POPULARITY
12 episodes with vascular biology
3 episodes with vascular biology
3 episodes with vascular biology
3 episodes with vascular biology
Focus Issue on Ischaemic Heart Disease, Vascular Biology and Medicine, and Brain Health
A Rebelião Saudável nasceu da união de diversos profissionais de saúde que pensam diferente e cujo foco é promover saúde e bem estar, com comida de verdade e sem medicamentos.Semanalmente a Rebelião se reune no app Telegram para discussão de tópicos importantes relacionados a Nutrição Humana e Qualidade de vida. Nessa semana, conversamos conversamos sobre Transcitose: O Elo Perdido entre LDL e Aterosclerose!Estudos comentados no Podcast:BOLANLE, I. O.; DE LIEDEKERKE BEAUFORT, G. C.; WEINBERG, P. D. Transcytosis of LDL Across Arterial Endothelium: Mechanisms and Therapeutic Targets. Arteriosclerosis, Thrombosis, and Vascular Biology, v. 45, p. 468–480, abr. 2025. DOI: 10.1161/ATVBAHA.124.321549.Subbotin VM. Excessive intimal hyperplasia in human coronary arteries before intimal lipid depositions is the initiation of coronary atherosclerosis and constitutes a therapeutic target. Drug Discov Today. 2016 Oct;21(10):1578-1595. doi: 10.1016/j.drudis.2016.05.017. Epub 2016 Jun 2. PMID: 27265770.Vídeo sobre transcitose no YouTube: https://youtu.be/j3p85NFtoa8
Focus Issue on Ischaemic Heart Disease, Vascular Biology, and Medicine and Brain Health
Focus Issue on Cardio-oncology, Vascular Biology and Medicine, and Brain Health
Want to add a healthy habit to your daily routine that is absolutely free and incredibly effective? Looking to reduce insulin resistance and lose visceral fat? Want to boost mental health and improve cognitive function? Look no further than walking! Tune in to hear us unpack the myriad of research-supported benefits. In this episode, we discuss the incredible benefits of walking, from lowering blood pressure to improving heart rate variability to reducing stress and so much more. Learn about the magic number when it comes to step count, our thoughts on walking in nature vs. on a treadmill, and get practical tips for getting those steps! Also in this episode: Naturally Nourished Teas are buy 3 get 1 FREE, use code FREETEA Gift cards at Naturally Nourished Detox Masterclass 1/8 Keto Masterclass 1/15 Walking Pad C2 use code ALIMILLERRD for savings Health Benefits of Walking Lowers Blood Pressure Hypertension: Brisk walking for 30 minutes, five days a week reduces blood pressure (Hypertension, 2020). Improves Cholesterol Levels Cholesterol: Effects on LDL and HDL cholesterol (Journal of the American Heart Association, 2021). Lipid Profiles: Walking improves triglycerides and HDL (Atherosclerosis, 2021). Reduces the Risk of Coronary Artery Disease Coronary Artery Disease Risk: 150 minutes of walking weekly (Circulation, 2022). Enhances Cardiorespiratory Fitness Reduces Systemic Inflammation Systemic Inflammation: Walking lowers CRP and IL-6 (Arteriosclerosis, Thrombosis, and Vascular Biology, 2020). Systemic Inflammation: Walking reduces inflammatory cytokines (The Journal of Endocrinology, 2022). Helps Maintain Healthy Weight and Prevent Obesity Improves Heart Rate Variability Heart Rate Variability: HRV improvement with regular walking (Heart, 2022). Prevents Peripheral Artery Disease Peripheral Artery Disease: Walking improves circulation and function in PAD patients (Journal of Vascular Surgery, 2021). Reduces Resting Heart Rate Enhances Endothelial Function Supports Recovery After Cardiac Events Improves Insulin Sensitivity Insulin Sensitivity: Improvements with post-meal walks (Diabetes Care, 2021). Enhances Glucose Regulation Boosts Fat Oxidation Fat Oxidation: Brisk walking boosts fat metabolism (Journal of Applied Physiology, 2022). Reduces Visceral Fat Reduction of visceral fat after 10,000 steps/day (Obesity, 2021). Promotes Energy Balance Energy Balance: 12,000 steps/day for maintaining weight (Medicine & Science in Sports & Exercise, 2020). Regulates Hormones Related to Metabolism Increases Mitochondrial Efficiency Improves Metabolic Flexibility Prevents Metabolic Syndrome Helps Manage Type 2 Diabetes Mental health Stress Reduction: Nature walks lower cortisol more than treadmill (Environmental Research, 2022). Stimulates Neurogenesis and Brain Plasticity Brain Connectivity: Walking improves default mode network activity (Journal of Aging Research, 2021). Enhances Neurotransmitter Balance Supports Autonomic Nervous System Regulation Improves Sensory Integration Vestibular Function: Enhancing balance and stability with walking (Frontiers in Neuroscience, 2021). Strengthens Cognitive Function Neurogenesis and Cognitive Function: Exercise-induced brain growth (Nature Neuroscience, 2021). Promotes Myelination and Nerve Health Enhances Emotional Regulation via the Vagus Nerve Reduces Neurological Disease Risk Synchronizes the Nervous System Through Rhythmic Movement Improves Sleep and Circadian Rhythm Bone and Joint Health Immune System Support Longevity and Reduced Mortality Gut Health Gut Health: Positive effects on microbiota diversity (Gut Microbes, 2020). The Science of Step Counts Thoughts on Nature vs. Treadmill Walking Cognitive Benefits: Nature walking improves attention restoration (Nature Neuroscience, 2021). Proprioception: Benefits of uneven terrain in natural settings (Journal of Sports Medicine, 2023). Motivation: Outdoor walkers maintain habits better than treadmill users (Behavioral Medicine, 2022). Immune Boosting: Increased NK cell activity in forest walkers (International Journal of Environmental Health Research, 2021). Sponsors for this episode: According to extensive research by the Environmental Working Group, virtually every home in America has harmful contaminants in its tap water. That's why you've got to check out AquaTru. AquaTru purifiers use a 4-stage reverse osmosis purification process, and their countertop purifiers work with NO installation or plumbing. It removes 15x more contaminants than ordinary pitcher filters and are specifically designed to combat chemicals like PFAS in your water supply. Naturally Nourished Podcast listeners can use code ALIMILLERRD at AquaTru.com to save 20% off.
Professor Erica Spatz MD talks to Dr Funmi Okunola MD about the effects of Long COVID on the heart. Professor Spatz is a cardiologist and clinical investigator at the Centre for Outcomes Research and Evaluation. She is the Associate Professor of Cardiology and Associate Professor of Epidemiology at Yale School of Medicine in the USA and is the Director of the Preventative Cardiovascular Health Program. REFERENCES1.Shah SM, Odanovic N, Kunnirickal S, Feher A, Pfau SE, Spatz ES. Chest pain and coronary endothelial dysfunction after recovery from COVID‐19: A case series. Clinical Case Reports. 2022 Apr;10(4):e05612.2.HilserJR, Spencer NJ, Afshari K, Gilliland FD, Hu H, Deb A, Lusis AJ, Wilson Tang WH, Hartiala JA, Hazen SL, Allayee H. COVID-19 Is a Coronary Artery Disease Risk Equivalent and Exhibits a Genetic Interaction With ABO Blood Type. Arteriosclerosis, Thrombosis, and Vascular Biology. 2024 Nov;44(11):2321-33.
Dupilimab received FDA approval as the first biologic treatment for adults with uncontrolled COPD, reducing exacerbations significantly in clinical trials. A study in JAMA Internal Medicine demonstrated that improper arm positioning during blood pressure measurements can lead to overestimated readings, potentially causing misdiagnosis. Another study in Atherosclerosis, Thrombosis, and Vascular Biology linked COVID-19 to long-term risks of major adverse cardiac events (MACE), with increased risks for patients hospitalized with COVID-19 and those with non-O blood types. These findings underscore the need for attention to proper clinical practices and long-term monitoring of cardiovascular health post-COVID-19.
Focus Issue on Ischaemic Heart Disease, Acute Cardiovascular Care, Vascular Biology and Medicine.
❤️ Bonjour,Bienvenue dans cet épisode consacré au renforcement musculaire
In this episode, Dr Chrisandra Shufelt returns (she was already our guest on Episode 28!) with more groundbreaking facts on HA and heart health but also an invitation to join her current research!Dr Shufelt, MD, is the chair of the division of general internal medicine and associate director of Women's Health Research Center. She is a women's health internist with Fellowship Training in Vascular Biology and Women's Health and a Certified Menopause Practitioner. Her NIH funded research focuses on young women with hypothalamic amenorrhea, evaluating the impact on immune and vascular health. Link to Dr Shufelt's research on Functional Hypothalamic Amenorrhea and Preclinical Cardiovascular Disease here(USA only) Join Dr Shufelt's new research here(All countries) Join the REVEAL (HA patients) registry hereTo reach out to Dr Shufelt, Contact her on X (Twitter) @CshufeltMDOr via Mayo Clinic https://www.mayo.edu/research/faculty/shufelt-chrisandra-l-m-d/bio-20542101To find support in your HA recovery:Get the "No Period. Now What?" book at noperiod.info/book.Get the French version "Je n'ai plus mes regles" book at noperiod.info/livreTo join the NPNW English support group, please visit noperiod.info/supportTo join the French support group, please visit noperiod.info/communauteTo make an appointment with Dr Sykes and get individual support to get your period back or improve your fertility, please go to noperiod.info/appointmentsTo make an appointment with Florence Gillet and get help with the body and mind changes happening in recovery please visit www.beyondbodyimage.comYou can find us on social mediaNo Period, Now What? on Instagram in EnglishNo Period, Now What? on Instagram in FrenchBeyond Body Image on FacebookBeyond Body Image on InstagramEmail us via allin@noperiodnowwhat.comIf you enjo...
N-acetyl cysteine (NAC) shows promise for heart attack preventionHeart attacks and strokes are a leading cause of death in developed countries - accounting for ~20% of all deaths in the U.S. Frequently, heart attacks and strokes are caused by blood clots (blood platelets that form when they are not needed, causing a narrowing/blockage of blood vessels) formed through arterial thrombosis. Current antiplatelet agents (e.g., aspirin) are effective but can increase major bleeding risk. As such, there is a growing need to prevent arterial thrombosis different from antiplatelet agents.A recent study published in Arteriosclerosis, Thrombosis, and Vascular Biology investigated the potential of NAC as an agent to prevent arterial thrombosis. Utilizing both [cell-based] human blood models and mouse (in vitro) models, the research demonstrated that NAC significantly delayed and even prevented thrombus formation dose-dependently without increasing bleeding risks.Findings:*NAC treatment extended clot formation times by up to 3.7 times compared to controls in the human blood [cell] model.*NAC entirely inhibited platelet aggregation and occlusive clot formation at higher doses than the above point in the cell model.*A 400 mg/kg (via injection in rodents) dose of NAC in mice effectively prevented arterial occlusion post-injury.*Lower doses (200 mg/kg - via injection in rodents) of NAC reduced clot stability, suggesting working as both an acute and preventative clotting therapy.The study showed that NAC interferes with von Willebrand factor (a large protein crucial for blood clotting) activity. NAC acts against VWF rather than platelets to prevent clot formation. Thus, providing a safer alternative to traditional antiplatelet drugs that carry higher bleeding risks. Support the Show.
Erythritol is a common sweetener used in baked goods, beverages, gum, and candy, and is often found in keto-friendly and other reduced-sugar products. However, recent research suggests that consuming even typical amounts of erythritol may elevate the risk of blood clots and cardiovascular events, such as heart attacks and strokes. Listen in this week as Dee explores the findings of this study and why erythritol might not be the safest option for reducing sugar intake.References: Cleveland Clinic. (2024, August 8). Cleveland Clinic study adds to increasing evidence that sugar substitute erythritol raises cardiovascular risk. https://newsroom.clevelandclinic.org/2024/08/08/cleveland-clinic-study-adds-to-increasing-evidence-that-sugar-substitute-erythritol-raises-cardiovascular-riskWitkowski, M., Wilcox, J., Province, V., Wang, Z., Nemet, I., Tang, W. W., & Hazen, S. L. (2024). Ingestion of the non-nutritive sweetener erythritol, but not glucose, enhances platelet reactivity and thrombosis potential in healthy volunteers. Arteriosclerosis Thrombosis and Vascular Biology. https://doi.org/10.1161/atvbaha.124.321019. Retrieved from https://www.ahajournals.org/doi/epdf/10.1161/ATVBAHA.124.321019
Cardiovascular disease might be the leading cause of death, but after my conversation with Dr. Mark Houston, I'm more convinced than ever that we have the power to change that narrative. We delved into the power of diet and lifestyle changes, the essential role of nitric oxide and the impressive results of innovative supplements like Vascanox HP by Calroy Health Sciences in managing blood pressure and cardiovascular disease risk. Dr. Houston's passion for prevention and the practical tips he shared made me feel hopeful and empowered. From understanding key tests to making everyday changes, this episode is all about giving you the tools to protect your heart health. Let's dive in and explore how we can all live longer, healthier lives. ~DrKF Check out the show notes at https://www.drkarafitzgerald.com/fxmed-podcast/ for the full list of links and resources. GUEST DETAILS Dr. Mark Houston, MD https://tinyurl.com/27thhcpr" Dr. Mark Houston is a Clinical Instructor at George Washington University. He is also Director of the Hypertension Institute and Vascular Biology and Medical Director of the division of Human Nutrition at St. Thomas Medical Group, St. Thomas Hospital and Health Services in Nashville, TN. He is on the faculty of A4M, for the FAARM and the Metabolic Medicine Institute (MMI) and George Washington University, and directs the Cardiovascular modules. He has also published seven best-selling books on vascular function. Dr. Houston has an active clinical practice, teaches, and does clinical research at St. Thomas Medical Group and Hospital. He founded the Hypertension Institute in 2000. THANKS TO OUR SPONSOR Calroy Health Sciences: Website New Frontiers Listeners, get your exclusive discount and resources from Calroy at http://calroy.com/drkf SHOW NOTES Hypertension Institute https://tinyurl.com/mr46hsph Metabolic Medicine Institute (MMI) https://tinyurl.com/2s39ryym Dr. Houston's Study: Effects of S-Allylcysteine-Rich Garlic Extract and Dietary Inorganic Nitrate Formula on Blood Pressure and Salivary Nitric Oxide… https://tinyurl.com/4y5ndbjn About Vascanox HP https://tinyurl.com/543tamcj About Arterosil HP https://tinyurl.com/4fr6nbtc Ovationlab Vascular Support Protocol https://tinyurl.com/ynpdphmy Prevalence and Factors Associated With Circadian Blood Pressure Patterns in Hypertensive Patients https://tinyurl.com/2c7xvwz2 Heart Disease and Stroke Statistics—2023 Update: A Report From the American Heart Association https://tinyurl.com/55shva8p CONNECT WITH DrKF on: YouTube: https://tinyurl.com/hjpc8daz Instagram: https://www.instagram.com/drkarafitzgerald/
Focus Issue on Vascular Biology and MedicineYour voice matters. Take the EHJ Podcast survey.
Focus Issue on Vascular Biology and Medicine
Focus Issue on Vascular Biology and Medicine
Focus Issue on Vascular Biology and Medicine
Thanks for listening or watching. Please hit subscribe where you're watching or listening so you don't miss out on future episodes. Please leave a review, it takes 30 seconds and really helps get these exciting messages out there. And if you or anyone you know could benefit from a mental health tune-up, head over to metpsy.com where myself and psychiatrist Dr. Rachel Brown coach you to better mental health. Discussion 7:40 Autoimmunity in Africa (Trowell & Burkitt, 1981) 18:20 Daughter's allergies (Goodrich, 2011) 20:46 Intestinal permeability & wheat (Visser et al., 2009) 22:28 Celiacs who are allergic to mitochondria (Cervio et al., 2007; Volta et al., 2002) 23:20 Increasing prevalence of Celiac (Catassi et al., 2010; Rubio–Tapia et al., 2009) 35:35 Wheat, goat grass, 33-mer (Brouns et al., 2022) 38:45 Wheat in Egypt (Abu-Zekry et al., 2008) 43:00 Wheat and T1DM (Ciacci & Zingone, 2016) 47:25 Wheat is a carcinogen (O'Farrelly et al., 1986) 50:50 Wheat and schizophrenia (Dohan, 1966) 52:38 Poison ivy and PUFA (Xia et al., 2004) 56:34 PUFA up to 20% of American diet (National Cancer Institute, 2019) 57:42 Brown & Goldstein and LDL (Goldstein et al., 1979) 58:54 Steinberg & Witztum and modified LDL (Steinberg et al., 1989) 1:00:00 OxLDL and auto-antibodies (Hörkkö et al., 1996) 1:00:02 Antiphospholipid syndrome and cardiolipin (Hörkkö et al., 1996; Tuominen et al., 2006) 1:09:16 400-1000x as oxidized as normal LDL (AOCS American Oil Chemists' Society, 2021) 1:11:56 All autoimmune diseases involve oxidative stress—seed oil toxicity (Pagano et al., 2014) 1:12:20 Oxidized linoleic acid induces beta-amyloid (Arimon et al., 2015) 1:14:00 Insulin resistance and oxLDL (Li et al., 2013) 1:19:06 Homicide and linoleic acid consumption (Drewitt-Smith & Rheinberger, 2019; Hibbeln, 2007; Hibbeln et al., 2004) 1:21:20 Smoking and CVD-free populations (Lindeberg et al., 1994; Sinnett & Whyte, 1973) 1:25:28 OxLDL and beta cells (Abderrahmani et al., 2007) Other References Hibbeln, J. R. (2007). From Homicide to Happiness – A Commentary on Omega-3 Fatty Acids in Human Society. Nutrition and Health, 19(1–2), 9–19. https://doi.org/10.1177/026010600701900204 Hibbeln, J. R., Nieminen, L. R. G., & Lands, W. E. M. (2004). Increasing homicide rates and linoleic acid consumption among five western countries, 1961–2000. Lipids, 39(12), 1207–1213. https://doi.org/10.1007/s11745-004-1349-5 Sinnett, P. F., & Whyte, H. M. (1973). Epidemiological studies in a total highland population, Tukisenta, New Guinea: Cardiovascular disease and relevant clinical, electrocardiographic, radiological and biochemical findings. Journal of Chronic Diseases, 26(5), 265–290. https://doi.org/10.1016/0021-9681(73)90031-3 Tuominen, A., Miller, Y. I., Hansen, L. F., Kesäniemi, Y. A., Witztum, J. L., & Hörkkö, S. (2006). A Natural Antibody to Oxidized Cardiolipin Binds to Oxidized Low-Density Lipoprotein, Apoptotic Cells, and Atherosclerotic Lesions. Arteriosclerosis, Thrombosis, and Vascular Biology, 26(9), 2096–2102. https://doi.org/10.1161/01.ATV.0000233333.07991.4a Volta, U., Rodrigo, L., Granito, A., Petrolini, N., Muratori, P., Muratori, L., Linares, A., Veronesi, L., Fuentes, D., Zauli, D., & Bianchi, F. B. (2002). Celiac disease in autoimmune cholestatic liver disorders. The American Journal of Gastroenterology, 97(10), 2609–2613. https://doi.org/10.1016/S0002-9270(02)04389-7
Focus Issue on Vascular Biology and Medicine
Dr. Bouchard discusses " Hypertension" with Dr. Suzanne Oparil, M.D. Distinguished Professor of Medicine. Professor of Cell, Developmental and Integrative Biology. Director, Vascular Biology and Hypertension Program. Section Chief of Vascular Biology and Hypertension.Hypertension is a pervasive problem and affects nearly 50% of the US population including over 90 million adults with uncontrolled hypertension and an estimated 34 million untreated. For an adult 40 years of age without high blood pressure, the lifetime risk of developing hypertension is 93% for African Americans, 92% for Hispanics, 86% for whites, and 84% for Chinese adults.
