Podcasts about MTOR

The First Lady of Nutrition welcomes Ross Pelton, aka The Natural Pharmacist, to discuss Rapamycin, the most effective life extension drug that has ever been discovered. Ann Louise and Ross waste no time diving into the science behind it. In layman's terms, Ross expounds on the relationship between mTOR and autophagy (your body's process of reusing old and damaged cell parts) and how the topics discussed in his fascinating new book, “Rapamycin, mTOR, Autophagy & Treating mTOR Syndrome,” provide us with a totally new understanding of metabolism, health, and the aging process. As Ross explains, the ratio between mTOR and autophagy is severely out of balance in most people living today, and he has named this condition ‘mTOR Syndrome.' Rapamycin helps correct the mTOR/autophagy ratio, which slows down the onset of virtually all age-related diseases. The goal is not just life extension, it is increased health span! The post The Most Promising Life Extension Drug You Never Heard Of – Episode 126: Ross Pelton first appeared on Ann Louise Gittleman. The post The Most Promising Life Extension Drug You Never Heard Of – Episode 126: Ross Pelton appeared first on Ann Louise Gittleman.

Sebastijan Orlić doktor znanosti kemijskog inženjerstva, Certificate in Exercise Nutrition, Precision nutrition, Certificirani Nutriogenomičar, Fitness instruktor. CSO Cidrani Biome, Team Specialist for GlycanAge, Consultant in the supplements industry at Lifecare Essentials Europe GmbH. Bivši Crossfit natjecatelj, iskusni poznavatelj svih benefita ali i nedostataka ovog sporta. Svjestan svog potencijala prekinuo je ovu vrstu aktivnosti jer kako kaže nije Crossfit za svakog. Tu smo se dotakli najvažnijeg aspekta svakog Crossfitera a to je oporavak. Na koje sve načine se može unaprijediti oporavak kao i suplementacija koja bi bila poželjna kod kvalitetnog oporavka. PODRŽI RAD PODCASTA JEDNOKRATNIM UPLATAMA NA PAY PAL: https://paypal.me/humanlabpodcast Hvala ti od srca na velikodušnosti! FACEBOOK GRUPA: Human LAB -Zdravlje, fitness, dugovječnost, medicina https://www.facebook.com/groups/humanLABpodcast *MYPROTEIN 40% popust na cijeli račun putem linka https://www.myprotein.hr/referrals.list?applyCode=MATEO-R7E ili korištenjem koda MATEO-R7E SkillShare - https://skillshare.eqcm.net/humanlab je odlična online platforma za učenje. Mjesto gdje na dohvat ruke imate ciljane i specifične edukacije iz toliko različitih područja da ni sami niste svjesni za što se sve može čovjek educirati. Bilo da je riječ o sportu, treningu ili video editingu, produktivnosti ili pak heklanju. SkillShare možete isprobati besplatno na mjesec dana putem linka. U tih mjesec dana možete pogledati koliko god stignete bez ograničenja, a ako se i odlučite na Skillshare i dalje. Putem ovog linka dobivate 40% popusta na godišnju pretplatu. Definitivno najbolje uložen novac u vlastitu edukaciju!! Dakle za besplatni probni mjesec i 40% popusta prijavite se na SkillShare Putem linka https://skillshare.eqcm.net/humanlab Lazarus Coffee https://bit.ly/3d9mIlK - Njihova misija je približiti ovu vrstu kave svakom kavoljupcu u Hrvatskoj i oduševiti svaki ukus. Specialty kava mnogo je više od samo kave. Prosječnih proizvoda ima dovoljno, i baš vam zato žele pružiti specialty. Jer prosječan život nije za nas! Budi iznad prosjeka, biraj Lazarus coffee baš kao što sam ga odabrao i ja. Kao osoba koja obožava pravi okus kave tako sam napokon pronašao i ja svog dobavljača. Možete iznajmiti kafe aparat ili pak dogovoriti pretplatu gdje će svakog mjeseca na vašu adresu stizati doza kvalitetne kave. A sve to možete provjetiti na linku: https://bit.ly/3d9mIlK Ukoliko jednostavno želite zahvaliti za trud i rad koji ulažem u ovaj podcast onda je ovo najbolji način. A ja obećavam kako će sav novac biti uložen u podizanje kvalitete podcasta. Link za direktnu uplatu! ( https://paypal.me/humanlabpodcast ) U svakom slučaju nemoj se osjećati loše ako to sada ne možeš učiniti. I lajk i komentar jednako su vrijedni kao i donacija. A možeš čak i podjeliti sa svojim društvom ovu epizodu. VREMENSKE OZNAKE: 00:00 - Intro 02:15 - Ispravak informacije iz prvog razgovora o fitoestrogenima 10:40 - Što definira kvalitetu života 20:45 - mTOR, AMPK, Sirtuini i dugovječnost 23:35 - Mitohondriji i dugovječnost 29:45 - Što je zapravo Autofagija 40:25 - Inzulin i inzulinska rezistencija 45:15 - Metformin i AMPK 47:45 - Peter Attia 55:15 - Kronični niskointenzivni upalni proces 59:45 - Gut health, AniBiome, fermentacija 01:28:10 - Postbiotici 01:33:30 - Umjetna sladila i mikrobiom 01:37:35 -Utjecaj Intermittent Fastinga na crijevnu floru 01:41:15 - Glikani, Glycan Age, Gordan Lauc, Biološka i kronološka dob 01:56:25 - Kolesterol i pretilost

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.30.510408v1?rss=1 Authors: Cai, Y., Kanyo, J., Wilson, R., Mansuri, M. S., Cardozo, P. L., Goshay, D., Tian, Z., Braker, A., Trinh, H. K., Lam, T., Brennand, K., Nairn, A. C., Grutzendler, J. Abstract: Amyloid deposits in Alzheimer's disease (AD) are surrounded by large numbers of plaque-associated axonal spheroids (PAAS). PAAS disrupt axonal electrical conduction and neuronal network function, and correlate with AD severity. However, the mechanisms that govern their formation remain unknown. To uncover the molecular architecture of PAAS, we applied proximity labeling proteomics of spheroids in human AD postmortem brains and mice. We then implemented a human iPSC-derived AD model recapitulating PAAS pathology for mechanistic studies. Using this strategy, we uncovered hundreds of previously unknown PAAS-enriched proteins and signaling pathways, including PI3K/AKT/mTOR. Phosphorylated mTOR was highly enriched in PAAS and strongly correlated with disease severity in humans. Importantly, pharmacological mTOR inhibition in iPSC-derived human neurons or AAV-mediated knockdown in mice, led to a marked reduction of PAAS pathology. Altogether, our study provides a novel platform to examine mechanisms of axonal pathology in neurodegeneration and to evaluate the therapeutic potential of novel targets. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

What is rapamycin? What is mTor? What is the connection between rapamycin and cancer? How does rapamycin activate autophagy? Who should and shouldn't take rapamycin? What are the benefits and risks of intermittent fasting? Thank you to our sponsor, LMNT. Listeners receive a free 8-serving sample pack with their purchase here. Thank you to our sponsor, InsideTracker. Listeners get 20% off on all products here. Ross Pelton, pharmacist and scientific director for Essential Formulas, Inc joins us to discuss rapamycin and its potential benefit for age-related diseases, its connection to cancer treatment, intermittent fasting, and more. Disclaimer: This is not medical advice. Always consult your doctor before adding any supplements or medications into your life. “Rapamycin is the most effective anti-aging drug that's ever been discovered.” “These days, people start eating at 7 in the morning and do breakfast, lunch and dinner and mid-meal snacks and dessert after supper and maybe an evening cocktail. So, from 7 in the morning until 7 at night, that's 12 hours, another 4 hours to finish digesting food, that's 16 hours. Whereas ancestral humans only had 4 hours of eating and digesting a day.” “You can't be in a go, go, go position all the time or you will burn yourself out.”“In animal studies, virtually every single type of age-related disease improves when the animals take rapamycin.” Listen to the SuperAge podcast wherever you get your pods. Connect with Ross Pelton:WebsiteBookArticles (1, 2, 3)

