yeah, I mean that open science approach to applaud that it's so vital and amplifies what's good to come out of this really important initiative. Now you mentioned the opioids and proteins that are secreted with exercise, exerkines is a term that's used and also I guess these extracellular vesicles (EVs) not electric vehicles. Can you tell us about exerkines and EVs and are they part of the story?Euan Ashley (25:25):Yeah, and actually in the human study there's a specific exosome analysis that will be reported there. Yeah, I think that when we think about this multi-system nature of exercise, and one of the fascinating things was to be able to have these omics in multiple tissues and think about how those tissues were signaling to each other. So obviously there are some tissues that are more fundamental to the exercise response. We think of those as the skeletal muscles. They literally the effectors of our ability to exercise. And I think we think of the heart and lungs in particular in the blood system of course, but we were seeing changes everywhere and it's one of the reasons we were seeing changes everywhere is that there are molecules that are essentially secreted into the circulation or locally by these exercising muscles, exerkines that have a number of positive benefits.(26:21):And it is possible if there's some mechanism towards mimicking some of what exercise does with a drug, then that's a good place to go look for it. And I think that this will also fuel those thoughts. I think we both, we'd agree that there isn't going to be one pill that will do all the magic of exercise, but I think there are probably things we will learn from the study where we say, well, this was a very positive benefit and it seems to be mediated by this particular molecule, and that's something that could potentially lead towards a more targeted drug. I think we'll definitely get into that and understanding just we're systems people are, again, I think we think in physiology, so when we see the tissues like connecting and communicating with each other, I think that just makes a lot of sense from a systems perspective.Eric Topol (27:10):Now getting onto the forthcoming work that's going to come out with the 2,400 people and the different groups that you mentioned, I wonder if it'll include things like biologic aging with DNA methylation, will it have immunomes to characterize the differences in the immune system? What kind of things might we expect? Obviously, you can't get tissue, but for blood samples and things like DNA methylation, can we get some more illumination on what's going on?Euan Ashley (27:41):Yeah, I think we can. And of course, ultimately the human is the organism we're most interested in. Interestingly, I'll say interestingly as well, we can get some tissue and huge credit to both the investigators who are doing this and most credit of all to the individuals who agreed to join the study because they actually agreed not just to give blood samples, but actually to give skeletal muscle samples. So a biopsy of the skeletal muscle and a biopsy of the fat pad. So we will actually have two other tissues in the humans, not this obviously vast range that we talked about with the rat study, but we'll have those two other tissues and we'll also then have the rat data, which is the other great thing. So we'll have this foundational insight that we can then bring to the human study with the humans as we mentioned before as well, we'll have not just endurance but strength trained, we'll have it in kids as well, and we'll have these higher intensity exercise.(28:36):I think we will be able to connect with this, as you mentioned, longevity literature or the health span literature where we can start to think about DNA methylation. We do have genomes of course, on all of the individuals. It won't be a study powered because it's thousands individuals, these kinds of numbers. It won't be powered to give us genetic predictors. If you think about the studies had to be hundreds of thousands of people and even more now in order to give us, let's say common variant predictive. So we won't be able to do that, but there's lots of connections we'll be able to make by being much closer to the effector systems, which is to say the proteins and the metabolites and those signals we're already seeing are very significant. And so, I do think that there'll be a lot of new signals that we'll see that are specific to humans that will connect into other bodies of work, for example, the longevity, and we'll see those in blood and I hope that we'll be able to connect also the skeletal and adipose tissue data as well.Eric Topol (29:37):One of the things that would be wonderful to connect if you can, our mutual friend and your colleague at Stanford, Tony Wyss-Coray has these organ clocks that have been validated now in the UK Biobank, and then you can see what's happening with the wealth of plasma proteins that have been validated across each organ. So without having to do tissue, you might get some real insights about organ clock. So I mean, I'm really looking forward to the people part of this. When do you think the next wave of output's going to come from MoTrPAC?Euan Ashley (30:11):Well, I think that another element of the study is that we have ancillary studies, so investigators who said, I want to be able to use MoTrPAC data and use some of the infrastructure, but I'm looking for funding for my parallel study. So some of those ancillary studies will start to come out over time, which I think will be interesting and will be a very good place to see the breadth of activity that has been triggered by this one investment. The human study is coming along. We're actually just now plotting the last two or three years of the consortium. Time has really gone by pretty fast, and we've had to scale back just a little bit on the total numbers of humans, but it should still be, I think probably the largest multi-omics study of humans that there has been. And I think if we were going to plan one of those, then planning it to study around exercise definitely, definitely makes sense. So there is some data that was, of course Covid happened in the middle of this, so that was a major challenge with hitting the original numbers. But there's some data from the humans who were recruited before Covid hit that will be coming out and hopefully in the relatively near future. And then the big study may still be a year or two away to get it finished. But after that, as we say, we hope that the data and the science will continue for I hope decades beyond just the collection of this repository.Eric Topol (31:41):That's great. You mentioned Covid and I did want to ask you about the folks with Long Covid who are suffering from fatigue and exercise intolerance and what do you think about this kind of vicious cycle? Because if they could exercise, it could help them get into a better state, but because of not being able to, it's just a negative feedback loop. Any thoughts about that?Exercise and the Immune SystemEuan Ashley (32:13):I mean, it's such a good point and it's one of course that we talk to many of our patients where they, for whatever reason, sometimes it's because they are struggling with weight or they're struggling with other mobility challenges, and now we have this very large population who are struggling with fatigue. As you mentioned, it's a group that we were somewhat familiar with because of flu and because EBV and other, I mean long syndromes were something we were familiar with. They were just kind of rare, and so there wasn't really much work done on trying to understand them. Now as you've, I think articulated better than anyone, we have this entire population of people because of the scale of Covid who have these symptoms that are recognizable for the first time and including on your podcast, you have had folks on that have discussed it. Some of the insights that have happened from actually applying science, I wish there was an answer that was buried here in MoTrPAC and maybe there is, there will certainly have data from before and after the pandemic and maybe there may be some insights that we can bring to that.(33:20):I certainly think we have a lot of insights on the interaction between infection and the immune system. We talked about the potential for the immune system to be ramped up in that potentially being one of the mechanisms through which this might help cancer. There's also the idea of, and we've seen this with the effect of vaccination on Long Covid, which perhaps surprisingly does seem to have a significant benefit for at least a group of people. The assumption there is that we're ramping up the immune system and it's having that extra effect on whether it's actually pools of hidden antigens that are hidden from the immune system or whether it's some other element of the kind of ensemble attack of the immune system that is related to the symptoms. But either way, I think we feel that having a more ramped up immune system is likely to be beneficial, but at a very real human level, the point you made is the hard one. If you're really fatigued and you just feel you can't exercise, then these benefits are just out of reach and you're in this negative feedback cycle and breaking that cycle is hard. I think we try to suggest people do it very gradually because you can get a lot of benefit from just a little exercise and that's something, so that's some way, and then hopefully people can build up slowly over time, but it's a really big challenge.Eric Topol (34:43):I hope we can crack the case on that because I know that's something holding these folks back and there's just millions of them out there. Now let's talk about the healthy folks that you see in clinic. What do you advise them about exercise besides the fact that one minute we'll give them five minutes, but do you advise them to have X amount of aerobic and X amount of resistance and in the general person, what would you tell them patients?Euan Ashley (35:13):Yeah, yeah, I do. So I suggest habit is everything. So I suggest to people that they exercise every day or take one day of rest because I think there is some benefit with the stress response and having a rest day. So I suggest five or six days a week if possible, trying to get into a habit of doing it. So pick a time that works for you. It could be first thing in the morning, could be last thing at night. The jury's out on when the best time to exercise is. What it's very, very clear is that getting the exercise done is what counts. Accumulating time is also what counts. I mean, if you're not someone who wants to pull on running kit and go out running, that's fine, but accumulating steps, accumulating physical activity and moving is key. So not having people overshoot being too ambitious, but if they're really motivated to do something, then I would say five or six times a week a combination of both aerobic and endurance exercise and strength.