Podcasts about hepcidin

In today's episode, I'm talking about the connection between birth control and iron levels and what you can do about it. If you're struggling with low iron, talk to your healthcare provider about developing a personalized plan that looks at optimizing your whole person. Birth control pills can affect your body in multiple ways: They contain synthetic estrogen This increases a hormone called hepcidin Hepcidin is your body's iron gatekeeper  -------- ➡️ Get Dr. Matt's free guide to overcoming iron deficiency Ask your lifestyle health questions on social media, tag @drwholeness and use #accumulatehealth. ➡️ Schedule an iron consultation https://calendly.com/ironconsultation/60min  

Have you considered the role of hepcidin in regulating your low iron levels? Hepcidin is the master iron regulating hormone. Hepcidin binds to and blocks ferroportin, an iron export protein, blocking it from iron and preventing it's absorption. In simpler terms it changes the amount of available iron receptors in the small intestines that can absorb iron.   Book a discovery call   ------------------------------------------------------------------------------------------------------ About Jennifer Harrington Jen is a Naturopath, Nutritionist, and Medical Herbalist. She focuses on natural ways to assist women transitioning into Menopause. She has been a clinical practitioner for over 21 years.  She is the Clinical Director of Menopause Natural Solutions. https://www.menopausenaturalsolutions.com/ The author of the book - From Invisible to Invincible, the natural menopause revolution. https://www.menopausenaturalsolutions.com/from-invisible-to-invincible She is available for consultation https://www.menopausenaturalsolutions.com/consultations   Menopause Natural Solutions on social media Instagram - https://www.instagram.com/menopausenaturalsolutions/ Facebook - https://www.facebook.com/menopausenaturalsolutions Youtube - https://www.youtube.com/channel/UC4_nm8vzh3zRNaUJeBy-USw

In this week's episode, we'll discuss new evidence on the critical role of hepcidin, the master regulator of iron metabolism, in the pathogenesis of polycythemia vera. Next, costimulatory molecules regulate mechanisms of CAR T cell dysfunction. Finally, we'll discuss how TREM2 is a novel receptor for IL-34, promoting differentiation of normal and leukemic myeloid cells. 

A client is undergoing a series of intravenous iron infusions to treat anemia. Her doctor has cleared her for massage, but her massage therapist still has questions—as they should. What are the cautions or contraindications for someone who needs to supplement iron intravenously? Let's find out.   Sponsors:     Books of Discovery: www.booksofdiscovery.com     Advanced-Trainings: www.advanced-trainings.com   Host Bio:                    Ruth Werner is a former massage therapist, a writer, and an NCBTMB-approved continuing education provider. She wrote A Massage Therapist's Guide to Pathology, now in its seventh edition, which is used in massage schools worldwide. Werner is also a long-time Massage & Bodywork columnist, most notably of the Pathology Perspectives column. Werner is also ABMP's partner on Pocket Pathology, a web-based app and quick reference program that puts key information for nearly 200 common pathologies at your fingertips. Werner's books are available at www.booksofdiscovery.com. And more information about her is available at www.ruthwerner.com.                    Recent Articles by Ruth:          “Unpacking the Long Haul,” Massage & Bodywork magazine, January/February 2022, page 35, www.massageandbodyworkdigital.com/i/1439667-january-february-2022/36.   “Chemotherapy-Induced Peripheral Neuropathy and Massage Therapy,” Massage & Bodywork magazine, September/October 2021, page 33, http://www.massageandbodyworkdigital.com/i/1402696-september-october-2021/34.           “Pharmacology Basics for Massage Therapists,” Massage & Bodywork magazine, July/August 2021, page 32, www.massageandbodyworkdigital.com/i/1384577-july-august-2021/34.       Resources:    Pocket Pathology: https://www.abmp.com/abmp-pocket-pathology-app   Anemia - Iron-Deficiency Anemia | NHLBI, NIH (no date). Available at: https://www.nhlbi.nih.gov/health/anemia/iron-deficiency-anemia (Accessed: 19 October 2022).   Foods High in Iron: Clams, Dark Chocolate, White Beans, and Many More (2019) Healthline. Available at: https://www.healthline.com/health/food-nutrition/foods-high-in-iron (Accessed: 19 October 2022).   Iron Infusion: Benefits, Side Effects, and What to Expect (no date). Available at: https://www.healthline.com/health/iron-infusion (Accessed: 19 October 2022).   Iron infusion: Uses, benefits, and what to expect (2017). Available at: https://www.medicalnewstoday.com/articles/318827 (Accessed: 19 October 2022).   Iron Sucrose (Intravenous Route) Side Effects - Mayo Clinic (no date). Available at: https://www.mayoclinic.org/drugs-supplements/iron-sucrose-intravenous-route/side-effects/drg-20075836 (Accessed: 19 October 2022).   Rossi, E. (2005) ‘Hepcidin - the Iron Regulatory Hormone', Clinical Biochemist Reviews, 26(3), pp. 47–49.   About our Sponsor: About Til Luchau and Advanced-Trainings.com:   As a Certified Advanced Rolfer™, Til was on the faculty of the Dr. Ida Rolf Institute® for 20 years, where he served as Coordinator and Faculty Chair of the Foundations of Rolfing Structural Integration program. The author of the Advanced Myofascial Techniques textbook series (which has been translated into 6 languages), his regular Myofascial Techniques and Somatic Edge columns have been featured in Massage & Bodywork magazine since 2009, and (along with Whitney Lowe) he co-hosts the popular Thinking Practitioner Podcast. He is the Director of Advanced-Trainings.com which since 1985 has offered short, credit-approved professional trainings and certification for manual therapists of all types, in person and online.   Website: Advanced-Trainings.com   Email: info@advanced-trainings.com   Facebook:  facebook.com/Advanced.Trainings1/   Instagram: instagram.com/tilluchau   YouTube: youtube.com/user/AdvancedTrainings  

In this episode, Dennis M. Bier MD Young Career Editor Kevin C. Klatt, PhD, RD speaks with first author, Sachelly Julián-Serrano and leader author, Rachael Z Stolzenberg-Solomon, of the recently published AJCN manuscript “Hepcidin-regulating iron metabolism genes and pancreatic ductal adenocarcinoma: a pathway analysis of genome-wide association studies”. In this episode, we dive into genetic epidemiology approaches, iron metabolism, and the risk of PDAC with our 2 guest authors from the Division of Cancer Epidemiology and Genetics at the National Cancer Institute.Be sure to connect with us on twitter ( Sachelly Julián-Serrano: @sachellyjs; AJCN: @AJCNutrition; Dr. Klatt: @kcklatt. Find all of the publications from the American Society for Nutrition (@nutritionorg; @jnutritionorg) at our website: https://nutrition.org/publications/.

Die Eisenversorgung in den Griff zu bekommen ist in der modernen Welt gar nicht so einfach. Es gibt klassische Eisenhemmer wie Kaffee, Weizenmehl oder Stress uvm. die du meiden solltest, genau so wie es viele Eisenverstärker und eisenreiche Lebensmittel gibt, die du ruhig öfters in deine Ernährung integrieren darfst. Wie sieht es außerdem aus mit Eisen supplements, Hepcidin, Training etc. ? All diese Zusammenhänge und vieles mehr gibt es in dieser Folge ! Viel Spaß!

During the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, the MPN Hub spoke to Marina Kremyanskaya, Icahn School of Medicine at Mount Sinai, New York, US. We asked, Is the hepcidin-mimetic PTG‑300 a promising treatment for therapeutic phlebotomy-dependent polycythemia vera (PV)?Currently, patients with PV require frequent phlebotomy. Kremyanskaya discusses promising results from a phase II clinical trial evaluating the safety and efficacy of PTG-300, a novel hepcidin-mimetic, in patients with PV who received three or more phlebotomies up to 6 months before treatment. Kremyanskaya highlights that the need for phlebotomy was eliminated in patients treated with PTG-300. In addition, PTG-300 was well tolerated. Hosted on Acast. See acast.com/privacy for more information.

Eisenmangel gehört für das Gros der Ärztinnen und Ärzte weltweit zum Tagesgeschäft. Ungefähr ein Drittel der Weltbevölkerung ist davon betroffen, was ihn zur häufigsten Ernährungsstörung weltweit macht. Die Ursachen für Eisenmangel sind mannigfaltig und reichen von der Komplikation chronischer Erkrankungen bis hin zu einem erhöhten Bedarf in der Schwangerschaft. In unserer neuen Podcastfolge “Eisenmangel: Erkenntnisse und offene Fragen” haben wir Forschungsergebnisse zu verschiedenen Themen aufgearbeitet. Wir beleuchten unter anderem einzelne Studien, die sich mit der unerwünschten Arzneimittelwirkung Hypophosphatämie beschäftigen, und fragen uns, ob hier das Sponsoring konkurrierender Pharmaunternehmen ein limitierender Faktor sein könnte. Außerdem klären wir für euch folgende Fragen: Welche neuen Empfehlungen gibt es zur Frequenz einer oralen Eisensubstitution? Welche diagnostischen Parameter sind bei Eisenmangel und Herzinsuffizienz zu beachten? Und ist die unerwünschte Arzneimittelwirkung Hypophosphatämie überhaupt klinisch relevant?