Regularly eating foods high in flavonoids, like fruits, cruciferous vegetables, and tea, might lower your risk of future heart disease. In a new study published in the journal Arteriosclerosis, Thrombosis, and Vascular Biology, Australian researchers determined that older women who consumed high levels of flavonoids were less likely to develop extensive abdominal aortic calcification. This […] The post 340. A diet high in flavonoids might lower your risk of heart disease appeared first on Dr. David Geier - Feel and Perform Better Than Ever.
Join the Sanders Sisters as they welcome the holidays and the last episode of their first season of Floss & FlipFlops! In this episode, the sisters discuss the 12 medical conditions on Santa's list that can indicate a bigger systemic complication, and how you can integrate your knowledge of these conditions in helping your patients achieve lifelong health! Floss and Flip-Flops with the Sanders sisters features hosts dental hygienist and speaker Katrina M. Sanders, RDH, and podiatrist Dr Elizabeth Sanders, DPM. Together, the sisters discuss the oral-systemic link and its impact—from your teeth down to your toes. The podcast is produced monthly by Dental Products Report® and Modern Hygienist®, in partnership with The Sanders sisters. For additional content for dental professionals visit DPR and MH at dentalproductsreport.com. Katrina Sanders, RDH, can be reached at: Website: katrinasanders.com Facebook Instagram LinkedIn EPISODE 12 REFERENCES: Tattersall, M. C., et. al. (2015). Asthma Predicts Cardiovascular Disease Events: The Multi-Ethnic Study of Atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology, 35(6), 1520-1525. Yeh, E. T. H., & Bickford, C. L. (2009). Cardiovascular Complications of Cancer Therapy: Incidence, Pathogenesis, Diagnosis, and Management. J Am Coll Cardiol, 53(24), 2231-2247. Chaikriangkrai, K., et. a l. (2015). Additive prognostic value of coronary artery calcium score and renal function in patients with acute chest pain without known coronary artery disease: up to 5-year follow-up. Int J Cardiovasc Imaging. 31(8), 1619-1626. Liu, Y., et. al. (2014). Kidney Stones and Cardiovascular Risk: A Metaanalysis of Cohort Studies. Am J Kidney Dis, 64(3), 402-410. Uddin, S. M. I., et. al. (2018). Erectile Dysfunction as an Independent Predictor of Future Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis. Circulation. doi:10.1161/circulationaha.118.033990 Clarson, L. E., et. al. (2015). Increased risk of vascular disease associated with gout: a retrospective, matched cohort study in the UK Clinical Practice Research Datalink. Annals of the Rheumatic Diseases, 74(4), 642-647 Beckman, J., Duncan, M., et al. HIV and PAD. March 12, 2018. Circulation; 10.1161.117.032647 van Nimwegen, F. A., et. al. (2015). Cardiovascular disease after Hodgkin lymphoma treatment: 40-year disease risk. JAMA Intern Med. doi: 10.1001/jamainternmed.2015.1180 Rodondi, N., et al. (2010). Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA, 304(12), 1365-1374. Larsson Susanna, C., et. al. (2019) Thyroid Function and Dysfunction in Relation to 16 Cardiovascular Diseases: A Mendelian Randomization Study. Circulation: Genomic and Precision Medicine, 0(0). doi:10.1161/CIRCGEN.118.002468 Adelborg, K., et. al. (2018). Migraine and risk of cardiovascular diseases: Danish population based matched cohort study. Bmj, 360. doi:10.1136/bmj.k 96 Chapple ILC, Potential mechanisms underpinning the nutritional modulation of periodontal inflammation. J Am Dent Assoc. 2009; 140 (2): 178-184. Hujoel P. Dietary carbohydrates and dental-systemic diseases. J Dental Res. 2009; 88 (6): 490-502. Lee M, et al "Current Helicobacter pylori infection is significantly associated with subclinical coronary atherosclerosis in healthy subjects: A cross-sectional study" PloS One 2018; 13(3): e0193646. Shah NH, LePendu P., Bauer-Mehren A., et al. (June 10, 2015). Proton Pump Inhibitor Usage and the risk of MI in the general population. LLoS ONE 10(6). Mercado FB, Marshall RI, Bartold PM. Inter-relationships between rheumatoid arthritis and periodontal disease. A Review. J Clin Periodontol 2003; 30: 761-772.
Videos: Ontario College of Physicians and Surgeons state unvaccinated are meantally ill (0:48) Pandemic Amnesty': Do you Forgive and Forget? (8:19) Experts try to calm the angry AI, w Elon Musk Part 2 – (8:00) MEP Clare Daly – Speech from Nov 23 (1:12) How Long Would Society Last During a Total Grid Collapse? (14:56) The ultimate stress buster: L-theanine Columbia University Medical Center, November 16, 2022 Honestly, who would have thought that stress can cause heart damage equivalent to smoking five cigarettes? This is according to a study conducted by Columbia University Medical Center and published in the American Journal of Cardiology. The study reveals how an amino acid known as L-theanine reduces both stress levels and heart rate. As a way to increase stress levels, scientists asked 12 participants to solve a mentally stressful task in four double blind trials. L-theanine was given to participants in one of the four trials before dealing with the stressful task. In the second group, study subjects took L-theanine midway through the work. In the third and fourth variations, subjects were respectively given a placebo and nothing at all before attempting the task. In comparison to the placebo group, there was a reduced amount of immunoglobulin (a stress marker in saliva released by the immune system after exposure to viruses, bacteria, and other foreign entities) and a lower heart rate in participants who took L-theanine. The researchers explained that L-theanine works by suppressing the sympathetic nervous system responsible for the ‘fight or flight' response during emergency situations. This is achieved by blocking a chemical known as glutamate (L-glutamic acid) that carries electric signals transmitted from nerve cells to the rest of the body cells. The conclusion was that L-theanine plays a major role in terms of influencing psychology (mind) and physiology (body) function during stressful situation. Greater flavonoid intake associated with less arterial calcification Edith Cowen University (Australia), November 23 2022. The December 2022 issue of Arteriosclerosis, Thrombosis, and Vascular Biology reported a study that uncovered a relationship between greater consumption of plant compounds known as flavonoids and decreased calcification in the abdominal aorta, which supplies blood to the abdominal organs and lower limbs. Greater abdominal aortic calcification has been associated with an increased risk of stroke, heart attack and dementia. The study included 881 participants in the Perth Longitudinal Study of Ageing Women. Dietary questionnaire responses were analyzed to determine total and individual flavonoid intake. Women whose total flavonoid intake was among the top 25% of participants had a 36% lower risk of extensive abdominal aortic calcification than women whose intake was among the lowest 25%. Among women whose intake of individual flavonoids known as flavan-3-ols and flavonols was among the top 25%, respective risks were 39% and 38% lower. Those who consumed 2–6 cups per day of black tea (the main source of total flavonoid intake in this study), had a 16%–42% lower risk of extensive abdominal aortic calcification than women who were not tea drinkers. “In most populations, a small group of foods and beverages—uniquely high in flavonoids—contribute the bulk of total dietary flavonoid intake,” first author Ben Parmenter noted. “The main contributors are usually black or green tea, blueberries, strawberries, oranges, red wine, apples, raisins/grapes and dark chocolate.” “Out of the women who don't drink black tea, higher total non-tea flavonoid intake also appears to protect against extensive calcification of the arteries,” he continued. “This implies flavonoids from sources other than black tea may be protective against abdominal aortic calcification when tea is not consumed.” “Abdominal aortic calcification is a major predictor of vascular disease events, and this study shows intake of flavonoids, that could protect against abdominal aortic calcification, are easily achievable in most people's diets,” he concluded. Researchers discover that vitamin C improves health for children of pregnant smokers Oregon Health & Science University, November 22, 2022 Researchers at Oregon Health & Science University have found that vitamin C supplementation to pregnant women unable to quit smoking significantly improves airway function and respiratory health in their offspring at 5 years of age. While previous studies have shown that vitamin C improves airway function in infants, this is the first study to demonstrate that the improvement in airway function can be maintained through preschool age. The study published this week in JAMA Pediatrics. Despite anti-smoking efforts and a steady decrease of smoking among the adult population over the past decade, the addictive properties of tobacco products can make quitting smoking incredibly challenging for many individuals. Roughly 10% of American women continue to smoke in pregnancy, each year resulting in about 400,000 infants being exposed to smoke in-utero, or in the uterus. In-utero smoke exposure from maternal smoking during pregnancy can be dangerous for a developing baby and is linked to poor health outcomes, including impaired fetal lung development, decreased airway function and an increased risk for wheezing and asthma. Additionally, decreased airway growth early in life causes increased risk for serious lifelong conditions, such as chronic obstructive pulmonary disease, which is now the third leading cause of death worldwide. For this study, participating women were enrolled in a double-blind, randomized controlled trial to receive either vitamin C (500 mg/day) or a placebo. Statistical analyses showed that the effect of vitamin C supplementation to pregnant smokers prior to 23 weeks of gestation consistently resulted in significantly better airway function in their offspring at 5 years old. While the findings may improve the health of the many children who face in-utero smoke exposure, these findings may have even broader implications: The results may potentially lead to better understanding of—and treatments for—the health impacts of other smoke exposures, including indoor and outdoor air pollution, vaping and wildfires. Decades of air pollution undermine the immune system, lymph nodes study finds Columbia University Irving Medical Center, November 23, 2022 The diminished power of the immune system in older adults is usually blamed on the aging process. But a new study by Columbia immunologists shows that decades of particulate air pollution also take a toll. The study found that inhaled particles from environmental pollutants accumulate over decades inside immune cells in lymph nodes associated with the lung, eventually weakening the cells' ability to fight respiratory infections. The findings—published Nov. 21 in Nature Medicine—offer a new reason why individuals become more susceptible to respiratory diseases with age. The Columbia researchers weren't initially looking at air pollution's influence on the immune system. More than ten years ago, they began to collect tissues from deceased organ donors to study immune cells in multiple mucosal and lymphoid tissues. Such cells have been largely inaccessible to researchers studying the immune system where sampling is limited to peripheral blood. “When we looked at people's lymph nodes, we were struck by how many of the nodes in the lung appeared black in color, while those in the GI tract and other areas of the body were the typical beige color,” says Donna Farber, Ph.D., the George H. Humphreys II Professor of Surgical Sciences at Columbia University , who led the study. And as the researchers collected more tissue from younger donors, they also noticed an age difference in the appearance of the lung's lymph nodes: Those from children and teenagers were largely beige while those from donors over age 30 looked were tinged with black and got darker with increasing age. “When we imaged the lung's blackened lymph nodes and found they were clogged with particles from airborne pollutants, we started to think about their impact on the lung's ability to fight infection as people age,” Farber says. In the new study, she and her colleagues examined tissues from 84 deceased human organ donors ranging in age from 11 to 93, all nonsmokers. They found that the pollutant particles in the lung's lymph nodes were located inside macrophages, immune cells that engulf and destroy bacteria, viruses, cellular debris, and other potentially dangerous substances. The macrophages containing particulates were significantly impaired: they were much less capable of ingesting other particles and producing cytokines—chemical “help” signals—that activate other parts of the immune system. Macrophages in those same lymph nodes that did not contain particulates were unimpaired. “We do not know yet the full impact pollution has on the immune system in the lung,” Farber adds, “but pollution undoubtedly plays a role in creating more dangerous respiratory infections in elderly individuals and is another reason to continue the work in improving air quality.” Biologist explains how cannabinoids cause tumor cells to commit suicide Compultense University (Spain): November 17, 2018 A molecular biologist from Compultense University in Madrid, Christina Sanchez, has been studying the molecular activity of cannabinoids for over a decade. Through her studies, she and colleagues found that tetrahydrocannabinol , (THC) which is the main psychoactive part of cannabis, kills tumerous cells while allowing healthy cells to be. It was an unexpected discovery when Sanchez and crew were studying brain cancer cells to grasp a better understanding of how they function. They observed that when cells were exposed to THC, the tumeral cells stopped growing then destroyed themselves. This occurred both in lab tests and animal trials. Sanchez first reported her miraculous findings back in 1998. According to Sanchez ,”After the discovery of this compound that is called THC, it was pretty obvious that this compound had to be acting on the cells, on our organism, through a molecular mechanism.” Research finds that the human body is designed to use cannabis compounds. In the eighties, research first showed the human body contains two targets for THC. One is the endocannabinoid system which processes THC through an endogenous framework. Then the various cannabinoid receptors throughout the body that use them. In conjunction, the body benefits from cannabinoids via these two natural systems. Cannabis is the only place in nature where some certain cannabinoids are found. Sanchez continues, “The endocannabinoids, together with the receptors and the enzymes that synthesize, that produce, the endocannabinoids and that degrade the endocannabinoids, are what we call the endocannabinoid system. We now know that the endocannabinoid system regulates a lot of biological functions: appetite, food intake, motor behavior, reproduction, and many, many other functions. And that's why the plant has such a wide therapeutic potential.” Cannabis cannabinoids, when consumed, work with the body's natural endocannabinoid system and bind to the receptors in the same manner as endogenous cannabinoids. The effects cancer-wise as demonstrated in animal models of breast and brain cancers is that the cancerous cells self destruct. A big advantage of cannabinoids is their unique ability to specifically target tumor cells with no effect on normal cells. This gives cannabinoids the advantage over chemotherapy which targets way more then the actual target Spending Time in the Forest or the Field: Investigations on Stress Perception and Psychological Well-Being University of Freiburg (Germany), November 16, 2022 Research suggests that stays in a forest promote relaxation and reduce stress compared to spending time in a city. The aim of this study was to compare stays in a forest with another natural environment, a cultivated field. Healthy, highly sensitive persons aged between 18 and 70 years spent one hour in the forest and in the field at intervals of one week. The primary outcome was measured using the Change in Subjective Self-Perception (CSP-14) questionnaire. Secondary outcomes were measured using the Profile Of Mood States (POMS) questionnaire and by analyzing salivary cortisol. The medicinal use of forests is of increasing interest worldwide. Forest air is refreshing because trees clean the air of pollutants such as nitrogen oxides and sulfur oxides, produce oxygen, and release volatile bioactive terpenes into the air . Research from Japan, South Korea], China, Taiwan, Australia, the United States, Italy, Norway, Iceland, Finland, and Austria suggests that spending time in the forest promotes relaxation, lowers stress hormones and blood pressure and strengthens the immune system. Most studies compared stays in the forest to stays in the city. Accordingly, forests potentially contribute to the prevention of stress-related diseases. Controlled studies have shown positive effects in high blood pressure, chronic heart failure, COPD and chronic neck pain. In addition, spending time in the forest seems to improve psychological well-being. Spending time in forests reduced adrenaline and noradrenaline in urine, cortisol in saliva and self-rated stress perception; it also induced relaxation in controlled trials. This indicates that forest stays can reduce stress. The available data also indicate that “forest bathing”, i.e., walking, standing or sitting in a forest with the purpose of relaxation, perceiving the environment and inhaling phytoncides stabilizes the autonomic nervous system by reducing the sympathetic and activating the parasympathetic tones. With regard to the immune system, which is linked to stress response and vegetative nerve system, an increase in the activity of natural killer cells and the expression of anti-cancer proteins such as perforin, granzyme A/B, granulysin could be demonstrated. In view of these findings, forests could make an important contribution to the prevention of stress-related diseases. As shown in previous studies, the stressful environment of a city was most often compared to a forest; it remains unclear whether forests have specific effects or are just acting as natural environments. Therefore, we wanted to compare two natural but polar-opposite environments. In cultivated fields, sensory impressions are different from the forest. In order to maximize profitability, fields are mostly structured into rectangular shapes and usually mainly one type of plant is found, while in a natural forest, different types of plants grow side by side. Accordingly, visual, auditory and olfactory impressions are less diverse in fields than in forestsThe play of light and shadow that characterizes the forest atmosphere is not found in fields. The plants are usually not tall enough to provide shade, whereas the height of the trees in the forest can provide a sense of shelter. Field paths are more often sealed than forest paths, which changes haptic perception when walking on them. Thus, there are significant differences in the types of sensory impressions between forests and fields. Highly sensitive persons (HSP), due to their subtle perception, intensely perceive stimuli that others might not even consciously notice. These stimuli may consist of the behavior or moods of other people, the media, medications, pain, and hunger [32]. They perceive stimuli, positively or negatively, to a higher degree, which may, on the one hand, lead to a prolonged reaction time, and on the other hand to more intense feelings and emotional excitability. Our main outcome results show that, as soon as one hour after entering the forest, participants felt a sense of security, relaxation and inner connectedness. In summer, forest interventions had a better effect on vitality. Our study was the first to use the CSP-14 questionnaire, and the comparisons between field and forest interventions were also novel. Forest interventions significantly lowered perceptions of depression, anxiety, hostility, fatigue, confusion and total mood disturbance, and greatly increased vigor. This study shows that forests are not the only kind of natural environment that can promote psychological well-being. The characteristics and qualities of natural environments might influence people's mood and well-being differently. There might also be differences dependent on the preferences of the respective individuals. We regard it as meaningful to study these different effects of nature on the human soul and body in more detail. In addition, future studies examining the effects of different natural environments on human health should respect seasonal aspects and weather conditions.