(36:07):Usually I suggest two to one in favor of aerobic exercise, but it's also possible I think to alternate and do more 50/50. I think the key is that both are featured and then I think a bit neglected because to be honest, our data on it is just not as good, but flexibility is really critical and particularly in the senior population and for a group who sit all day long, I think for those two groups in particular, flexibility is really under-recognized as a major component. Even in my cardiology clinic, I've helped several patients just get over their back pain by teaching them some back stretching exercises. And so, I think that's neglected. So I suggest all three of those and really it's whatever works for the individual. I think the key is to find, it might be working in a group format, it might be going to a gym, it might just be taking regular walks. The key is to get moving and not sit. Get moving and do it regularly and get into the habit.Individualized Exercise?Eric Topol (37:09):Yeah, and actually on that point about potential individualization in the future, I noticed that you and some people that worked in your lab and others, Svexa is a company you started for exercise. Can you tell us about that?Euan Ashley (37:26):Yeah, this was a PhD student who was in my lab many years ago and was doing his PhD joint between the Karolinska Institute in Sweden. And of course, the country of Sweden has a long history of exercise physiology, science, and as he came out, we realized that there was the potential for optimization of training for individuals, whether they're recreational athletes or elite athletes in the Olympics. And he was interested in taking this and running with it, which he did. So the company originally Silicon Valley exercise analytics, but shortened now to Svexa builds, builds products to help people basically individualize their training. And we work, say with recreational athletes on an individual basis, we work with a lot of Olympic athletes in multiple countries and the technology building the sort of magic sauce that many of these coaches even up to and including Olympic coaches have into a format that can be spread and amplified to many more people is one of the themes.(38:29):And when we think about professional athletes and the company works with a number of well-known brand name teams that are in soccer leagues and in national football league here in the US and really across professional sport, what we're thinking of there is optimizing performance. Of course, all the teams want to win, but reducing injury is the other key part because the management of load, these are professional athletes, they're getting up every day in training and they're trying to optimize their training and their coaches are trying to do that. And it's been a fairly data free zone over the years, but meanwhile, we actually have learned a lot about how to measure individuals and how to measure what training works, and if you think about a team that might be paying 20 million a year for their star player, if that player gets injured, that's a pretty expensive thing. And so, investing a little bit in understanding the training load, helping the coaches understand the data, and then adapting that to each individual in the team so that their chance of injury is lower. That's really a lot of what the company spends its time thinking about.Eric Topol (39:36):Now, do you use sensors like lactate and glucose and AI of their body and how do you figure this stuff out?Euan Ashley (39:45):Yeah, all of that is possible. It's interesting, some sports have a kind of culture of measurement. For example, lactate measurements, which as your listeners will know, is it requires a small blood sample usually from the finger or from the ear lobe. Some sports like swimming have done that for years. But other sports, it's just not been so much in the culture. So I would say that from the company perspective, we work with whatever data is available and we'll make recommendations if people want to think about wearable devices. Of course, the digital era is around us, and you can get a lot from just a standard watch in terms of heart rate, heart rate variability in terms of accelerometry and movement. You can do a lot with just that, but there's lots more. Many of these teams have GPS signals so they know how far an athlete moves in a given game, how fast they move, how much time they spend at tool speed versus medium speed.(40:37):So we can use all of that. And as you say, yes, AI for sure is a large part of what we do and a couple of different ways actually. One is just for the analysis of the data, but another is this idea of scaling expertise. This is something in the AI community. I know you talked about a lot where you could take the expertise of let's say a physician with a very specialized practice or an Olympic coach for a marathon runner and basically make a language model that contains that expertise and then allow many people, thousands of people potentially to benefit from that expertise that we'd otherwise be sort of locked up with next available appointment is 18 months down the road, but if your AI can potentially reflect a lot of what you have, a lot of your expertise, not all of it, we hope, but probably a lot of it, then that expertise could potentially be offered much more broadly. And if it's to help people exercise more and more effectively, it's going to be a lot of good that I think can come from that.Eric Topol (41:33):Yeah. No, it's really interesting. I think there's unlimited opportunities there. It's like Moneyball to the 10th power. It's like all this data that's in sports that gets me, I guess to the last question I had for you, and that is the elite athlete or athlete hard. These are people that are working out endurance just to the max, these extremists, and they're prone to heart issues like atrial fibrillation. Why is that? What's going on with these people that they exercise too much? Is it just the lack of moderation, extremism or what's going on?Euan Ashley (42:10):Yeah, well, so it's interesting that of course you mentioned atrial fibrillation. I think that really is the only downside of exercise, even fairly extreme exercise that I've ever been, I think that we've ever had really good data for. And I would say that over the years, and I've been one way or another touching the exercise science world for 20 years and more now and certainly have been asked very often, surely these people are doing themselves harm. And the reality is, although every now and again there's a study that shows some harm or they measure troponin, they measure something in the blood and someone says, oh, they must be doing themselves harm. It's been very hard to find it. The reality is atrial fibrillation though really is, especially for those ultra endurance athletes, that's for real. And that is, we don't know that it's associated with a mortality impact necessarily, but it's definitely annoying and it slows down.Endurance Athletes and Atrial Fibrillation(43:03):We have athletes who come in and say they're cycling up a hill and suddenly they drop their power drops and they realize they've gone into atrial fibrillation. I used to play basketball with someone who would go into atrial fibrillation, so I would know when to try and get past him once he went into atrial fibrillation. But that's a real thing, and I think one of your questions was why I think I have a lot of close friends who are ultra endurance runners. They're among some of the most chilled and happiest people I know. I think those benefits of exercise are what they're enjoying, and I think there's a literature on addiction to exercise. So there is a small number of people who get addicted to that feeling and addicted to the chemical matter in their brain and can't stop, and they really do get to the point of doing themselves harm.(43:53):Fortunately, I think that's a pretty small number. And overall, although there are many consequences of chronic long-term exercise, almost all of them seem to be positive. The other one that you and I are probably very familiar with is the calcium scans that we see now much more often, it's common for people who've exercised a lot to have more calcium in their hearts. Now they have a lower risk of that. They have lower risk of heart attacks in general, one or two studies muddied the waters just a little. But in general, it's very clear they have very positive health benefits and yet they have more calcium. So they are an exception. We've seen in our sports cardiology clinic here at Stanford, several athletes every month, several will come in with this finding and we are explaining to them, this doesn't mean they have the same risk as someone who hasn't exercised at that level who would have that calcium score. It does seem to be very different, and it may be that there's a stabilization of those plaques in the arteries. I don't think we understand the biology that well, but we understand the epidemiology quite well, which is that their risk really is still low.Eric Topol (44:59):Yeah, no, it's interesting that there's still some uncertainties there and MoTrPAC may help guide us or at elucidate some of them. I guess it does bring up one other thing I got to get to with you because we didn't really get to the question of moderate to higher intensity, not to the level of the ultra exercises, but if you just do steps or do you sweat like hell, where do you draw the line? Or is that really part a function of age and ability? When you recommend exercise, because obviously you're rational and there's others out there that are exercising three or four hours a day and they're going to extreme craziness, but just in a reasonable thing, do you think just telling people who are 70 that walking is good enough or do you try to encourage them to push it?Euan Ashley (45:59):Yeah, I do encourage people to push it a bit because I think there's clear evidence that higher intensity, some degree of higher intensity exercise really does provide more benefit. But I think my main message first is because for most people, the potential of moderate versus high is in the distance and in the future for most people, we need to get them off the couch and get them on their feet. So my emphasis is that you can go a long way with just a little movement, even a little standing. And then I think if they're really getting into the habit and really doing some exercise then, and if they don't have a prior history of let's say, heart attack or other medical issues that might make high intensity exercise risky, if they don't have those, then I absolutely do get to the point where I recommend some amount of higher intensity exercise, because I think there is some evidence that it has a little extra benefit.Eric Topol (46:51):Oh, that's great. Well, this is the most in-depth conversation I've ever had with anybody on exercise, so Euan I really appreciate it. I mean, I knew you from all your work in genomics of course, and we've had some overlap from time to time, but the exercise stuff is fantastic. Did I miss anything?Euan Ashley (47:09):No, I don't think so. Just underline again to anyone who's listening if they're interested to play with this data, it's very much out there. It's a tool for the world, and they can go to https://motrpac-data.org/ and even you can do some analysis without downloading any data either. If you just have a favorite gene or a favorite protein, you can type that in and take a look at some of the tools we have there. But yeah, really appreciate the conversation and very fun to chat about what has been a really, really fun project.Eric Topol (47:39):Well, thank you and all the folks at MoTrPAC, all the hard work and of course the funding that got it going to give it that runway of several years. So we'll look forward to more. I hope to convene with you again when some of the other studies come out, and thanks so much.*****************************************************Thanks for listening, reading or watching!The Ground Truths newsletters and podcasts are all free, open-access, without ads.Please share this post/podcast with your friends and network if you found it informativeVoluntary paid subscriptions all go to support Scripps Research. Many thanks for that—they greatly helped fund our summer internship programs for 2023 and 2024.Thanks to my producer Jessica Nguyen and Sinjun Balabanoff for audio and video support at Scripps Research.Note: you can select preferences to receive emails about newsletters, podcasts, or all I don't want to bother you with an email for content that you're not interested in. Get full access to Ground Truths at erictopol.substack.com/subscribe