Jodi Flaws is a Professor of Comparative Biosciences and the Principal Investigator at the Reproductive Toxicology Laboratory in the College of Veterinary Medicine at the University of Illinois. Her lab studies the effects of environmental pollutants on the development and function of the human body, specifically relating to endocrine and reproductive health. Joining her is Karen Chiu, a PhD student whose work focuses on the impact and mechanism of various chemicals on the gut microbiome. On the podcast today Dr. Flaws and Karen Chiu discuss some of the health-damaging chemicals that have become ubiquitous in our food supply, personal care items, and even our carpeting and mattresses. They describe some of the physiological effects of these pollutants, including potentially deleterious changes to the gut microbiota and early reproductive aging. They also share tips for reducing and mitigating exposure to these compounds. After recording this podcast Karen talked with me a bit about organic foods - are they worth the additional cost to avoid some of these toxic chemicals? It turns out that while they are exposed to fewer pesticides, hormones, and antibiotics than conventional foods, it’s not true that organic foods are totally free of these contaminants. If you see the "USDA Organic" label, you can assume the food is at least 95% organic, while a product that claims to be “made with” organic ingredients is at least 70% organic. In her opinion, organic foods and products are the way to go when possible, given their lighter chemical load. It’s always a good idea to wash your produce to get as much of the pesticide residues off whether it be organic or conventional. Here’s the outline of this interview with Jodi Flaws and Karen Chiu: [00:00:30] Paper: Chiu, Karen, et al. "The Impact of Environmental Chemicals on the Gut Microbiome." Toxicological Sciences (2020). [00:01:25] Background and interest in environmental chemicals. [00:03:35] Endocrine-disrupting chemicals. [00:04:37] Phthalates and how they affect the body. [00:06:08] Effects of Phthalates on the microbiome. [00:07:15] Butyrate; Podcast: Microbiome Myths and Misconceptions, with Lucy Mailing, PhD. [00:08:58] Potential effects of pesticides: increased lipid accumulation, decreased glucose tolerance, increased expression of adipogenic genes; Review: Xiao, Xiao, John M. Clark, and Yeonhwa Park. "Potential contribution of insecticide exposure and development of obesity and type 2 diabetes." Food and Chemical Toxicology 105 (2017): 456-474. [00:10:44] Reducing exposure to phthalates. [00:12:26] Environmental Working Group (EWG) database. [00:14:09] Bisphenols. [00:16:51] "BPA-free" - not necessarily safer. [00:18:13] Effects of bisphenols on the gut microbiome. [00:18:43] Bisphenol exposure in mice, effects on microbiome; Study: Javurek, Angela B., et al. "Effects of exposure to bisphenol A and ethinyl estradiol on the gut microbiota of parents and their offspring in a rodent model." Gut Microbes 7.6 (2016): 471-485. [00:19:00] Akkermansia beneficial for intestinal immunity; Study: Ottman, Noora, et al. "Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function." PloS one 12.3 (2017). [00:20:24] Podcast: How to Use Probiotics to Improve Your Health, with Jason Hawrelak, PhD. [00:21:12] Persistent organic pollutants: polychlorinated biphenyls (PCBs), Polycyclic aromatic hydrocarbons (PAHs), Perfluorochemicals (PFCs), flame retardants and their adverse health effects. [00:24:42] Exercise can attenuate change in the gut microbiome caused by PCBs; Study: Choi, Jeong June, et al. "Exercise attenuates PCB-induced changes in the mouse gut microbiome." Environmental health perspectives 121.6 (2013): 725-730. [00:25:54] Hepcidin; Podcast: The Athlete’s Gut: Why Things Go Wrong and What to Do About It, with Megan Hall. [00:27:20] Strategies for limiting exposure. [00:29:20] Heavy Metals - lead, cadmium, arsenic and their effects on the microbiome. [00:32:49] Higher arsenic levels can lead to higher Citrobacter population; Study: Wu, Fen, et al. "The role of gut microbiome and its interaction with arsenic exposure in carotid intima-media thickness in a Bangladesh population." Environment international 123 (2019): 104-113. [00:33:29] Arsenic exposure increases TMAO; Study: Kuroda, Kaoru Yoshida Yoshinori Inoue Koichi, Hua Chen Hideki Wanibuchi Shoji Fukushima, and Ginji Endo. "Urinary excretion of arsenic metabolites after long-term oral administration of various arsenic compounds to rats." Journal of Toxicology and Environmental Health Part A 54.3 (1998): 179-192. [00:34:18] Chris Masterjohn and Chris Kressor on TMAO. [00:34:40] Glyphosate alters gut microbiota; Studies: Blot, Nicolas, et al. "Glyphosate, but not its metabolite AMPA, alters the honeybee gut microbiota." PloS one 14.4 (2019) and Aitbali, Yassine, et al. "Glyphosate based-herbicide exposure affects gut microbiota, anxiety and depression-like behaviors in mice." Neurotoxicology and teratology 67 (2018): 44-49. [00:40:33] Pig GI tract similar to humans; Dr. Sharon Donovan. [00:42:34] Siloxanes (silicone products). [00:43:52] Siloxanes; Associated with hypothyroid in cats: Poutasse, Carolyn M., et al. "Silicone pet tags associate tris (1, 3-dichloro-2-isopropyl) phosphate exposures with feline hyperthyroidism." Environmental science & technology 53.15 (2019): 9203-9213; associated with age of menopause: Chow, Erika T., and Shruthi Mahalingaiah. "Cosmetics use and age at menopause: is there a connection?." Fertility and sterility 106.4 (2016): 978-990. [00:45:03] Nicolas Taleb; Incerto series. [00:45:31] Hot flashes and potential causes. [00:45:51] Podcast: The Postmenopausal Longevity Paradox and the Evolutionary Advantage of Our Grandmothering Life History, with Kristen Hawkes, PhD. [00:47:23] Link between phthalate exposure and hot flashes (research coming soon). [00:50:29] Genetic mutation in sperm linked to autism risk. Study: Breuss, Martin W., et al. "Autism risk in offspring can be assessed through quantification of male sperm mosaicism." Nature Medicine 26.1 (2020): 143-150. [00:50:45] Effects of phthalates on men include early reproductive aging; Study: Barakat, Radwa, et al. "Prenatal exposure to DEHP induces premature reproductive senescence in male mice." Toxicological Sciences 156.1 (2017): 96-108. [00:51:14] Things to do to reduce exposure; CertiPUR-US. [00:55:17] Contact Dr. Flaws. Instagram. [00:57:13] heeds.org for information on endocrine-disrupting chemicals.

Years ago, my own gut problems motivated me to seek answers outside the existing medical establishment, and with the help of my wife Julie I was able to get my diet and health back on track. Having now worked with thousands of athletes on their own health challenges and performance goals, it’s clear there are specific pitfalls that can accompany a high-level training regimen. On this podcast, NBT Scientific Director and coach Megan Hall is with me to discuss the latest science and clinical practice on the athlete’s gut. She talks about the importance of having a healthy GI system, why athletes struggle in this area, and specifically what to do when problems arise. We also discuss what I did to regain my own gut health. Be sure to see the end of the show notes for the outline Megan wrote to prepare for this podcast. It’s an excellent resource for anyone seeking solutions for their own gut problems. Here’s the outline of this interview with Megan Hall: [00:00:54] Podcast: Microbiome Myths and Misconceptions, with Lucy Mailing. [00:01:40] The importance of gut health. [00:03:13] Podcasts focusing on gut health, with Michael Ruscio, Jason Hawrelak, and Lauren Petersen. [00:03:51] Study: Lupien-Meilleur, Joseph, et al. "The interplay between the gut microbiota and gastrointestinal peptides: potential outcomes on the regulation of glucose control." Canadian Journal of Diabetes (2019). [00:04:12] Gut-muscle axis; Studies: Ticinesi, Andrea, et al. "Aging gut microbiota at the cross-road between nutrition, physical frailty, and sarcopenia: is there a gut–muscle axis?." Nutrients 9.12 (2017): 1303; and Lustgarten, Michael Sandy. "The role of the gut microbiome on skeletal muscle mass and physical function: 2019 update." Frontiers in Physiology 10 (2019): 1435.  [00:05:43] Why athletes struggle with gut health; Studies: Costa, R. J. S., et al. "Systematic review: exercise‐induced gastrointestinal syndrome—implications for health and intestinal disease." Alimentary pharmacology & therapeutics 46.3 (2017): 246-265; and Clark, Allison, and Núria Mach. "Exercise-induced stress behavior, gut-microbiota-brain axis and diet: a systematic review for athletes." Journal of the International Society of Sports Nutrition 13.1 (2016): 43. [00:06:59] Article: de Oliveira, Erick P. "Runner's diarrhea: what is it, what causes it, and how can it be prevented?." Current opinion in gastroenterology 33.1 (2017): 41-46. [00:07:27] The 3 main causes of exercise-induced diarrhea: GI ischemia and reperfusion, mechanical and nutritional. [00:13:25] UCAN SuperStarch. [00:15:03] FODMAP fibers can increase gut symptoms; Study: Lis, Dana M., et al. "Low FODMAP: a preliminary strategy to reduce gastrointestinal distress in athletes." Medicine & Science in Sports & Exercise 50.1 (2018): 116-123. [00:17:30] Exercise-induced endotoxemia and ischemic injuries; Lipopolysaccharide (LPS) [00:18:08] Podcast: A Statin Nation: Damaging Millions in a Brave New Post-health World, with Malcolm Kendrick. [00:19:05] Nutrition and immune system in athletes; Studies: 1, 2, 3, 4. [00:20:03] Common gut symptoms we see. [00:21:37] Nutrient deficiencies and overloads: zinc, magnesium, iron. [00:22:27] Iron overload impedes cardiovascular benefits of exercise; Study: Rossi, Emilly Martinelli, et al. "Chronic Iron Overload Restrains the Benefits of Aerobic Exercise to the Vasculature." Biological Trace Element Research (2020): 1-14. [00:25:08] Hepcidin; exercise increases hepcidin, which can lead to iron deficiency; Study: Goto, Kazushige, et al. "Resistance exercise causes greater serum hepcidin elevation than endurance (cycling) exercise." Plos one 15.2 (2020): e0228766. [00:27:55] What to do about GI symptoms. [00:28:07] Dr. Josh Turknett’s 4-Quadrant Model, described in this podcast: How to Win at Angry Birds: The Ancestral Paradigm for a Therapeutic Revolution. [00:28:19] Dietary manipulations; Autoimmune Protocol (AIP). [00:29:30] How Chris fixed his gut. [00:30:07] Book: The Paleo Diet for Athletes by Loren Cordain, PhD. [00:32:41] Lundburg rice tests for arsenic. [00:32:59] Training fuel: Carb + protein + fat vs. simple carbs alone. [00:37:18] Ultramarathon runners still in ketosis with up to 600g carbohydrate per day; Study: Edwards, Kate H., Bradley T. Elliott, and Cecilia M. Kitic. "Carbohydrate intake and ketosis in self-sufficient multi-stage ultramarathon runners." Journal of Sports Sciences 38.4 (2020): 366-374. [00:38:00] Team Sky’s James P Morton on promoting endurance training adaptation in skeletal muscle by nutritional manipulation; Study: Hawley, John A., and James P. Morton. "Ramping up the signal: promoting endurance training adaptation in skeletal muscle by nutritional manipulation." Clinical and Experimental Pharmacology and Physiology 41.8 (2014): 608-613. Also see article: The IRONMAN Guide to Ketosis, by Megan Hall and Tommy Wood. [00:38:24] “Sleep-low” strategy; Study: Marquet, Laurie-Anne, et al. "Enhanced endurance performance by periodization of carbohydrate intake:“sleep low” strategy." Medicine & Science in Sports & Exercise 48.4 (2016): 663-672. [00:40:23] Probiotics; Study: Wosinska, Laura, et al. "The Potential Impact of Probiotics on the Gut Microbiome of Athletes." Nutrients 11.10 (2019): 2270; Serum-derived Bovine Immunoglobulin in SBI Protect. [00:40:57] Testing if all else fails: blood, stool, Organic Acids Test (OAT). [00:43:05] Basic blood chemistry tests for gut health. [00:47:32] Gut microbiome testing; Onegevity Gutbio test. [00:48:44] Treatment for gut pathology. [00:49:08] Jason Hawrelak’s Probiotic Advisor. [00:49:48] Podcast: How to Manage Stress, with Simon Marshall, PhD. [00:50:52] Dietary fat causing intestinal permeability. [00:52:04] Blog post: Is a high-fat or ketogenic diet bad for your gut? by Lucy Mailing. [00:54:44] Getting enough calories. [00:55:00] Relative Energy Deficiency in Sport (RED-S); Podcast: How to Identify and Treat Relative Energy Deficiency in Sport (RED-S), with Nicky Keay. [00:55:10] Studies on the detrimental effects of energy deficiency in athletes: 1. Torstveit, Monica Klungland, et al. "Within-day energy deficiency and metabolic perturbation in male endurance athletes." International journal of sport nutrition and exercise metabolism 28.4 (2018): 419-427 and 2. Fahrenholtz, Ida Lysdahl, et al. "Within‐day energy deficiency and reproductive function in female endurance athletes." Scandinavian journal of medicine & science in sports 28.3 (2018): 1139-1146. [00:56:35] Study: Hough, John, et al. "Daily running exercise may induce incomplete energy intake compensation: a 7-day crossover trial." Applied Physiology, Nutrition, and Metabolism 45.4 (2020): 446-449. [01:00:18] Fiber - timing and type. [01:02:27] Orthorexia. [01:05:02] Only 12% of Americans are metabolically healthy; Study: Araújo, Joana, Jianwen Cai, and June Stevens. "Prevalence of Optimal Metabolic Health in American Adults: National Health and Nutrition Examination Survey 2009–2016." Metabolic syndrome and related disorders 17.1 (2019): 46-52. [01:06:40]  Become an NBT Patron and gain access to the Elite Performance Members Club Forum. [01:07:05] Megan's outline for this podcast.