Welcome to Episode 118 of Autism Parenting Secrets. The topic this week is on genes and how better understanding your genetic makeup can lead to better focus and decision making.  Bob Miller is our guest and he's back with some exciting new insights.  This discussion will build on our first discussion - see Episode 109.So please watch that episode first in order to get the most out of this one.Bob Miller is a Traditional Naturopath specializing in the field of genetic-specific nutrition. In 1993, he opened the Tree of Life practice and he has served as a traditional naturopath for 27 years. He created an online certification course on genetic nutrition that has empowered over 900 health professionals and he founded Functional Genomic Analysis, an online software program that organizes and analyzes genetic SNPS for functional health professionals across the world.This is going to be more of a presentation than a discussion because of the nature of the material.  While genes are important, there's something even more impactful. The secret this week is…GENETICS Loads The Gun, ENVIRONMENT Pulls the TriggerYou'll Discover:A Potential Root Cause You Can't Overlook (3:28)The Combination of Factors That Makes People Very Sick (7:31)Why Some People Have Symptoms From Toxic Exposure And Others Don't (10:45)What is the NADPH Steal (13:33)Why Heme Oxygenase and Bilirubin Are Worth Looking At (18:34)What Might Be Behind “Hangry” (24:02)How Software Makes Connections We Couldn't Make Before (38:01)When Ice Cream Helps (44:12)A Misconception That Is Absolutely False (49:25)About Our Guest:For the past several years, Bob Miller has been engaged exclusively with functional nutritional genetic variants and related research, specializing in nutritional support for those with chronic Lyme disease.Bob lectures nationally and internationally at seminars to educate health care practitioners about genetic variants and nutritional supplementation for achieving optimal health, and holds live webinars every other Thursday evening for health professionals. In 2016, he created an online certification course on genetic nutrition for health professionals now training over 900 health professionals in the program.Bob is a frequent guest on many podcasts such as Dr. Jill Carnahan, Better Health Guy, Dr. Joseph Mercola, and many others.To support his growing genetic research efforts, in 2015, Bob founded and personally funds, the NutriGenetic Research Institute to research the relationship between genetic variants and presenting symptoms.His first research project on genetic variants in those with chronic Lyme disease, was one of two winners for research by the ILADS international meeting held in Helsinki, Finland. His Phase II study of Lyme disease was presented at the American ILADS conference in November 2016, Phase III was presented at the International ILADS conference in Paris, France in May 2017 and his Phase IV study on mTOR and Autophagy in Lyme disease was presented in Boston, November 2017. Phase V was presented in Warsaw, Poland in June 2018 and his Phase VI was another winner presented in Chicago, Illinois in November of 2018 which showed increased variants in the Heme pathway and Mast Cell genes. Phase VII presented in Madrid, Spain in June of 2019 research showed how genetic variants in genes related to the production of and utilization of NAD+ and NADPH are creating what is now referred to as the ‘NADPH Steal'. In 2020, he presented his research at the online ILADS conference on genetic mutations in the synthesis and utilization of bile.Bob has created 72 nutritional supplement products exclusively for health professionals for Professional Health Products and Functional Genomic Nutrition through Compounded Nutrients.  The products he formulated are based upon his genetic research and are designed to support function that may be impaired by genetic weakness.Bob is the founder and president of Functional Genomic Analysis, an online software program that organizes and analyzes genetic SNPS for functional health professionals across the world.Memberships:National Association of Certified Natural Health ProfessionalsAmerican Association of Nutritional ConsultantsBoard Certified Naturopath - American Naturopathic Certification & Accreditation BoardBob MillerTree of Life References In This Episode:Watch the VIDEO version of this discussion hereAccess the complete presentation PDF hereAutism Parenting Secrets Episode 109, Genes are CLUES, Not Destiny Additional Resources:Take The Quiz: What's YOUR Top Autism Parenting Blindspot?Free Resource: 33 Mistakes Most Autism Parents Make and How To Avoid ThemGot a Picky Eater? - this can helpTo learn more about Cass & Len, visit us at www.autismparentingsecrets.comBe sure to follow Cass & Len on Instagram If you enjoyed this episode, share it with your friends.Don't forget to subscribe to the show on Apple Podcasts to get automatic episode updates for our "Autism Parenting Secrets!"And, finally, please take a minute to leave us an honest review and rating on Apple Podcasts. They really help us out when it comes to the ranking of the show and we read every single one of the reviews we get. Thanks for listening!

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.17.508382v1?rss=1 Authors: Prem, S., Dev, B., Peng, C., Mehta, M., Alibutud, R., Connacher, R. J., St. Thomas, M., Zhou, X., Matteson, P., Xing, J., Millonig, J., DiCicco-Bloom, E. Abstract: Autism spectrum disorder (ASD) is defined by common behavioral characteristics, raising the possibility of shared pathogenic mechanisms. Yet, vast clinical and etiological heterogeneity suggests personalized phenotypes. Surprisingly, our iPSC studies find that six individuals from two distinct ASD-subtypes, idiopathic and 16p11.2 deletion, have common reductions in neural precursor cell (NPC) neurite outgrowth and migration even though whole genome sequencing demonstrates no genetic overlap between the datasets. To identify signaling differences that may contribute to these developmental defects, an unbiased phospho-(p)-proteome screen was performed. Surprisingly despite the genetic heterogeneity, hundreds of shared p-peptides were identified between autism subtypes including the mTOR pathway. mTOR signaling alterations were confirmed in all NPCs across both ASD-subtypes, and mTOR modulation rescued ASD phenotypes and reproduced autism defects in controls. Thus, our studies demonstrate that genetically distinct ASD subtypes have common defects in neurite outgrowth and migration which are driven by the shared pathogenic mechanism of mTOR signaling dysregulation. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

VIDEOS : WES2022 | Yuval Noah Harari and Vanessa Nakate in conversation (3:19) Why Colleges Are Becoming Cults [Full Series] | Dr. Lyell Asher (15:00 to 43:42 Gary Null Speaking Out at the NYS Assembly Hearing  (25:00)   Astragulus found to inhibit breast cancer cell proliferation Fujian University of Traditional Medicine (China), September 8, 2022 Huang qi (Astragalus) is one of the fundamental herbs in traditional Chinese medicine, with earliest records of its use dating back over 2,000 years ago. Now, a study in BMC Complementary and Alternative Medicine has found that astragulus is also able to prevent the spread of breast cancer cells in the body. In the study, researchers from the Fujian University of Traditional Chinese Medicine in China looked at how astragulus extract can affect breast cancer cells and the process behind this biological effect. They also looked at the primary isoflavones in the extract, as well as its anti-proliferative activity on three breast cancer lines: MCF-7 (ER+), SK-BR-3 (HER2+) and MDA-MB-231 (triple-negative). They did this by exposing these breast cancer cells to the extract for 48 hours. In addition, they examined the effect of astragulus extract on phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathways, a primary intracellular signaling pathway that contributes to cell proliferation, growth, migration, metabolism, and apoptosis. The results of the study showed that the treatment of astragulus exhibited anti-proliferative activity on breast cancer cells. Furthermore, the therapy promoted the death of breast cancer cells. These suggested that it's ability to inhibit breast cancer cell growth was linked to its ability to inhibit PI3K/Akt/mTOR activity. Moreover, the researchers found that the Huang qi extract contains four types of isoflavones, such as campanulin, ononin, calycosin, and formononetin, which contributed to the inhibitory effect of Huang qi extract on breast cancer cells proliferation. Vitamin D supplementation could help critically ill patients University Hospital Würzburg (Germany) September 12 2022. Findings from a review and meta-analysis reported in Critical Care suggest that providing critically ill patients with vitamin D supplements may improve some clinical outcomes, including survival. “Upon ICU admission, the majority of patients have significantly reduced 25-hydroxyvitamin D levels, which remain significantly reduced over the entire ICU length of stay,” Johannes Menger and colleagues wrote. “In these patients, significantly reduced vitamin D (25-hydroxyvitamin D) serum levels are frequent and independently associated with higher incidence and severity of sepsis.” Sixteen randomized, controlled trials that evaluated vitamin D supplementation's association with mortality were identified. Vitamin D supplementation was associated with a 22% lower risk of overall mortality in comparison with a placebo or standard care. Among studies that reported 28-day mortality, vitamin D supplementation was associated with a trend toward lower a lower risk. Receiving vitamin D by injection or intravenously had the strongest effect. Patients who received vitamin D spent an average of 3.13 days less in the ICU and 5 fewer days on a ventilator than those who received a placebo. “The results of this systematic review and meta-analysis suggest that vitamin D supplementation may be associated with reduced overall mortality in critically ill patients,” they concluded. Natural compound could reduce breast cancer risk in some women Luteolin may inhibit growth of human breast cancer cells in postmenopausal women taking hormone replacement therapy University of Missouri-Columbia, September 9, 2022 More than 100 women die from breast cancer every day in the United States. The odds increase in postmenopausal women who have taken a combined estrogen and progestin hormone replacement therapy; these women also have an increased risk of developing progestin-accelerated breast tumors. Now, University of Missouri researchers have found that luteolin, a natural compound found in herbs such as thyme and parsley as well as vegetables such as celery and broccoli, could reduce the cancer risk for women who have taken hormone replacement therapy. “Most older women normally have benign lesions in breast tissue,” Hyder said. “These lesions typically don't form tumors until they receive the ‘trigger'– in this case, progestin–that attracts blood vessels to cells essentially feeding the lesions causing them to expand.” His newest study shows that when the supplement luteolin is administered to human breast cancer cells in the lab, benefits can be observed including the reduction of those vessels “feeding” the cancer cells causing cancer cell death. Hyder's lab has found that as human breast cancer cells develop, they tend to take on stem cell-like properties, which can make them harder to kill. Here, luteolin was used to monitor stem cell-like characteristics of breast cancer cells and his team saw a vast reduction in this phenomenon, further proving that the natural compound exerts its anti-tumor effects in a variety of ways. “We feel that luteolin can be effective when injected directly into the bloodstream, so IV supplements may still be a possibility,” Hyder said. “But, until the supplement is tested for safety and commercialized, which we hope will happen after further testing and clinical trials, women should continue consuming a healthy diet with fresh fruits and vegetables.” CBD shows health benefits in estrogen-deficient mice that model postmenopause Rutgers University, September 14, 2022 A Rutgers study points to cannabidiol (CBD), a major component of hemp and medical marijuana used to treat conditions such as chronic pain, inflammation, migraines, epilepsy, autoimmune diseases, depression, and anxiety, as a possible treatment for postmenopausal women whose ovaries no longer make estrogen. In a study published in Frontiers in Pharmacology, scientists reported that when estrogen-deficient mice were fed CBD, a non-intoxicating compound extracted from hemp, they showed marked improvement in several areas. Their bloodstreams more readily disposed of glucose, and they burned more energy. In addition, their bone density improved, they had less inflammation in gut and bone tissues and they possessed higher levels of beneficial gut bacteria. “This preclinical study is the first to suggest the therapeutic potential of CBD for alleviating symptoms of estrogen deficiency,” said Diana Roopchand, an assistant professor in the Department of Food Science of the Rutgers School of Environmental and Biological Sciences (SEBS) and senior author on the study. “There is much anecdotal evidence of CBD's health benefits for menopausal and postmenopausal women, but our study is the first to investigate some of the claims in an established preclinical model of postmenopause.” Over 18 weeks, researchers fed the estrogen-deficient mice a steady diet of either tiny, CBD-laced peanut butter balls or peanut butter balls without CBD. The untreated estrogen-deficient mice developed symptoms that resembled those of postmenopausal human females, such as metabolic dysfunction, evidence of inflammation, lower bone density, and lower levels of beneficial gut bacteria. However, in mice that ingested CBD, these conditions were significantly improved. Mediterranean diet and depression among older individuals Harokopio University (Greece), September 9, 2022 According to news originating from Athens, Greece,research stated, “In Europe, depression is one of the most frequent mental disorders across all age groups, but particularly in people aged 65 years and over, and higher depressive symptoms have been reported among individuals with chronic diseases (e.g., diabetes and heart disease).” Research from Harokopio University stated, “To evaluate the role of adherence to the Mediterranean diet (MedDiet) in depression in a sample of older people living in the Mediterranean basin. Standard procedures were used to determine socio-demographic, lifestyle, and clinical characteristics of the participants, as well as their dietary habits, and depressive symptoms were evaluated using the Geriatric Depression Scale (GDS). Participants classified as having mild or severe depression were less educated and physically active, and more diabetic, and they reported less adherence to the MedDiet. Adherence to the MedDiet was associated with the absence of depression [(OR, 95% CI): 0.65, 0.50 – 0.85]. In addition, daily tea drinking was also related to the absence of depression [(OR, 95% CI): 0.51, 0.40 – 0.65].” According to the news editors, the research concluded: “Greater adherence to the MedDiet and daily tea drinking seem to have a beneficial effect on depressive symptoms in older adults.” High cholesterol leads to long-term liver scarring and immune cell dysfunction in lab study University of Southern California, September 15, 2022 There's a long-established link between a high-fat, high-sugar diet and fatty liver disease, which can lead to life-threatening conditions such as cirrhosis and liver cancer. Now, new research from the Keck School of Medicine of USC adds some detail and dimension to this picture. The lab study, published in Frontiers in Immunology, is the first-ever to focus on how different amounts of cholesterol as part of a diet high in fat and sugar affect fatty liver disease progression. Modeling the disease in mice, the investigators demonstrated that high cholesterol intake can make fatty liver disease worse—driving inflammation and scarring—and that, importantly, scar tissuecan persist even after switching to a diet low in cholesterol. The findings also indicated that a high-cholesterol diet can create long-lasting dysfunction in a specific population of immune cells previously shown to play a role in fatty liver disease. “We saw that you may have a high-fat and high-sugar diet, but when you add high cholesterol to that, it will accelerate the process that causes inflammation in your liver,” said corresponding author Ana Maretti-Mira, Ph.D., an assistant research professor of medicine at USC. “People focus on high cholesterol as a risk for heart disease, but we showed that your liver may also be affected, causing inflammation, scarring and, potentially, cirrhosis.” High cholesterol makes fatty liver disease worse The researchers fed mice a high-fat, high-sugar diet shown to cause a form of advanced fatty liver disease similar to human illness. The mice were split into three groups that received different amounts of cholesterol in their food for 20 weeks—midlife for the animals. The low-cholesterol group received one-quarter the cholesterol compared to medium; the high-cholesterol group received 25 times more than the low-cholesterol group. After 20 weeks, the livers of mice from all three groups showed accumulation of fat, a benign feature of fatty liver disease, but the high-cholesterol group had more advanced disease, with increased inflammation and scar tissue. For the following 10 weeks, mice from all three groups received low cholesterol as part of a diet that remained high in fat and sugar. At the end of that time, that change in diet had reversed inflammation in the original high-cholesterol mice, but had not reduced scar tissue. This finding shows that damage caused by high cholesterol can be hard to undo. The high-fat, high-sugar diet given to mice in the study has unfortunate similarities to the typical Western diet in humans. “Our daily diet has lots of carbohydrates, such as sugary drinks, bread, rice and pasta,” Maretti-Mira said. “Then there's high fat, since everybody likes deep fried foods. At the same time, we don't have the same active life we used to, so we end up eating much more than our body needs.”