In this 20 minute episode we talk with Michael Twyman, MD, founder of Apollo Cardiology, about two aging-related chronic diseases; Cardiovascular disease (CVD) and Alzheimer's disease (AD). There is a growing body of evidence linking cardiovascular health and risk factors of CVD to AD. A study published in the Journal of American Heart Association using data from over 430,000 individuals from the UK Biobank found that those who had coronary heart disease (CHD) before the age of 45 had a 13% increased risk of developing AD compared to those who did not have CHD. Tune in for more insights.This episode is sponsored by CardioDiagnostics.

In this 20 minute episode we talk with Michael Twyman, MD, founder of Apollo Cardiology, about two aging-related chronic diseases; Cardiovascular disease (CVD) and Alzheimer's disease (AD). There is a growing body of evidence linking cardiovascular health and risk factors of CVD to AD. A study published in the Journal of American Heart Association using data from over 430,000 individuals from the UK Biobank found that those who had coronary heart disease (CHD) before the age of 45 had a 13% increased risk of developing AD compared to those who did not have CHD. Tune in for more insights.This episode is sponsored by CardioDiagnostics.

Commentary by Dr. Candice Silversides

HEALTH NEWS   ·         Personalized nutrition more effective than general diet advice, study finds ·         Vitamin K1 may improve insulin sensitivity and blood sugar levels for pre-diabetics   ·         Frequent salting of food increases the risk of stomach cancer ·         A 30-year US study links ultra-processed food to higher risk of early death ·         Mechanism outlined by which inadequate vitamin E can cause brain damage ·         About 90% of US adults are on the way to heart disease, study suggests       Personalized nutrition more effective than general diet advice, study finds King's College London, May 8, 2024 (Medical Xpress) Personalized nutrition approaches can improve several key health metrics, including lower weight, lower cholesterol, better mood, improved gut health, lower heart disease risk, and better metabolic health. Improvements for those following personalized guidance were also greater in some areas than for those following current, generalized government advice. In this study, researchers wanted to see if a personalized diet plan, tailored to an individual's biology, lifestyle, and health history, would have a greater impact than generic nutrition advice such as avoiding red meat. 347 Americans took part in the study, with researchers comparing the effects of following an 18-week personalized program to generic US government-issued nutrition advice. While both groups improved their health overall, participants on the personalized diet plan lost more weight than the control group and lowered their triglyceride levels more—decreasing their risk of heart disease. Participants following the personalized diet plan were also twice as likely to report improved mood, twice as likely to feel less hungry, and more than four times more likely to report better sleep quality and energy levels compared with the control group.   Vitamin K1 may improve insulin sensitivity and blood sugar levels for pre-diabetics Ahvaz Jundishapur University (Iran), May 6, 2024 (Nutraingredients) Supplements containing vitamin K1 (phylloquinone) may improve glycemic status and insulin sensitivity for premenopausal and pre-diabetic women, says a new study. “To the best of our knowledge, the present study is the first one that investigated the effects of vitamin K1 supplementation on the glycemic status and insulin sensitivity via different forms of [osteocalcin] in pre-diabetic women,” wrote the researchers in the European Journal of Clinical Nutrition . Osteocalcin (cOC) is a vitamin K-dependent protein. Without adequate vitamin K, the osteocalcin remains inactive (uncarboxylated osteocalcin, ucOC), and thus not effective. The new study used phylloquinone at a daily dose of 1,000 micrograms for four weeks. Eighty-two pre-diabetic and pre-menopausal women participated in the study and were randomly assigned to either the vitamin K1 group or placebo. Results showed that cOC levels increased as a result of K1 supplementation, while ucOC levels decreased, compared with placebo. In addition, results of the two hour post-oral glucose tolerance test showed improvements in both glucose and insulin levels in the K1 group, compared with placebo. Data from the insulin sensitivity index (ISI) showed increases in the K1 group, they added.    Frequent salting of food increases the risk of stomach cancer Medical University of Vienna (Austria), May 8, 2024 (Eurekalert) In Asian countries, where high-salt foods are popular, the link between high salt consumption and stomach cancer has already been proven. A long-term study by MedUni Vienna has now shown for the first time that this risk is also reflected in the cancer statistics in Europe. As the analysis recently published in the specialist journal Gastric Cancer shows, people who frequently add salt to their food are around 40 per cent more likely to develop stomach cancer than those who do not use the salt shaker at the table. Data from more than 470,000 adults from the large-scale British cohort study "UK-Biobank" was analysed. This revealed that people who said they always or frequently added salt to their food were 39 per cent more likely to develop stomach cancer over an observation period of around 11 years than those who never or rarely added an extra pinch of salt to their food.  In the list of the most common types of cancer worldwide, stomach cancer is in fifth place. The risk of this tumour disease increases with age, but the latest statistics paint a worrying picture of an increase in adults under the age of 50.  "Our research shows the connection between the frequency of added salt and stomach cancer in Western countries too," emphasises first author Selma Kronsteiner-Gicevic. "With our study, we want to raise awareness of the negative effects of extremely high salt consumption and provide a basis for measures to prevent stomach cancer," summarises study leader Tilman Kühn.   A 30-year US study links ultra-processed food to higher risk of early death Harvard University, May 8, 2024 (Medical Xpress) Higher consumption of most ultra-processed foods is linked to a slightly higher risk of death, with ready-to-eat meat, poultry, and seafood based products, sugary drinks, dairy based desserts, and highly processed breakfast foods showing the strongest associations, finds a 30-year US study in The BMJ today. Mounting evidence links ultra-processed foods to higher risks of obesity, heart disease, diabetes and bowel cancer, but few long term studies have examined links to all cause and cause specific deaths, especially due to cancer. To address this knowledge gap, researchers tracked the long-term health of 74,563 female registered nurses from 11 US states in the Nurses' Health Study and 39,501 male health professionals from all 50 US states in the Health Professionals Follow-up Study with no history of cancer, cardiovascular diseases, or diabetes at study enrollment. Compared with participants in the lowest quarter of ultra-processed food intake (average 3 servings per day), those in the highest quarter (average 7 servings per day) had a 4% higher risk of total deaths and a 9% higher risk of other deaths, including an 8% higher risk of neurodegenerative deaths. The association between ultra-processed food intake and death varied across specific food groups, with meat, poultry, and seafood-based ready-to-eat products showing the strongest and most consistent associations, followed by sugar-sweetened and artificially-sweetened beverages, dairy-based desserts, and ultra-processed breakfast food.   Mechanism outlined by which inadequate vitamin E can cause brain damage Oregon State University, May 3, 2024 (Daily Science)   Researchers at Oregon State University have discovered how vitamin E deficiency may cause neurological damage by interrupting a supply line of specific nutrients and robbing the brain of the "building blocks" it needs to maintain neuronal health. The research showed that zebrafish fed a diet deficient in vitamin E throughout their life had about 30 percent lower levels of DHA-PC, which is a part of the cellular membrane in every brain cell, or neuron. Other recent studies have also concluded that low levels of DHA-PC in the blood plasma of humans is a biomarker than can predict a higher risk of Alzheimer's disease. Just as important, the new research studied the level of compounds called "lyso PLs," which are nutrients needed for getting DHA into the brain, and serve as building blocks that aid in membrane repair. It showed the lyso PLs are an average of 60 percent lower in fish with a vitamin E deficient diet. The year-old zebrafish used in this study, and the deficient levels of vitamin E they were given, are equivalent to humans eating a low vitamin E diet for a lifetime. In the United States, 96 percent of adult women and 90 percent of men do not receive adequate levels of vitamin E in their diet. "This research showed that vitamin E is needed to prevent a dramatic loss of a critically important molecule in the brain, and helps explain why vitamin E is needed for brain health," said Maret Traber, at OSU and lead author on this research.   About 90% of US adults are on the way to heart disease, study suggests Brigham and Women's Hospital & Harvard Medical School, May 8, 2024 (Medical Xpress) Nine of 10 American adults are in the early, middle or late stages of a syndrome that leads to heart disease, a new report finds, and almost 10% have the disease already. "Poor cardiovascular, kidney, and metabolic health is widespread among the U.S. population," concludes a team led by Dr. Muthiah Vaduganathan of Brigham and Women's Hospital and Harvard Medical School in Boston. Researchers looked specifically at rates of what the American Heart Association has dubbed cardiovascular, kidney and metabolic (CKM) syndrome Among adults age 20 or older, only 10.6% did not have some level of CKM syndrome. About 26% fell into the early stage 1 category, meaning they were gaining dangerous levels of body fat. Nearly half (49%) of adults fell into stage 2 CVM syndrome, and 5.4% were stage 3. According to the study, 9.2% of adults were in stage 4, with full-blown heart disease and, in some cases, failed kidneys. The bottom line: "Almost 90% of US adults met criteria for CKM syndrome (stage 1 or higher) and 15% met criteria for advanced stages, neither of which improved between 2011 and 2020," according to the Boston researchers.