Myeloproliferative Neoplasms Update — Part 2: Our interview with Dr Gerds highlights the following topics and cases from his practice: Common misconceptions about MPNs (0:00) Alterations of the JAK-STAT signaling pathway in MPNs (1:43) Case: A 61-year-old woman with primary MF and mutations in JAK2, EZH2 and CALR receives ruxolitinib (4:29) Prognostic significance of the JAK2, EZH2 and CALR mutations associated with MF (7:20) Dosing and activity of ruxolitinib for MF (8:53) Management of ruxolitinib-associated cytopenias and effect of ruxolitinib on disease pathogenesis (12:19) Evolution of clinical research with the selective JAK2 inhibitor fedratinib for MF (15:32) Association between fedratinib and thiamine levels; cytopenias associated with fedratinib (17:20) Efficacy of fedratinib as second-line treatment for patients with disease progression on ruxolitinib (18:38) Risks and benefits associated with pacritinib therapy (20:00) Case: A 66-year-old man who presents with anemia is diagnosed with MF and a Type 1 CALR mutation (21:48) Risk of infections associated with ruxolitinib (23:12) Evaluation of ruxolitinib for the treatment of graft-versus-host disease (27:05) Activity of the JAK1/2 inhibitor momelotinib in patients with MF (28:23) Hepcidin suppression and improvement of anemia in patients with MF; effect of novel JAK inhibitors, including fedratinib and momelotinib (30:03) Results of the SIMPLIFY 2 study evaluating momelotinib versus best available therapy for patients with MF previously treated with ruxolitinib (32:28) Use of JAK inhibitors for rheumatoid arthritis (35:29) Novel agents and approaches under investigation for MPNs (36:48) Perspective on the potential role of venetoclax for patients with MPNs (40:30) Case: A 75-year-old woman previously diagnosed with ET and a JAK2 V617F mutation is found to have disease transformation to PV on reassessment 12 years later (43:34) Efficacy and side effects of the MDM2 antagonist idasanutlin in the treatment of PV (47:36) Importance of maintaining hematocrit control in patients with PV (50:15) Role of ruxolitinib for patients with PV (51:55) Case: A 45-year-old woman with persistent headaches is diagnosed with ET and a JAK2 V617F mutation (54:08) Therapeutic options for patients with ET (56:47) Perspective on the need for aspirin for ET (59:17) Role of interferon and PI3-kinase inhibitors in the treatment of MPNs (1:00:37) Select publications