This month on Episode 40 of Discover CircRes, host Cynthia St. Hilaire highlights four original research articles featured in the September 2 and September 16 issues of the journal. This episode also features an interview with Dr Jun Yoshioka, and Dr Yoshinobu Nakayama, from the City University of New York, about their study, Interaction of ARRDC-4 with GLUT1 Mediates Metabolic Stress in the Ischemic Heart.   Article highlights:   Jin, et al. Gut Dysbiosis Promotes Preeclampsia   Mengozzi, et al. SIRT1 in Human Microvascular Dysfunction   Hu, et al. Racial Differences in Metabolomic Profiles and CHD   Garcia-Gonzales, et al. IRF7 Mediates Autoinflammation in Absence of ADAR1   Cindy St. Hilaire:        Hi, and welcome to Discover CircRes, the podcast of 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 be highlighting some articles from September 2nd, and September 16th issues of CircRes. And I'm also going to have a conversation with Dr Jun Yoshioka, and Dr Yoshinobu Nakayama, from the City University of New York, about their study, Interaction of ARRDC-4 with GLUT1 Mediates Metabolic Stress in the Ischemic Heart. But, before I get to the interview, I'm going to highlight a few articles.                                       The first article is from our September 2nd issue, and it's titled, Gut Dysbiosis Promotes Preeclampsia by Regulating Macrophages, and Trophoblasts. The first author is Jiajia Jin, and the corresponding author is Qunye Zhang from the Chinese National Health Commission.                                       Preeclampsia is a late-stage pregnancy complication that can be fatal to the mother, and the baby. It's characterized by high blood pressure, and protein in the urine. The cause is unknown, but evidence suggests the involvement of inflammation, and impaired placental blood supply. Because gut dysbiosis can influence blood pressure, and inflammation has been observed in preeclamptic patients, Jin and colleagues examined this link more closely. They found that women with preeclampsia had altered gut microbiome. Specifically, a reduction in a species of bacteria that produced short-chain fatty acids, and lower short-chain fatty acid levels in their feces, in their serum, and in their placentas. And preeclamptic women had lower short-chain fatty acid levels in their feces, in their serum, and in their placentas compared with women without preeclampsia.                                       They found that fecal transfers from the preeclampsia women to rats with a form of the condition exacerbated the animals' preeclampsia symptoms, while fecal transfers from control humans alleviated the symptoms. Furthermore, giving rats an oral dose of short-chain fatty acids or short-chain fatty acid producing bacteria decreased the animals' blood pressure, reduced placental inflammation, and improved placental function. This work suggests that short-chain fatty acids, and gut microbiomes could be a diagnostic marker for preeclampsia. And microbial manipulations may even alleviate the condition.                                       The second article I want to share is also from our September 2nd issue, and it's titled, Targeting SIRT1 Rescues Age and Obesity-Induced Microvascular Dysfunction in Ex Vivo Human Vessels. And this study was led by Alessandro Mengozzi from University of Pisa.                                       With age, the endothelial lining of blood vessels can lose its ability to control vasodilation, causing the vessel to narrow and reduce blood flow. This decline in endothelial function has been associated with age related decrease in the levels of the enzyme, SIRT1. And artificially elevating SIRT1 in old mice improves animals' endothelial function. Obesity, which accelerates endothelial dysfunction, is also linked to low SIRT1 levels.                                       In light of these SIRT1 findings, Mengozzi, and colleagues examined whether increasing the enzyme's activity could improve the function of human blood vessels. The team collected subcutaneous microvessels from 27 young, and 28 old donors. And both age groups included obese, and non-obese individuals. SIRT1 levels in the tissue were, as expected, negatively correlated with age and obesity, and positively correlated with baseline endothelium dependent vasodilatory function. Importantly, incubating tissue samples from older, and obese individuals with a SIRT1 agonist, restored the vessel's vasodilatory functions. This restoration involved a SIRT1 induced boost to mitochondrial function, suggesting that maintaining SIRT1 or its metabolic effect might be a strategy for preserving vascular health in aging, and in obesity.                                       The third article I want to share is from our September 16th issue. And this one is titled, Differences in Metabolomic Profiles Between Black And White Women and Risk of Coronary Heart Disease. The first author is Jie Hu, and the corresponding author is Kathryn Rexrode, and they're from Brigham and Women's Hospital, and Harvard University.                                       In the US, coronary heart disease, and coronary heart disease-related morbidity, and mortality is more prevalent among black women than white women. While racial differences in coronary heart disease risk factors, and socioeconomic status have been blamed, this group argues that these differences alone cannot fully explain the disparity. Metabolomic variation, independent of race, has been linked to coronary heart disease risk. Furthermore, because a person's metabolome is influenced by genetics, diet, lifestyle, environment and more, the authors say that it reflects accumulation of many cultural, and biological factors that may differ by race.                                       This group posited that if racial metabolomic differences are found to exist, then they might partially account for differences in coronary heart disease risk. This study utilized plasma samples from nearly 2000 black women, and more than 4500 white women from several different cohorts. The team identified a racial difference metabolomic pattern, or RDMP, consisting of 52 metabolites that were significantly different between black, and white women. This RDMP was strongly linked to coronary heart disease risk, independent of race, and known coronary heart disease risk factors. Thus, in addition to socioeconomic factors, such as access to healthcare, this study shows that racial metabolomic differences may underlie the coronary heart disease risk disparity.                                       The last article I want to share is also from our September 16th issue, and it is titled, ADAR1 Prevents Autoinflammatory Processes in The Heart Mediated by IRF7. The first author is Claudia Garcia-Gonzalez, and the corresponding author is Thomas Braun, and they are from Max Planck University.                                       It's essential for a cell to distinguish their own RNA from the RNA of an invading virus to avoid triggering immune responses inappropriately. To that end, each cell makes modifications, and edits its own RNA to mark it as self. One type of edit made to certain RNAs is the conversion of adenosines to inosines. And this is carried out by adenosine deaminase acting on RNA1 or ADAR1 protein. Complete loss of this enzyme causes strong innate immune auto reactivity, and is lethal to mice before birth. Interestingly, the effects of ADAR1 loss in specific tissues is thought to vary. And the effect in heart cells in particular has not been examined.                                     This study, which focused on the heart, discovered that mice lacking ADAR1 activity specifically in cardiomyocytes, exhibit autoinflammatory myocarditis that led to cardiomyopathy. However, the immune reaction was not as potent as in other cells lacking ADAR1. Cardiomyocytes did not exhibit the sort of upsurge in inflammatory cytokines, and apoptotic factors seen in other cells lacking ADAR1. And the animals themselves did not succumb to heart failure until 30 weeks of age. The author suggests that this milder reaction may ensure the heart resists apoptosis, and inflammatory damage because, unlike some other organs, it cannot readily replace cells.   Cindy St. Hilaire:        Today I have with me, Dr Jun Yoshioka, and Dr Yoshinobu Nakayama, and they're from City University of New York. And today we're going to talk about their paper, Interaction of ARRDC4 With GLUT1 Mediates Metabolic Stress in The Ischemic Heart. And this is in our September 2nd issue of Circulation Research. So, thank you both so much for joining me today.   Jun Yoshioka:             Thank you for having us. We are very excited to be here.   Cindy St. Hilaire:        It's a great publication, and also had some really great pictures in it. So, I'm really excited to discuss it. So, this paper really kind of focuses on ischemia, and the remodeling in the heart that happens after an ischemic event. And for anyone who's not familiar, ischemia is a condition where blood flow, and thus oxygen, is restricted to a particular part of the body. And in the heart, this restriction often occurs after myocardial infarctions, also called heart attacks. And so, cardiomyocytes, they require a lot of energy for contraction, and kind of their basic functions. And in response to this lack of oxygen, cardiomyocytes switch their energy production substrate. And so, I'm wondering if before we start talking about your paper, you can just talk about the metabolic switch that happens in a cardiac myocyte in the healthy state versus in the ischemic state.   Jun Yoshioka:             Sure. As you just said, that the heart never stops beating throughout the life. And it's one of the most energy demanding organs in the body. So, under normal conditions, cardiac ATP is mainly derived from fatty acid oxidation, and glucose metabolism contributes a little bit less in adult cardiomyocytes. However, under stress conditions such as ischemia, glucose uptake will become more critical when oxidative metabolism is interrupted by a lack of oxygen. That is because glycolysis is a primary anaerobic source of energy. We believe this metabolic adaptation is essential to preserve high energy phosphates and protect cardiomyocytes from lethal injuries. The concept of shifting the energy type of stress preference toward glucose, as you just said, has been actually long proposed as an effective therapy against MI. For example, GIK glucose insulin petition is classic.                                       Now, let me explain how glucose uptake is regulated. Glucose uptake is facilitated by multiple isophones of glucose transporters in cardiomyocytes. Mainly group one and group four, and the minor, with a minor contribution of more recently characterized STLT1. In this study, we were particularly interested in group one because group one is a basal glucose transporter.                                       Dr Ronglih Liao, and Dr Rong Tian's groups reported nearly two decades ago that the cardiac over-expression of group one prevents development of heart failure, and ischemic damage in mice. Since they are remarkable discoveries, the precise mechanism has not yet been investigated enough, at least to me. Especially how acute ischemic stress regulates group one function in cardiomyocytes. We felt that this mechanism is important because there is a potential to identify new strategies around group one, to reduce myocardiac ischemic damage. That is why we started this project hoping to review a new mechanism by which a protein family, called alpha-arrestins, controls cardiac metabolism under both normal, and diseased conditions.   Cindy St. Hilaire:        That is a perfect segue for my next question, actually, which is, you were focusing on this arrestin-fold protein, arrestin domain-containing protein four or ARRDC4. So, what is this family of proteins? What are arrestin-fold proteins? And before your study, what was known about a ARCCD4, and its relationship to metabolism, and I guess specifically cardiomyocyte metabolism?   Jun Yoshioka:             So, the arrestin mediated regulation of steroid signaling is actually common in cardiomyocytes. Especially beta, not the alpha, beta-arrestins have been well characterized as an adapter protein for beta-adrenergic receptors. Beta-arrestins combine to activate beta-adrenergic receptors on the plasma membrane, promote their endosomal recycling, and cause desensitization of beta-adrenergic signaling. Over the past decade, however, this family, the arrestin family, has been extended to include a new class of alpha-arrestins. But unlike beta-arrestins, the physiological functions of alpha-arrestins remain largely unclear based in mammalian cells. Humans, and mice have six members of alpha-arrestins including Txnip, thioredoxin interacting protein called Txnip, and five others named alpha domain-containing protein ARRDC1 2, 3, 4 and 5. Among them Txnip is the best studied alpha-arrestin. And Txnip is pretty much the only one shown to play a role in cardiac physiology.                                       Txnip was initially thought to connect alternative stress and metabolism. However, it is now known that the Txnip serves as an adapter protein for the endocytosis of group one, and group four to mediate acute suppression of glucose influx to cells. In fact, our group has previously shown that the Txnip knockout mice have an enhanced glucose uptake into the peripheral tissues, as well as into the heart. Now, in this study, our leading player is ARRDC4. The arrestin-domains of ARRDC4 have 42% amino acid sequence similarities to Txnip. This means that the structurally speaking ARRDC4 is a brother to Txnip. So, usually the functions of arrestins are expected to be related to their conserved arrestin-domains. So, we were wondering whether two brothers, Txnip, and ARRDC4, may share the same ability to inhibit the glucose transport. That was a starting point where we initiated this project.   Cindy St. Hilaire:        That's great. And so, this link between ARRDC4, and the cardiac expression of gluten one and gluten four, I guess, mostly gluten one related to your paper, that really wasn't known. You went about this question kind of based on protein homology. Is that correct?   Jun Yoshioka:             That is right.   Cindy St. Hilaire:        And so, ARRDC4 can modulate glucose levels in the cell by binding, and if I understand it right, kind of helping that internalization process of glute one. Which makes sense. You know, when you have glucose come into the cell, you don't want too much. So, the kind of endogenous mechanism is to shut it off, and this ARRDC4 helps do that. But you also found that this adapter protein impacts cellular stress, and the cellular stress response. So, I was wondering if you could share a little bit more about that because I thought that was quite interesting. It's not just the metabolic impact of regulating glucose. There's also this cellular stress response.   Jun Yoshioka:             Right? So, Txnip is known to induce oxidative stress. But about the ARRDC4, we found that ARRDC4 actually does not induce oxidative stress. Instead, we found that it reproducibly causes ER, stress rather than oxidative stress. So, let Yoshinobu talk about the ER stress part. Yoshinobu, can you talk about how you found the ER stress story?   Yoshinobu Nakayama: So, then let's talk about the, yeah, ER stress caused by ARRDC4. The ER stress caused by ARRDC4, year one was the biggest challenge in this study, because it's a little bit difficult to how we found a link of the glucose metabolism to the effect of the ARRDC4, only our stress. And at the other point of the project, we noticed that a ARRDC4 causes ER stress reproducibly, but we did not know how. So, both group one, and ARRDC4 are membrane proteins mainly localized near the plasma membrane. Then how does ARRDC4 regulate the biological process inside in the plasma radical? So, we then hypothesize that ARRDC4 induces intercellular glucose depravation by blocking cellular glucose uptake, and then interferes with protein glycosylation, thereby disturbing the ER apparatus. That makes sense because inhibition of group one trafficking by ARRDC4 was involved in the unfolded protein response in ischemic cardiomyocytes.   Cindy St. Hilaire:        So how difficult was that to figure out? How long did that take you?   Yoshinobu Nakayama: How long? Yeah. Is this the question?   Cindy St. Hilaire:        It's always a hard question.   Yoshinobu Nakayama: I think it's not several weeks. Maybe the monthly, months project. Yeah.   