中午好好休息睡個午覺吧 Support this show: https://open.firstory.me/user/ckgk7ej6h3uud081394y4caub 意見回饋：https://forms.gle/WG82GMGhZi22cuSU6 Reference: Dutheil, F., Danini, B., Bagheri, R., Fantini, M. L., Pereira, B., Moustafa, F., Trousselard, M., & Navel, V. (2021). Effects of a short daytime nap on the Cognitive Performance: A Systematic Review and Meta-Analysis. International Journal of Environmental Research and Public Health/International Journal of Environmental Research and Public Health, 18(19), 10212. https://doi.org/10.3390/ijerph181910212 Paz, V., Dashti, H. S., & Garfield, V. (2023). Is there an association between daytime napping, cognitive function, and brain volume? A Mendelian randomization study in the UK Biobank. Sleep Health, 9(5), 786–793. https://doi.org/10.1016/j.sleh.2023.05.002 Leave a comment and share your thoughts: https://open.firstory.me/user/ckgk7ej6h3uud081394y4caub/comments 這是Vitamind專門製作的正念冥想節目，幫你抵抗分心焦慮的情緒。 每週日更新，你隨時服用。 歡迎來找我們合作聊天～ Instagram: @itsvitamind Email: tiffany@itsvitamind.com Powered by Firstory Hosting

In this nugget we look at the evidence for diet to improve prostate cancer outcomes and the influence diet can have on erectile dysfunction. ED HPFS paper https://bjui-journals.onlinelibrary.wiley.com/doi/10.1111/bju.15765 2022 PC review Gupta, N., Patel, H.D., Taylor, J. et al. Systematic review of the impact of a plant-based diet on prostate cancer incidence and outcomes. Prostate Cancer Prostatic Dis 25, 444–452 (2022). https://doi.org/10.1038/s41391-022-00553-2 UK Biobank study - Parra-Soto S, Ahumada D, Petermann-Rocha F, Boonpoor J, Gallegos JL, Anderson J, et al. Association of meat, vegetarian, pescatarian and fish-poultry diets with risk of 19 cancer sites and all cancer: findings from the UK Biobank prospective cohort study and meta-analysis. BMC Med. 2022;20:79. PC in HPFS study Loeb S, Fu BC, Bauer SR, Pernar CH, Chan JM, Van Blarigan EL, et al. Association of plant-based diet index with prostate cancer risk. Am J Clin Nutr. 2022;115:662–70. https://plantbasedhealthprofessionals.com/optimising-prostate-health-on-a-plant-based-diet

Subscribe to our channel: https://www.youtube.com/@optispan Related episodes: People are GETTING THIS WRONG about Supplements & My Supplement List | 17 - Healthspan Medicine #2: https://youtu.be/_UXk_ynCNUs Transforming Our Understanding of Healthcare Through Geroscience | 11 - LS #4: https://youtu.be/LCPvF-SlZIU We typically think of prescription drugs as targeted treatments designed to address the underlying mechanisms and biochemical pathways associated with specific diseases or conditions. For example, healthcare providers commonly prescribe statins that lower cholesterol levels and reduce cardiovascular disease risk by inhibiting the enzyme involved in cholesterol synthesis. Similarly, doctors might prescribe antibiotics to target bacterial infections by disrupting the bacteria's growth or killing them outright. But prescription drugs may have multiple uses or indications beyond their original intended purpose. A recent preprint from the biotech startup EPITERNA describes a study exploring the link between prescription drugs and human lifespan. Researchers analyzed more than 40 years of prescription drug data from over 500,000 patients in the UK Biobank to examine how commonly prescribed medications affect mortality risk. Many drugs have negative consequences for lifespan for reasons that include drug resistence, drug dependency, and side effects such as organ damage and immunosuppression—but a number of drugs actually appear to be beneficial for longevity. In this episode, Matt goes over the study's top-performing drugs for lifespan, and discusses how we might interpret and extend these intruiging findings about common prescription medications. Producers: Tara Mei, Nicholas Arapis Video Editor: Jacob Keliikoa DISCLAIMER: The information provided on the Optispan YouTube channel is intended solely for general educational purposes and is not meant to be, nor should it be construed as, personalized medical advice. No doctor-patient relationship is established by your use of this channel. The information and materials presented are for informational purposes only and are not a substitute for professional medical advice, diagnosis, or treatment. We strongly advise that you consult with a licensed healthcare professional for all matters concerning your health, especially before undertaking any changes based on content provided by this channel. The hosts and guests on this channel are not liable for any direct, indirect, or other damages or adverse effects that may arise from the application of the information discussed. Medical knowledge is constantly evolving; therefore, the information provided should be verified against current medical standards and practices. More places to find us: Twitter: https://twitter.com/optispanpodcast Twitter: https://twitter.com/optispan Twitter: https://twitter.com/mkaeberlein Linkedin: https://www.linkedin.com/company/optispan https://www.optispan.life/ Hi, I'm Matt Kaeberlein. I spent the first few decades of my career doing scientific research into the biology of aging, trying to understand the finer details of how humans age in order to facilitate translational interventions that promote healthspan and improve quality of life. Now I want to take some of that knowledge out of the lab and into the hands of people who can really use it. On this channel I talk about all things aging and healthspan, from supplements and nutrition to the latest discoveries in longevity research. My goal is to lift the veil on the geroscience and longevity world and help you apply what we know to your own personal health trajectory. I care about quality science and will always be honest about what I don't know. I hope you'll find these videos helpful!