Dr Carolyn Lam:                Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to The Journal and it's editors. We're your co-hosts. I'm Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr Greg Hundley:             And I'm Greg Hundley, also Associate Editor from the Pauley Heart Center in Richmond, Virginia, VCU Health Sciences. Dr Carolyn Lam:                How well are we doing with guideline-directed stroke prevention therapy in atrial fibrillation? Well, there are going to be very important results that you need to hear about from Get With the Guidelines Atrial Fibrillation. That's our feature paper coming right up in a future discussion. But first, you've got Greg and I discussing really important papers that we've spotted in The Journal. Greg. Dr Greg Hundley:             Absolutely, Carolyn. And my favorite kind of follows from that 'cause it's really about left atrial electromechanical remodeling following two years of high intensity exercise training in sedentary middle-aged adults, kind of like me. The studies from Ben Levine at University of Texas Southwestern Medical Center in Dallas. So, what he's driving at here are moderate-intensity exercises associated with a decrease in incidents of atrial fibrillation. However, extensive training in competitive athletes is associated with an increased atrial fibrillation risk.                                                 So, in this study, they're looking at the effects of 24 months of high-intensity exercise training on left atrial mechanical as well as electrical remodeling in sedentary, healthy, middle-aged adults. So, he had 61 individuals, their average age was 53.5 years, quite young, who were randomized to 10 months of exercise training followed by 14 months of maintenance exercise and some stretching or stretching and balance control. He also had another group of 14 master's athletes that were added for a comparison and he looked at three of the echocardiograms to assess left atrial and left ventricular volumes and also had signal average EKG's for filtered P-wave durations and atrial light potentials. He made assessments at baseline, so before everyone started, and 10 and 24 months. Dr Carolyn Lam:                Hold on, hold on. Let's really understand here how much exercise were these sedentary middle-aged adults subjected to. Dr Greg Hundley:             So, let's talk about that because that was very interesting because a lot of us are out there exercising. So briefly the way he started this, there was an initial phase that was comprised of six months of regressive training during which an increase in the frequency, the duration, and the intensity of exercise, including two high-intensity aerobic interval sessions per week that were prescribed to peak training load. The peak training load included five to six hours of exercise per week that included two interval sessions, at least one being an hour-long session, and then two 30-minute sessions.                                                 Once you got that peak training load, that was sustained for four months and then he made these 10-month measurements as part of his study design. Now following that phase, a 14-month sort of a continuation, all of the 24 months, a 14-month period of maintenance exercise was completed where the frequency of high-intensity intervals was reduced to once per week plus continuous training all the way to that 24-month time point. And during the maintenance phase, participants performed a total of about three hours a week of aerobic exercise. Dr Carolyn Lam:                Well, don't keep us in suspense now. What did the study show? Dr Greg Hundley:             So at the 24 month time point of high-intensity exercise, it led to a disproportionate dilation of the left atrium compared to the left ventricle. So, mechanical changes, but no electrical remodeling was seen. And interesting, and remember he had that comparison cohort with master's athletes. Those participants randomized exercise training demonstrated lower absolute left atrial and left ventricular volumes, but a similar left atrial to left ventricular ratio after 24 months of exercise training.                                                 So, what's going on here, if you're middle-aged or young, some of us like to think, and you start one of these aggressive training sessions, you do have some changes mechanically in the shaping of your left atrium and left ventricle, but they're concordant, but no electrical remodeling that was observed in this situation. So, how do those elite athletes develop atrial fibrillation in the electrical remodeling? Don't know. It may be they need a longer duration of exercise. Maybe they start at a different time point because these are relatively sedentary individuals, and maybe their training regimen is very different.                                                 So, more research is needed, but it was interesting that these middle-aged folks that start with this little bit more aggressive regimen really didn't develop the electrical remodeling. So, Carolyn, you've got a couple of papers that are sort of tied together. Dr Carolyn Lam:                Indeed. A couple of papers centered on lipoprotein little A. Now, we know that lipoprotein little A levels predict the risk of myocardial infarction and this has been shown in populations of European ancestry, however there's very little data available in other ethnic groups. And so, this was addressed by Dr Paré from McMaster University and the Interheart Investigators who looked at more than 6000 cases of first myocardial infarction and more than 6800 controls, all from the Interheart study, and were stratified by ethnicity and included African, American, Chinese, European, Latin American, South Asian, and Southeast Asian ancestries.                                                 Lipoprotein little A concentration was measured in each participant, first using an SA that was insensitive to iso-form size and then iso-form size itself was also assessed by Western Blot in a subset of more than 4200 participants. So, what they found was that lipoprotein little A concentration and iso-form size varied markedly among the ethnic groups. Africans had the highest concentrations with the smallest iso-form size whereas Chinese had the lowest concentrations with the largest iso-form size.                                                 Furthermore, higher lipoprotein little A concentrations were associated with an increased risk of myocardial infarction and carried an especially high population burden in South Asians and Latin Americans. And a high concentration above 15 milligrams per deciliter was associated with significantly increased risk of myocardial infarction in all populations except Arabs and Africans. The iso-form size, on the other hand, was inversely associated with lipoprotein little A concentrations and did not significantly contribute to the risk. Dr Greg Hundley:             So, Carolyn, how do we use this clinically? I mean, do we measure this in folks? Dr Carolyn Lam:                Yeah. So, there are two take-home messages. I think one is about the monitoring or measuring and it supports a clinical use of the actual lipoprotein A concentration rather than iso-form size as a marker of myocardial infarction in this ethnically diverse population. But this is, other than Africans and Arabs where, remember that cut off did not seem to associate with a risk of MI's in these two ethnicities. The second take-home is that the effects of clinical interventions that reduce lipoprotein A should be investigated especially in South Asians and Latin Americans where the population attributable risk is really high. And that actually brings me to the second study.                                                 So, we've always been looking for intervention that can reduce lipoprotein A and this current paper is really interesting 'cause it talks about insights from the Fourier trial. So, we may finally have a therapy that can reduce it. Dr O'Donoghue from the TIMI study group and Brigham and Women's Hospital in Boston, Massachusetts and colleagues looked at the relationship between lipoprotein A levels, PCSK9 inhibition, and cardiovascular risk in the Fourier trial, which you remember is a randomized trial of Evolocumab versus placebo in patients with established atherosclerotic cardiovascular disease.                                                 So, they found that patients with a higher concentration of lipoprotein little A were at increased risk of coronary events independent of the LDL concentration. And individuals with a higher baseline LP little A concentration tended to have a greater relative and absolute coronary risk reduction with Evolocumab and therefore a lower number needed to treat. It was as low as four T for individuals with a lipoprotein A above the median versus 105 number needed to treat for those at or below a lipoprotein A level below the median. Dr Greg Hundley:             So should we start checking this in all our patients now, these lipoprotein little A levels? Dr Carolyn Lam:                Yeah. So, this issue was discussed beautifully in a company editorial by Dr Thanassoulis from McGill University Health Center. And here he mentions that there remains tremendous clinical inertia honestly for the measurement of lipoprotein A in North America and in fact, worldwide. For this to be successful, we really need to be proactively screening our patients with myocardial infarction and stroke and especially those with premature events or a family history. And particular attention will need to be made on screening individuals with recurrent events despite adequate lipid or LDL lowering who frequently may still have high lipoprotein little A. It's encouraging to know that the most recent version of the US Lipid Guidelines has newly recommended LP little A measurements in select individuals as a risk enhancer and so this should further raise awareness of lipoprotein little A as a risk marker.                                                 Finally, the editorialist mentioned that common misconception that we have a lack of therapeutic options to lower high LP little A. Still, we need to remember that these individuals may obtain significant benefit from more aggressive lifestyle modifications. And now we have these results of this trial that suggest that PCSK9 may be one of the few drugs that can lower lipoprotein little A. And so, the editorialist actually ended with targeting therapy for lipoprotein A is around the corner and a test of this hypothesis is really imminent, so we should watch this space. Dr Greg Hundley:             Yeah, so it sounds like another wonderment of PCSK9 inhibitors. Dr Carolyn Lam:                Yeah. Dr Greg Hundley:             Well Carolyn, let me jump in and finish our chat here talking about iron. This particular paper is from Dr Jean-Sébastien Silvestre from Paris, France, and he's looking at the iron regulator Hepcidin. So, we know that iron deficiency is frequent in patients with coronary artery disease and increases morbidity in those with high risk profiles such as those with diabetes and anemia and then conversely, excess iron is also detrimental to cardiac function. We see this with iron overload cardiomyopathies and as a major co-morbidity in patients with genetic hemochromatosis.                                                 