Cindy St. Hilaire:        Okay. It's always fun when, you know, you're focusing on one angle, and then all of a sudden you realize, oh, there's this whole other thing going on. So, I thought it was a really elegant tie-in between the metabolism, but also just the cellular stress levels. It was really nice.                                       So, you created a full body knockout of ARRDC4 in the mouse, and you did all the proper kind of phenotyping. And at baseline everything's normal, except there's a little bit of changes in the blood glucose levels. But I also noticed when you looked at the expression of ARRDC4 in different tissues, it was very high in the lungs, and also in the intestines. And so, I know your study didn't focus on those tissues, but I was wondering if you could possibly speculate what ARRDC4 is doing in those tissues? Is it something similar? Do those cells under stress have any particular metabolic switching that's similar?   Jun Yoshioka:             Well, actually we don't have any complete answer for that question, because like you said, we didn't focus on lung, and other tissues. But I could say that actually the brother of ARRDC4, Txnip, is also highly expressed in lung, and bronchus, and in those organs. So, it's interesting because, which means that, the molecule is very oxygen sensitive, I will say. Both brothers. But that's all we know for now. But that's a very great point. And then we are excited to, you know.   Cindy St. Hilaire.        Yeah.   Jun Yoshioka:             Move on to the other tissues.   Cindy St. Hilaire:        I was thinking about it just because I've actually recently reviewed some papers on pulmonary hypertension. So, when I saw that expression, that was the first thing I thought of was, oh, they should put these mice in a sugen/hypoxia model, and see what happens.   Jun Yoshioka:             Right?   Cindy St. Hilaire:        So, there's an idea for you, Yoshinobu. A K-99 grant or something. And also, because it's a full body knockout, even when you're looking at the heart, obviously the cardiomyocytes are really the most metabolically active cell, but cardiac fibroblasts are also a major component of the heart tissue. And so, do you know, is the, I guess, effects or the protectiveness of the ARRDC4 knockout heart, is it mostly because of the role in the cardiomyocytes or is there a role for it also in the fibroblast?   Yoshinobu Nakayama: Yeah, that's a very great question. Yeah. So, although we use the systemic knockout mice in the study, we believe that the beneficial effect of ARRDC4 deficiency is cardiac, autonomous. But this is because cardioprotection was demonstrated in the isolated heart experiments. But, you know, root is still uniformly expressing all cell types within the heart.                                       To address this, we have tested the specific effects of ARRDC4 on cardiac fibroblasts, and inflammatory cells. ARRDC4 knockout hearts had a twofold increase in myocardial glucose uptake over wild-type hearts during insulin-free perfusion. However, an increase in glucose uptake in isolated cardiac fibroblast or inflammatory cells was relatively mild, with about 1.2 fold increase over wild-type cells.                                       Thus we conclude that cardiomyocytes are the measure contributed to the cardiac metabolic shift. And then the mechanism within cardiomyocytes should play the major role in cardioprotection.   Jun Yoshioka:             I might, at one point, because, you know, the fibroblasts, they don't need to beat, right?   Cindy St. Hilaire:        Right.   Jun Yoshioka:             The inflammasome cells. They don't need to beat neither. So, they don't need that much energy. So, the cardiomyocytes energy metabolism is very important. So, that's why this mechanism is kind of more important in cardiomyocytes than other cell types.   Cindy St. Hilaire:        Yeah. And I think, you know, your phenotyping of the mice at baseline show that there's really no effect in a cell that's not under stress. So, it's really, really nice finding. Yeah.                                       This article, I should say, is featured on the cover of the September 2nd Circulation Research issue. And it's got this really nice 3D modeling of the binding of ARRDC4 to glute one. And I was reading the paper, and the methods said, you use some AI for that. So, I'm sure other people have heard, too, AI in protein modeling is important. But AI in art, right? There's that new DALL-E 2 program. So how are you able to do this? How did that work?   Jun Yoshioka:             So, our study used is called AlphaFold, which applies the artificial intelligence-based deep learning method. AlphaFold, nowadays, everybody really is interested in AlphaFold. AlphaFold uses structural, and genetic data to come up with a model of what the protein of interest should look like. So, that is also how we got the protein structure, ARRDC4. We think that the ability of AlphaFold to precisely predict the protein structure from amino acid sequence would be a huge benefit to life sciences, including of course, cardiovascular science research, because of high cost, and technical difficulties in experimental methods.                                       It's very useful if you can computationally predict the complex from individual structures of ARRDC4. And group one, which is actually structure of group one, is available in a protein data bank. But ARRDC4, it was not available. That's why we used AlphaFold.                                       And then we use the docking algorithm called Hdoc. So, based on these AI analysis, we could successfully identify specific residues in a C terminal arrestin domain as an international interface, that regulates group one function. So, we believe this AI method will pretty much accelerate efforts to understand the protein, protein interactions. And we believe that will enable more advanced drug discovery, for example, in very near future.   Cindy St. Hilaire:        Yeah, it's really great. I started thinking about it in terms of some of the things I'm studying. So yeah, it was really nice. Jun Yoshioka:             Try next time.   Cindy St. Hilaire:        Yeah, I will, I will. Actually, I went to the website, and was playing with it before I got on the call with you. So, how do you think your findings can be leveraged towards informing clinical decision making or even developing therapeutics?   Jun Yoshioka:             So, let me talk about what needs to be done. There are more things we must do.   Cindy St. Hilaire:        Always. Yeah.   Jun Yoshioka:             One of the most clinically relevant questions is whether ARRDC4 inhibition actually can mitigate development of post MI heart failure, and reduce mortality in the chronic phase, not the acute phase. Because in this paper we just did the seven day post MI, which is kind of like acute to subacute phase. But you never know what's going to happen in the chronic phase, right? And that is actually not so simple to answer because there are so many issues that you should consider. For example, Dr E. Dale Abel's lab has reported previously that cardiomyacites, specific group one, knockout in mice does not really accelerate the transition from compensated hypotrophy to heart failure. Also, the same group has shown that the overexpression group one does not actually prevent LV dysfunction in the mouse model of pressure overload. So, it is possible that ARRDC knockout can be, do much, or even harmful to LV remodeling in a chronic phase because chronic phase, it's not, it's getting hypoxy conditions, right?   Cindy St. Hilaire:        Yeah. So, it really might be something, I guess, personalized medicine is not the phrase I'm looking for. But I guess temporarily modulated, it would be something maybe we can figure out in an acute phase versus.   Jun Yoshioka:             Chronic phase.   Cindy St. Hilaire:        Yeah. Yeah.   Jun Yoshioka:             This makes sense. Because, you know, high capacity of ATP synthesis, by oxidating metabolism, could be important for chronic heart failure. So, it's selecting substrates. Energy substrates is no longer, you know, that issue. So, I'm not sure I'm answering your question, but this is the point that we consider to move on to the next.   Cindy St. Hilaire:        Well, that's great. And I think that was my next question, really. What is next? Are you really going to try to pinpoint where you could possibly target?   Jun Yoshioka:             Right. So, the first point we have to figure out about chronic phase, and another point we are interested in, is what's going on at the level of mitochondria. Does ARRDC4 knockout hearts have a different activity of electron transport chain or glycolytic enzymes within mitochondria?   Cindy St. Hilaire:        Or even mitochondrial fission infusion because it's, you know, it's a machinery.   Jun Yoshioka:             Yeah. And how about the other essential pathways in glucose metabolism such as mTOR, AMPK and HEF1, and so on. So, all these must be determined to help understand the more precise role of ARRDC4 in cardiac metabolism, we believe. Cindy St. Hilaire:        It's a wonderful study, and now we have even more questions to ask using your great model. Congratulations again.   Yoshinobu Nakayama: Thank you so much.   Cindy St. Hilaire:        Dr Yoshioka, and Dr Nakayama.   Jun Yoshioka:             Thank you.   Cindy St. Hilaire:        A wonderful paper, and congrats on getting the cover, and thank you so much for joining me today.   Jun Yoshioka:             Thanks well so much for having us.   Yoshinobu Nakayama: Thank you.   Cindy St. Hilaire:        That's it for the highlights from our September 2nd, and our September 16th issues of Circulation Research. Thank you so much for listening. Please check out our CircRes Facebook page, and follow us on Twitter, and Instagram with the handle @circres, and hashtag discovercircres. Thank you to our guests, Dr Jun Yoshioka, and Dr Yoshinobu Nakayama.                                     This podcast is produced by Ishara Ratnayaka, edited by Melissa Stonerm, and supported by the editorial team of Circulation Research. Some of the copy text for 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.                                       This program is copyright of the American Heart Association 2022. The opinions expressed by speakers in this podcast are their own, and not necessarily those of the editors or of the American Heart Association. For more information, please visit ahajournals.org.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.10.507436v1?rss=1 Authors: Onimus, O., Valjent, E., Fisone, G., Gangarossa, G. Abstract: Antipsychotics share the common pharmacological feature of antagonizing the dopamine 2 receptor (D2R) which is abundant in the striatum and involved in both the therapeutic and side effects of this drugs class. Pharmacological blockade of striatal D2R, by disinhibiting the D2R-containing medium-size spiny neurons (MSNs), leads to a plethora of molecular, cellular and behavioral adaptations which are central in the action of antipsychotics. Here, we focused on the cell type-specific (D2R-MSNs) regulation of some striatal immediate early genes (IEGs), such as cFos, Arc and Zif268. Taking advantage of transgenic mouse models, pharmacological approaches and immunofluorescence analyses, we found that haloperidol-induced IEGs in the striatum required the synergistic activation of A2a (adenosine) and NMDA (glutamate) receptors. At the intracellular signaling level, we found that the PKA/DARPP-32 and mTOR pathways synergistically cooperate to control the induction of IEGs by haloperidol. By confirming and further expanding previous observations, our results provide novel insights into the regulatory mechanisms underlying the molecular/cellular action of antipsychotics in the striatum. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.12.507553v1?rss=1 Authors: Franco-Garcia, A., Guerrero-Bautista, R., Hidalgo, J., Milanes, M. V., Gomez-Murcia, V., Nunez, C. Abstract: Stress is an important trigger of relapses in cocaine use. These relapses engage the activity of memory-related nuclei, such as the basolateral amygdala (BLA) and the dentate gyrus (DG). Further, preclinical research signals D3 receptor (D3R) antagonists as promising therapeutic tools to attenuate cocaine reward and relapse. Therefore, we assessed the effect of SB-277011-A, a D3R antagonist, in the activity of Akt/mTOR and MEK/ERK1/2 pathways in these areas during the reinstatement of cocaine-induced conditioned place preference (CPP) evoked by psychological (restraint) and physiological (tail pinch) stress. Both stimuli reactivated the extinguished cocaine-CPP, but only restrained animals decreased their locomotor activity during reinstatement. Moreover, p-Akt, p-mTOR and p-ERK1/2 activity in the BLA and DG of restrained animals decreased during the reactivation of cocaine memories, contrasting to tail-pinched mice. While D3R blockade prevented stress-induced CPP reactivation and plasmatic corticosterone enhancement, SB-277011-A distinctly modulated Akt, mTOR and ERK1/2 activities in the BLA and DG based on the stressor and the dose of antagonist. Corticosterone may be partially responsible for these variations as we found high correlations among its levels and mTOR and/or Akt activity in the BLA and DG of restrained animals receiving SB-277011-A. Besides, locomotor activity of animals receiving 48 mg/kg of the antagonist highly correlated with p-mTOR/mTOR and p-ERK1/2 /ERK1/2 in the BLA during restraint- and tail pinch-induced relapse in cocaine-CPP, respectively. Hence, our study endorses D3R antagonists as therapeutic tools to prevent stress-induced relapses in drug use through a complex balance of Akt/mTOR and MEK/ERK1/2 pathways in memory-processing brain nuclei. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter's Weekly Newsletter Dr. Matt Kaeberlein is a globally recognized expert on the biology of aging and recurring on The Drive. In this episode, Matt explains his research findings on nutrition as it relates to aging and longevity, including the results from his recent review article in Science. From there, he and Peter dive deep into the literature on calorie restriction (CR), explaining the nuance, benefits for lifespan and healthspan, and potential downsides of CR. He discusses the epigenetic changes that occur with age and potential benefits and downsides of epigenetic reprogramming, often viewed as a panacea for reversing aging. Matt also explains the impact of dietary protein on aging, including the interesting dichotomy around how protein, a critical macronutrient, and rapamycin, a geroprotective molecule, have opposite effects on mTOR. Additionally, he talks about low-protein vs. high-protein diets and their effects on muscle mass and mortality, as well as the impact of IGF-1 signaling and growth hormone on lifespan. We discuss: Challenges with understanding the effects of nutrition and studying interventions for aging [3:30]; How Peter's and Matt's convictions on nutrition and thoughts optimal health have evolved [8:15]; Calorie restriction for improving lifespan in animal models [16:15]; Utility of epigenetic clocks and possibility of epigenetic reprogramming [22:00]; Mutations and changes to the epigenome with aging [31:45]; Epigenetic reprogramming: potential benefits and downsides and whether it can work in every organ/tissue [35:15]; First potential applications of anti-aging therapies and tips for aging well [43:00]; Impact of calorie restriction on the immune system, muscle mass, and strength [47:00]; Insights from famous calorie restriction studies in rhesus macaques [55:00]; An evolutionary perspective of the human diet [1:03:45]; Antiaging diets: Separating fact from fiction—Matt's 2021 review in Science [1:12:30]; Mouse models of time-restricted feeding in the context of calorie restriction [1:19:30]; Nutritional interventions that consistently impact lifespan in mice, and concerns around efficacy in humans [1:27:00]; Differing impact of calorie restriction when started later in life [1:31:00]; Lifespan extension with rapamycin in older mice [1:37:15]; Relationship between protein intake and aging, and mouse studies showing protein restriction can extend lifespan [1:43:30]; Impact of protein intake on mTOR, and why inhibition of mTOR doesn't cause muscle loss [1:50:45]; Low-protein vs. high-protein diets and their effects on muscle mass, mortality, and more [1:55:30]; The impact of IGF-1 signaling and growth hormone on lifespan [2:06:30]; Parting thoughts on the contribution of nutrition to healthspan and lifespan [2:19:45]; More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