Focus Issue on Vascular Biology and Medicine
Videos: Neil Oliver – ‘…they're herding people like sheep… Large Observational Study On COVID-19 Vaccines Impact of Women's Menstrual Cycles Post Vaccination – Trial Site News The Dark Side of Electric Cars – Jhonny Harris 4.How The US Stole The Philippines – Jhonny Harris Cardamonin shows promise for treating aggressive breast cancer Florida A&M University, August 3, 2022 Cardamonin—a natural compound found in the spice cardamom and other plants—could have therapeutic potential for triple-negative breast cancer, according to a new study using human cancer cells. The findings also show that the compound targets a gene that helps cancer cells elude the immune system About 10-15% of breast cancers are triple-negative, which means they don't have receptors for estrogen or progesterone and don't make excess amounts of a protein called HER2. These tumors are difficult to treat because they don't respond to the hormone-based therapies used for other types of breast cancer. They also tend to be more aggressive and have a higher mortality rate than other breast cancers. “The fact that cardamonin has been used for centuries as a spice and, more recently, as a supplement shows that its intake is safe and may bring health benefits,” said Mendonca. “Our research shows that cardamonin holds potential for improving cancer therapy without as many side effects as other chemotherapeutic agents.” For the new study, the researchers investigated how cardamonin affected the expression of the programmed cell death ligand 1 (PD-L1) gene, which is found in tumor cells. PD-L1 is overexpressed during breast cancer progression and plays a critical role in helping breast cancer cells evade the body's immune system. They found that cardamonin treatment caused a dose-dependent decrease in cell viability in both cell lines. It also reduced PD-L1 expression in the Caucasian cell line but not the African American cell line, indicating that cells from different races may respond differently to cardamonin because of genetic variations among races. Persistent Low Wages Linked to Faster Memory Decline in Later Life Columbia University's Mailman School of Public Health, August 2 2022Sustained low wages are associated with significantly faster memory decline, according to a new study by Columbia University Mailman School of Public Health. While low-wage jobs have been associated with health outcomes such as depressive symptoms, obesity, and hypertension, which are risk factors for cognitive aging, until now no prior studies had examined the specific relationship between low wages during working years and later-life cognitive functioning. The findings are published in the American Journal of Epidemiology.”Our research provides new evidence that sustained exposure to low wages during peak earning years is associated with accelerated memory decline later in life,” said Katrina Kezios, Ph.D., postdoctoral researcher in the Department of Epidemiology at Columbia University Mailman School of Public Health and first author. “This association was observed in our primary sample as well as in a validation cohort.”The researchers found that, compared with workers never earning low wages, sustained low-wage earners experienced significantly faster memory decline in older age. They experienced approximately one excess year of cognitive aging per a 10-year period; in other words, the level of cognitive aging experienced over a 10-year period by sustained low-wage earners would be what those who never earned low wages experienced in 11 years.”Our findings suggest that social policies that enhance the financial well-being of low-wage workers may be especially beneficial for cognitive health,” said senior author Adina Zeki Al Hazzouri, Ph.D., assistant professor of epidemiology at Columbia Mailman School and the Columbia Butler Aging Center. “Future work should rigorously examine the number of dementia cases and excess years of cognitive aging that could be prevented under different hypothetical scenarios that would increase the minimum hourly wage.”Research links red meat intake, gut microbiome, and cardiovascular disease (ASCVD) in older adultsTufts University, August 3, 2022Over the years, scientists have investigated the relationship between heart disease and saturated fat, dietary cholesterol, sodium, nitrites, and even high-temperature cooking, but evidence supporting many of these mechanisms has not been robust. Recent evidence suggests that the underlying culprits may include specialized metabolites created by our gut bacteria when we eat meat. A new study led by researchers at the Friedman School of Nutrition Science and Policy at Tufts University and Cleveland Clinic Lerner Research Institute quantifies the risk of ASCVD associated with meat intake and identifies underlying biologic pathways that may help explain this risk. The study of almost 4,000 U.S. men and women over age 65 shows that higher meat consumption is linked to higher risk of ASCVD—22 percent higher risk for about every 1.1 serving per day—and that about 10 percent of this elevated risk is explained by increased levels of three metabolites produced by gut bacteria from nutrients abundant in meat. Higher risk and interlinkages with gut bacterial metabolites were found for red meat but not poultry, eggs, or fish. The study, published in the journal Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB) on August 1, is the first to investigate the interrelationships between animal source foods and risk of ASCVD events, and the mediation of this risk by gut microbiota-generated compounds as well as by traditional ASCVD risk pathways such as blood cholesterol, blood pressure, and blood sugar. Highlights In this community-based cohort of older U.S. men and women, higher intakes of unprocessed red meat, total meat (unprocessed red meat plus processed meat), and total animal source foods were prospectively associated with a higher incidence of ASCVD during a median follow-up of 12.5 years. The positive associations with ASCVD were partly mediated (8-11 percent of excess risk) by plasma levels of TMAO, gamma-butyrobetaine, and crotonobetaine. The higher risk of ASCVD associated with meat intake was also partly mediated by levels of blood glucose and insulin and, for processed meats, by systematic inflammation but not by blood pressure or blood cholesterol levels. Intakes of fish, poultry, and eggs were not significantly associated with ASCVD. The 3,931 study subjects were followed for a median of 12.5 years, and their average age at baseline was 73. The study adjusted for established risk factors such as age, sex, race/ethnicity, education, smoking, physical activity, other dietary habits, and many additional risk factors. Diets higher in calcium and potassium may help prevent recurrent symptomatic kidney stones, study findsMayo Clinic, August 2, 2022Kidney stones can cause not only excruciating pain but also are associated with chronic kidney disease, osteoporosis and cardiovascular disease. If you've experienced a kidney stone once, you have a 30% chance of having another kidney stone within five years.Changes in diet are often prescribed to prevent recurrent symptomatic kidney stones. However, little research is available regarding dietary changes for those who have one incident of kidney stone formation versus those who have recurrent incidents.Mayo Clinic findings show that enriching diets with foods high in calcium and potassium may prevent recurrent symptomatic kidney stones.The findings, which were published in Mayo Clinic Proceedings, show that lower dietary calcium and potassium, as well as lower intake of fluids, caffeine and phytate, are associated with higher odds of experiencing a first-time symptomatic kidney stone.Of the patients who had first-time stone formation, 73 experienced recurrent stones within a median of 4.1 years of follow-up. Further analysis found that lower levels of dietary calcium and potassium predicted recurrence.Fluid intake of less than 3,400 milliliters per day, or about nine 12-ounce glasses, is associated with first-time stone formation, along with caffeine intake and phytate, the study finds. Daily fluid intake includes intake from foods such as fruits and vegetables. Low fluid and caffeine intake can result in low urine volume and increased urine concentration, contributing to stone formation. Phytate is an antioxidant compound found in whole grains, nuts and other foods that can lead to increased calcium absorption and urinary calcium excretion.Low dietary calcium and potassium was a more important predictor than fluid intake of recurrent kidney stone formation, says Api Chewcharat, M.D., the article's first author. The study concludes that diets with daily intake of 1,200 milligrams of calcium may help prevent first-time and recurrent kidney stones.Dr. Chewcharat says the takeaway is that patients should add more fruits and vegetables that are high in calcium and potassium to their diets. Fruits that are high in potassium include bananas, oranges, grapefruits, cantaloupes, honeydew melons and apricots. Vegetables include potatoes, mushrooms, peas, cucumbers and zucchini.Could acupuncture help ward off diabetes?Edith Cowan University, August 2, 2022 A new study from Edith Cowan University has found acupuncture therapy may be a useful tool in avoiding type 2 diabetes. The research team investigated dozens of studies covering the effects of acupuncture on more than 3600 people with prediabetes, a condition which sees higher-than-normal blood glucose levels without being high enough to be diagnosed as diabetes.The findings showed acupuncture therapy significantly improved key markers, such as fasting plasma glucose, two-hour plasma glucose, and glycated haemoglobin, plus a greater decline in the incidence of prediabetes.There were also no reports of adverse reactions among patients. Green tea helps support healthy glucose in metabolic syndrome patients Ohio State University, August 1 2022. Findings from a trial reported in the supplement of Current Developments in Nutrition revealed that consuming green tea extract improved glucose levels in adults with metabolic syndrome: a cluster of factors that increase the risk of diabetes and cardiovascular disease. Supplementation with green tea extract was also associated with improvement in intestinal health, including a reduction in leaky gut. The trial was a follow-up to a study published in 2019 that found protective effects for green tea against inflammation induced by nonalcoholic steatohepatitis (NASH) in mice. In the current crossover trial, 21 individuals with metabolic syndrome and 19 healthy participants received 1 gram of green tea extract or a placebo for 28 days. This period was followed by another treatment period in which participants who previously received the extract were given a placebo and those who received a placebo received the extract. Fasting blood glucose, insulin and lipid levels were measured at the beginning of each treatment period and at days 14 and 28. Supplementation with green tea extract was associated with lower fasting glucose and markers of intestinal inflammation in comparison with the placebo. In separately published findings, green tea extract was associated with decreases in small intestinal permeability (leaky gut).
References Dr Guerra's notes Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:436 JAMA. 2008;299(11):1345-1350 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message
References Dr. Guerra lecture notes Prog Neurobiol. 2018 Apr-May; 163-164: 27–58. Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:28–40 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support
In this episode of the Heart podcast, Digital Media Intern, Dr. Andrew Perry, is joined by Dr. Alan Daugherty, from the University of Kentucky, and Editor-in-Chief of the Arteriosclerosis, Thrombosis, and Vascular Biology journal. They discuss the latest developments in transcriptomics and how they might be used to understand the causes of vascular disease. If you enjoy the show, please subscribe to the podcast to get episodes automatically downloaded to your phone and computer. Also, please consider leaving us a review at https://itunes.apple.com/gb/podcast/heart-podcast/id445358212?mt=2
Focus Issue on Vascular Biology and Medicine
Don Ingber is the Founding Director of the Wyss Institute for Biologically Inspired Engineering @ Harvard University, the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children's Hospital, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences. He received his B.A., M.A., M.Phil., M.D. and Ph.D. from Yale University.Ingber is a pioneer in the field of biologically inspired engineering, and at the Wyss Institute, he currently leads scientific and engineering teams that cross a broad range of disciplines to develop breakthrough bio-inspired technologies to advance healthcare and to improve sustainability. His work has led to major advances in mechanobiology, cell structure, tumor angiogenesis, tissue engineering, systems biology, nanobiotechnology and translational medicine. Through his work, Prof. Ingber also has helped to break down boundaries between science, art and design.Ingber has authored more than 500 publications and almost 200 patents, founded 7 companies, and has presented over 550 plenary presentations and invited lectures world-wide. He is a member of the National Academy of Engineering, National Academy of Medicine, National Academy of Inventors, American Institute for Medical and Biological Engineering, and the American Academy of Arts and Sciences. Prof. Ingber has been the scientific founder of seven companies: Neomorphics, Tensegra, Boa Biomedical, FreeFlow Medical Devices, Unravel Bio, StataDx, and Emulate.Thank you for listening!BIOS (@BIOS_Community) unites a community of Life Science innovators dedicated to driving patient impact. Alix Ventures (@AlixVentures) is a San Francisco based venture capital firm supporting early stage Life Science startups engineering biology to create radical advances in human health.Music: Danger Storm by Kevin MacLeod (link & license)
References Infect Immun. 2018 Jul; 86(7): e00035-18 J Biol Chem. 2019 Jun 7;294(23):9213-9224 Egyptian Journal of Basic and Applied Sciences. 2018. (5) 4 : 237-244 Arteriosclerosis, Thrombosis, and Vascular Biology. 2019. (39) 3: 432-445 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support
In this week's podcast, Mark and Brian talk to Professor Noel Caplice. Noel Caplice is the Professor of Cardiovascular Sciences in the Department of Medicine and is the Director of the Centre for Research in Vascular Biology at University College Cork. He is also a consultant cardiologist in Cork University Hospital. He previously held professional positions in pharmacology and medicine at the Mayo Clinic, Rochester, Minnesota, USA, where he was an interventional cardiologist and directed the Vascular Stem Cell Laboratory. Prof Caplice discusses his research and clinical practice and speaks on how his research informs his clinical practice. He also talks about the idea of mentorship and critical thinking. In addition, the importance of lifelong learning was a central part to our discussion. Prof Caplice offers advice for upcoming scientists and doctors who may be interested in combining research and clinical practice. Hosts: Mark Vesey, Brian Curtin
Focus Issue on Vascular Biology and Medicine
Raspberries, ellagic acid reveal benefits in two studies Oregon State University, October 1, 2021. Articles that appeared recently in the Journal of Berry Research report that raspberries and compounds present in the fruit could help support healthy body mass and motor function, including balance, coordination and strength. In one study, Neil Shay and colleagues at Oregon State University fed mice a high fat, high sugar diet plus one of the following: raspberry juice concentrate, raspberry puree concentrate, raspberry fruit powder, raspberry seed extract, ellagic acid (a polyphenol that occurs in a relatively high amount in raspberries), raspberry ketone, or a combination of raspberry ketone and ellagic acid. Additional groups of animals received a high fat, high sugar diet alone or a low fat diet. While mice that received the high fat and sugar diet alone experienced a significant increase in body mass, the addition of raspberry juice concentrate, raspberry puree concentrate or ellagic acid plus raspberry ketone helped prevent this effect. Of note, mice that received raspberry juice concentrate experienced gains similar to those of animals given a low fat diet. "We hope that the findings from this study can help guide the design of future clinical trials," Dr Shay stated. In another study, Barbara Shukitt-Hale, PhD, and her associates at Tufts University's Human Nutrition Research Center on Aging gave 19 month old rats a control diet or a diet enhanced with raspberry extract for 11 weeks. Psychomotor behavior was assessed during week 7 and cognitive testing was conducted during weeks 9-10. Animals that received raspberry performed better on psychomotor coordination and balance, and had better muscle tone, strength and stamina than those that received a control diet. "These results may have important implications for healthy aging," stated Dr Shukitt-Hale. "While further research in humans is necessary, animal model studies are helpful in identifying deficits associated with normal aging." Massage doesn't just make muscles feel better, it makes them heal faster and stronger Harvard University, October 6, 2021 Massage has been used to treat sore, injured muscles for more than 3,000 years, and today many athletes swear by massage guns to rehabilitate their bodies. But other than making people feel good, do these "mechanotherapies" actually improve healing after severe injury? According to a new study from researchers at Harvard's Wyss Institute for Biologically Inspired Engineering and John A. Paulson School of Engineering and Applied Sciences (SEAS), the answer is "yes." Using a custom-designed robotic system to deliver consistent and tunable compressive forces to mice's leg muscles, the team found that this mechanical loading (ML) rapidly clears immune cells called neutrophils out of severely injured muscle tissue. This process also removed inflammatory cytokinesreleased by neutrophils from the muscles, enhancing the process of muscle fiber regeneration. The research is published in Science Translational Medicine. "Lots of people have been trying to study the beneficial effects of massage and other mechanotherapies on the body, but up to this point it hadn't been done in a systematic, reproducible way. Our work shows a very clear connection between mechanical stimulation and immune function. This has promise for regenerating a wide variety of tissues including bone, tendon, hair, and skin, and can also be used in patients with diseases that prevent the use of drug-based interventions," said first author Bo Ri Seo, Ph.D., who is a Postdoctoral Fellow in the lab of Core Faculty member Dave Mooney, Ph.D. at the Wyss Institute and SEAS. Seo and her coauthors started exploring the effects of mechanotherapy on injured tissues in mice several years ago, and found that it doubled the rate of muscle regeneration and reduced tissue scarring over the course of two weeks. Excited by the idea that mechanical stimulation alone can foster regeneration and enhance muscle function, the team decided to probe more deeply into exactly how that process worked in the body, and to figure out what parameters would maximize healing. They teamed up with soft robotics experts in the Harvard Biodesign Lab, led by Wyss Associate Faculty member Conor Walsh, Ph.D., to create a small device that used sensors and actuators to monitor and control the force applied to the limb of a mouse. " The device we created allows us to precisely control parameters like the amount and frequency of force applied, enabling a much more systematic approach to understanding tissue healing than would be possible with a manual approach," said co-second author Christopher Payne, Ph.D., a former Postdoctoral Fellow at the Wyss Institute and the Harvard Biodesign Lab who is now a Robotics Engineer at Viam, Inc. Once the device was ready, the team experimented with applying force to mice's leg muscles via a soft silicone tip and used ultrasound to get a look at what happened to the tissue in response. They observed that the muscles experienced a strain of between 10-40%, confirming that the tissues were experiencing mechanical force. They also used those ultrasound imaging data to develop and validate a computational model that could predict the amount of tissue strain under different loading forces. They then applied consistent, repeated force to injured muscles for 14 days. While both treated and untreated muscles displayed a reduction in the amount of damaged muscle fibers, the reduction was more pronounced and the cross-sectional area of the fibers was larger in the treated muscle, indicating that treatment had led to greater repair and strength recovery. The greater the force applied during treatment, the stronger the injured muscles became, confirming that mechanotherapy improves muscle recovery after injury. But how? Evicting neutrophils to enhance regeneration To answer that question, the scientists performed a detailed biological assessment, analyzing a wide range of inflammation-related factors called cytokines and chemokines in untreated vs. treated muscles. A subset of cytokines was dramatically lower in treated muscles after three days of mechanotherapy, and these cytokines are associated with the movement of immune cells called neutrophils, which play many roles in the inflammation process. Treated muscles also had fewer neutrophils in their tissue than untreated muscles, suggesting that the reduction in cytokines that attract them had caused the decrease in neutrophil infiltration. The team had a hunch that the force applied to the muscle by the mechanotherapy effectively squeezed the neutrophils and cytokines out of the injured tissue. They confirmed this theory by injecting fluorescent molecules into the muscles and observing that the movement of the molecules was more significant with force application, supporting the idea that it helped to flush out the muscle tissue. To pick apart what effect the neutrophils and their associated cytokines have on regenerating muscle fibers, the scientists performed in vitro studies in which they grew muscle progenitor cells (MPCs) in a medium in which neutrophils had previously been grown. They found that the number of MPCs increased, but the rate at which they differentiated (developed into other cell types) decreased, suggesting that neutrophil-secreted factors stimulate the growth of muscle cells, but the prolonged presence of those factors impairs the production of new muscle fibers. "Neutrophils are known to kill and clear out pathogens and damaged tissue, but in this study we identified their direct impacts on muscle progenitor cell behaviors," said co-second author Stephanie McNamara, a former Post-Graduate Fellow at the Wyss Institute who is now an M.D.