So, among the multiple regulators of iron homeostasis is Hepcidin. It plays an instrumental role in fine-tuning systemic iron trafficking by modulating the transfer of dietary, recycled, and stored iron from intracellular compartments to extracellular fluids. Hepcidin is a catatonic peptide hormone. It's produced primarily by hepatocytes, but also, it's produced in macrophages. So, given the role of Hepcidin to locally regulate cardiac function and that inflammation guides cardiac remodeling after acute MI, the investigators hypothesized that inflammatory macrophages may control cardiac repair through a Hepcidin-dependent mechanism. And until now, the role of Hepcidin in some other cardiac diseases challenged by inflammation hasn't really been explored. Dr Carolyn Lam:                Huh, interesting. So, what did they find? Dr Greg Hundley:             Great question and let's lead to the main results of this study. The hormone Hepcidin, they found, was produced by a distinct sub-population of inflammatory cardiac macrophages residing in infarcted heart tissue and the deletion of Hepcidin in macrophages improved tissue remodeling and stimulated cardiomyocyte renewal in both, just as our wonderful basic science studies have, in both adult mice with myocardial infarction, neonatal animals with apical resection and also in human subjects. And so, this study provided novel insights into the complex roles of the immune response during cardiac repair following MI and suggests and deleterious role for the macrophage-derived Hepcidin in cardiac repair.                                                 Interesting, Carolyn. Another role for iron in acute MI and more research to come. Dr Carolyn Lam:                Indeed. Well, thanks Greg. Let's move on to our feature discussion, shall we?                                                 For our feature discussion today, we are talking about the first results from the Get With the Guidelines atrial fibrillation. That is huge, and I have none other than the first author, Dr Jonathan Piccini from Duke Clinical Research Institute, as well as Dr William Lewis from Case Western Reserve University here to discuss these really important results, so listen up. I think to start with it is such an honor to have you with us, Bill. I mean, as Chair of the Get With the Guidelines atrial fibrillation work group, could you give us a background on how did this start? How far has it come? Dr William Lewis:             The Get With the Guidelines program started in 2000. Greg Fonarow figured out that if we put in place mechanisms to improve adherence, that we could get people on appropriate therapies. In 2012, there was some focus on atrial fibrillation and I had been participating in the program since 2004 and I kept telling them that A-fib was a big, big problem. And in 2012, they said, "Let's do this," so we built this program to try to improve adherence in atrial fibrillation. Get With the Guidelines is a national, hospital-based, quality improvement program that improves adherence to guidelines over time and it has been very successful at doing that.                                                 So, by 2013 we were ready to start enrolling patients and we started getting patients in the database and we're now up to about 162 hospitals nationwide, in the United States, and we've enrolled about 75000 patients in the program. So, it's been very successful from that standpoint. Dr Carolyn Lam:                Congratulation. And today we're actually going to be talking about that very question you asked. Adherence. How well are we adhering to guideline-directed stroke prevention therapy for atrial fibrillation? Jonathan, wanna share the key results? Dr Jonathan Piccini:         I think you're getting exactly to the point of what was the rationale for this study and I think most individuals that are familiar with the field and atrial fibrillation and also clinicians across the world who are treating patients with atrial fibrillation know that most large reports, most nationwide studies have shown that adherence for oral anticoagulation to prevent stroke in patients with atrial fibrillation usually ranges in the 50, 60, 70 percent range at best. And there's been some notable publications in the past several years from nationwide registries that have shown rates as low as 50 percent or lower in high-risk patients. So, one of the main goals of the program, as Bill articulated, was to try and improve the use of oral anticoagulation in patients who had a guideline recommendation. So, patients who had a CHA2DS2-VASc score of two and higher with atrial fibrillation.                                                 And so, looking at over 30000 admissions between 2013 and 2017 and the guidelines A-fib program, we saw that just under 60 percent of patients who had known AF at the time of admission were on oral anticoagulation. And not surprisingly, the patients who were on oral anticoagulation had lower rates of stroke during their hospitalization. But the major finding from the program was that in this quality improvement program, the program was able to improve adherence to oral anticoagulation at discharge from 60 percent to admission all the way up to 93.5 percent in the overall cohort. And if you looked at results over time, adherence improved from 80 percent at discharge all the way to 96 percent and those improvements were sustained in follow up as well. Dr Carolyn Lam:                Could you tell us, what do you think are the key elements that help this improvement? Is it just because there's a program and people know they're being watched? Is it that there was a change? I mean, when you say oral anticoagulants I bet you mean both Warfarin and the newer oral anticoagulants, so how much did that help? What do you think is the key ingredient here? Dr Jonathan Piccini:         It was several things. Having visited several of these hospitals and spoken with them about the impact of the program, I think you can't emphasize enough that if you don't measure something, you can't really expect to improve it. So, just the fact that hospitals were having systematic data on their atrial fibrillation patients at discharge illustrating who was and who was not getting oral anticoagulation makes a big difference. Between the program itself and the conferences affiliated with the program and teaching sessions affiliated with the program, there's a heavy emphasis on education of the importance of guideline recommended treatments for atrial fibrillation, so that's a second component.                                                 And then there's an iterative relationship between the sites and the American Heart Association where improvements in the rates of oral anticoagulation are recognized and celebrated. And I think it's not any one thing, in my opinion. I think it's all of those things taken together. And again, Bill, who's been with the program since its inception probably has additional thoughts on that as well. Dr Carolyn Lam:                Bill, did you expect such remarkable results? Dr William Lewis:             No. I actually didn't expect 96, but in a previous study where we were looking at patients who had had a stroke in the stroke database, we were able to achieve 93 percent adherence. And so, 96 is remarkable and it's the highest number that's ever been seen in any A-fib program. I was going to mention about the idea of what makes the special sauce, if you will, and I think John put forth a number of items. I think, again, celebrating success, those kinds of things, but I think that docs, by their very nature, are very competitive and when you get a data report that says you're doing x percent and somebody else is doing y percent and their percentage is higher, you tend to get motivated to actually do better. And so, we provide these reports in the program to hospitals so that they can measure their success against other institutions. Dr Carolyn Lam:                That's such a good idea. And, you know, I practice here in Asia and there aren't these very massive programs that are accepted in many places. So, what do you think is the generalizability of something like this? Dr Jonathan Piccini:         That's such a critical question because a limitation is that these are hospitals that are saying voluntarily, "We want to commit to the program because we think quality care for atrial fibrillation patients is important." And so, you could argue that, well, these results really don't generalize to your run of the mill hospital in different parts of the world. And I think while that's a limitation, it's also a call for what the next steps are. So, having visited many of these hospitals, these are real hospitals of brick and mortar that face many of the same challenges other health systems and hospitals across the world do and I think the key message is that a hospital that implements these types of interventions is very likely to see the same improvement with their patients. And so, I think that's a very important message and a very positive message for patients all over the US and all over the world. Dr William Lewis:             I agree. I think it's, not turn-key, it's much more generalizable than we had ever expected. So, community hospitals do this. The American Heart Association is using other Get With the Guidelines programs in China. I think that there is a lot that has to do with the support that's provided by the program and the tools that are made available to them to be able to make it so that you can recreate it in a hospital. I agree, it is more difficult in some hospitals than others. Dr Carolyn Lam:                John, before we end, what are the take-home messages for clinicians listening out there? Dr Jonathan Piccini:         I'd have two messages. The first message is that this study shows that with some assistance any healthcare system or hospital can achieve optimal adherence to these medications for their patients and thus in so doing achieve a significant benefit for the public health. And the second message I would have, which isn't necessarily specifically related to the paper, but I think it's equally important, that this is just the beginning for the American Heart Association and the Heart Rhythm Society Get With the Guidelines A-fib registry. Though stroke prevention is obviously just one of many different aspects of quality care for atrial fibrillation and so keep an eye out 'cause you'll be seeing a lot of studies coming out about how Get With the Guidelines A-fib is better informing care and treatment for atrial fibrillation across many different therapy domains, including catheter ablation and rate control and other interventions for rhythm control. And again, on behalf of all the co-authors and the American Heart Association, the Heart Rhythm Society sponsors, we really appreciate to have the opportunity to talk about the program. Dr Carolyn Lam:                Thank you so much for sharing that with us.                                                 Audience, you heard it right here on Circulation on the Run. Don't forget to tune in again next week.                                                 This program is copyright American Heart Association 2019.  