What if there was a compound that helped you not just extend your lifespan but do it healthily as well? That compound is Rapamycin. Today's guest is an expert on the topic and has even authored a book entitled Rapamycin, mTOR, Autophagy & Treating mTOR Syndrome. Ross Pelton, aka The Natural Pharmacist, is a certified clinical nutritionist. He was named one of the top 50 most influential pharmacists in America by American Druggist Magazine for his work in natural medicine in 1999. In this episode, he joins Corinna Bellizzi to discuss the multiple health benefits of Rapamycin and how it facilitates mTOR and autophagy. Listen to their educational and informative chat to learn which simple lifestyle and nutrition habits can affect your body's anti-aging capacity. Key takeaways from this episode:- The meaning of mTOR- How Rapamycin works in the body- How the body benefits from autophagy- How intermittent fasting helps autophagy- Rapamycin optimizes the body against multiple diseases in animal models- How Rapamycin contributes to anti-aging and living a longer healthier life Guest Social Links:LinkedIn: https://www.linkedin.com/in/naturalpharmacist/ Book: https://www.lifeextension.com/rapa

On todays episode Zarb and Gamble reflect on how powerful last week's episode was and touch on the key standouts around being true to yourself. The influence's around us and our environments play a massive role in this because they should support us in being who we truly are, not what we think we should be based off external influence. This episode is brought to you by our amazing sponsor's Mtor apparel https://mtorapparel.com.au/ Newy Design Co. https://studio.newydesignco.com.au/themasteredmindset/ Sunnyholt Off-Grid Touring https://sunnyholtoffgridtouring.com.au/