-Ph.D. student at Harvard Medical School (HMS). "While the inflammatory response is important for regeneration in the initial stages of healing, it is equally important that inflammation is quickly resolved to enable the regenerative processes to run its full course." Seo and her colleagues then turned back to their in vivo model and analyzed the types of muscle fibers in the treated vs. untreated mice 14 days after injury. They found that type IIX fibers were prevalent in healthy muscle and treated muscle, but untreated injured muscle contained smaller numbers of type IIX fibers and increased numbers of type IIA fibers. This difference explained the enlarged fiber size and greater force production of treated muscles, as IIX fibers produce more force than IIA fibers. Finally, the team homed in on the optimal amount of time for neutrophil presence in injured muscle by depleting neutrophils in the mice on the third day after injury. The treated mice's muscles showed larger fiber size and greater strength recovery than those in untreated mice, confirming that while neutrophils are necessary in the earliest stages of injury recovery, getting them out of the injury site early leads to improved muscle regeneration. "These findings are remarkable because they indicate that we can influence the function of the body's immune system in a drug-free, non-invasive way," said Walsh, who is also the Paul A. Maeder Professor of Engineering and Applied Science at SEAS and whose group is experienced in developing wearable technology for diagnosing and treating disease. "This provides great motivation for the development of external, mechanical interventions to help accelerate and improve muscle and tissue healing that have the potential to be rapidly translated to the clinic." The team is continuing to investigate this line of research with multiple projects in the lab. They plan to validate this mechanotherpeutic approach in larger animals, with the goal of being able to test its efficacy on humans. They also hope to test it on different types of injuries, age-related muscle loss, and muscle performance enhancement. "The fields of mechanotherapy and immunotherapy rarely interact with each other, but this work is a testament to how crucial it is to consider both physical and biological elements when studying and working to improve human health," said Mooney, who is the corresponding author of the paper and the Robert P. Pinkas Family Professor of Bioengineering at SEAS. "The idea that mechanics influence cell and tissue function was ridiculed until the last few decades, and while scientists have made great strides in establishing acceptance of this fact, we still know very little about how that process actually works at the organ level. This research has revealed a previously unknown type of interplay between mechanobiology and immunology that is critical for muscle tissue healing, in addition to describing a new form of mechanotherapy that potentially could be as potent as chemical or gene therapies, but much simpler and less invasive," said Wyss Founding Director Don Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at (HMS) and the Vascular Biology Program at Boston Children's Hospital, as well as Professor of Bioengineering at SEAS. Vitamin E could help protect older men from pneumonia University of Helsinki (Finland), October 7 2021. An article that appeared in Clinical Interventions in Aging reported a protective role for vitamin E against pneumonia in older men. For the current investigation, Dr Harri Hemilä of the University of Helsinki, Finland analyzed data from the Alpha-Tocopherol Beta-Carotene (ATBC) Cancer Prevention Study conducted in Finland. The trial included 29,133 men between the ages of 50 to 69 years who smoked at least five cigarettes daily upon enrollment. Participants received alpha tocopherol (vitamin E), beta carotene, both supplements, or a placebo for five to eight years. The current study was limited to 7,469 ATBC participants who started smoking at age 21 or older. Among this group, supplementation with vitamin E was associated with a 35% lower risk of developing pneumonia in comparison with those who did not receive the vitamin. Light smokers who engaged in leisure time exercise had a 69% lower risk compared with unsupplemented members of this subgroup. The risk in this subgroup of developing pneumonia by age 74 was 12.9%. Among the one-third of the current study's population who quit smoking for a median period of two years, there was a 72% lower risk of pneumonia in association with vitamin E supplementation. In this group, exercisers who received vitamin E experienced an 81% lower pneumonia risk. Dr Hemilä observed that the benefit for vitamin E in this study was strongest for older subjects—a group at higher risk of pneumonia. "The current analysis of individual-level data suggests that trials on vitamin E and pneumonia on nonsmoking elderly males are warranted," he concluded. Toxic fatty acids to blame for brain cell death after injury New York University, October 7, 2021 Cells that normally nourish healthy brain cells called neurons release toxic fatty acids after neurons are damaged, a new study in rodents shows. This phenomenon is likely the driving factor behind most, if not all, diseases that affect brain function, as well as the natural breakdown of brain cells seen in aging, researchers say. Previous research has pointed to astrocytes—a star-shaped glial cell of the central nervous system—as the culprits behind cell death seen in Parkinson's disease and dementia, among other neurodegenerative diseases. While many experts believed that these cells released a neuron-killing molecule to "clear away" damaged brain cells, the identity of this toxin has until now remained a mystery. Led by researchers at NYU Grossman School of Medicine, the new investigation provides what they say is the first evidence that tissue damage prompts astrocytes to produce two kinds of fats, long-chain saturated free fatty acids and phosphatidylcholines. These fats then trigger cell death in damaged neurons, the electrically active cells that send messages throughout nerve tissue. Publishing Oct. 6 in the journal Nature, the study also showed that when researchers blocked fatty acid formation in mice, 75 percent of neurons survived compared with 10 percent when the fatty acids were allowed to form. The researchers' earlier work showed that brain cells continued to function when shielded from astrocyte attacks. "Our findings show that the toxic fatty acids produced by astrocytes play a critical role in brain cell death and provide a promising new target for treating, and perhaps even preventing, many neurodegenerative diseases," says study co-senior author Shane Liddelow, Ph.D. Liddelow, an assistant professor in the Department of Neuroscience and Physiology at NYU Langone Health, adds that targeting these fats instead of the cells that produce them may be a safer approach to treating neurodegenerative diseasesbecause astrocytes feed nerve cells and clear away their waste. Stopping them from working altogether could interfere with healthy brain function. Although it remains unclear why astrocytes produce these toxins, it is possible they evolved to destroy damaged cells before they can harm their neighbors, says Liddelow. He notes that while healthy cells are not harmed by the toxins, neurons become susceptible to the damaging effects when they are injured, mutated, or infected by prions, the contagious, misfolded proteins that play a major role in mad cow disease and similar illnesses. Perhaps in chronic diseases like dementia, this otherwise helpful process goes off track and becomes a problem, the study authors say. For the investigation, researchers analyzed the molecules released by astrocytes collected from rodents. They also genetically engineered some groups of mice to prevent the normal production of the toxic fats and looked to see whether neuron death occurred after an acute injury. "Our results provide what is likely the most detailed molecular map to date of how tissue damage leads to brain cell death, enabling researchers to better understand why neurons die in all kinds of diseases," says Liddelow, also an assistant professor in the Department of Ophthalmology at NYU Langone. Liddelow cautions that while the findings are promising, the genetic techniques used to block the enzyme that produces toxic fatty acids in mice are not ready for use in humans. As a result, the researchers next plan is to explore safe and effective ways to interfere with the release of the toxins in human patients. Liddelow and his colleagues had previously shown these neurotoxic astrocytes in the brains of patients with Parkinson's, Huntington's disease, and multiple sclerosis, among other diseases. Clinical trial for nicotinamide riboside: Vitamin safely boosts levels of important cell metabolite linked to multiple health benefits University of Iowa Health Care, October 3, 2021 In the first controlled clinical trial of nicotinamide riboside (NR), a newly discovered form of Vitamin B3, researchers have shown that the compound is safe for humans and increases levels of a cell metabolite that is critical for cellular energy production and protection against stress and DNA damage. Studies in mice have shown that boosting the levels of this cell metabolite -- known as NAD+ -- can produce multiple health benefits, including resistance to weight gain, improved control of blood sugar and cholesterol, reduced nerve damage, and longer lifespan. Levels of NAD+ diminish with age, and it has been suggested that loss of this metabolite may play a role in age-related health decline. These findings in animal studies have spurred people to take commercially available NR supplements designed to boost NAD+. However, these over-the-counter supplements have not undergone clinical trials to see if they work in people. The new research, reported in the journal Nature Communications, was led by Charles Brenner, PhD, professor and Roy J. Carver Chair of Biochemistry at the University of Iowa Carver College of Medicine in collaboration with colleagues at Queens University Belfast and ChromaDex Corp. (NASDAQ: CDXC), which supplied the NR used in the trial. Brenner is a consultant for ChromaDex. He also is co-founder and Chief Scientific Adviser of ProHealthspan, which sells NR supplements under the trade name Tru NIAGEN®. The human trial involved six men and six women, all healthy. Each participant received single oral doses of 100 mg, 300 mg, or 1,000 mg of NR in a different sequence with a seven-day gap between doses. After each dose, blood and urine samples were collected and analyzed by Brenner's lab to measure various NAD+ metabolites in a process called metabolomics. The trial showed that the NR vitamin increased NAD+ metabolism by amounts directly related to the dose, and there were no serious side effects with any of the doses. "This trial shows that oral NR safely boosts human NAD+ metabolism," Brenner says. "We are excited because everything we are learning from animal systems indicates that the effectiveness of NR depends on preserving and/or boosting NAD+ and related compounds in the face of metabolic stresses. Because the levels of supplementation in mice that produce beneficial effects are achievable in people, it appears than health benefits of NR will be translatable to humans safely." The next step will be to study the effect of longer duration NR supplementation on NAD+ metabolism in healthy adults, but Brenner also has plans to test the effects of NR in people with diseases and health conditions, including elevated cholesterol, obesity and diabetes, and people at risk for chemotherapeutic peripheral neuropathy. Prior to the formal clinical trial, Brenner conducted a pilot human study -- on himself. In 2004, he had discovered that NR is a natural product found in milk and that there is pathway to convert NR to NAD+ in people. More than a decade of research on NR metabolic pathways and health effects in mice and rats had convinced him that NR supplementation had real promise to improve human health and wellness. After consulting with UI's institutional review board, he conducted an experiment in which he took 1 gram of NR once a day for seven days, and his team analyzed blood and urine samples using mass spectrometry. The experiment showed that Brenner's blood NAD+ increased by about 2.7 times. In addition, though he reported immediate sensitivity to flushing with the related compound niacin, he did not experience any side effects taking NR. The biggest surprise from his metabolomic analysis was an increase in a metabolite called NAAD, which was multiplied by 45 times, from trace levels to amounts in the micromolar range that were easily detectable. "While this was unexpected, I thought it might be useful," Brenner says. "NAD+ is an abundant metabolite and it is sometimes hard to see the needle move on levels of abundant metabolites. But when you can look at a low-abundance metabolite that goes from undetectable to easily detectable, there is a great signal to noise ratio, meaning that NAAD levels could be a useful biomarker for tracking increases in NAD+ in human trials." Brenner notes this was a case of bidirectional translational science; having learned something from the initial human experiment, his team was able to return to laboratory mice to explore the unexpected NAAD finding in more detail. Brenner's mouse study showed that NAAD is formed from NR and confirmed that NAAD levels are a strong biomarker for increased NAD+ metabolism. The experiments also revealed more detail about NAD+ metabolic pathways. In particular, the researchers compared the ability of all three NAD+ precursor vitamins -- NR, niacin, and nicotinamide -- to boost NAD+ metabolism and stimulate the activity of certain enzymes, which have been linked to longevity and healthbenefits. The study showed for the first time that oral NR is superior to nicotinamide, which is better than niacin in terms of the total amount of NAD+ produced at an equivalent dose. NR was also the best of the three in stimulating the activity of sirtuin enzymes. However, in this case, NR was the best at stimulating sirtuin-like activities, followed by niacin, followed by nicotinamide. The information from the mouse study subsequently helped Brenner's team design the formal clinical trial. In addition to showing that NR boosts NAD+ in humans without adverse effects, the trial confirmed that NAAD is a highly sensitive biomarker of NAD+ supplementation in people. "Now that we have demonstrated safety in this small clinical trial, we are in a position to find out if the health benefits that we have seen in animals can be reproduced in people," says Brenner, who also is co-director of the Obesity Research and Education Initiative, professor of internal medicine, and a member of the Fraternal Order of Eagles Diabetes Research Center at the UI. Protecting the ozone layer is delivering vast health benefits Montreal Protocol will spare Americans from 443 million skin cancer cases National Center for Atmospheric Research, October 7, 2021 An international agreement to protect the ozone layer is expected to prevent 443 million cases of skin cancer and 63 million cataract cases for people born in the United States through the end of this century, according to new research. The research team, by scientists at the National Center for Atmospheric Research (NCAR), ICF Consulting, and U.S. Environmental Protection Agency (EPA), focused on the far-reaching impacts of a landmark 1987 treaty known as the Montreal Protocol and later amendments that substantially strengthened it. The agreement phased out the use of chemicals such as chlorofluorocarbons (CFCs) that destroy ozone in the stratosphere. Stratospheric ozone shields the planet from harmful levels of the Sun's ultraviolet (UV) radiation, protecting life on Earth. To measure the long-term effects of the Montreal Protocol, the scientists developed a computer modeling approach that enabled them to look to both the past and the future by simulating the treaty's impact on Americans born between 1890 and 2100. The modeling revealed the treaty's effect on stratospheric ozone, the associated reductions in ultraviolet radiation, and the resulting health benefits. In addition to the number of skin cancer and cataract cases that were avoided, the study also showed that the treaty, as most recently amended, will prevent approximately 2.3 million skin cancer deaths in the U.S. “It's very encouraging,” said NCAR scientist Julia Lee-Taylor, a co-author of the study. “It shows that, given the will, the nations of the world can come together to solve global environmental problems.” The study, funded by the EPA, was published in ACS Earth and Space Chemistry. NCAR is sponsored by the National Science Foundation. Mounting concerns over the ozone layer Scientists in the 1970s began highlighting the threat to the ozone layer when they found that CFCs, used as refrigerants and in other applications, release chlorine atoms in the stratosphere that set off chemical reactions that destroy ozone. Concerns mounted the following decade with the discovery of an Antarctic ozone hole. The loss of stratospheric ozone would be catastrophic, as high levels of UV radiation have been linked to certain types of skin cancer, cataracts, and immunological disorders. The ozone layer also protects terrestrial and aquatic ecosystems, as well as agriculture. Policy makers responded to the threat with the 1987 Montreal Protocol on Substances that Deplete the Ozone Layer, in which nations agreed to curtail the use of certain ozone-destroying substances. Subsequent amendments strengthened the treaty by expanding the list of ozone-destroying substances (such as halons and hydrochlorofluorocarbons, or HCFCs) and accelerating the timeline for phasing out their use. The amendments were based on Input from the scientific community, including a number of NCAR scientists, that were summarized in quadrennial Ozone Assessment reports. To quantify the impacts of the treaty, the research team built a model known as the Atmospheric and Health Effects Framework. This model, which draws on various data sources about ozone, public health, and population demographics, consists of five computational steps. These simulate past and future emissions of ozone-destroying substances, the impacts of those substances on stratospheric ozone, the resulting changes in ground-level UV radiation, the U.S. population's exposure to UV radiation, and the incidence and mortality of health effects resulting from the exposure. The results showed UV radiation levels returning to 1980 levels by the mid-2040s under the amended treaty. In contrast, UV levels would have continued to increase throughout this century if the treaty had not been amended, and they would have soared far higher without any treaty at all. Even with the amendments, the simulations show excess cases of cataracts and various types of skin cancer beginning to occur with the onset of ozone depletion and peaking decades later as the population exposed to the highest UV levels ages. Those born between 1900 and 2040 experience heightened cases of skin cancer and cataracts, with the worst health outcomes affecting those born between about 1950 and 2000. However, the health impacts would have been far more severe without the treaty, with cases of skin cancer and cataracts rising at an increasingly rapid rate through the century. “We peeled away from disaster,” Lee-Taylor said. “What is eye popping is what would have happened by the end of this century if not for the Montreal Protocol. By 2080, the amount of UV has tripled. After that, our calculations for the health impacts start to break down because we're getting so far into conditions that have never been seen before.” The research team also found that more than half the treaty's health benefits could be traced to the later amendments rather than the original 1987 Montreal Protocol. Overall, the treaty prevented more than 99% of potential health impacts that would have otherwise occurred from ozone destruction. This showed the importance of the treaty's flexibility in adjusting to evolving scientific knowledge, the authors said. The researchers focused on the U.S. because of ready access to health data and population projections. Lee-Taylor said that the specific health outcomes in other countries may vary, but the overall trends would be similar. “The treaty had broad global benefits,” she said. What is Boron? The trace mineral boron provides profound anti-cancer effects, in addition to maintaining stronger bones. Life Extension, September 2021 Boron is a trace mineral found in the earth's crust and in water. Its importance in human health has been underestimated. Boron has been shown to have actions against specific types of malignancies, such as: Cervical cancer: The country Turkey has an extremely low incidence of cervical cancer, and scientists partially attribute this to its boron-rich soil.1 When comparing women who live in boron-rich regions versus boron-poor regions of Turkey, not a single woman living in the boron-rich regions had any indication of cervical cancer.2(The mean dietary intake of boron for women in this group was 8.41 mg/day.) Boron interferes with the life cycle of the human papillomavirus (HPV), which is a contributing factor in approximately 95% of all cervical cancers.1 Considering that HPV viruses are increasingly implicated in head and neck cancers,3,4 supplementation with this ultra-low-cost mineral could have significant benefits in protecting against this malignancy that is increasing in prevalence. Lung cancer: A study conducted at the University of Texas MD Anderson Cancer Center between 1995 and 2005 found that increased boron intake was associated with a lower risk of lung cancer in postmenopausal women who were taking hormone replacement therapy. Prostate cancer: Studies point to boron's ability to inhibit the growth and spread of prostate cancer cells. In one study, when mice were exposed to boric acid, their tumors shrank by as much as 38%.6 One analysis found that increased dietary boron intake was associated with a decreased risk of prostate cancer.7 Several human and animal studies have confirmed the important connection between boron and bone health. Boron prevents calcium loss,8 while also alleviating the bone problems associated with magnesium and vitamin D deficiency.9 All of these nutrients help maintain bone density. A study in female rats revealed the harmful effects a deficiency in boron has on bones, including:10 Decreased bone volume fraction, a measure of bone strength, Decreased thickness of the bone's spongy inner layer, and Decreased maximum force needed to break the femur. And in a study of post-menopausal women, supplementation with3 mg of boron per day prevented calcium loss and bone demineralization by reducing urinary excretion of both calcium and magnesium.8 In addition to its bone and anti-cancer benefits, there are nine additional reasons boron is an important trace mineral vital for health and longevity. It has been shown to:1 Greatly improve wound healing, Beneficially impact the body's use of estrogen, testosterone, and vitamin D, Boost magnesium absorption, Reduce levels of inflammatory biomarkers, such as high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor α (TNF-α), Raise levels of antioxidant enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase, Protect against pesticide-induced oxidative stress and heavy-metal toxicity, Improve the brain's electrical activity, which may explain its benefits for cognitive performance, and short-term memory in the elderly, Influence the formation and activity of key biomolecules, such as S-adenosyl methionine (SAM-e) and nicotinamide adenine dinucleotide (NAD+), and Potentially help ameliorate the adverse effects of traditional chemotherapeutic agents. Because the amount of boron varies in the soil, based on geographical location, obtaining enough boron through diet alone can be difficult. Supplementing with low-cost boron is an effective way to maintain adequate levels of this overlooked micronutrient.