You have likely heard the saying “You are what you eat.” But what if I told you that how well your parents were eating in the days and months before you were conceived may actually help to determine how your body works—at the cellular level—for your entire life? As it turns out, you were optimized to survive in your parents' nutritional environment. The Leading Voices in Food interviews international nutritionist Andrew Prentice. About Andrew Prentice Dr Andrew Prentice, professor of international nutrition that the London School of Hygiene and Tropical Medicine. He is founder and head of the United Kingdom's medical research councils, International Nutrition Group in Gambia, Africa. Andrew directs research focused largely on maternal and child health in developing countries with emphasis on early human growth and development, iron infection than anemia, nutritional genetics and epigenetics and calcium and vitamin D and bone health. Andrew is a distinguished scholar on the effects of diet on human health and disease and as a world leader in global health research, he has made major contributions in many areas, two of which are the regulation of Human Energy Balance and obesity and the effects of malnutrition on maternal and child health and poor populations. Interview Summary You live and work in a very remote setting in the middle of the African Bush. Could you explain why? I do live a very strange life, but at the same time it's a very wonderful one. I live within a community that we have been studying--and when I say studying, that sounds as if it's us studying them. Really, they've really been participating in the work we do for over seven decades. Can you believe it? And they have a very good understanding that they're contributing to global health. So I love this population very much. I've been working with them for 40 years and not only that, it gives us some really great opportunities to do some unusual science and I've come to the conclusion that the best way I can do that is actually to live here within that community. So what are some of the main nutritional challenges for people living in that part of the world? Well, let's start off with the sort of global picture and what the World Health Organization and others would genuinely generally articulate in terms of stunting. So eradicating stunting has been part of the goal, reducing it by half has been part of the Millennium Development Goals, going onto the Sustainable Development Goals. And yet there are still at least $160 million stunted children around the world. And it's the World Health Organization target to reduce that by half by 2025, which is very ambitious. Now, why does it matter? I don't care if someone is shorter or taller than another person. But the problem is that stunting is a reflection of the fact that a child has been undernourished for many months, probably years. And so if you look at the patterns across the poor countries of this world, you see that their growth falls away from what would be the normal standard reference curves very rapidly in the first two years of life. And that then has an effect on brain development and cognitive development, and what we call human capital. So that's why we care about it. Are there also affects on resistance to disease? Indeed, so stunted child will be much more likely to die and just in his normal life, but also if admitted to hospital will have a much higher case fatality rate. So we do know that this marker of former under-nutrition is a really strong prognostic indicator of how well or badly a child will do. You're helping paint a picture of the human toll of this because otherwise we just get lost in the numbers, you know, so many millions of people are under nourished and the children affected by stunting. But you've really made it pretty clear that there are very dramatic effects on the lives of children. There are indeed and that's what drives me. I mean on the one hand I'm fascinated, but on the other hand determined to try and do something about it. So that then really brings us on to the next challenge, which is how well have you guys in the nutrition field being doing? And unfortunately the answer to that is very badly. So if we try to intervene with all the sensible things, you know--feeding children better, educating mothers how to look after them better, and we do that even under the rigorously controlled conditions of a randomized trial...we find that we can only get back about one eighth of the deficit in terms of stunting. So that is extremely discouraging and then on top of that, recently people have said, well the nutrition doesn't do so well because of the unhygienic conditions that people are living in. So there have just recently been published, huge trials that have what's called wash water, sanitation and hygiene, and they've really tried to improve the sanitation and hygiene. But unfortunately they have had an absolutely no result. Zero effect on growth. So we're really scratching our heads as to why we can't fix this move the needle. And that's one of the things that drives me to do really quite basic fundamental research. I believe that we just don't understand things well enough and when we do understand them better, we'll be able to fix them better. Can you give an example or two of the kind of basic research you're talking about? I'd love to. I'll give you a couple of stories. The first one is about iron and anemia. So the children here, by the time they're a year old, are profoundly iron deficient and anemic way below even the fifth percentile of the African American data. So they're very anemic. And the question has been why and what can we do about it? So iron is incredibly cheap. It's easy to give it out to children and yet still, when we do that, again under the rigorous conditions of trials, we don't improve very much. We got a bit of an improvement, but we don't certainly don't get rid of the anemia. And so the recent insight we've had on that has been elucidated by the discovery of this new hormone Hepcidin. So Hepcidin is the master regulator of iron metabolism. And I like to use the analogy that Hepcidin is to iron what insulin is to glucose. It really is that important and it's an exquisite molecule it's produced by the liver. But evolution has taught it to do two things. First of all, it's senses iron status. And secondly, it senses threat of infection. Now what's important about these two things is that iron and infection have been intimately linked over evolutionary time. So iron feeds bugs, feeds infections at least as much if not more than it feeds the human host. So that's why the molecule has learned to detect these two things. Now, what we've discovered very recently is that actually children are up-regulating their Hepcidin in response to low grade inflammation and the threat of infection, and that when Hepcidin is upregulated, it's positively blocking the absorption of iron in the duodenum. So, that's really a really important discovery. And incidentally, what seems to be driving up the Hepcidin is respiratory infections. So for the first time, we're able to link the probability...this needs further work, but the probability that actually it's actually respiratory infections that are driving up Hepcidin, which is blocking iron absorption which is this causing a secondary anemia. And, if that's all true, that points to a direct novel directions for therapeutic interventions. And so it's completely turned our old nutritional feeding on its head. Doctors in the past would assume that children are very poorly evolved to absorb iron: so these poor little things, we've got to throw lots of iron at them to overcome this. And in fact what we have now discovered is that in fact they're spending a lot of physiological time positively blocking iron absorption. You're painting a picture that the body is sequestering iron so that it doesn't feed infections that could then prosper even more in the body. Is Malaria a player in this picture? Yes, malaria is a big part of this. What is now clear that being on deficient and anemic is very protective against malaria in young kids. So we're sort of faced with this dilemma. What do we do about this? On the one hand, you could say, well, it's best to leave the children anemic because they're protected from malaria. I would not subscribe to that view at all. I would say, no, we've got to get rid of the malaria. We've got to get rid of the infections and we've got to give these children iron in order to improve their cognitive development and brain function. So let's look at a bigger picture of the world's nutrition landscape and I know that it's changed a lot during the time you've been working on global health. What are some of the key trends that you've seen in the nutrition landscape across the world? So I've described to you already the struggle we have with getting rid of stunting. Now the unpleasant paradox here is that actually as countries pass through the demographic economic transition and become richer then stunting disappears really quite quickly and anemia disappears quickly. So if we look at DHS surveys over various generations, South America, for instance, is a good example, where they used to be a ton of stunting and now it's really disappearing. Okay. That's the good news. The bad news is of course it's inevitably replaced by obesity and overweight and the consequent problems associated with that. Are you seeing that even in places like Gambia? We see it among the adults and particularly adult women. It's a really strange phenomenon here. There's very little obesity and overweight in men, increasing, but there's not that much. Whereas in women we have very high rates and so that tells us something interesting--if men have almost none, and women have a lot, it's not genetic. It's very much behavioral and you know, women are the ones who produce all the food and they also like to be fat and men like women fat. So there's quite a lot of social stuff going on here as well. Are there any indications that obesity rates are increasing and children? Not yet in the Gambia but elsewhere in Africa? Yes, definitely. And you do see some of the very well off Gambian kids who are definitely overweight. So, I mean in this is interesting. I know you because you're very familiar with this field, but you will know probably better than I, that you get this switchover, that obesity starts off being a disease of the rich in poor countries, but then as countries develop it switches over and it becomes a disease of the poor. And we will see that transition I'm quite sure in Africa, and I think we are seeing it already as things develop. Some of your work has to do with the topic of epigenetics and not everyone listening will be fully familiar with this term. Could you explain what epigenetics is and the nature of your work on that topic? Yes, certainly. So I think everybody will be familiar with genetics. So the genes we inherit from our parents, and everybody will know that there are, give or take and very, very rare mutations within our lifetimes. That they're the same. And every cell of the body contains exactly the same DNA apart from the germ cells, the egg and the sperm, but every other cell contains. It's actually the same DNA. So the question is how does that same message create an eye cell or a liver cell or a kidney cell, and that, amongst other things is regulated by epigenetics. So epigenetics refers to the signals and there are many ways that this can occur. I'll keep it simple by just talking about methylation. So methyl groups are added to certain areas of the genome and these can modulate how the genes are expressed. So I like to use a musical analogy. Genes are the actual notes that have been written by the composer on the staff and epigenetics relates to the grace notes or the instructions the composer writes on top of it to play this faster or slower or fortissimo or pianissimo. So that's a really good analogy actually. And that's what epigenetics is about. What work are you doing on this topic? Well, we've been so lucky here. We've come across some fascinating findings. We have a very profound seasonality in the Gambia. So, I'm speaking to you in the end of October, the rain has just finished, we probably won't get another rain for another eight months now. So that changes the foods that are consumed, the whole dietary patterns, very profoundly. So you have a quasi-experiment of nature. People are randomized, or conceptions occurring in different months are randomized, to a different nutritional background. And to cut a long and very complex story short, what we've discovered is that the day a baby is conceived or the month it's conceived in, has a really profound effect on certain of the marks within the epigenome. And these relate to marks that are laid down in the very first few days of life. So if I could expand on that a little bit, when sperm meets egg, each of those has epigenetic marks from the parents. So the sperm carries the father's epigenetic marks, which incidentally were laid down during the father's fetal life. So that means that the paternal grandmother was influencing those marks and the egg, those marks are laid down in the probably in the adolescent period and in the 14 weeks leading up to the release of that day. Now what happens when they fuse is that most of those marks are removed. It's called erasure and they have to be removed in order to create pluripotent cells that can then become things other than sperm and egg. They can become all the other cells that are needed for the body. And so the erasure happens very, very quickly and then patterns are laid back down within the first seven, eight, nine days of conception. And that's what we study. And as I say, we've found that there a very profound differences in those patterns that are laid down in the very first few days of human development according to the month of babies conceived in. And it's really quite remarkable. We hope its going to tell us a lot about how parental nutrition can affect the lifelong health of these babies and any babies around the world. What strikes me as being profoundly important, that certainly a child inherits the genetics from their parents, but it sounds like what's going on in the lives of the parents during critical times like prior to pregnancy and things will affect the child's genetics beyond what the parents just would have passed along anyway. Is that correct? We think so, tied up in this are some intricate, probably evolutionary tricks that have developed over many, many millennia. It would make sense that a baby develops in the way that would be best suited to its environment. So if these areas of the genome that we're studying are able to detect the nutritional circumstance that that egg finds itself in the fallopian tube and in the womb as it's embedding, which of course will reflect the mother's nutritional status. If it can detect that, it can record what it sees and then it can adapt the phenotype, adapt the baby according to that information. That would make a lot of sense and we think, we speculate, that that's what's going on and there's a huge amount of work ahead of us to try and understand the biology. But actually, more importantly in a way, although we think we need to understand the biology first, I was going to say more importantly is would this give what we could call it a pathway to impact. If we understand this better, can we advise mothers, and fathers incidentally, how better to eat in the weeks and months leading up to them conceiving a baby, which would ultimately, we hope, have a lifelong effect on that baby's health. Now, the intriguing thing, and the thing I really love, is that we're able to study this simply because of this wonderful experiment with nature. But I speculate that this affects any moms around the world, so it's not just an issue for Gambian mums or African mums. I think this will be a universal finding once we can sort it all out. Your work contributes to the science showing that early malnutrition experiences put an individual at risk for things like obesity and diabetes later in life. Could you explain how and why that works? But also explain, if you would, whether they're epigenetic possibilities there like, do malnutrition experiences in a mother or father contribute to the likelihood of child might be a risk for those things later in life. Indeed. Thanks for the question, because that opens up a couple of answers. The best thing is to just expand a little bit on what you've said about what we call the developmental origins of health and disease theory. So we have known since the days of Elsie Winterson and Ari McCants at Cambridge, but brought to the fore, really by David Barker in Southampton, that babies' fetal experiences which can be measured by their size at birth have a profound effect on their risk of, for instance, heart disease or diabetes or hypertension as you've indicated, some six or seven decades later. So the question as you posed it is, well, how, how could those facts be linked together? One answer of course, is that what it could be an anatomical change. If the baby hasn't gotten enough of the right nutrients to develop enough renal tubules, then it will have a deficit of renal tubules for the whole of its life, which would cause a potentially drive up hypertension. So that's one possibility. The hot money has been put on epigenetics, that maybe epigenetics is a process by which the epigenomes could be affected by the early undernutrition and could then be giving this unhealthy readout for the rest of that person's life. And that's part and parcel of what we're trying to get to the bottom of it. Just to say again, that the reason for really wanting to do this so fast is that it should lead us, I think, to better next generation interventions if we can solve that. All the biology that's going on. You mentioned earlier in the podcast that the sustainable development goals wished to reduce stunting by half, by the year 2025, and yet there are so many millions of children around the world affected by stunting. Do you see any hope that's an achievable goal? Oh, definitely. Yes. I think the world is progressing and I think one of the very important things for we nutritionists to keep in mind is that the world is changing and in a way that's one of the reasons I love to live and work among the population because I can watch the change that's going on. One of the things that happens here actually is that a lot of money is sent back to families here from people who have migrated abroad. So people who drive your taxi around Duke or anywhere else, are possibly Gambians and possibly sending money back and that's having a profound effect. So I think at the end of the day, wealth and the transmission of wealth and the sharing of wealth around the world will help these things and they will sort themselves out at the deficit once again of moving almost straight over and inevitably over into the problems of overweight and obesity. But I do see a lot of hope. There's one other thing I'd like to mention, which is that I also mentioned that these wash interventions were profoundly unsuccessful. And I think my interpretation of what's gone on there is that they simply haven't been ambitious enough. They've put on the hat of, well, whatever we do must be affordable for very poor people and for poor governments. And I think that's, I mean it was a good start, but it's almost insulting saying that we must keep poor people in poverty and there's nothing better we can do then, you know, offer them soap and tell them how to wash their hands. I think people have a right to live in very good housing. I think everybody has an aspiration to live in very good housing. And once that occurs, I think a lot of the nutritional problems will disappear. So it's a bit intriguing to hear a nutritionist saying, actually nutrition just at the moment might not be able to solve all this. We've really got to have help from what we call them, nutrition sensitive interventions, in concert with the nutrition specific intervention. So that's the way that my thinking at least is going. Produced by Deborah Hill, Duke World Food Policy Center, Sanford School of Public Policy