What is intelligence? In the middle of the 20th century, the inner workings of the human brain inspired computer scientists to build the first “thinking machines”. But how does human intelligence actually relate to the artificial kind?This is the first episode in a four-part series on the evolution of modern generative AI. What were the scientific and technological developments that took the very first, clunky artificial neurons and ended up with the astonishingly powerful large language models that power apps such as ChatGPT?Host: Alok Jha, The Economist's science and technology editor. Contributors: Ainslie Johnstone, The Economist's data journalist and science correspondent; Dawood Dassu and Steve Garratt of UK Biobank; Daniel Glaser, a neuroscientist at London's Institute of Philosophy; Daniela Rus, director of MIT's Computer Science and Artificial Intelligence Laboratory; Yoshua Bengio of the University of Montréal, who is known as one of the “godfathers” of modern AI.On Thursday April 4th, we're hosting a live event where we'll answer as many of your questions on AI as possible, following this Babbage series. If you're a subscriber, you can submit your question and find out more at economist.com/aievent. Get a world of insights for 50% off—subscribe to Economist Podcasts+If you're already a subscriber to The Economist, you'll have full access to all our shows as part of your subscription. For more information about how to access Economist Podcasts+, please visit our FAQs page or watch our video explaining how to link your account. Hosted on Acast. See acast.com/privacy for more information.

What is intelligence? In the middle of the 20th century, the inner workings of the human brain inspired computer scientists to build the first “thinking machines”. But how does human intelligence actually relate to the artificial kind?This is the first episode in a four-part series on the evolution of modern generative AI. What were the scientific and technological developments that took the very first, clunky artificial neurons and ended up with the astonishingly powerful large language models that power apps such as ChatGPT?Host: Alok Jha, The Economist's science and technology editor. Contributors: Ainslie Johnstone, The Economist's data journalist and science correspondent; Dawood Dassu and Steve Garratt of UK Biobank; Daniel Glaser, a neuroscientist at London's Institute of Philosophy; Daniela Rus, director of MIT's Computer Science and Artificial Intelligence Laboratory; Yoshua Bengio of the University of Montréal, who is known as one of the “godfathers” of modern AI.On Thursday April 4th, we're hosting a live event where we'll answer as many of your questions on AI as possible, following this Babbage series. If you're a subscriber, you can submit your question and find out more at economist.com/aievent. Get a world of insights for 50% off—subscribe to Economist Podcasts+If you're already a subscriber to The Economist, you'll have full access to all our shows as part of your subscription. For more information about how to access Economist Podcasts+, please visit our FAQs page or watch our video explaining how to link your account. Hosted on Acast. See acast.com/privacy for more information.

Welcome to the Olink® Proteomics in Proximity podcast! Below are some useful resources mentioned in this episode:  UK Biobank Pharma Proteomics Project (UKB-PPP), one of the world's largest scientific studies of blood protein biomarkers conducted to date, https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/news/uk-biobank-launches-one-of-the-largest-scientific-studies  UKB-PPP online resources developed by Nick Lehner and Maria Wörheidehttps://metabolomips.org/ukbbpgwas/ Metabolomics and Proteomics Core in Munich:https://www.helmholtz-munich.de/en/core-facility-overview/metabolomics-and-proteomicshttps://www.helmholtz-munich.de/core-facilitiesStefanie.hauck@helmholtz-munich.de ClinspectM (https://clinspect-m.mscoresys.de/) consortium in the Munich area dedicated to move proteomics forward to clinical applicationMore joint initiatives towards Germany-wide benchmarking and standardized processes are in the making, follow the news on https://www.mscoresys.de/ Research articlesSun, B.B., Chiou, J., Traylor, M. et al.  Plasma proteomic associations with genetics and health in the UK Biobank. 2023 Nature, DOI: 10.1038/s41586-023-06592-6 https://www.nature.com/articles/s41586-023-06592-6Petrera A, von Toerne C, Behlr J, et al. Multiplatform Approach for Plasma Proteomics: Complementarity of Olink Proximity Extension Assay Technology to Mass Spectrometry-Based Protein Profiling. (2020) Journal of Proteome Researchhttps://pubs.acs.org/doi/pdf/10.1021/acs.jproteome.0c00641Multicenter Collaborative Study to Optimize Mass Spectrometry Workflows of Clinical Specimens. Kardell O, von Toerne C, Merl-Pham J, König AC, Blindert M, Barth TK, Mergner J, Ludwig C, Tüshaus J, Eckert S, Müller SA, Breimann S, Giesbertz P, Bernhardt AM, Schweizer L, Albrecht V, Teupser D, Imhof A, Kuster B, Lichtenthaler SF, Mann M, Cox J, Hauck SM. J Proteome Res. 2024 Jan 5;23(1):117-129. doi: 10.1021/acs.jproteome.3c00473. Epub 2023 Nov 28. PMID: 38015820 https://pubs.acs.org/doi/10.1021/acs.jproteome.3c00473 Olink tools and softwareOlink® Explore 3072, the platform utilized by the UK Biobank to measure ~3000 proteins in plasma: https://olink.com/products-services/explore/Olink® Explore HT, Olink's most advanced solution for high-throughput biomarker discovery, measuring 5400+ proteins simultaneously with a streamlined workflow and industry-leading specificity: https://olink.com/products-services/exploreht/  Subscribe to the podcast on your favorite player or app:Apple Podcasts: https://apple.co/3T0YbSm  Spotify Podcasts: https://open.spotify.com/show/2sZ2wxO...   Google Podcasts: https://podcasts.google.com/feed/aHR0...  Amazon Music:

In this groundbreaking interview with world expert Dermatologist Richard Weller, we discuss sunlight, skin cancer and the profound findings of large population-based studies that INCREASED ultraviolet (UV) light and greater sunlight is associated with LESS all cause mortality, less cardiovascular mortality and less cancer mortality, including skin cancer mortality  K Biobank analysis, Stevenson et al. 2023 (pre-print)]. Professor Richard Weller is a UK dermatologist, researcher and world expert on the effect of ultraviolet (UV) light on systemic health. His discovery of nitric oxide (NO) release in the skin on UV-A exposure was pivotal in understanding the cardiovascular benefits of sunlight. This interview is key in overturning the unreasonable sun-phobic narratives that disproportionately weight sun melanoma avoidance (misguided in causal model) while failing to appreciate the systemic and whole body, life extending benefits of UV light. Enjoy and share this episode!--------------------------------------------------------------LEARN how to GET HEALTHY SUN EXPOSURE  - PRESALE Offer !✅ Dr Max's Solar Callus Course