For more information, contact us at 859-721-1414 or myhealth@prevmedheartrisk.com. Also, check out the following resources:  ·Newsletter Sign Up·Jubilee website·PrevMed's website·PrevMed's Rumble channel·PrevMed's YouTube channel·PrevMed's Facebook page·PrevMed's Instagram·PrevMed's LinkedIn·PrevMed's Twitter ·PrevMed's Pinterest

Dr. Lieff's Book: https://www.amazon.com/Secret-Language-Cells-Biological-Conversations/dp/1948836041Dr. Lieff's Twitter: https://twitter.com/jonlieffmdThe University Of Clinical Research: https://www.theuniversityofclinicalresearch.com/Text Me: (949) 415-6256My podcast is Random Musings From The Clinical Trials GuruListen on Spotify: https://open.spotify.com/show/7JF6FNvoLnBpfIrLNCcg7aGET THE BOOK! https://www.amazon.com/dp/1090349521/...Text "guru" to 855-942-5288 to join VIP list!My blog: http://www.TheClinicalTrialsGuru.comMy CRO and Site Network: http://www.DSCScro.comMy CRA Academy: http://www.TheCRAacademy.comMy CRC Academy: http://www.TheCRCacademy.comLatinos In Clinical Research: http://www.LatinosinClinicalResearch.comThe Clinical Research Circle: https://www.youtube.com/channel/UCgOSm8EN_M7xf9Xfw1m778wMy TikTok: DanSfera

Timestamps: Listen in to learn more about:[6:35] Dr. Cohen's philosophical "aha" moment[13:00] What is the cause of age-related decline[28:03] How do you prioritize health aspects that increase longevity[35:00] The role of mTOR, AMPK, and fasting[39:04] The importance of breath and sleep[41:12] Dr. Cohen's experiments with the LiveO2 system[49:09] How Dr. Mike's theories of metabolic and physiologic flexibility fit in with Dr. Cohen's experience[59:28] Fasting, mTOR, sarcopenia, and research[1:07:05] What would Dr Cohen try to target in terms of increasing longevity?Connect with Dr. CohenWebsite: Pure Clean PerformanceEmail: rick@purecleanperformance.comGuest BioDr. Rick Cohen, M.D. is a leading authority in the fields of nutrition, sports performance and longevity medicine. He received his undergraduate degree in Biomedical Engineering with honors of distinction from Duke University in Durham, North Carolina and his medical degree from Hahnemann Medical University in Philadelphia, Pennsylvania.Over the past 20 years, Rick has used his knowledge to create innovative health and performance protocols and specially-formulated nutritional products to bring thousands of sport enthusiasts and elite athletes to higher levels of performance. Rick's passion for athletics extends beyond his work; in fact, it is a major part of his personal life satisfaction and well-being. He played ice hockey in college and competed on the world stage in the sport of luge, his wife is a nationally-ranked triathlete and his kids both were college athletes. So he personally understands how frustrating it can be to balance family, career, and an athletic passion. That experience is exactly what led him to create PureClean Performance.Flex Diet Podcast SponsorThis podcast is brought to you by the Physiologic Flexibility Certification course. In the course, I talk about the body's homeostatic regulators and how you can train them. The benefit is enhanced recovery and greater robustness. We cover breathing techniques, CWI, sauna, HIIT, diet, and more. Enrollment opens Monday, September 5 and closes at midnight Monday, September 12.For more on this topic check out:Flex Diet Podcast Episode 164: How to use testing to improve your metabolic health: An interview with Sam MillerFlex Diet Podcast Episode 144: Peptides - bleeding edge performance, muscle, and recovery with Dr. Andy Galpin & Dr. Ryan Greene