Erica is a registered dietitian, currently completing a PhD at the University of Central Florida in Orlando. Previously she was employed as a Clinical and Sports Dietitian at the Mayo Clinic in Jacksonville, Florida, where Erica provided individual sports nutrition consultation to endurance and team sport athletes, in addition to providing care and educating oncology patients in the hospital. She has a M.A. in Exercise Science and Health Promotion from FAU, in addition to a B.S. in Nutrition and Dietetics from UNF. She is also a Certified Strength and Conditioning Specialist with the NSCA, and a Certified Sports Nutritionist with the ISSN. In This Episode We Discuss Defining iron deficiency and iron deficiency anaemia Iron-deficiency anaemia: diagnosis and symptoms Why is iron so crucial for athlete performance? The role of hepcidin Dilutional pseudoanaemia Heel strike hemolysis How sources of iron differ in quality or bio-availability Supplementation: dosage, forms, etc.

In this episode, Dr Nirala Jacobi is in conversation with world class gastroenterologist Dr Lenny Weinstock about Small Intestinal Bacterial Overgrowth (SIBO) and its connection to different conditions in the body. Dr Weinstock is board certified in gastroenterology and internal medicine, is the president of Specialists in Gastroenterology and the Advanced Endoscopy Centre, he teaches at Barnes Jewish Hospital and is an associate professor of clinical medicine and surgery at Washington University School of Medicine.  Dr Weinstock is also a primary investigator at the Sundance Research Centre and has written more than 80 articles, abstracts, editorials, and book chapters. He is passionate about SIBO and its connection to different conditions, such as Restless Leg Syndrome and Rosacea.   Topics discussed in this episode include: Dr Weinstock's approach to SIBO treatment in his Specialists in Gastroenterology Clinic Relapse rate after Rifaximin use Dr Mark Pimentel has mentioned relapse is hastened by adhesions - Dr Weinstock's take on this and Dr Weinstock's experience in his clinic. What are some triggers for SIBO? Autoimmune Irritable Bowel Syndrome (IBS) Post infectious IBS - damage to the migrating motor complex via an autoimmune attack on vinculin. Anatomical reasons Classical reasons Surgical reasons Adhesions Postural orthostatic tachycardia syndrome (POTS) Ehlers-danlos Preventative therapy for SIBO Rifaximin use with prokinetic therapy Bifidobacterium Lactis HN019 as a therapeutic prokinetic. Testing for anti-vinculin antibodies on SIBO patients. POTS What's the connection to SIBO? Why is the prevalence increasing? What is the connection between POTS and Mast Cell Activation Syndrome (MCAS)? Is there a potential for LPS and endotoxins to be travelling through nerves in the body? Restless Leg Syndrome (RLS), what it is, why do we get it, and what is the connection with SIBO? About hepcidin as an indicator of low serum iron in light of inflammation and how this is related to SIBO. For example: iron as a substrate for bacteria and how the body may respond by upregulating hepcidin to withhold iron from bacteria. Hepcidin as an antimicrobial peptide and its role in infectious diseases. The link between hepcidin and RLS. Why endorphins may be upregulated to protect the dopamine function in the brain in the setting of iron deficiency. Dr Weinstock's treatment strategies for RLS What to do if patient is unresponsive to Rifaximin therapy in light of SIBO positive testing. Low dose naltrexone (LDN) - its use in RLS. Low iron that does not respond to oral supplementation and the possible links to hepcidin. Biofilm therapy Exploring the 3 types of IBS in SIBO IBS - D IBS - M IBS - C The potential for large intestinal bacterial overgrowth (LIBO) to skew a hydrogen rise in SIBO tests that show consistent high methane from baseline. Treatment discussion for IBS - C Dr Jacobi's recommendation of BioGaia Protectis reuteri probiotic for methanogen treatment. 5 drops twice daily used in the study Dr Jacobi mentions. A couple of herbs Dr Jacobi uses for methane dominant SIBO treatment Garlic Myrrrh Dr Weinstock's clinical insights into the ileocecal valve (ICV) being chronically open and allowing reflux of bacteria up into small intestine from the large intestine.   Resources Dr Weinstock's Specialists in Gastroenterology Clinic BioGaia Protectis Bifidobacterium Lactis HN019 as a therapeutic prokinetic.

In episode 32, I tell the story of my personal story with iron overload, and weigh in on the proper use of blood tests and strategies to manage anemia, hemochromatosis, and everything in between. It's important to realize that these are the extremes, and there is a large middle space where we need to not only manage how much iron we accumulate, but how we direct it away from its disease-promoting roles and into its health-promoting roles. This is a great primer on iron as well as a source of insights you may not have encountered elsewhere, such as the importance of oxidative stress as an independent regulator of ferritin, and the potential dangers of supplements designed to protect against oxidative stress like milk thistle, Protandim, sulforaphane, and green tea extract, for people at risk of anemia. You can find the show notes to this episode at chrismasterjohnphd.com/32. This episode is also brought to you by US Wellness Meats. Head to grasslandbeef.com and enter "Chris" at checkout to get 15% off your order as long as the final price is over $75 and you order fewer than 40 pounds of meat. You can use "Chris" to get the same discount twice. This episode is brought to you by Kettle and Fire Bone Broth. Use the link kettleandfire.com/chris to get $10 off your first order. In this episode, you will find all of the following and more: 0:33 Cliff Notes; 10:30 Introduction; 13:12 My personal story with iron overload; 30:12 The physiological roles of iron: hemoglobin, myoglobin, nitric oxide synthase, iron-sulfur clusters in the cytochromes of the electron transport chain, guanylyl cyclase, thyroid peroxidase (TPO), myeloperoxidase (MPO), oxygen transport, energy and ATP production, cellular regulation, thyroid hormone production, immunity; 38:20 Iron as a source of oxidative stress: free iron, hydrogen peroxide, and the hydroxyl radical, oxidative stress as an independent regulator of ferritin; 41:10 Regulation of iron status; Ferritin, long-term storage, protector against pathogens, protector against oxidative stress; Transferrin, short-term iron storage; Hepcidin, master coordinator of iron metabolism; HFE, communicator between transferrin and hepcidin; 49:10 Regulation of dietary absorption of plant and animal iron; 51:00 Measuring and assessing iron status: complete blood count (MCH, MCV, RDW, CHr), full iron panel, sensitivity and specificity of transferrin saturation versus ferritin, differential interpretation of ferritin as a marker of iron overload, inflammation, or oxidative stress; 1:11:43 What to do for anemia: differentiate potential causes, iron in foods (heme, nonheme, vitamin C, polyphenols, phytate, calcium), iron in supplements (iron-saturated lactoferrin, heme iron, liposomal iron), avoid Nrf2-stimulating supplements (like Protandim, sulforaphane, milk thistle, green tea extract), importance of followup measurements of ferritin 01:21:03 What to do for iron overload: blood donation, dietary management, phlebotomy, chelation, importance of followup  