Episode 67: Covid, Food, and HIV. Medical students discuss the relationship between high cholesterol and COVID-19, the effect of food order in postprandial glucose and insulin, and HIV history. Moderated by Hector Arreaza, MD. During this episode you will listen to three medical students discussing some topics that they found interesting during their family medicine rotation. All the credit goes to them because they read these topics and provided a very good summary. I hope you enjoy it.____________________High Cholesterol and COVID-19By Milan Hinesman, MS3, Ross University School of MedicineGiven the current state of the world, there's been a lot more attention to COVID-19 presentation, risks, and treatment. One study conducted by Dr. Kun Zhang and collaborators shows that there may be a relationship between higher total cholesterol levels and ApoB levels to increased risk of COVID-19 infection[1]. Dr. Zhang used a mendelian randomization from the UK Biobank data to test for lipid effects on COVID susceptibility and severity. The study performed analysis of data from the host genetics initiative consisting of more than 14,000 cases and more than one million controls showing a potential positive causal effect between high total cholesterol and ApoB and COVID susceptibility. A mendelian randomization is a process of taking genes which functions are already known and measuring their response to exposure to a disease in observational studies[2]. In short, high cholesterol and high ApoB are linked to COVID-19 infection.This is Rio Bravo qWeek, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it's sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. __________________________Impact of food order on glucose after meals. By Yvette Singh, MS3, American University of the CaribbeanIn the management of diabetes, health care providers usually assess glycemic control with fasting plasma glucose and pre-prandial glucose measurements, as well as by measuring Hemoglobin A1c. Therapeutic goals for Hemoglobin A1c and pre-prandial glucose levels have been established based on the results of controlled clinical trials. Unfortunately, many patients with diabetes fail to achieve their glycemic goals. Elevated glucose after eating may be the cause of poor glycemic control leading to vascular complications. Postprandial hyperglycemia is one of the earliest abnormalities of glucose homeostasis associated with type 2 diabetes. This is one of the important therapeutic targets for glycemic control. Current studies show that the amount and timing of carbs in the diet primarily influence blood glucose levels. Other studies also show that eating whey protein before meals, as well as changing the macronutrients in meals, reduces postprandial glucose levels; however, these studies did not have patients with type 2 diabetes. The main author of this study was Alpana P. Shukla and many other collaborators. The title is Food Order Has a Significant Impact on Postprandial Glucose and Insulin Levels, published by the American Diabetes Association on Diabetes Care in July 2015.This study was performed to analyze the order of food consumption with vegetables, protein and carbohydrates and its effects on postprandial glucose in overweight/obese patients with type 2 diabetes being treated with metformin. Subjects were studied for 1 week. They were given a meal with the same number of calories, after fasting for 12 hours: 55g protein, 68g carbs, and 16g fat. They were asked to eat carbs first, then to eat vegetables and protein fifteen minutes later. This order was reversed during the second week. Their postprandial glucose and insulin levels were measured at 30/60/120 mins after meals. The statistical studies showed an average post prandial glucose decrease by more than 25% when protein was consumed first. As well as the average post prandial insulin levels decreased by more than 40%. These results demonstrated that the timing of carbs during a meal has a significant impact on glucose and insulin levels comparable to some pharmacological agents. Reduced insulin excretion with this meal pattern may also improve insulin sensitivity. This may help patients with type 2 diabetes control their HbA1c, and possibly help reverse early diabetes. Educating patients about this approach is not controlling how much they are eating or restricting their diet so patients will likely comply with this recommendation. Eat your protein first!The potential problems of this study are that it was a small sample size (11 patients), limited food types, and insulin was measured only up to 120 minutes after meals. Further studies are needed to demonstrate the full effectiveness of this recommendation.___________________HIV Series Part I: HIV HistoryBy Robert Dunn, MS3, Ross University School of Medicine This is an HIV series for the Rio Bravo qWeek Podcast. The following episodes will include some of the history of HIV, transmissibility, the PARTNER-1 and PARTNER-2 studies, and will finalize with a full episode on HIV prevention. Today we are starting with HIV history.Prejudice against those with HIV stems from the history surrounding the virus. Between 1981-1983, cases of rare infections like Pneumocystis carinii pneumonia (PCP) and aggressive cancers like Kaposi Sarcoma were appearing predominantly amongst gay men and injection drug users. Even children were presenting with AIDS creating misconceptions of how the disease was transmitted by touch. By 1982, this syndrome was referred to as the Gay-Related Immunodeficiency (GRID), which we now know as AIDS. Some History of HIVThe start of the Human Immunodeficiency Virus (HIV) was thought to have started in the Democratic Republic of Congo in 1920 when the virus crossed species to humans and gave its ability to infect humans[4]. In 1981, five young gay men in Los Angeles, California, presented with a rare lung infection called Pneumocystis carinii pneumonia (PCP). Two other groups of men also presented with a rare and aggressive cancer called Kaposi Sarcoma, in New York and California. By December of the same year, the first case of PCP was found in an injection drug user. And by the end of the year, there were 270 reported cases of this severe immunodeficiency and about 121 of them had already died from it, almost 50%. In 1982, due to the prevalence of these rare diseases being present among gay men, the syndrome was called the Gay-Related Immune Deficiency (GRID). The CDC later officially called the disease the Acquired Immune Deficiency Syndrome (AIDS). The term “gay cancer” was used in Venezuela before AIDS was known.In 1983, the disease was found in both women and children. In May 1983, in a joint conference between the Pasteur Institute in France and the National Cancer Institute, they announced that LAV and HTLV-III were the same virus and the cause of AIDS.In 1985, Ryan White, a teenager with hemophilia was banned from school when he was diagnosed with HIV after he received contaminated blood products. Ryan later died at 18 years old due to AIDS-related illnesses. At the same time, the FDA licensed the first commercial blood test to detect HIV. A foundation was later created to provide primary care and medications for low-income HIV patients.In 1987, the first antiretroviral drug, Zidovudine (AZT) was approved by the FDA to treat for HIV. In 1991, the famous basketball player Magic Johnson announced he tested positive for HIV and retired immediately. After his retirement he planned to educate young people about the virus which helped dispel stereotypes. Also in 1991, the famous singer of Queen announced he had AIDS and died the next day.In 1993, the movie Philadelphia with Tom Hanks promoted further discussion about HIV and AIDS. In June 1995, the first protease inhibitor was approved by the Food and Drug Administration (FDA), which started the era for Highly Active Antiretroviral Therapy (HAART). This brought down the rate of AIDS-related deaths and hospitalizations by 60-80%. Of special note, in 1986, the FDA passed the policy to ban all men who had sex with men (MSM) from 1977 onward, from donating blood or plasma to avoid the risk of transmitting HIV or Hepatitis A. This policy was amended in December 2015, when the revised policy said any MSM within the last 12 months, would need to wait at least 1 year before donating blood. In light of the COVID-19 pandemic, the FDA amended it its policy once more to decrease the wait time to 3 months form the last time the man had sex with another man.____________________________Conclusion: Now we conclude our episode number 67 “Covid, Food, and HIV.” Kudos to Milan, Yvette and Robert, they presented relevant information for our practice of medicine. They taught us that high cholesterol is a risk for COVID-19 infection; Also, when you eat proteins first, your glucose and insulin after meals are lower than when you eat carbs first; and you will be hearing from Robert for a couple episodes regarding HIV. Today he gave us a little piece of HIV history. Even without trying, every night you go to bed being a little wiser.Thanks for listening to Rio Bravo qWeek. If you have any feedback about this podcast, contact us by email RBresidency@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. This podcast was created with educational purposes only. Visit your primary care physician for additional medical advice. This week we thank Hector Arreaza, Milan Hinesman, Yvette Singh, and Robert Dunn. Audio edition: Suraj Amrutia. See you next week! _____________________References:Zhang, K. Dong, S. Guo, et. al., Causal Associations Between Blood Lipids and COVID-19 Risk: A Two-Sample Mendelian Randomization Study. Arteriosclerosis, Thrombosis, and Vascular Biology, originally published on September 9, 2021. https://doi.org/10.1161/ATVBAHA.121.316324. What is Mendelian Randomization and How Can it be Used as a Tool for Medicine and Public Health? Opportunities and Challenges, Webinar announcement given by Professor George Davey Smith on November 27, 2018. Centers for Disease Control and Prevention, https://www.cdc.gov/genomics/events/precision_med_pop.htm Alpana P. Shukla, Radu G. Iliescu, Catherine E. Thomas and Louis J. Aronne, Food Order Has a Significant Impact on Postprandial Glucose and Insulin Levels, Diabetes Care 2015 Jul; 38(7): e98-e99. https://doi.org/10.2337/dc15-0429. History of HIV and AIDS Overview. Avert, October 10, 2019. https://www.avert.org/professionals/history-hiv-aids/overview. Accessed on September 21, 2021. Shaw, Maggie. FDA's Revised Blood Donation Guidance for Gay Men Still Courts Controversy. AJMC, April 3, 2020. https://ajmc.com/view/fdas-revised-blood-donation-guidance-for-gay-men-still-courts-controvery. Accessed on September 21, 2021. BAYER, R. (2015), Science, Politics, and the End of the Lifelong Gay Blood Donor Ban. Milbank Quarterly, 93: 230-233. https://doi.org/10.1111/1468-0009.12114. Ways HIV can be Transmitted. Centers for Disease Control and Prevention, April 21, 2021. https://www.cdc.gov/hiv/basics/hiv-transmission/ways-people-get-hiv.html. Accessed on September 21, 2021.
Credits: 0.25 AMA PRA Category 1 Credit™ CME/CE Information and Claim Credit: https://www.pri-med.com/online-education/podcast/frankly-speaking-cme-237 Overview: Solid evidence shows that adverse pregnancy outcomes (APOs) correlate with an increased risk of cardiovascular disease (CVD) in women. Evidence is also becoming clearer that lactation and breastfeeding may have CV protective benefits as well. Social determinants of health play a significant role in these diseases; facts support that Black, Hispanic and Asian American women suffer from worse pregnancy outcomes than White American women. Join us while we discuss the recent American Heart Association (AHA) guideline update regarding the association of increased risk of CVD and metabolic disease with APOs and what can be done to reduce these risks. Episode resource links: Adverse Pregnancy Outcomes and Cardiovascular Disease Risk: Unique Opportunities for Cardiovascular Disease Prevention in Women. Nisha I. Parikh, MD, MPH, Chair, Juan M. Gonzalez, MD, Cheryl A.M. Anderson, PhD, Suzanne E. Judd, PhD, Kathryn M. Rexrode, MD, Mark A. Hlatky, MD, Erica P. Gunderson, PhD, Jennifer J. Stuart, ScD, Dhananjay Vaidya, PhD, Vice Chair, On behalf of the American Heart Association Council on Epidemiology and Prevention; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; and the Stroke Council. https://www.ahajournals.org/doi/abs/10.1161/CIR.000000000000096 Schwartz, EB. (reviewing Parikh NI et al. Circulation 2021 Mar 29). Preventing Heart Disease in Women: New Guidance from the American Heart Association. NEJM: Journal Watch, April 12, 2021. https://www.jwatch.org/na53433/2021/04/12/preventing-heart-disease-women-new-guidance-american-heart?ijkey=3l3eCvQLl Clinical Statements and Guidelines. AHA/ACOG Presidential Advisory. Volume 137, Issue 24, 12 June 2018, Pages e843-e852. https://doi.org/10.1161/CIR.0000000000000582 https://www.jwatch.org/na53433/2021/04/12/preventing-heart-disease-women-new-guidance-american-heart Guest: Susan Feeney, DNP, FNP-BC, NP-C Music Credit: Richard Onorato
Credits: 0.25 AMA PRA Category 1 Credit™ CME/CE Information and Claim Credit: https://www.pri-med.com/online-education/podcast/frankly-speaking-cme-237 Overview: Solid evidence shows that adverse pregnancy outcomes (APOs) correlate with an increased risk of cardiovascular disease (CVD) in women. Evidence is also becoming clearer that lactation and breastfeeding may have CV protective benefits as well. Social determinants of health play a significant role in these diseases; facts support that Black, Hispanic and Asian American women suffer from worse pregnancy outcomes than White American women. Join us while we discuss the recent American Heart Association (AHA) guideline update regarding the association of increased risk of CVD and metabolic disease with APOs and what can be done to reduce these risks. Episode resource links: Adverse Pregnancy Outcomes and Cardiovascular Disease Risk: Unique Opportunities for Cardiovascular Disease Prevention in Women. Nisha I. Parikh, MD, MPH, Chair, Juan M. Gonzalez, MD, Cheryl A.M. Anderson, PhD, Suzanne E. Judd, PhD, Kathryn M. Rexrode, MD, Mark A. Hlatky, MD, Erica P. Gunderson, PhD, Jennifer J. Stuart, ScD, Dhananjay Vaidya, PhD, Vice Chair, On behalf of the American Heart Association Council on Epidemiology and Prevention; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; and the Stroke Council. https://www.ahajournals.org/doi/abs/10.1161/CIR.000000000000096 Schwartz, EB. (reviewing Parikh NI et al. Circulation 2021 Mar 29). Preventing Heart Disease in Women: New Guidance from the American Heart Association. NEJM: Journal Watch, April 12, 2021. https://www.jwatch.org/na53433/2021/04/12/preventing-heart-disease-women-new-guidance-american-heart?ijkey=3l3eCvQLl Clinical Statements and Guidelines. AHA/ACOG Presidential Advisory. Volume 137, Issue 24, 12 June 2018, Pages e843-e852. https://doi.org/10.1161/CIR.0000000000000582 https://www.jwatch.org/na53433/2021/04/12/preventing-heart-disease-women-new-guidance-american-heart Guest: Susan Feeney, DNP, FNP-BC, NP-C Music Credit: Richard Onorato
ACCEL Lite: Featured ACCEL Interviews on Exciting CV Research
The causes of heart attacks are shifting in this era of better control of cholesterol, blood pressure, and smoking and fewer instances of fatty plaque rupturing and causing blood clots. But a different cause of clots seems to be on the rise: superficial erosion. The underlying cause of clots is a hot research area because we can learn how to personalize treatment of acute heart attacks instead of using a one-size-fits-all approach. In this interview, Deepak Bhatt, MD, FACC; Peter Libby, MD, FACC; and Matt Cavender, MD, MPH, FACC, share a vascular biology update on vulnerable plaques. For 20+ insider interviews like these every month with CME/MOC credit, subscribe to ACCEL at www.ACC.org/ACCEL.