Ronnie Helvy is on his way for a screening test. He's in his sixties and wants an assessment to check for a variety of cancers. He isn't currently displaying any symptoms but is seeking reassurance. His blood will undergo a series of tests in exchange for over a thousand pounds. The outcome might be able to determine whether he is susceptible to cancers that some of his family have died from. It sounds like a good thing. Or is it?Advances in health screening have allowed us to see far into our bodies' future. During the pandemic home testing became an everyday routine. The same technology has helped develop new tools that can sequence our DNA quickly. Simple tests are making the process less intrusive than ever before.These improvements have also seen the development of a number of major national screening programmes. Including Our Future Health and the UK Biobank. Both of these are large scale research studies to help researchers prevent chronic health conditions. They could also inform the NHS on how to implement generalised screening across more of the population.Private health clinics are also offering health check-ups -- tests that could spot future warning signs. Home-testing kits can be ordered from the internet. But what does this information tell us? And is it information we can trust? We look at whether the private industry is acting responsibly when it comes to genetic testing.The BBC's Health Correspondent Matthew Hill finds out whether screening programmes can really help us live both better and longer lives. And he asks: can diagnosing conditions decades before they might affect us cause more harm than good?The promise of diagnosing conditions early is an exciting one. But there are fears among some health professionals that more screening might not be entirely helpful. We take a look at what lessons from the past could tell us about the current surge in screening. And we consider some of the dilemmas it might present us with.Presenter: Matthew Hill Producer: Robbie Wojciechowski Editor: Richard CollingsContributors: Dr Paul Cornes, Oncologist and International Advisor on cancer Prof. Clare Turnbull, Division of Genetics and Epidemiology at the Institute of Cancer Research Helen Wallace, Deputy Director of GeneWatch UK Prof Sir John Bell, Regius Professor of Medicine at the University of Oxford and the UK's Life Sciences Champion

This episode kicks off the New Year with something we seem to all be so interested in, right behind belly fat, and that's longevity. Is it just me or is it even 30-somethings now trying to reverse aging? Unpacking all that this is and isn't could be a philosophical episode all on its own. Instead, I'd thought we'd take a look at 4 ways testing your longevity is possible, at home. Now, these tests are not fool-proof. And if you have an old injury or condition, you won't be able to do one or more. Yet, say some of the researchers, that's the reason to pay attention – close attention – to the things you can control! So, knowing is good.  But also.. Please… don't let this discourage you. It's not too late.  An article in Inc. magazine got my attention the other day.  Apparently a 60-year-old startup founder is 3x as likely to found a successful startup as a 30-year-old startup founder and 1.7 times more likely to have it wind up in the top 0.1 percent of all companies.  You can't do that – or anything meaningful – sick, old, tired or with stale ideas.  So whether you're one of our healthpreneurs or not, you're at an advantage if you're truly healthy.  Can you do 20 push ups? Sit and stand (barefoot on the floor unassisted)? Walk between at a minimum of 3.3 mph? and hang from a pull up bar for at least 30 seconds?  You're not only going to live longer but you can run your business (or family, home and organizations you volunteer for) like a boss. The first quarter of 2024 the Flipping 50 Membership is going to focus on benchmarking, improving and retesting. In addition to testing those progress chart tracking we always encourage (measurements, body composition and objective ratings of our daily health) we're targeting these.   Here's how you can start this at home! (or inside our membership? Do this with us the weekend of the 13th and 14th!  Community Member Question: Intermittent Fasting and Exercise Molly asked, “Debra  I have been wanting to incorporate fasting into my health regime.  However with your current recommendations of working out in a fed state I have found it is very difficult to get enough protein and to maintain the fasted state. I read the book Feast Fast Repeat and it goes against a lot of the information you recommend. It's difficult for me to fast for 18 to 20 hours and feel good. Just wondering what your thoughts are on fasting?”  Start earlier. That makes it simple! You don't have “dinner” at dinner time.. You have a last high protein meal at 3 or 4pm.  Fasting has a purpose. Getting off a plateau. You can kickstart with an 18 or 20 hour fast but there is NO reason if you're an active person to do this regularly. Rotate.., 12, 14, 15, 18 ….  Rotating the amount of carbs you have also becomes important. Overall, lower than you've probably had before in your life (remember when you'd have two bagels at a sitting?) But you might toggle between 50 and 100 grams a day. If you always go long fasting, if you also restrict calories when you are in an eating window, and if you never vary carbs and always go low, you will have no metabolic flexibility. For the majority of humans that just won't work. Your body is getting stressed by each of those things and never rewarded and replenished. Just where is that energy to do work and fun stuff going to come from?  If this was your first book? Keep reading. It's good but there are dozens of ways to fast. They include just going lower calorie for 5 days (with higher fat and lower protein), and using bone broth or doing smoothies twice daily. There are so many ways to start. But for intermittent fasting to be the goal then starting to extend your overnight fast is the beginning. Hit 12 hours. Try 13 and 14. See how you do. But don't always do it.  Your week should NOT ever look the same every day or you lose metabolic flexibility. If your goal is to stay active and gain muscle and bone density … tell me in a 20 hour fast how you manage to get micronutrients in. What we all have to do is prioritize. It's not intermittent fasting and exercise. It's intermittent fasting OR exercise. Which do you need most right now and why?  Also relevant: do you have any emotional eating tendencies or a history of eating disorder or diet and binge? If yes, this is a slippery slope for you. (see resources) Testing Your Longevity with 4 Tests PUSHUPS  Can you do 20 pushups? For females this is the goal as estimated based on the male-only study finding 40 pushups for men significantly decreased risk of cardiovascular risk. Further, it was a better indicator than sub-maximal treadmill tests. While VO2 capacity is associated with longevity, assessing VO2 max is limited to those first with access to a lab and those highly motivated to endure the discomfort a true test requires.  