Are you A Healthcare Practitioner? Join The Estima Certification Program HereJoin the Hello Betty AMA here: https://www.hellobetty.club/ama We'd like to thank our sponsors, Athletic Greens - redeem an exclusive offer here: athleticgreens.com/stephanieLMNT Electrolytes - A FREE 7-flavor sample pack! - https://www.drinklmnt.com/DrEstimaOrion Red Light Therapy - get 10% off your order with Promo Code “STEPHANIE10” https://www.orionrlt.ca/?ref=StephanieLumen - get $25 off your order with Promo Code “DRSTEPHANIE25” https://www.lumen.me/?fid=1799Ancestral Supplements - Use Promo Code “ASA10” for 10% off any purchase https://shop.ancestralsupplements.com/discount/Tribe10?rfsn=5900205.652074&utm_source=refersion&utm_medium=affiliate&utm_campaign=5900205.652074PRIMEADINE - get 10% Off your Order with Promo Code “DRSTEPHANIE10” - https://oxfordhealthspan.com/products/best-spermidine-supplementBIOOPTIMIZERS - receive 10% off your order with Promo Code "ESTIMA" - www.biooptimizers.com/drstephanie  Episode Overview: 0:00 Introduction2:00 Exercising on your Period7:00 Workout Planning19:00 Endurance Style Exercise26:30 Luteal Phase Push 29:00 Post Menopausal Weight Training   35:00 Collagen Use for Recovery 40:00 Perimenopausal Stress Impacts48:00 Exogenous Ketones  51:45 Fasted Workouts for Women57:00 Fear of MTOR1:01:40 Creatine Post Workout1:05:00 Amino Acids1:10:00 Low Blood Glucose1:17:45 Intermittent Fasting1:22:00 Perimenopausal Fasting 1:23:30 Experimentation Follow Me On Instagram: https://www.instagram.com/dr.stephanie.estimaGet yourself a copy of my best-selling book, The Betty Body - https://bettybodybook.comJoin the Hello Betty Community here - https://hellobetty.club/ Dr. Mindy Pelz'z Links:https://www.youtube.com/TheResetterPodcasthttp://drmindypelz.comhttp://youtube.com/drmindypelz/

This bonus, talking all things protein, we revisit our episode with Dr. Gabrielle Lyon to get a clear concise bullet point breakdown of takeaways from Dr. Lyon around nutrition and training. We also talk about what practices Gabby has put into place since this discussion. Questions hit: How much protein do I need? Why is 1 gram per ideal body weight the recommendation? Why 30-55 grams of protein per meal?  What are the important things to remember about your first and last meal of the day?  Taking protein into consideration, how do I now think about fats, carbs, and cholesterol? Are supplemental BCAAs a waste of money? Leucine? Why is this one picked out of the crowd? What is it doing for me? Where can I get it?  mTOR? Why is it important? Why it has a bad wrap? Connect with Gabby @gabbyreece | Linktree For show notes and past guests, please visit gabriellereece.com/podcast The Gabby Reece Show talks to top experts with the goal of extracting the best information you will need to navigate the universe of health, fitness, relationships, parenting, and business. Gabby keeps it simple but gets to the heart of the conversation with the hopes of providing you with realistic takeaways. Dr. Gabrielle Lyon Helpful Links: www.drgabriellelyon.com Instagram: @drgabriellelyon & @freedomreads_ Learn more about your ad choices. Visit megaphone.fm/adchoices

For more information, contact us at 859-721-1414 or myhealth@prevmedheartrisk.com. Also, check out the following resources:  ·Newsletter Sign Up·Jubilee website·PrevMed's website·PrevMed's YouTube channel·PrevMed's Facebook page·PrevMed's Instagram·PrevMed's LinkedIn·PrevMed's Twitter ·PrevMed's Pinterest

Featuring an interview with Dr Brian Slomovitz, including the following topics: Comparative efficacy and safety of commercially available PARP inhibitors for ovarian cancer (OC) (0:00) Patient- and disease-specific considerations in the selection and sequencing of treatment for OC with BRCA mutations (11:39) Mechanism of action of mirvetuximab soravtansine; recent efficacy and safety data with mirvetuximab for platinum-resistant OC from the SORAYA trial (15:13) Potential integration of mirvetuximab soravtansine into the treatment algorithm for platinum-resistant OC; emerging data with niraparib/dostarlimab and adavosertib for OC (20:23) Ongoing clinical trials evaluating tumor treating fields and upifitamab rilsodotin for OC (24:57) Recent follow-up data with pembrolizumab/bevacizumab/chemotherapy for metastatic cervical cancer (CC) from the KEYNOTE-826 trial (27:30) Efficacy and safety data with lenvatinib/pembrolizumab from the KEYNOTE-775 trial for endometrial cancer (EC); benefit of lenvatinib/pembrolizumab in subsequent lines of therapy (32:13) Updated data with dostarlimab for microsatellite instability (MSI)-high EC; ongoing clinical trials evaluating immunotherapy versus chemotherapy alone for MSI-high EC (35:47) HER2-low data with T-DXd for breast cancer and its potential role in therapy for EC; emerging role of mTOR inhibitors; ongoing investigations and unmet needs in OC, CC and EC (40:01) CME information and select publications

Featuring a slide presentation and related discussion from Dr Brian Slomovitz, including the following topics: Recent data with PARP inhibitors alone and in combination with other agents as maintenance therapy for advanced ovarian cancer; recent data with novel agents (0:00) Efficacy data with pembrolizumab/chemotherapy from the KEYNOTE-826 trial; biologic rationale for targeting tissue factor and emerging data with tisotumab vedotin for cervical cancer (16:45) PFS2 data (disease progression on next line of therapy after first progression) with lenvatinib/pembrolizumab for advanced endometrial cancer; recent data with dostarlimab and mTOR inhibitors (23:58) CME information and select publications

Pharmacological approaches to longevity using drugs like rapamycin and Acarbose via targeting signaling molecules like mTOR and insulin continue to see growing support. Today we speak with Bradley S Rosen MD whose practice focuses on Living Healthier and Longer through Biogerontology. Dr Rosen graduated with a degree in Mathematics and Statistics and an MD from the University of Florida. His residency was at Jules Stein Eye Institute at UCLA, followed by 2 Retina Fellowships at the Lions Eye Institute and the Royal Victorian Eye and Ear Hospital in Melbourne, Australia. In 2013 Dr. Rosen, M.D. joined a growing number of scientists and clinicians who are becoming increasingly interested in the fact that the hallmarks of aging themselves can and should be targeted for therapy.https://mtormd.com/ @DrBradleyRosen1Lu, Yuancheng, Benedikt Brommer, Xiao Tian, Anitha Krishnan, Margarita Meer, Chen Wang, Daniel L. Vera, et al. “Reprogramming to Recover Youthful Epigenetic Information and Restore Vision.” Nature 588, no. 7836 (December 3, 2020): 124–29. https://doi.org/10.1038/s41586-020-2975-4.Jiang, Zhou, Juan Wang, Denise Imai, Tim Snider, Jenna Klug, Ruby Mangalindan, John Morton, et al. “Short Term Treatment with a Cocktail of Rapamycin, Acarbose and Phenylbutyrate Delays Aging Phenotypes in Mice.” Scientific Reports 12, no. 1 (December 2022): 7300. https://doi.org/10.1038/s41598-022-11229-1.https://www.nature.com/articles/s41598-022-11229-1 *** CONNECT WITH ROBERT LUFKIN MD ON SOCIAL MEDIA ***Web: https://robertlufkinmd.com/ Twitter:https://twitter.com/robertlufkinmdYoutube: https://www.youtube.com/RobertLufkinMD*** MEMBERSHIP ***https://robert-lufkin.mykajabi.com/membership *** SPONSORSHIPS & BRANDS ***We do work with sponsors and brands. If you are interested in working with us for your health industry product or service, please contact us at: https://robertlufkinmd.com/contact  NOTE: This is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have. Never disregard professional medical advice or delay in seeking it because of something you have seen here. Robert Lufkin MD may at any time and at its sole discretion change or replace the information available on this channel. To the extent permitted by mandatory law, Robert Lufkin MD shall not be liable for any direct, incidental, consequential, indirect or punitive damages arising out of access to or use of any content available on this channel, including viruses, regardless of the accuracy or completeness of any such content.Disclaimer: We are ambassadors or affiliates for many of the brands we reference on the channel.Support the show

Nutrition expert Danny Lennon:▹ Effects on building muscle▹ Casein vs. whey before bed▹ Whey vs. EAAs▹ Training fasted vs. fed▹ Effects on losing weight▹ Different metabolic effects▹ Influence on NEAT and appetite regulation▹ Effects on mental energy and health▹ Influence on circadian rhythm▹ Sharper mind through intermittent fasting?▹ Optimal hypertrophy vs. health (mTOR cancer risk)More about Alpha Progression:https://alphaprogression.com/apphttps://facebook.com/groups/alphaprogressionapphttps://instagram.com/alphaprogressionMore about Danny:https://www.instagram.com/dannylennon_sigmahttps://sigmanutrition.comDEUTSCHErnährungsexperte Danny Lennon▹ Einfluss auf Muskelaufbau▹ Kasein vs. Whey vorm Schlafen▹ Whey vs. EAAs▹ Training auf nüchternen Magen▹ Einfluss auf Gewichtsverlust▹ Unterschiedliche Stoffwechseleffekte▹ Auswirkung auf NEAT und Appetitregulation▹ Einfluss auf mentale Energie und Gesundheit▹ Auswirkung auf circadianen Rhythmus▹ Besserer Fokus durch Intermittierendes Fasten?▹ Optimale Hypertrophie vs. Gesundheit (mTOR Krebsgefahr)Mehr über Alpha Progression:https://alphaprogression.com/apphttps://facebook.com/groups/alphaprogressionhttps://instagram.com/alphaprogressionMehr über Danny:https://www.instagram.com/dannylennon_sigmahttps://sigmanutrition.com