Carolyn: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore.     Today, we will be discussing an interesting Danish nationwide cohort study on the return to the workforce following first hospitalization for heart failure, but first here's your summary of this week's journal.     The first paper addresses a common question asked by patients who have survived an aortic dissection. Will this happen to me again? First author, Dr. Isselbacher, and corresponding author, Dr. Lindsay, and investigators of the International Registry of Aortic Dissection investigated this in the largest systematic analysis to date of patients presenting to hospital with a recurrent aortic dissection.     In this large registry, the authors identified 204 patients with recurrent aortic dissection and compared these to 3624 patients in the registry with an initial aortic dissection. They found that patients with recurrent dissection were more likely to have Marfan syndrome, but not bicuspid aortic valve. Descending aortic dimensions were greater in those with recurrent dissections than those with only an initial dissection, and this was independent of the sentinel dissection type. In multivariable analysis, the diagnosis of Marfan syndrome was independently predictive of a recurrent aortic dissection with a hazards ratio of 8.6.     Furthermore, they found that the patient's age at the time of first dissection correlated with the anatomic pattern of aortic involvement. In younger patients, dissection of the proximal aorta tended to be followed by dissection of the distal aorta, whereas the reverse was true among older patients suggesting divergent mechanisms of disease.     In summary, therefore, this study shows that recurrent aortic dissection while in common does occur and in fact affected 5% of those in this registry. The data really illustrate the importance of syndromic forms of aortic dissection and suggest that occurrence of a recurrent dissection should raise suspicion of a genetic etiology of aortic disease.     The next study provides pre-clinical data suggesting that counteracting increased hepcidin may be a therapeutic target for treatment of intracerebral hemorrhage. In this study from first author, Dr. Xiong, corresponding author, Dr. Yang, and colleagues from Xinqiao Hospital, the Third Military Medical University in China, parabiosis and intracerebral hemorrhage mouse models were combined with in vitro and in vivo experiments to investigate the roles of hepcidin in brain iron metabolism after intracerebral hemorrhage. Hepcidin in an important iron regulatory peptide hormone that controls cellular iron efflux.     The authors found that increased hepcidin-25 was found in the serum and astrocytes after intracerebral hemorrhage. In hepcidin-deficient mice with intracerebral hemorrhage, there was improvement in brain iron efflux and protection from oxydative brain injury and cognitive impairment, whereas, the administration of human hepcidin-25 peptide in these mice aggravated the brain injury and cognitive impairment.     In vitro studies showed that increased hepcidin inhibited intracellular iron efflux in  brain microvascular endothelial cells, but this phenomenon was rescued by a hepcidin antagonist. Additionally, toll-like receptor 4 signally pathway increased hepcidin expression, whereas, a toll-like receptor 4 antagonist decrease brain iron levels and improve cognition following intracerebral hemorrhage.     In summary, the study showed that increased hepcidin expression caused by inflammation prevented brain iron efflux and aggravated oxidative brain injury and cognitive impairment, thus, counteracting increased hepcidin maybe a mechanistic target to promote brain iron efflux and attenuate oxidative brain injury following intracerebral hemorrhage.     The next basic science paper provides fascinating insights into the similarities between advanced atherosclerotic lesions and tuberculous granulomas, both of which are characterized by a necrotic lipid core and a fibrous cap. First author Dr. Clement, corresponding author Dr. Mallat, and colleagues from the University of Cambridge Addenbrooke's Hospital in United Kingdom looked at the C-type lectin receptor 4E which has been implicated in the events leading to granuloma formation in tuberculosis.     The authors hypothesized that the same C-type lectin receptor 4E may be involved in the formation of atherosclerotic lesions as well. They addressed this hypothesis by examining the impact of receptor activation on macrophage functions in vitro and on the development of atherosclerosis in mice. They showed that C-type lectin receptor 4E was expressed within human and mouse atherosclerotic lesions and was activated by necrotic lesion extracts. The receptor signaling in macrophages inhibited cholesterol efflux and induced endoplasmic reticulum stress responses leading to the induction of proinflammatory mediators and growth factors.     Furthermore, repopulation of LDL receptor-deficient mice with C-type lectin 4E receptor-deficient bone marrow reduced lipid accumulation, endoplasmic reticulum stress, macrophage inflammation, and proliferation within developing arterial lesions that's significantly limiting atherosclerosis.     In summary, this paper shows that C-type lectin receptor 4E orchestrates major pathophysiologic events during pluck development and progression, and thus, provides a mechanistic explanation for the close association between necrotic lipid core formation and the development of inflammatory advanced atherosclerotic lesions.     The last paper examined the impact of optimal medical therapy in the dual antiplatelet therapy or DAPT study. In this paper from first author, Dr. Resor, corresponding author, Dr. Mauri, from the Brigham and Women's Hospital in Boston and colleagues, authors sought to assess the impact of optimal medical therapy use on long term patient outcomes and on the treatment benefit and risk of continued dual antiplatelet therapy, and they did this using data from the DAPT study which was a randomized placebo control trial comparing 30 versus 12 months of final prudent therapy on the background of aspirin after coronary stenting.     Optimal medical therapy was defined as a combination of statin, beta blocker, and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker used in patients with an ACC/AHA class 1 indication for each medication. Endpoints included myocardial infarction, major adverse cardiovascular and cerebral vascular events or MACE, and GUSTO moderate or severe bleeding events.     Of 11,643 randomized patients with complete medication data, 63% were on optimal medical therapy. Between 12 and 30 months, continued final prudent therapy reduced myocardial infarction compared to placebo in both groups and had consistent effects on the reduction in MACE, and an increased bleeding regardless of the optimal medical therapy status. In other words, the P for interaction was nonsignificant for these comparisons.     Importantly, patients on optimal medical therapy had lower rates of myocardial infarction, MACE, and bleeding compared to patients not on optimal medical therapy. Rates of stent thrombosis in death did not differ. The take home message is therefore, that more emphasis on the use of optimal medical therapy after coronary stenting is needed, but the decision to continue dual antiplatelet therapy beyond 12 months should be made irrespective of the optical medical therapy status.     Those were your summaries. Now, for our feature paper.     Our feature paper today discusses a really important, but frankly, often neglected outcome in heart failure, and that is return to the workforce following first hospitalization for heart failure, and I'm really pleased to have the first and last author of this really special Danish paper, Dr. Rasmus Rorth and Dr. Soren Kristensen, both from the University of Copenhagen, here to join me today. Hello, gentlemen.   Soren: Hello and thank you for having us, Carolyn.   Rasmus: Hello.   Carolyn: As a very special third guest, we actually have editorialist, Dr. Martin Cowie from Imperial College London as well. Hi, Martin.   Martin: Hi, Carolyn. Nice to be part of the conversation.   Carolyn: This is going to be so fun. Let's get straight into this. Rasmus, maybe you could start by telling us. This return to work concept is hardly addressed in guidelines, it's so important, and yet, you are one of the first if not the first to take a look at it. What inspired you to do this?   Rasmus: First of all, we are very inspired to work with heart failure because heart failure is a common costly, disabling, and deadly disease, and furthermore, information on young patients with heart failure is vast.  We know that they have a high hospitalization rate and a low mortality rate compared to all the patients. We also know from some of the big trials that young heart failure patients report low quality of life. Therefore, we wanted in this study to examine return to work for a number of reasons.     First of all, it gives off some information of the patient's performance basis and we get some information of their quality of life and mental status, and one more reason that is not that common for us as clinicians to think about is also for society, the economic burden these patients play in the society, and all of these reasons inspired us to get into this exciting field.   Carolyn: I really appreciated that you did this because the patients that I see here in Asia are on average 10 years younger than the heart failure patients that have been seen in other European registries and so on, so it is a very, very important aspect because my heart failure patients are often the sole breadwinners of families here. Could you, maybe, Soren, share with us what are those unique resources that you manage to look at this in such detail in the Danish registries?   Soren: The unique quality in Denmark is that you have the unique identifying numbers for all the citizens of Denmark and these numbers are not only used in the health systems. They're also used for administrative registries for tax paying and for state funds and pensions. We were able to link information from the hospital discharge registries with information on tax paying and whether or not people are getting pensions. In that way, we could follow all patients who stayed in Denmark at least to see whether or not they were receiving any funds, any pension, or sick leave money, or things like this from the state, or whether they upheld a position. That's what makes the Danish system a bit unique, that we have this ability to track the patients across all the fields of society and also that we have a public health system which all patients are included in, and the private sector is negligible in Denmark.   Carolyn: Wow. Listening to that is making all epidemiologist everywhere really drool. That is such a precious system to look at this. What were your main findings, Rasmus?   Rasmus: Maybe I should explain a bit about the setting. This is a nationwide-based study starting where we identify the patient with the first heart failure hospitalization, 18 to 60 years in the period from 1997 to 2012, and we followed them onwards. In our primary analysis, we only included patients in the workforce, that means either employed or available for the labor market at time hospitalization. That is the setting of the study.   Carolyn: Could you share your main findings and your take home messages?   Rasmus: Our primary outcome of this study is that after one year, 25% of the patients did not return to the workforce and we had a low mortality, only 7% died.   Carolyn: Twenty-five percent didn't return to the workforce?   Rasmus: Yeah, and keeping in mind, Carolyn, these are patients in the workforce at their first hospitalization and also young patients. Our take home patient from this paper is that patient in the workforce at heart failure hospitalization had a low mortality for the high risk of [inaudible 00:13:41] from the workforce at one year of followup. Furthermore, we look at some association effect associated with returning to work, and we found that young age, male sex, and high level of education were associated with high likelihood of returning to work.   Carolyn: Martin, you wrote just a beautiful editorial. I have to say I was chuckling and enjoying it as I read it. I could hear your voice in it. What do you make of these results in the interpretation?   Martin: I was really pleased to see something published by this really important topic that is largely ignored, and as you said in your introduction, the guidelines, if you read them you'll think that nobody of working age ever develops heart failure. There's no mention at all about return to work. There's no mention of the kind of urgent need to be able to provide people with the counseling about the heart failure and how it might impact their work, and also, no interaction, no mention of interaction with employers to tell them, "Yes, this person have this condition, but actually, could do their job or stay in the same job," or "How we can help support them?"     I think this article which is so good to see graded publish in Circulation and I think we have to see it in the context of other occupational rehabilitation work which shows that if you don't get people back to work quite quickly after a major event in their lives, then you'll never get them back, and that's got huge consequences for them in their mental health, their economic, social, family, and never mind the healthcare system. It's really nice to see this work and I hope many people read it and quote it.   Carolyn: Martin, you've been to Asia. You know that our patients are strikingly young, but I wonder, do you think these results are extrapolatable outside of Denmark?   Martin: I think this comment and not an editorial, Denmark, of course, is a relatively small country. It's wealthy. It's different from the states, but it's very different from Asia as you say, so lots of heart failure patients in Asia are young, of working age, and quite often, their families depend on them.     I think the tactics may have to be different to different countries, but the general principles are the same that we, as a heart failure team, as heart failure doctors, have to think about the person not just in terms of the left atrium and left ventricle, or even of the whole body function, but actually, what is their role in their family, what are they trying to achieve in life, how can we support them about way, because otherwise, we're really failing our patient.     I think, in Asia even more than in some wealthy, rich countries where there's a lot of safety nets, it's really important. I'd be interested in your comment, Carolyn, on what you think we can do to improve right across the world in terms of occupational rehab.   Carolyn: First, I think it begins with awareness and that's why I just wanted to tell Soren and Rasmus how much I enjoyed this paper and I will be citing it because I think it's so important especially in the younger heart for the community, but can I ask you, Soren or Rasmus, have these findings changed your practice in any way or to be even more provocative, do you think that maybe return to work should be a benchmark to evaluate heart failure programs?   Rasmus: Martin also points out that, first of all, we need to shed light on this hidden fact of heart failure, and afterwards, I think it's also a very good policy metrics to use in the future to see how our patients do.   Carolyn: Are there efforts in Denmark to improve this as a yardstick?   Soren: I'm quite sure that, by large, it's not really registered who is working, who is not working there. There's not much attention to it. We're all focusing very much on the performance of the patient of the NYHA class and so on, so I think we should put more emphasis on this issue and we should, as Martin also added, that we should discuss with the patients if they could change their job or their positions in some ways to better cope if they lost some of their performance, because we're both think and we both agree with Martin that it's a huge quality of life to be able to maintain your job in one way or the other, and we should definitely put more focus on that, but I'm afraid to say that I don't think we put much focus on it in Denmark at this time, but hopefully, we will.   Martin: I think you're right, the attitude have to change across the world, don't they, and they start with the heart failure team and the patients because I think most doctors and nurses and patients assume diagnosis of heart failure, that means really nothing can be the same again, but we really should be trying to return people to their optimal function, and I'm sure we can do a lot more, but perhaps, we need to upscale the workforce and knowing about the key things about occupational counseling, and maybe also [inaudible 00:18:30] interact with employers a little bit more without patient's permission to give them the confidence to have this person re-enter the workforce in a supported way because I'm sure the employers value many of these people and would be pleased to see them still in the workforce.   Rasmus: Exactly. I even think that could be like a fair way of trying to help the patient by relieving them from their job, which is actually will be a big mistake for some patients [inaudible 00:18:54] as a physician to help them with making sure they don't have to return to their job and fill out the statements and everything, but this may not be the best for the patient.   Martin: Exactly.   Carolyn: Gentlemen, I have enjoyed this conversation so much. Thank you for taking the time to discuss this very important paper.     You've been listening to Circulation on the Run. Tune in next week for more.  

Vincent, Michael, and Michele discuss how iron might disperse bacterial biofilms in carotid arterial plaques, and controlling Salmonella by modulating host iron homeostasis. 

Dr Hal Drakesmith tells us how his work on iron availability can help us fight infections. Iron plays essential biochemical roles in oxygen binding, ATP synthesis and DNA metabolism. The level of iron available in different tissues is controlled by the small peptide hormone hepcidin. Dr Hal Drakesmith studies how hepcidin is modulated during infections, since iron availability plays an important role in the course of major infectious diseases such as HIV, malaria and Hepatitis C. Genetic variation plays an important role in individual susceptibility to many common diseases. New insights into genetic variants which modulate gene expression allow us to better understand why people develop these diseases. We can then target treatments much more effectively. Ultimately, we will be able to identify patients at risk of developing disease.

Dr Hal Drakesmith tells us how his work on iron availability can help us fight infections. Iron plays essential biochemical roles in oxygen binding, ATP synthesis and DNA metabolism. The level of iron available in different tissues is controlled by the small peptide hormone hepcidin. Dr Hal Drakesmith studies how hepcidin is modulated during infections, since iron availability plays an important role in the course of major infectious diseases such as HIV, malaria and Hepatitis C. Genetic variation plays an important role in individual susceptibility to many common diseases. New insights into genetic variants which modulate gene expression allow us to better understand why people develop these diseases. We can then target treatments much more effectively. Ultimately, we will be able to identify patients at risk of developing disease.