Pros: The push up is a test of multiple things including upper body strength as well as core. Overall, it's a functional use of the body. If you can do it horizontally, good form and posture vertically is far more likely.  Cons:  If you're at all compromised, as many are, with ability to stabilize the scapular (shoulder blades) or with shoulder rotator cuff issues, and can't maintain good form head to toe the push up can be injurious at worst or increase poor mechanics at best.  Flip:  I'd much rather that we all could do at least a few pull ups.  WALKING PACE Can you walk a pace between 3-4 mph? It's actually 3.3 that supports bone density, while slower paces don't. So, there's that too.  If you're over 60, the effect of slow vs fast walk (at least 3-4 mph) is even more pronounced in reducing all-cause mortality. Like 53% less. Map out a mile of relatively flat surface. Warm up, test your speed. When returning to retest be sure you do the exact same course.  Pros:  This is directly related to our independence later in life. Being able to walk at a respectable pace (I wouldn't designate this as fast) is a factor of weight and mobility, muscle and joint and metabolic health. Inability to perform this one already indicates a need to buff other areas to compensate.  Cons:  If you're compromised due to a previous injury or a condition in feet, ankles, knees, hips or significantly overweight there is already a limited ability to walk, this test is not a possibility.  Next up for testing your longevity is a challenging one!! So I hope you're warmed up!  SIT RISE TEST  A study in the European Journal of Preventive Cardiology found how well you do the stand to sit to stand test indicates your risk of mortality.  Stand barefoot, cross one leg over the other and lower yourself to a sitting position. Then try to stand back up.  Attempt to do so without touching the floor with your hand, knees, elbows, forearms or sides of your legs.  You begin with 10 points. Subtract half a point each time you use a body part to shift to one side before levering up. Also subtract half a point if you lose balance.  In the study those that scored less than 8 points were twice as likely to die within the following six years. Those that scored less than 5 were three times as likely to die within the following six years.   An increase in your score of any kind reduces your mortality rate by 21%.  Pros:  This requires flexibility, balance, mobility and muscle strength. Any lack of balance, flexibility, strength or being overweight make the test harder. Each of these components is correlated to risk of mortality.  Cons:  Compromise in a joint that limits the performance of this test may not reveal that some level of these functional components are present in other joints and are evidenced in other activities.  You need a tool for testing your longevity with this next test. They aren't costly and some gyms likely also have them.  GRIP STRENGTH  In 2018 the grip strength test was determined to correlate to overall body strength and muscle mass.  Low overall muscle strength (as correlated with grip strength) is a health hazard to all health outcomes except for colon cancer, prostate cancer and lung cancer.  You can buy a dynamometer to test grip or for an easier at home or gym option, hang from a pull up bar. For men 60, and for women 30 seconds is a good target, suggest some researchers. Yet, it's an increase or decrease that you want to watch. A six-pound decrease (as tested on with the hand grip tool – but that may correlate to any reduced time hanging) correlates with 16 percent higher risk of dying from any cause.  To improve grip strength, you don't want to just work on grip strength however. Don't go around the house squeezing tennis balls. That's not really the value of the test. Improve your overall skeletal muscle strength. Other ways to assess total body strength are a one-rep max or estimated 1-rep max by doing a 10-rep max. Grip strength is far less intimidating and less injurious. But make no mistake your bench press, row or pull up, or leg press weight should also be improving.  Are You Built to Last (and Love It?) This small battery of tests are simple ways to assess your function. Every test has limitations. You may not be able to do one or more of them. The best use of them is in addition to outcomes like body fat percent (30% is obese), waist girth (for women, 35 inches significantly increases health risk), amount of muscle mass (in pounds or kilograms) primarily to know if you're gaining, losing or at very least preserving are additional objective measures. You may already be using these without knowing the significance of them.  Flipping 50 Members have access to a Progress tracking both objective and subjective measures of progress. If you're not inside the members area yet with a course, membership, or downloadable freebie, you can start here. https://www.flippingfifty.com/login The point in measuring and interpreting these is realizing the habits you've had to this point got you the results you have at this point. If you wish to change the outcome, you change the habits related to them. An injury or condition may have limited your ability to perform a certain test. This awareness can still be an asset if it highlights the need to strengthen other areas of your health span longevity.  Need support? Join us for a masterclass Jan 10, 2024 https://www.flippingfifty.com/olderandstronger Resources:  Masterclass: https://www.flippingfifty.com/olderandstronger  Membership: https://www.flippingfifty.com/cafe  Smart Scale: https://www.flippingfifty.com/givescale Handgrip:  Power Plate: https://www.flippingfifty.com/powerplate – use code flipping50 for 25% off and free massage gun with purchase References: Araújo CGS, Castro CLB, Franca JFC, Araújo DS. Sitting–rising test: Sex- and age-reference scores derived from 6141 adults. European Journal of Preventive Cardiology. 2020;27(8):888-890. doi:10.1177/2047487319847004 Celis-Morales C A, Welsh P, Lyall D M, Steell L, Petermann F, Anderson J et al. Associations of grip strength with cardiovascular, respiratory, and cancer outcomes and all cause mortality: prospective cohort study of half a million UK Biobank participants  BMJ  2018;  361 :k1651 doi:10.1136/bmj.k1651 de Brito LBB, Ricardo DR, de Araújo DSMS, Ramos PS, Myers J, de Araújo CGS. Ability to sit and rise from the floor as a predictor of all-cause mortality. European Journal of Preventive Cardiology. 2014;21(7):892-898. doi:10.1177/2047487312471759 Stamatakis E, Kelly P, Strain T, et al Self-rated walking pace and all-cause, cardiovascular disease and cancer mortality: individual participant pooled analysis of 50 225 walkers from 11 population British cohorts British Journal of Sports Medicine 2018;52:761-768. Yang J, Christophi CA, Farioli A, et al. Association Between Push-up Exercise Capacity and Future Cardiovascular Events Among Active Adult Men. JAMA Netw Open. 2019;2(2):e188341. doi:10.1001/jamanetworkopen.2018.8341  