La thrombocytopénie thrombotique immunitaire induite par certains vaccins contre la COVID, dont ceux produits par AstraZeneca et Johnson et Johnson, a fait couler beaucoup d'encre dans l'actualité. Quels sont les risques réels, les symptômes à surveiller et la conduite à adopter pour le pharmacien ? Pierre Lemieux, pharmacien au CIUSSS de la Mauricie et du Centre du Québec, a bien voulu nous éclairer sur le sujet. Références : 1. Thrombocytopénie immunitaire prothrombotique induite par le vaccin – TIPIV (ou TTIV) en contexte de vaccination contre la COVID-19. INSPQ. Version du 19 avril 2021 https://publications.msss.gouv.qc.ca/msss/fichiers/directives-covid/dgaumip-030-rev1_thrombocytopenie-tipiv-%20vaccin-covid-19.pdf 2. Comité consultatif national de l'immunisation (CCNI). Recommandations sur l'utilisation des vaccins contre la COVID-19. Mise à jour du 23 avril 2021. https://www.canada.ca/content/dam/phac-aspc/documents/services/immunization/national-advisory-committee-on-immunization-naci/recommendations-use-covid-19-vaccines/recommandations-utilisation-vaccins-covid-19-fr.pdf 3. Mahase E. AstraZeneca vaccine: Blood clots are “extremely rare” and benefits outweigh risks, regulators conclude BMJ 2021; 373 :n931 doi:10.1136/bmj.n931 https://www.bmj.com/content/373/bmj.n931 4. Les thromboses (caillots sanguins) et les vaccins contre la COVID-19. Thrombose canada Foire aux questions. Avril 2021. https://thrombosiscanada.ca/wp-uploads/uploads/2021/04/COVID-19-vaccine-and-Thrombosis-FAQs-April-2-2021_FR.pdf 5. Tacquet et al. Cerebral venous thrombosis: a retrospective cohort study of 513,284 confirmed COVID-19 cases and a comparison with 489,871 people receiving a COVID-19 mRNA vaccine, preprint https://osf.io/a9jdq/ 6. Katsanos et al. The Impact of SARS‐CoV‐2 on Stroke Epidemiology and Care: A Meta‐Analysis Ann Neurol. 2020 Dec 9 : 10.1002/ana.25967 (2020) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753413/ ; 7. Andreas Greinacher et coll. Anti-SARS-CoV-2 Spike Protein and Anti-Platelet Factor 4 Antibody Responses Induced by COVID-19 Disease and ChAdOx1 nCov-19 vaccination, 09 April 2021, PREPRINT (Version 1) available at Research Square https://www.researchsquare.com/article/rs-404769/v1 8. Scully et coll. Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination. NEJM April 16, 2021. DOI: 10.1056/NEJMoa2105385 https://www.nejm.org/doi/full/10.1056/NEJMoa2105385 9. Gowthami M et coll. Heparin-Induced Thrombocytopenia A Focus on Thrombosis. Arteriosclerosis, Thrombosis, and Vascular Biology. 2021;41:141–152 https://www.ahajournals.org/doi/pdf/10.1161/ATVBAHA.120.315445 10. CDC. Coronavirus Disease 2019 (COVID-19) Vaccines https://www.cdc.gov/vaccines/acip/meetings/slides-2021-04-23.html 11. The Gamalaya Center Statement https://sputnikvaccine.com/newsroom/pressreleases/the-gamaleya-center-statement/ 12. Greinacher A. et coll. Towards Understanding ChAdOx1 nCov-19 Vaccine-induced Immune Thrombotic Thrombocytopenia (VITT). 2021. Preprint. https://assets.researchsquare.com/files/rs-440461/v1/8eabf306-6fd4-4a89-a7a3-8f4d06c89a55.pdf
Focus Issue on Vascular Biology and Medicine
Dr. Barend Mees joins us to discuss the upcoming 24th European Vascular Course, and how they are adapting surgical simulation to virtual education. Dr. Mees is a consultant Vascular & Endovascular Surgeon in the department of Vascular Surgery at MUMC+ in Maastricht. He currently is Associate Professor and Deputy Head of the department of Vascular Surgery. His clinical area of interest is the endovascular treatment of complex aortic disease and peripheral arterial disease. He is the research coordinator of the department of Vascular Surgery and has obtained a PhD in Vascular Biology from Erasmus MC, INSERM (U689, Paris) and Max-Planck Institute (Bad Nauheim, Germany). His main research focus areas are vascular biology, tissue engineering and training in innovative endovascular techniques. Dr. Mee is the inventor of the MAZE Box, a novel hands-on training simulator for Endovascular Surgery and tutor for Vascular International. Dr. Mees is an examiner of the UEMS FEBVS examination since 2017. He is organizer of the I-MEET congress and course director of the European Vascular Course. He has been Secretary of the Dutch Society for Vascular Surgery since 2018. European Vascular Course - March 7-8, 2021 Watch the MAZE box in action! What other topics would you like to hear about? Let us know more about you and what you think of our podcast through our Listener Survey or email us at AudibleBleeding@vascularsociety.org. Follow us on Twitter: @AudibleBleeding
What is Metabolic Syndrome and how is it related to obesity and Type 2 Diabetes? Vivian Tran, Ph.D. candidate in the Vascular Biology and Immunopharmacology group at La Trobe University, shares what her studies on mice have revealed about Metabolic Syndrome, the cardiovascular complications of Diabetes, and the risk factors of obesity. Listen to learn more about: The differences in fat distribution between men and women and the associated obesity risks Whether or not obesity should be considered a Type 2 Diabetes cause The different types of fat cells and which type is more dangerous to your health Metabolic Syndrome is not one disease; it is a group of medical conditions that occur together in the same person. These conditions include high blood pressure, heart disease, stroke, Type 2 Diabetes, obesity, and high cholesterol. Due to rising rates of obesity, it is estimated that nearly one third of the U.S. population suffers from Metabolic Syndrome. Vivian has set out to find the answers to questions including why more men than women die from Metabolic Syndrome related cardiovascular events when more women than men are diagnosed with the disease. Could this be due to the difference in fat distribution and the presence of subcutaneous versus visceral fat cells in men and women? Vivian explains the differences in the health risks associated with belly fat in comparison to fat on other areas of the body and the dangerous of visceral fat, which can attach itself to internal organs. Her research on the role of fat tissue surrounding blood vessels and how it affects vascular function in those with Metabolic Syndrome could lead to major advancements in the prevention of cardiovascular disease in those who suffer from it. For more information follow Vivian on Twitter at https://twitter.com/vivianvtran Available on Apple Podcasts: apple.co/2Os0myK
On today’s episode of JIMMY RANTS on The LLVLC Show, we take a look at a new “study” that makes a dubious connection between Keto and coronary calcium. “How can they say with a straight face that this is a low-carbohydrate diet? It’s not even close!” - JIMMY MOORE One of the major benefits of eating a low-carb diet are the incredible cardiovascular health improvements that happen as a result of restricting carbohydrate and increasing fat and protein. Lower triglycerides, lower blood sugar, lower blood insulin, lower inflammation, higher HDL cholesterol, reduced blood pressure, and more are the signs that you’re eating less carbs in your diet. But a new study from Chinese researchers is now claiming a low-carb diet, especially one consisting of animal-based fat and protein, Will lead to progression of coronary artery calcium (CAC). In this episode of JIMMY RANTS on The LLVLC Show, I read from the October 16, 2020 study published by Chinese researchers in the journal Arteriosclerosis, Thrombosis, and Vascular Biology entitled “Low-Carbohydrate Diet Score and Coronary Artery Calcium Progression.” They claim that the participants in the “low-carb“ cohort saw the greatest progression of CAC as compared to the moderate and higher carb cohorts. What do they consider low-carb—45-49% of total energy intake! Oh, I have so much to say about this very bad scientific study and you can hear all about it in today’s episode!
Focus Issue on Vascular Biology and Medicine
This month on Episode 16 of the Discover CircRes podcast, host Cindy St. Hilaire highlights four featured articles from the August 28 and September 11 issues of Circulation Research. This episode features an in-depth conversation with Drs Andrew Murphy and Michelle Flynn from The Baker Heart and Diabetes Institute at Monash University in Melbourne, Australia regarding their study Transient Intermittent Hyperglycemia Accelerates Atherosclerosis By Promoting Myelopoiesis. Article highlights: Fish, et al. KRAS Mutations Cause Arteriovenous Malformations Ehling, et al. B55a in Vascular Biology Barrett, et al. Platelet Activity and Vascular Health in COVID-19 Furmanik, et al. Nox5 in VSMC Phenotype and Calcification Cindy St. Hilaire: Hi. Welcome to Discover CircRes, the podcast to the American Heart Association's journal, Circulation Research. I'm your host, Dr Cindy St. Hilaire, from the Vascular Medicine Institute at the University of Pittsburgh. And today I'm going to share with you four articles selected from our late August and early September issues of Circulation Research. I'm also going to speak with Drs Andrew Murphy and Michelle Flynn from The Baker Heart and Diabetes Institute at Monash University in Melbourne, Australia regarding their study Transient Intermittent Hyperglycemia Accelerates Atherosclerosis By Promoting Myelopoiesis. So first, the highlights. The first article I'm sharing with you is titled Somatic Gain of KRAS Function in the Endothelium is Sufficient to Cause Vascular Malformations that Require MEK but not PI 3-Kinase Signaling. First authors are Jason Fish, Carlos Perfecto Flores-Suarez, and Emily Boudreau. And the corresponding authors are Jason Fish and Joshua Wythe, and they're from University of Toronto and Baylor College of Medicine. Arterial venous malformations, or AVMs, are tangles of blood vessels in which the arteries are directly connected to the veins without going through the capillary bed. These are thought to be present from birth and when they occur in the brain, they can cause an array of symptoms such as headaches or seizures, but they are also the leading cause of hemorrhagic stroke in children and young adults. This is because the venous system is not muscularized to respond to the pressure forces that are exerted on arteries. These pressure forces cause distension and eventual leakage at the site of AVMs. Vessel tissue recovered from patients undergoing AVM repair has been shown to contain sematic gain of function mutations in the protein RAS GTPase, which is encoded by the gene, KRAS. However, whether these gain of function mutations directly cause AVMs has not been established. This study now shows that endothelial cells with constitutive expression of gain of function KRAS mutants in mice and zebra fish causes vascular malformations and cranial hemorrhages. Inhibiting a MEK kinase, which is a downstream mediator of RAS signaling, prevented hemorrhages in the mutant KRAS carrying fish. In vitro studies also showed that overactive RAS GTPase protein caused excessive angiogenic behavior of endothelial cells. Together, this work confirms the link between gain of function KRAS mutations and brain AVMs, and suggests that MEK inhibition could be a potential strategy for nonsurgical treatment. The second article I want to share with you is titled B55a/PP2A Limits Endothelial Cell Apoptosis During Vascular Remodeling: A Complimentary Approach To Kill Pathological Vessels. The first author is Manuel Ehling and the corresponding author is Massimiliano Mazzone. And the work was completed at Leuven Center for Cancer Biology in Belgium. Building a mammalian vascular system is a dynamic process that is dependent on both growth of new vessels, as well as the pruning of unwanted ones. But while much is known about molecular mechanisms underlying angiogenesis, comparatively little is understood about the mechanisms regulating vascular pruning. This study discovered that suppression of the protein phosphatase 2 subunit, B55A, is a key protein regulating the pruning process. They found that in mouse vascular development, B55a is widely expressed. However, in adult mice expression is restricted only to sites of active angiogenesis. Deletion of B55a in mice caused death in mid to late stages of embryogenesis as a result of vascular problems that appeared to be due to excessive vessel pruning. Switching off B55a in adult mice when the vascular development is for the most part complete did not cause any apparent problems. They did find though, that inhibition of B55a significantly delayed growth of tumors that form from the injection of cancerous cells. Inhibition of B55a produced tumors with less dense vasculature and reduced metastatic potential. Thus, the author suggests that ramping up blood vessel pruning, be it inhibition of B55a, could be a novel strategy for limiting tumor growth. The next article I want to share is titled Platelet and Vascular Biomarkers Associated With Thrombosis and Death in COVID-19. The first author is Tessa Barrett and the corresponding author is Jeffrey Berger, and they're from New York University. Our knowledge of the complications of COVID-19 is evolving every day. Laboratory testing done to date suggests that approximately 30% of hospitalized COVID-19 patients go on to develop thrombotic events. Platelets are central characters in both arterial and venous thrombosis, and it is known that virus platelet interactions can stimulate a pro-coagulant and inflammatory state during a viral infection. Further, recent studies have reported COVID-19 patients have hyperactive platelets and autopsies of COVID-19 patients exhibit micro and macro thrombi across vascular beds, even in patients without clinical thrombosis. This group then hypothesized that biomarkers of platelet activation are associated with incident thrombosis or death in COVID-19 patients. To test this, they randomly selected 100 COVID-19 positive patients and analyzed banked samples collected on the day of the COVID-19 diagnosis to investigate in vivo platelet activity, as well as vascular health biomarkers. They show for the first time that biomarkers of platelet activation at the time of diagnosis are associated with thrombosis or death in patients hospitalized with COVID-19. Their findings suggest platelet activation mechanisms may contribute to adverse events and highlight the potential role of antiplatelet therapy in this disease. The last article I want to share with you before we switch to our interview is titled Reactive Oxygen-Forming Nox5 Links Vascular Smooth Muscle Cell Phenotypic Switching and Extracellular Vesicle-Mediated Vascular Calcification. The first authors are Malgorzata Furmanik and Martijn Chatrou. And the corresponding author is Leon Schurgers from Maastricht University in The Netherlands. Vascular calcification is an active process regulated by several mechanisms, including vascular smooth muscle cell apoptosis, osteochondral genic transdifferentiation, extracellular vesicle release, and cellular senescence. In healthy adult arteries, smooth muscle cells maintain a contractile phenotype. However, various insults such as oxidative or mechanical stress, can induce smooth muscle cells to lose their contractility and this process of de-differentiation is termed phenotypic switching. And phenotypic switching is thought to precede the development of vascular disease. Patients with conditions such as chronic kidney disease have mineral imbalances in their circulation and also exhibit higher levels of vascular calcification. However, the mechanisms behind these observations are not well defined. This group found that extracellular calcium can enter the smooth muscle cells via extracellular vesicles and this increased cytosolic calcium concentration. Increased calcium induces expression and activity of Nox5 in NADPH oxidase. Activation of Nox5 increased production of reactive oxygen species, which in turn decreased contractile marker expression, and also promoted calcification in vitro. Intracellular calcium signaling also further enhanced extracellular vesicle secretion, and decreased extracellular vesicle uptake. This then promoted the accumulation of extracellular vesicles in the extracellular matrix, which is a mechanism that promotes calcification. Together, these data suggest that mineral imbalances, such as those seen in chronic kidney disease patients, contribute to loss of smooth muscle cell contractility, which promotes osteochondral genic transdifferentiation. For the interview portion today, I have with me Drs Andrew Murphy and Michelle Flynn from the Baker Heart and Diabetes Institute and Monash University in Melbourne Australia. And we're going to be discussing their manuscript titled Transient Intermittent Hyperglycemia Accelerates Atherosclerosis by Promoting Myelopoiesis. But really I like the running title, which is Hyperglycemic Spikes Accelerate Atherosclerosis. So thank you both very much for joining me today. Michelle Flynn: Thanks for having us. Cindy St. Hilaire: So before we start to ‘stalk a bit about what the details of this study is, could you maybe give us a little primer on what you've done that led up to this study? Andrew Murphy: Yeah, so this really was a continuation of a study that began actually when I was in my postdoc in Allan Tall lab and working with Ira Goldberg’s lab with the postdoc Prabhakara R Nagareddy there. We've shown along with Ed Fisher’s group at NYU, that mice that had established atherosclerotic lesions that were then made diabetic, failed to have lesion regression compared to those that were non-diabetic with normalized plasma cholesterol levels. We showed that if we gave an SGLT-2 inhibitor to normalize glucose that regression then started to occur. And then we found that this was primarily driven by myelopoiesis, suddenly increased production of monocytes, which through that entered the plaque. And so from that, that was in the hyperglycemic model which is sort of a very rare patient group these days, because most people are on well-controlled glucosteroid drugs. And really the SGLT-2 inhibitors have been a game changer in that scenario. And what we were trying to do with this study was bring it into a more clinically relevant setting that might show the potential importance of glucose on a much larger population. Cindy St. Hilaire: Excellent. Maybe you could give us an introduction to the link between what's known about diabetes and cardiovascular disease and the interplay? Michelle Flynn: So diabetic and pre-diabetic patients actually account for 65% of all cardiovascular deaths, which really indicates that diabetes itself plays a major factor alongside other things like obesity and hypercholesterolemia. And so we've previously shown that hyperglycemia was actually driving atherosclerosis in a chronic hyperglycemic setting. So given that kind of vascular disease actually affects both diabetic and pre-diabetic patients, we suspected that it may not just be chronic hyperglycemia or really intense hyperglycemia that could be driving this issue. And so what we were actually looking at in this paper was how more transient levels of hyperglycemia, which actually occur quite often in both diabetic patients and pre-diabetic patients, how much this can contribute to cardiovascular disease. Andrew Murphy: I guess this link between poor glucose control and cardiovascular disease is obviously very well established. The interesting part is that HbA1c only predicts part of the risk. If you look at fasting blood glucose, again, that's only partially responsible, but if you look at postprandial or two hour glucose loads, you'll see that that is more predictive of cardiovascular events than the other two measures. And it seems to be a continuum. So even if you are a healthy or non-diabetic individual, you obviously still have those postprandial events and depending how high that goes up is thought to be a predictive of future cardiovascular outcomes. And so obviously that's worse than people with pre-diabetes and then again worse with people that have actual, full blown diabetes. Cindy St. Hilaire: And what is a transient hyperglycemic event? What would do that in maybe you and me who don't have diabetes versus someone who has diabetes or is pre-diabetic? Michelle Flynn: So essentially what we're modeling with this transient hyperglycemia is that postprandial increase in glucose after you have a meal, which in people who have impaired glucose tolerance is going to be more pronounced than in someone who has a normal glucose tolerance. Cindy St. Hilaire: Got it. And so how did you test this in the mice? Michelle Flynn: We did this by developing a novel model of transient hyperglycemia. So we used ordinary wild type mice that weren't diabetic, and we injected them with glucose intraperitoneally, which then increased blood glucose levels in the plasma after about 15 minutes up to about 15 to 20 millimolar. And then after about two hours, this decreased back down to baseline levels. So this was very similar to what you actually see in a postprandial event. And by doing this four times throughout the day, we were able to mimic what you might see in a patient who has had several meals across the day who has impaired glucose tolerance. Andrew Murphy: One other advantage with the model that we used was that we were trying to really isolate the effects of glucose. And so by injecting glucose intraperitoneally in otherwise healthy mice, it bypasses the incretin response, which we know loses efficacy, I guess, in people that are diabetic. And so we were just really mimicking acute glucose rises that would occur after a meal. And then obviously in this wild type mouse the insulin response would then kick in to clear the glucose so it really tests that glucose hypothesis. Cindy St. Hilaire: So it's really digging in deeply on the actual sugar component, not just eating in general or other aspects. So in some of your experiments, or I guess in actually most of them, you show that the injection of glucose, it increased the plaque size in these mice, but it didn't alter the cholesterol levels. So can you explain a bit what's going on there? A little bit about the mechanism you discovered and kind of specifically introducing RAGE and the S100A8 and A9 axis? Michelle Flynn: Yeah, so what we showed was that regardless of cholesterol levels, we were seeing an increase in clot plaque size, and this was actually driven by the monocytes and neutrophils which were increased in the circulation of these mice. And then these are able to infiltrate into the plaque where they promote plaque progression. And