We discover how 500,000 whole genome from UK Biobank will help medical research, plumb the depths of the ‘dark genome' with Nucleome, and Larry Moran tells us how much of our DNA is just junk.Please fill out our short listener survey hereFull show notes, transcript and references online at GeneticsUnzipped.com Follow us on Twitter @GeneticsUnzipThis episode of Genetics Unzipped was written and presented and produced by Kat Arney with audio production by Emma Werner.This podcast is produced by First Create the Media for the Genetics Society - one of the oldest learned societies dedicated to promoting research, training, teaching and public engagement in all areas of genetics.

In part one of our two-part episode on Cormac McCarthy's blood-soaked phantasmagorical 1985 masterpiece Blood Meridian, David and Tamler talk about the historical sources of the novel, the cosmic questions the book poses, the capriciousness of the near-constant violence, and the ethical neutrality of McCarthy's prose. We also get into the religious imagery, the gnostic elements, and the judge – what to make of the judge?  Plus a new meta-analysis refutes the common wisdom that “opposites attract.” But did we ever really believe that anyway?   Thanks to our beloved Patreon supporters for selecting this topic for the listener selected episode! https://phys.org/news/2023-08-evidence-opposites-dont.html Evidence of correlations between human partners based on systematic reviews and meta-analyses of 22 traits and UK Biobank analysis of 133 traits | Nature Human Behaviour https://en.wikipedia.org/wiki/Blood_Meridian Sponsored by: BetterHelp: You deserve to be happy. BetterHelp online counseling is there for you. Connect with your professional counselor in a safe and private online environment. Our listeners get 10% off the first month by visiting BetterHelp.com/vbw. Promo Code: VBW