what we found was that the increase in monocytes and neutrophils was due to an increase in their production within the bone marrow. And this was in turn due to the signaling by a protein heterodimer of S100A8 and A9, which signals via the receptor RAGE in the bone marrow on the progenitors of these cells, which induces their proliferation and differentiation. And then that produces an increase in the production of those immune cells, which promote plaque progression. Cindy St. Hilaire: Interesting. So it's really independent of kind of the basic thing that everyone thinks about, or I guess as non-scientists think about, is cholesterol. The public really focus on cholesterol, but what your study's showing is there's this whole other glucose mediated immune arm to it. What else does this S100A8-A9 regulate? Andrew Murphy: So S100A8 and A9 has some intracellular roles, which may direct the development of the model itself, but really a lot of its extracellular roles and so on is promoting sterile inflammation, chemotaxis, so activation of local immune cells. And in the context of diabetes and obesity, many of other diseases, it can signal via RAGE, as Michelle said, but it can also signal by TLR4. And so it seems as though in those diseases driven mainly by glucose, such as the modeling of postprandial hyperglycemia or all kinase in general, it will signal via RAGE, but we've also shown in the setting of obesity that it will signal via TLR4 to stimulate things like interleukin 1 beta. We've also had a paper just recently in Circulation with Prabhakara Nagareddy’s group where we've shown post myocardial infarction that prime neutrophils in the heart to eventually release IL1-beta and cause myelopoiesis in that way. Cindy St. Hilaire: Wow, so this is really kind of an early activator of a much bigger immune response, whether it's in atherosclerosis or MI or probably, I don't know, a handful other things, I guess, right? Andrew Murphy: It seems to be really important when neutrophils are involved. So in a setting of an MI, we know that they come into the heart very early and become activated and it really makes them about 40% of the cytosol proteins of the cells. So when it degranulates or lyses, they are kind of neutral, at least in the predominant protein. Cindy St. Hilaire: Okay. So this is released in NETs in NETosis then? Andrew Murphy: That's what we're sort of discovering so far. So I guess all I can say is, stay tuned, this is a story for another day. Cindy St. Hilaire: Okay. That's really interesting though. Andrew Murphy: We haven’t looked in gglucose driven events yet. Cindy St. Hilaire: Yeah and actually one of the interesting things I've learned from your study, I had known about GLUT1 and that GLUT1 was I guess the constituently active of the glucose transporters, but I didn't realize it was so high on neutrophils and that neutrophils were so dependent metabolically on glucose. Can you maybe tell a little bit more about that story? Michelle Flynn: Yes. So the neutrophil itself is actually very highly dependent on glycolysis because it doesn't actually have many mitochondria. So compared to most cells, they have very few mitochondria so they can't really rely upon the oxidative phosphorylation for their general metabolism. And so they predominantly rely on glucose coming into the cell and then being shuttled through glycolysis to generate their energy. And yeah this does seem to be predominantly due to uptake of glucose through GLUT1. Cindy St. Hilaire: And then that excess glucose, the byproduct, is reactive oxygen species and upregulation and this cascade of- Michelle Flynn: Yes, yes that's correct. Cindy St. Hilaire: Okay, great. So currently we use HbA1c as a biomarker for overall kind of glucose regulation in diabetic patients. And based on your studies and perhaps the studies of others, would neutrophil numbers or even S100A8 or A9 be a better metric to figure out where a pre-diabetic or even a healthy patient is in terms of their glucose tolerability? Michelle Flynn: Yeah. That could actually be an interesting marker to look at. Given that neutrophils and S100 are also associated with obesity and diabetes in general, and as well as the risk for cardiovascular disease. So with the progression of diabetes, you could expect that the levels of these would increase as well. Andrew Murphy: We've shown previously when we first discovered that the S100 was important in diabetes, that in the Pittsburgh study with Trevor Orchard's group, he had followed people with type one diabetes for 20 years, that those that did develop a cardiovascular event had a higher S100A8 and A9 levels and that correlated with neutrophils. And so it certainly seems to be a marker of predictive outcomes. And so those that do have poorer glycemic control will have higher neutrophils. That's well known. And so perhaps you're right that probably in combination with HbA1c or things like two hour post glucose challenges, S100A8 and A9 and perhaps neutrophil counts would also be a nice predictive measure of potential cardiovascular outcomes of that person. Cindy St. Hilaire: Wow. That'd be really great because you could then maybe kind of more fine tune and predict which patients might be more or less susceptible to cardiovascular events. Andrew Murphy: That's right. Yeah. I think one other important aspect would be if HbA1c is deemed to be relatively well under control, yet you still have a high level of S100A8 and A9, that perhaps those transient spikes are contributing. You're not picking that up in the HbA1c, which looks like the average over approximately a month. And so that could be a nice way to add value onto that score. Cindy St. Hilaire: Interesting. I didn't realize it was that stable about over a month. All right. So I'm relatively healthy. I'm not pre-diabetic, but if I eat a whole bunch of cake or a whole bunch of ice cream or drink a lot of beer, does that create un me a transient hyperglycemic event that is of the same range we're talking about and what do your findings suggest for people who are relatively healthy and things we should be aware about regarding eating habits and things like that? Andrew Murphy: Yeah. I think it's a really good question. And it's sort of hard to give you an exact answer to that right now. We need to look at that in people, model these sort of same spikes in people, but what we I guess don't know yet, even in the preclinical models is how high and how long does that glucose have to be? And I think that's one of the most important questions first. So is there a danger zone where these neutrophils start be the innate senses of hyperglycemia that start to then release S100A8 and A9 to cause these downstream events? But what our data does show is that if you're doing this, having a binge night or a binge day once a week for your life, then that's probably not going to be a great thing. Cindy St. Hilaire: Yeah. All right. So you need to figure out is one scoop of ice cream okay, but two not so great. Andrew Murphy: Maybe if it's two different flavors it'll be okay. Cindy St. Hilaire: Maybe, right? That's great. So, I mean, is there a way we could potentially therapeutically target this signaling axis or is it too ubiquitous in terms of what it regulates? Is there a way to harness what you've found potentially in the clinic? Michelle Flynn: Yeah, so there's an inhibitor of S100A8 and A9 that prevents its binding to RAGE. It's currently approved as an Orphan Drug for systemic sclerosis in both the US and the UK. And that drug itself, we tested in our preclinical mouse model, and we found that it was in fact able to prevent their production of these immune cells, as well as prevent the accelerated atherosclerosis in response to these transient hypoglycemic spikes. Andrew Murphy: So another sort of line of thinking that we're exploring is that we could actually target neutrophil metabolism itself. And so now we're sort of understanding, are there certain proteins that are more abundantly expressed in neutrophils and not other cells in the body that would regulate glycolysis? I know that might sound a bit of a pie in the sky sort of idea, because glycolytic pathway's quite regulated, but there we have found some proteins that are rich in neutrophils and not other cells that may be responsible for the early steps of glycolysis. And so whether that can be harnessed or not, we'll have to see in the future, but it might be a way of more directly targeting neutrophils rather than approaching that's important in sterile inflammation. Cindy St. Hilaire: That makes sense. That is such a cool idea and this is really such a beautiful story. It's one of those papers that you just read it and it's just such a logical progression, but it's also really interesting and I really appreciated all those bone marrow transplants. I did those in grad school, so well done. It's a beautiful story. And then I'm just really happy that you published it with us. So thank you so much for joining me today. Andrew Murphy: Yeah thanks for having us. Michelle Flynn: Thank you. Cindy St. Hilaire: That's it for highlights from the late August and early September issues of Circulation Research. Thank you so much for listening. Please check out the Circulation Research Facebook page and follow us on Twitter and Instagram with the handle @CircRes and #DiscoverCircRes. Thank you to our guests, Drs Andrew Murphy and Michelle Flynn. This podcast is produced by Rebecca McTavish and Ashara Ratnayaka, edited by Melissa Stoner, and supported by the Editorial Team of Circulation Research. Some of the copy text for the highlighted articles is provided by Ruth Williams. I'm your host, Dr Cindy St. Hilaire, and this is Discover CircRes, your on-the-go source for the most exciting discoveries in basic cardiovascular research.
Dr Bernhard Hochreiter combines biology and physics to study how the proteins in our cells behave and interact with each other. In this episode, we talk about what it's like to be straddling multiple disciplines, and discuss the issue of how negative results are rarely published.Bernhard recently completed his PhD in the lab of Johannes Schmid, at the Institute of Vascular Biology and Thrombosis Research, which is part of the Medical University of Vienna (@MedUni_Wien).For more information about Nice To Know, follow me on Twitter @RobynSciences or email nicetoknowthepodcast@gmail.com. I'm always on the lookout for new scientists to talk to! This series was made with the support of the Marie Curie Alumni Association.
Focus Issue on Vascular Biology
Jane Ferguson: Hi, everyone. Welcome to episode 29 of Getting Personal: Omics of the Heart, the podcast from Circulation: Genomic and Precision Medicine. I'm Jane Ferguson from Vanderbilt University Medical Center and an associate editor at Circ: Genomic and Precision Medicine. Let's dive in and see what's new in the June issue. First up, Validation of Genome-Wide Polygenic Risk Scores for Coronary Artery Disease in French Canadians from Florian Wünnemann, Guillaume Lettre and colleagues from the University of Montreal. Polygenic scores have the potential to be used to predict disease risk, but have not been broadly validated in different populations. This team was interested in whether polygenic risk scores that have been found to predict coronary artery disease in European ancestry subjects in the UK Biobank would also predict disease in French Canadians. They calculated two different polygenic risk scores in over 3600 cases and over 7000 controls and tested their ability to predict prevalent, incident and recurrent CAD. Both scores predicted prevalent CAD, but did not perform as well in predicting incident or recurrent disease. This maybe because the majority of subjects were on statant treatment. Overall, the study confirms that polygenic risk scores for CAD developed in European ancestry can be used in other populations of European ancestry. However, further work is needed to develop and validate polygenic risk scores in other ancestries and to explore whether well performing risk scores can be developed to predict incident or recurrent disease. Our next paper comes from Farnaz Shoja-Taheri, Michael Davis and colleagues from Emory University and is entitled Using Statistical Modeling to Understand and Predict Pediatric Stem Cell Function. Stem cell therapy is emerging as a potential therapeutic option for treating pediatric heart failure, which otherwise can only be cured through heart transplantation. The success of stem cell therapy depends on many variables, including the reparative ability of the infused cells. In this paper, the author set out to test whether they could predict the behavior of c-kit+ progenitor cells or human CPCs using RNA seq and computational modeling. They obtained CPCs from 32 patients, including eight neonates whose cells are thought to have the highest reparative capacity, and they performed RNA sequencing. The team had previously developed regression models that could link gene expression data from sequencing to phenotypes in the cells, and they tested these models in the CPC cell lines. They tested seven neonate cell lines in vitro and found that cellular proliferation and the chemotactic potential of condition media matched what was predicted by the RNA seq-based model. They used pathway analysis to identify potential mechanisms regulating CPC performance and identified several genes related to immune response, including interleukins and chemokines. They further confirmed the presence of cytokines at the protein level that were associated with well performing cells showing that at least one of the outcomes could be functionally predicted using an ELISA ASA. This type of approach may prove useful to inform ongoing clinical trials to stem cell therapy in congenital heart disease. The next paper, Systems Pharmacology Identifies an Arterial Wall Regulatory Gene Network Mediating Coronary Artery Disease Side Effects of Antiretroviral Therapy comes to us from Itziar Frades, Johan Björkegren, Inga Peter and colleagues from the Icahn School of Medicine at Mount Sinai. They were interested in understanding mechanisms whereby antiretroviral therapy for HIV leads to increased risk for coronary artery disease. They analyzed the transcriptional responses to 15 different antiretroviral therapy or ART drugs in human cell lines and cataloged the common transcriptional signatures. They then cross-referenced these against gene networks associated with CAD and CAD related phenotypes. They found that 10 of 15 ART response networks were enriched for differential expression and connectivity in an atherosclerotic arterial wall of regulatory gene network identified as causal for CAD. They used cholesteryl ester loaded foam cells in an in vitro model to validate their findings and found that ART treatment increased cholesteryl ester accumulation in foam cells which was prevented when the key network regulator gene, PQBP1, was silenced. Their study highlights a gene network which is altered in response to ART and which promotes foam cells formation, highlighting a mechanistic link between HIV treatment and CAD. Targeting this network potentially through PQBP1 maybe a way to reduce the risk of CAD in individuals treated with antiretroviral drugs. The next paper comes from Brooke Wolford, Whitney Hornsby, Cristen Willer, Bo Yang and colleagues from the University of Michigan and is entitled Clinical Implications of Identifying Pathogenic Variants in Individuals With Thoracic Aortic Dissection. They were interested in whether exome sequencing in individuals with thoracic aortic dissection could identify disease associated variance. They conducted exome sequencing in 240 patients and 258 controls and screened 11 genes for potentially pathogenic variance. They identified 24 variance in six genes across 26 cases with no potentially pathogenic variance identified in the controls. They found that carriers of pathogenic variance had significantly earlier age of onset of dissection, higher rates of root aneurysm and greater incidents of aortic disease in family members, while patients without identified variance had more hypertension and a higher rate of smoking. Their study suggests that genetic testing should be considered in patients with thoracic artery dissection particularly in individuals with early age of onset before age 50 and no hypertension with the possibility of cascade screening to follow to identify at risk family members before onset of dissection and possible death. Our next paper is a research letter from Seyedeh Zekavat, Pradeep Natarajan and colleagues from Harvard Medical School, Investigating the Genetic Link Between Arterial Stiffness and Atrial Fibrillation. They aimed to investigate whether arterial stiffness is causal for atrial fibrillation using Mendelian randomization to probe genetic causality. They calculated the genetic component of the arterial stiffness index or ASI, a noninvasive measure of arterial stiffness, in over 131,000 individuals in the UK Biobank. They then assessed whether the genetic predictors of ASI defined as the top six independent variance were also associated with atrial fibrillation in over 225,000 participants in the UK Biobank and in over 588,000 individuals from a multi-ethnic GWAS. They found that the ASI genetic risk score was significantly associated with incident atrial fibrillation in both the UK Biobank and the multi-ethnic AF GWAS. The association held true even after adjustment for age, sex, smoking status, prevalent heart failure, prevalent hypertension, prevalent CAD, prevalent hypercholesterolemia, prevalent diabetes, heart rate, alcohol intake and exercise frequency in the UK Biobank participants. Because some people have hypothesized that atrial fibrillation may actually precede and cause arterial stiffness, the team did the reverse Mendelian randomization experiment and tested whether genetic predictors of AF were associated with the arterial stiffness index. They found no association suggesting that AF does not cause arterial stiffness. In summary, this paper provides genetic evidence supporting arterial stiffness as a causal contributor to atrial fibrillation and suggests that future randomized controlled studies would be warrantied to assess whether methods to reduce arterial stiffness could be protective against atrial fibrillation. The next research letter comes from Scott Damrauer, Kara Hardie, Reed Pyeritz and colleagues from the University of Pennsylvania and is entitled FBN1 Coding Variants and Nonsyndromic Aortic Disease. In this study, the authors were interested in characterizing the frequency of variance associated with Marfan syndrome in the general population. They analyzed data from the Penn Medicine BioBank looking at 12 variance in the FBN1 gene all of which have been reported to associate with Marfan syndrome. Of almost 11,000 individuals who underwent exome sequencing, they identified 70 individuals who were carriers of one of the 12 preselected FBN1 variance. These individuals ranged in age from age 28 to 87 years and 56% of them were male. They combed through clinical data from the participant's electronic health records, including office notes, diagnostic tests and imaging studies. Two individuals had a clinical diagnosis of Marfan syndrome while 21 individuals had evidence of cardiovascular phenotypes related to Marfan syndrome including mitral valve disease, dilated sinus of valsalva, dilated ascending aorta, descending thoracic or abdominal aneurysms or dissections or had undergone surgical procedures involving the mitral valve or thoracic aorta. Compared to age and sex matched controls without known or suspected pathogenic FBN1 variance, the FBN1 variant carriers were significantly more likely to have Marfan syndrome related cardiovascular disease. Although the majority of individuals carrying FBN1 variance did not have documented cardiovascular disease in this study, the data were somewhat limited, meaning that some affected individuals could have been missed. Thus, while the penetrance of these variance appears to be variable, the severe consequences of these FBN1 variance observed in some individuals suggests that clinical screening for carries of these variance is important. To round up this month's issue, we have a scientific statement led by Ferhaan Ahmad and Elizabeth McNally on Establishment of Specialized Clinical Cardiovascular Genetics Programs: Recognizing the Need and Meeting Standards. This statement comes from the American Heart Association Council on Genomic and Precision Medicine, the Council on Arteriosclerosis, Thrombosis and Vascular Biology, the Council on Basic Cardiovascular Sciences, the Council on Cardiovascular and Stroke Nursing, the Council on Clinical Cardiology and the Stroke Council. In this statement, the writing group lays out the importance of establishing specialized centers of care for individuals affected by inherited cardiovascular diseases. As cardiovascular genetics as a field continues to grow and as genomic medicine becomes part of practice, it is essential for programs to evolve to include this new knowledge and specialization. There are significant challenges in interpreting genetic test results and in evaluating counseling and managing the care of genetically at risk family members who have inherited pathogenic variance, but not yet shown signs of disease. Establishing specialized programs to combine cardiovascular medicine and genetics expertise is an effective way to allow for the integration of multiple types of clinical and genetic data and to improve diagnosis, prognostication and cascade family testing in affected individuals and their families. Training individuals in genetic cardiology will allow for improved care and management of risk in affected or at risk individuals and potentially pave the way for genotype specific therapy. This important and timely scientific statement outlines current best practices for delivering cardiovascular genetic evaluation and care in both the pediatric and the adult settings with a focus on team member expertise and conditions that most benefit from genetic evaluation. That's all for this month. Thank you as always for listening and come back next month for the next installment of papers in Genomic and Precision Medicine. This podcast was brought to you by Circulation: Genomic and Precision Medicine and the American Heart Association Council on Genomic and Precision Medicine. This program is copyright American Heart Association 2019.
Ivor Cummins is a Biochemical Engineer who in 2012 was disturbed by a set of his own abnormal blood test results. Consultation with multiple doctors yielded little insight into the cause of his elevated cholesterol, ferritin and GGT so he turned to his analytical roots to study the problem. In the process, he evaluated hundreds of scientific papers, ultimately concluding that that flawed hypotheses and a breach of the scientific method have resulted in the current “diabesity” epidemic. Ivor is here today with Dr. Tommy Wood talking on topics related to his well-referenced new book, Eat Rich, Live Long: Mastering the Low-Carb & Keto Spectrum for Weight Loss and Great Health. They also discuss the trouble with polyunsaturated oils, advice on fat loss for the insulin sensitive, and the best test for cardiovascular disease risk (hint: it’s not LDL). If you enjoy this podcast, Ivor is a regular presenter at low-carb/keto events and maintains an active blog and social media presence. Here’s the outline of this interview with Ivor Cummins: [00:00:17] Keto Summit, Dave Feldman. [00:00:48] Boundless Health Podcast with Dr. Bret Scher. [00:01:57] Podcast: The True Root Causes of Cardiovascular Disease, with Dr. Jeffry Gerber. [00:02:15] Book: Eat Rich, Live Long: Mastering the Low-Carb & Keto Spectrum for Weight Loss and Great Health, by Ivor Cummins and Jeffry Gerber, MD. [00:02:29] Videos: here and here. [00:03:20] Insulin, IGF-1, acellular carbs. [00:03:56] Sunlight exposure, 25-OH-D video. [00:04:37] Minerals, Study: DiNicolantonio, James J., James H. O’Keefe, and William Wilson. "Subclinical magnesium deficiency: a principal driver of cardiovascular disease and a public health crisis." Open Heart 5.1 (2018): e000668. [00:05:28] Gabor Erdosi, Lower Insulin Facebook Group. [00:05:43] Video: Roads to Ruin? from Physicians for Ancestral Health 2017 conference. [00:06:01] Guðmundur Jóhannsson, gut health; Podcast: Foodloose Iceland. [00:07:40] Study: Schwalfenberg, Gerry K., and Stephen J. Genuis. "The importance of magnesium in clinical healthcare." Scientifica 2017 (2017). [00:08:10] Industrial seed oils. [00:09:05] Unilever sells its margarine business. [00:10:17] Studies: Alvheim, Anita Røyneberg, et al. "Dietary Linoleic Acid Elevates the Endocannabinoids 2‐AG and Anandamide and Promotes Weight Gain in Mice Fed a Low Fat Diet." Lipids 49.1 (2014): 59-69. And: Alvheim, Anita R., et al. "Dietary Linoleic Acid Elevates Endogenous 2‐AG and Anandamide and Induces Obesity." Obesity 20.10 (2012): 1984-1994. [00:10:48] Studies: Nanji, Amin A., and Samuel W. French. "Dietary factors and alcoholic cirrhosis." Alcoholism: Clinical and Experimental Research 10.3 (1986): 271-273. And: Kirpich, Irina A., et al. "Alcoholic liver disease: update on the role of dietary fat." Biomolecules 6.1 (2016): 1. [00:12:09] Book: Deep Nutrition: Why Your Genes Need Traditional Food, by Cate Shanahan, M.D. [00:12:45] Studies: 1. Ramsden, Christopher E., et al. "The Sydney Diet Heart Study: a randomised controlled trial of linoleic acid for secondary prevention of coronary heart disease and death." The FASEB Journal 27.1 Supplement (2013): 127-4. 2. Frantz, Ivan D., et al. "Test of effect of lipid lowering by diet on cardiovascular risk. The Minnesota Coronary Survey." Arteriosclerosis, Thrombosis, and Vascular Biology 9.1 (1989): 129-135. 3. Strandberg, Timo E., et al. "Mortality in participants and non-participants of a multifactorial prevention study of cardiovascular diseases: a 28 year follow up of the Helsinki Businessmen Study." Heart 74.4 (1995): 449-454. 4. Rose, G. A., W. B. Thomson, and R. T. Williams. "Corn oil in treatment of ischaemic heart disease." British medical journal 1.5449 (1965): 1531. [00:13:47] Study: Hooper, Lee, et al. "Reduction in saturated fat intake for cardiovascular disease." The Cochrane Library (2015). [00:15:28] Study: Ip, Clement, Christopher A. Carter, and Margot M. Ip. "Requirement of essential fatty acid for mammary tumorigenesis in the rat." Cancer Research 45.5 (1985): 1997-2001. [00:16:28] Study: Pearce, Morton Lee, and Seymour Dayton. "Incidence of cancer in men on a diet high in polyunsaturated fat." The Lancet 297.7697 (1971): 464-467. [00:16:56] Breast milk composition is now almost 50% PUFA. [00:17:50] David Bobbett. [00:19:59] Book structure. [00:20:51] Fat-loss for the insulin sensitive. [00:21:10] Videos: Jeff Gerber interviews Simon Saunders and Marty Kendall. [00:23:03] Ghrelin. [00:24:21] Protein and lean body mass. [00:26:05] Glucagon, mTOR. [00:26:22] Ron Rosedale. [00:26:34] Valter Longo. [00:27:02] IGF-1 U-shaped curve. [00:28:06] Study: Levine, Morgan E., et al. "Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population." Cell metabolism 19.3 (2014): 407-417. [00:28:49] Book: Protein Power: The High-Protein/Low Carbohydrate Way to Lose Weight, Feel Fit, and Boost Your Health - in Just Weeks! By Michael Eades and Mary Dan Eades. [00:30:39] Study: Levine, Morgan E., et al. "Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population." Cell metabolism 19.3 (2014): 407-417. [00:31:06] NHANES. [00:31:18] Study: Cohen, Evan, et al. "Statistical review of US macronutrient consumption data, 1965–2011: Americans have been following dietary guidelines, coincident with the rise in obesity." Nutrition 31.5 (2015): 727-732. [00:32:20] Kitavans. [00:34:05] Hyperlipid and Denise Minger. [00:36:37] Icelandic diets for longevity [00:39:07] Cardiovascular disease. [00:39:35] Basic lipid panel. [00:39:45] Study: Castelli, William P. "Lipids, risk factors and ischaemic heart disease." Atherosclerosis 124 (1996): S1-S9. [00:40:24] Ratios. [00:41:54] Study: Johnson, Kevin M., David A. Dowe, and James A. Brink. "Traditional clinical risk assessment tools do not accurately predict coronary atherosclerotic plaque burden: a CT angiography study." American Journal of Roentgenology 192.1 (2009): 235-243. Commentary: Ware, William R. "The mainstream hypothesis that LDL cholesterol drives atherosclerosis may have been falsified by non-invasive imaging of coronary artery plaque burden and progression." Medical hypotheses 73.4 (2009): 596-600. [00:42:30] Familial Hypercholesterolemia and CVD. [00:43:27] cholesterolcode.com, remnant cholesterol, Plasma Atherogenic Index. [00:44:36] Podcast: Health Outcome-Based Optimal Reference Ranges for Cholesterol [00:46:06] Coronary calcium scan. [00:46:25] Study: Nasir, Khurram, et al. "Interplay of Coronary Artery Calcification and Traditional Risk Factors for the Prediction of All-Cause Mortality in Asymptomatic Individuals Clinical Perspective." Circulation: Cardiovascular Imaging 5.4 (2012): 467-473. [00:47:54] Longitudinal score. [00:49:41] Plaque density. [00:50:11] Interview with Matt Budoff. [00:52:37] Video: Dr. Eades at Low Carb Breckenridge, Agatston score. [00:54:38] The Fat Emperor. [00:54:53] Low-carb Breckenridge 2018. [00:55:10] Ketofest, Keto Con, Low-carb USA, Refind Health. [00:55:45] Widowmaker movie.
Do we recognize shock early enough? How do we prioritize our interventions? How can we tell whether we’re making our patient better or worse? World wide, shock is a leading cause of morbidity and mortality in children, mostly for failure to recognize or to treat adequately. So, what is shock? Simply put, shock is the inadequate delivery of oxygen to your tissues. That’s it. Our main focus is on improving our patient’s perfusion. Oxygen delivery to the tissues depends on cardiac output, hemoglobin concentration, the oxygen saturation of the hemoglobin you have, and the environmental partial pressure of oxygen. At the bedside, we can measure some of these things, directly or indirectly. But did you notice that blood pressure is not part of the equation? The reason for that is that blood pressure is really an indirect proxy for perfusion – it’s not necessary the ultimate goal. The equation here is a formality: DO2 = (cardiac output) x [(hemoglobin concentration) x SaO2 x 1.39] + (PaO2 x 0.003) Shock CAN be associated with a low blood pressure, but shock is not DEFINED by a low blood pressure. Compensated Shock: tachycardia with poor perfusion. A child compensates for low cardiac output with tachycardia and a increase in systemic vascular resistance. Decompensated Shock: frank hypotension, an ominous, pre-arrest phenomenon. Shock is multifactorial, but we need to identify a primary cause to prioritize interventions. How they "COHDe": Cardiogenic, Obstructive, Hypovolemic, and Distributive. Cardiogenic Shock All will present with tachycardia out of proportion to exam, and sometimes with unexplained belly pain, usually due to hepatic congestion. The typical scenario in myocarditis is a precipitous decline after what seemed like a run-of-the-mill URI. Cardiogenic shock in children can be from congenital heart disease or from acquired etiologies, such as myocarditis. Children, like adults, present in cardiogenic shock in any four of the following combinations: warm, cold, wet, or dry. "Warm and Dry" A child with heart failure is “warm and dry” when he has heart failure signs (weight gain, mild hepatomegaly), but has enough forward flow that he has not developed pulmonary venous congestion. A warm and dry presentation is typically early in the course, and presents with tachycardia only. "Warm and Wet" If he worsens, he becomes “warm and wet” with pulmonary congestion – you’ll hear crackles and see some respiratory distress. Infants with a “warm and wet” cardiac presentation sometimes show sacral edema – it is their dependent region, equivalent to peripheral edema as we see in adults with right-sided failure. “Warm” patients – both warm and dry and warm and wet -- typically have had a slower onset of their symptoms, and time to compensate partially. Cool patients are much sicker. "Cold and Dry” A patient with poor cardiac output; he is doing everything he can to compensate with increased peripheral vascular resistance, which will only worsen forward flow. Children who have a “cold and dry” cardiac presentation may have oliguria, and are often very ill appearing, with altered mental status. "Cold and Wet" The sickest of the group, this patient is so clamped down peripherally that it is now hindering forward flow, causing acute congestion, and pulmonary venous back-up. You will see cool, mottled extremities. Cardiogenic Shock: Act Use point-of-care cardiac ultrasound: Good Squeeze? M-mode to measure fractional shortening of the myocardium or anterior mitral leaflet excursion. Pericardial Effusion? Get ready to aspirate. Ventricle Size? Collapsed, Dilated, Careful with fluids -- patients in cardiogenic shock may need small aliquots, but go quickly to a pressor to support perfusion Pressor of choice: epinephrine, continuous IV infusion: 0.1 to 1 mcg/kg/minute. Usual adult starting range will end up being 1 to 10 mcg/min. Avoid norepinephrine, as it increases systemic vascular resistance, may affect afterload Just say no to dopamine: increased mortality when compared to epinephrine Obstructive Shock Mostly one of two entities: pulmonary embolism or cardiac tamponade. Pulmonary embolism in children is uncommon – when children have PE, there is almost always a reason for it – it just does not happen in normal, healthy children without risk factors. Children with PE will either have a major thrombophilic comorbidity, or they are generously sized teenage girls on estrogen therapy. Tamponade -- can be infectious, rheumotologic, oncologic, or traumatic. It’s seen easily enough on point of care ultrasound. If there is non-traumatic tamponade physiology, get that spinal needle and get to aspirating. Obstructive Shock: Act Pulmonary embolism (PE) with overt shock: thrombolyse; otherwise controversial. PE with symptoms: heparin. Tamponade: if any sign of shock, pericardiocentesis, preferentially ultrasound-guided. Hypovolemic Shock The most common presentation of pediatric shock; look for decreased activity, decreased urine output, absence of tears, dry mucous membranes, sunken fontanelle. May be due to obvious GI losses or simply poor intake. Rapid reversal of hypovolemic shock: may need multiple sequential boluses of isotonic solutions. Use 10 mL/kg in neonates and young infants, and 20 mL/kg thereafter. Hypovolemic Shock: Act Tip: in infants, use pre-filled sterile flushes to push fluids quickly. In older children, use a 3-way stop cock in line with your fluids and a 30 mL syringe to "pull" fluids, turn the stop cock, and "push them into the patient. Titrate to signs of perfusion, such as an improvement in mental status, heart rate, capillary refill, and urine output. When concerned about balancing between osmolality, acid-base status, and volume status, volume always wins. Our kidneys are smarter than we are, but they need to be perfused first. Distributive Shock The most common cause of distributive shock is sepsis, followed by anaphylactic, toxicologic, adrenal, and neurogenic causes. Septic shock is multifactorial, with hypovolemic, cardiogenic, and distributive components. Children with sepsis come in two varieties: warm shock and cold shock. Distributive Shock: Act Warm shock is due to peripheral vascular dilation, and is best treated with norepinephrine. Cold shock is due to a child’s extreme vasoconstriction in an attempt to compensate. Cold shock is the most common presentation in pediatric septic shock, and is treated with epinephrine. Early antibiotics are crucial, and culture everything that seems appropriate. Shock: A Practical Approach "How FAST you FILL the PUMP and SQUEEZE" Sometimes things are not so cut-and-dried. We'll use a practical approach to diagnose and intervene simultaneously. Look at 4 key players in shock: heart rate, volume status, contractility, and systemic vascular resistance. How FAST you FILL the PUMP and SQUEEZE First, we look at heart rate -- how FAST? Look at the heart rate – is it sinus? Could this be a supraventricular tachycardia that does not allow for enough diastolic filling, leading to poor cardiac output? If so, use 1 J/kg to synchronize cardiovert. Conversely, is the heart rate too slow – even if the stroke volume is sufficient, if there is severe bradycardia, then cardiac output -- which is in liters/min – is decreased. Chemically pace with atropine, 0.01 mg/kg up to 0.5 mg, or use transcutaneous pacing. If the heart rate is what is causing the shock, address that first. Next, we look at volume status. How FAST you FILL the PUMP and SQUEEZE Look to FILL the tank if necessary. Does the patient appear volume depleted? Try a standard bolus – if this improves his status, you are on the right track. Now, we look at contractility. How FAST you FILL the PUMP and SQUEEZE Is there a problem with the PUMP? That is, with contractility? Is this in an infarction, an infection, a poisoning? Look for signs of cardiac congestion on physical exam. Put the probe on the patient’s chest, and look for effusion. Look to see if there is mild, moderate, or severe decrease in cardiac contractility. If this is cardiogenic shock – a problem with the pump itself -- begin pressors. And finally, we look to the peripheral vascular resistance. How FAST you FILL the PUMP and SQUEEZE Is there a problem with systemic vascular resistance – the SQUEEZE? Look for signs of changes in temperature – is the patient flushed? Is this an infectious etiology? Are there neurogenic or anaphylactic concerns? After assessing the heart rate, optimizing volume status, evaluating contractility, is the cause of the shock peripheral vasodilation? If so, treat the cause – perhaps this is a distributive problem due to anaphylaxis. Treat with epinephrine. The diagnosis of exclusion in trauma is neurogenic shock. Perhaps this is warm shock, both are supported with norepinephrine. All of these affect systemic vascular resistance – and the shock won’t be reversed until you optimize the peripheral squeeze. Summary The four take-home points in the approach to shock in children To prioritize your innterventions, remember how patients COHDe: Cardiogenic, Obstructive, Hypovolemic, and Distributive. Your patient's shock may be multifactorial, but mentally prioritize what you think is the MAIN case of the shock, and deal with that first. To treat shock, remember: How FAST You FILL The PUMP and SQUEEZE: Look at the heart rate – how FAST. Look at the volume status – the FILL. Assess cardiac contractility – the PUMP, and evaluate the peripheral vascular tone – the SQUEEZE. In pediatric sepsis, the most common type is cold shock – use epinephrine (adrenaline) to get that heart to increase the cardiac output. In adolescents and adults, they more often present in warm shock, use norepinephrine (noradrenaline) for its peripheral squeeze to counteract this distributive type of shock. Rapid-fire word association: Epinephrine for cardiogenic shock Intervention for obstructive shock Fluids for hypovolemic shock Norepinephrine for distributive shock References Agha BS, Sturm JJ, Simon HK, Hirsh DA. Pulmonary embolism in the pediatric emergency department. Pediatrics. 2013 Oct;132(4):663-7. Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013; 41:580-637. Jaff MR et al. for the American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; American Heart Association Council on Peripheral Vascular Disease; American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011; Apr 26;123(16):1788-830. Levy B et al. Comparison of norepinephrine-dobutamine to epinephrine for hemodynamics, lactate metabolism, and organ function variables in cardiogenic shock. A prospective, randomized pilot study. Crit Care Med. 2011; 39:450. Micek ST, McEvoy C, McKenzie M, Hampton N, Doherty JA, Kollef MH. Fluid balance and cardiac function in septic shock as predictors of hospital mortality. Crit Care. 2013; 17:R246. Osman D, Ridel C, Ray P, et al. Cardiac filling pressures are not appropriate to predict hemodynamic response to volume challenge. Crit Care Med. 2007; 35:64-8. Ventura AM, Shieh HH, Bousso A, Góes PF, de Cássia F O Fernandes I, de Souza DC, Paulo RL, Chagas F, Gilio AE. Double-Blind Prospective Randomized Controlled Trial of Dopamine Versus Epinephrine as First-Line Vasoactive Drugs in Pediatric Septic Shock. Crit Care Med. 2015;43(11):2292-302. This post and podcast are dedicated to Natalie May, MBChB, MPHe, MCEM, FCEM for her collaborative spirit, expertise, and her super-charged support of #FOAMed. You make a difference. Thank you. Undifferentiated Shock Powered by #FOAMed -- Tim Horeczko, MD, MSCR, FACEP, FAAP
Benita Katzenellenbogen, John Katzenellenbogen, and Zeynep Madak-Erdogan explain how designer estrogens can deliver the the therapeutic benefits of natural estrogens with less cancer risk.
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Zorina Galis is the Chief of Vascular Biology and Hypertension Branch at the National Institute of Health. Coming from Transylvania she had to prove herself as a scientist in a new country. We chat about her move from Pharma to helping people at NIH. Continue Reading→
Donald E. Ingber, Founding Director of the Wyss Institute, Judah Folkman Professor of Vascular Biology at Harvard Medical School, and Professor of Bioengineering at the Harvard School of Engineering and Applied Sciences, talks about his article "Mechanobiology and Developmental Control," which he wrote with Tadanori Mammoto and Akiko Mammoto for the 2013 Annual Review of Cell and Developmental Biology. He discusses the role of physical and mechanical forces in the control of cell development and disease, which he says is as important as chemicals and genes.
Dr. R. Wayne Alexander. Angiotensin II, Oxidative Stress and Vascular Biology. Recorded 2013-09-09.
Wed, 1 Jan 2003 12:00:00 +0100 https://epub.ub.uni-muenchen.de/16651/1/10_1159_000070715.pdf Schymeinsky, J.; Walzog, B. ddc:61
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