Ross Pelton, the Natural Pharmacist, discusses how the prescription drug rapamycin can increase longevity.  The discovery of rapamycin resulted in scientific studies that have enabled scientists to gain a totally new understanding of the aging process and how we might use this new information to improve health and delay the onset of age-related diseases. The topics in this book are collectively one of the most important breakthroughs in the science of life extension that has ever been discovered. The Rapamcyin Story: An interview with Ross Pelton, author of Rapamycin, mTOR, Autophagy & Treating mTOR Syndrome. https://www.lifeextension.com/magazine/2022/6/rapamycin Rapamycin: A Quantum Leap in Life Extension: Article was published in the Aug. 4, 2022 issue of the Townsend Leter. https://www.townsendletter.com/article/466-anti-aging-and-rapamycin/ Rapamycin: Extending Health Span and Life Span:  Article was published in Integrative Medicine: May 2022. http://imjournal.com/oa/index.html?fid=Pelton Order At:  LifeExtension.com/rapa

Most of us want to live longer, healthier years. Research is indicating that our longevity is no more just about the genetic cards we are dealt, but actually we have more controllable elements at our finger tips than ever before. Host Amelia Phillips and Dr Norman Swan, a multi-award winning producer, broadcaster and Physician journalist, discuss the latest longevity and anti-aging research. They also discuss the latest on supplements and therapies such as Metformin, NAD, NMN, resveratrol, mTOR and rapamycin. They discuss simple lifestyle changes to diet, exercise, and education that can dramatically improve longevity, plus the anti-aging skin treatments, and BAG (brain age gap) therapies, to protect our brain from the effect of ageing.  So You Want To Live Younger Longer  Dr Norman's New Book, now available. Badie Winkle: Instagram granny - Amelia wants to have her energy at 94! David Sinclair Lifespan Podcast: Deep dive into longevity medicines.  About the guest: Dr Norman Swan, a multi-award winning producer, broadcaster and Physician journalist. He hosts two popular podcasts; The Health Report and Coronacast, which won a walkley award last year. He is one of Australia's most trusted doctors appearing regularly in the media to help disseminate the large amount of confusing health research.  About the host: Amelia Phillips is an exercise, nutrition, parenting and business expert with a career spanning 26 years in health. She's a registered exercise scientist, nutritionist and researcher (with a masters of human nutrition). She is the co-founder of health tech company 12WBT which grew from start-up. After a successful exit, she now consults to health companies, presents and appears in the media. Amelia had four kids in five years and is dedicated to empowering women to build a life after kids on the foundation of health (mental and physical), love and purpose.  If you have a question for Amelia, reach out via Insta @_amelia_phillips, email ap@ameliaphillips.com.au or text an audio question to: 0417458772 Find out more at www.ameliaphillips.com.au CREDITSHost: Amelia Phillips                                                                                                        Guest: Dr Norman SwanAudio Producer: Darren RothMusic: Matt Nicholich                                                                                                      Production Partner: Nova Entertainment Pty Ltd Healthy Her acknowledges the Traditional Owners of the Land we have recorded this podcast on, the Gadigal people of the Eora Nation. We pay our respects to their Elders past and present and extend that respect to all Aboriginal and Torres Strait Islander cultures. See omnystudio.com/listener for privacy information.See omnystudio.com/listener for privacy information.

In response to several requests from listeners, we have as our guest today, Dr. Matt Kaeberlein, a professor of pathology at the University of Washington. Matt is well-known for his investigations into the basic mechanisms of aging. Much of his research in this area is focused on identifying interventions that promote healthspan and lifespan. In today's interview, we talk to Matt about the biology of aging and what he has learned about slowing the aging process.  In 1999, Matt and his colleague Mitch McVey discovered that overexpression of the SIR2 gene is sufficient to extend lifespan in yeast. SIR stands for silent information regulator, and we have an interesting discussion about how Matt's research and 1999 discovery have elevated SIR2 to the forefront of aging research. Also, some of Matt's most recent and fascinating investigations have been into rapamycin, the only known pharmacological agent to extend lifespan.  His research has shed new light on the role rapamycin plays in delaying age-related dysfunction in rodents, dogs, and humans. We also have a fun discussion with Matt about his research showing that rapamycin may have the potential to reduce the mortality of companion dogs. The paper that came out of this research landed Matt on the front page of the New York Times and received prominent play in the national and overseas media. Other topics we cover include: Matt's attempts to uncover the molecular mechanism behind lifespan extension via calorie restriction. His research into mTOR, which is a protein in every cell, and how inhibiting mTOR has been shown to extend the lifespan of insects, rodents, and animals. Matt's 2006 study that showed fasting extends lifespan in worms more than caloric restriction. And an article Matt published last year that summarized several of the most popular anti-aging diets, comparing them with classical caloric restriction. In addition to his work in his Kaeberlein Lab, Matt is the co-director of the Nathan Shock Center of Excellence in the Basic Biology of Aging and the founding director of the Healthy Aging and Longevity Research Institute at the University of Washington. He also is the founder and co-director of the Dog Aging Project. Show notes: [00:02:53] Dawn asks Matt and his youth and where he grew up. [00:03:06] Ken asks if it is true that Matt spent a good deal of his youth “up to no good.” [00:04:20] Dawn mentions that while Matt got decent grades in school, it wasn't until he went to college that he became studious. Dawn asks Matt if it true that he had originally decided to skip college. [00:05:42] Dawn asks how Matt ended up in Bellingham at Western Washington. [00:06:41] Dawn asks how in the world, despite not liking high school and working a morning shift at UPS for two years after graduating, Matt decided to head off for college and major in biochemistry of all things. [00:08:01] Ken asks what led Matt to travel across the country to Boston and MIT's biology program. [00:09:57] Ken asks why Matt decided to focus his research on the biology of aging. [00:11:57] Matt talks about what he did following his Ph.D. [00:13:15] Dawn asks Matt what kind of research he did at the University of Washington Department of Genome Sciences for his post-doc, and how this research related to aging. [00:15:10] Ken mentions that it was during Matt's undergrad that he decided to focus on the question, “To what extent are the mechanisms of aging evolutionarily conserved?” Ken asks Matt what caused him to arrive at that for his central focus. [00:19:36] Dawn mentions that the discovery by Matt, and Mitch McVey, that overexpression of SIR2 (Silent Information Regulator) is sufficient to extend life span in yeast is credited with promoting SIR2 to the forefront of aging research. Dawn goes on to mention that SIR genes are determinants of life span in yeast mother cells. Dawn asks Matt to give a quick primer on the SIR genes a...

In this episode, Dr. Armstrong and Corbin Bruton discuss the basics of hypertrophy, muscle memory, mTOR, and the importance of strength training for growing and maintaining muscle.Have questions you want answered and topics you want discussed on "Aging Well"? Send us an email at agingwell.podcast@gmail.com or record your question for us to use in an upcoming episode:https://www.speakpipe.com/AgingWellPodcast

Welcome to Episode 109 of the Autism Parenting Secrets. This week we have an amazing guest who provides a compelling, cutting-edge approach that you likely have not heard of.  We're talking about genetic-specific nutrition.Our guest is Bob Miller. In 1993, he opened the Tree of Life practice and he has served as a traditional naturopath for 27 years. In 2016, he created an online certification course on genetic nutrition for health professionals now training over 900 health professionals in the program.Bob is the founder and president of Functional Genomic Analysis, an online software program that organizes and analyzes genetic SNPS for functional health professionals across the world.Getting more informed so you can take better actions to support your child and yourself is the opportunity.  And the secret this week is…Genes are CLUES, Not Destiny You'll Discover:What is Functional Genomics? (5:00)What The Science Says (7:39)How Mold Wreaks Havoc (14:42)Why You Need To Be Careful With Omega 3s and Fish Oil (18:22)Even More Reasons To Avoid High Fructose Corn Syrup (21:02)The Link Between Inflamation, Histamine and Mast Cell Activation (30:07)What You Need To Know About MTHFR (34:03)The Miracle Molecule (38:54)Minimizing Exposure To Glyphosate Is Essential (41:51)How Glutamine and Glutamate Play A Role (53:58)The 3D Chess Game Played Underwater (58:34)About Our GuestFor the past several years, Bob Miller has been engaged exclusively with functional nutritional genetic variants and related research, specializing in nutritional support for those with chronic Lyme disease.Bob lectures nationally and internationally at seminars to educate health care practitioners about genetic variants and nutritional supplementation for achieving optimal health, and holds live webinars every other Thursday evening for health professionals. In 2016, he created an online certification course on genetic nutrition for health professionals now training over 900 health professionals in the program.Bob is a frequent guest on many podcasts such as Dr. Jill Carnahan, Better Health Guy, Dr. Joseph Mercola, and many others.To support his growing genetic research efforts, in 2015, Bob founded and personally funds, the NutriGenetic Research Institute to research the relationship between genetic variants and presenting symptoms.His first research project on genetic variants in those with chronic Lyme disease, was one of two winners for research by the ILADS international meeting held in Helsinki, Finland. His Phase II study of Lyme disease was presented at the American ILADS conference in November 2016, Phase III was presented at the International ILADS conference in Paris, France in May 2017 and his Phase IV study on mTOR and Autophagy in Lyme disease was presented in Boston, November 2017. Phase V was presented in Warsaw, Poland in June 2018 and his Phase VI was another winner presented in Chicago, Illinois in November of 2018 which showed increased variants in the Heme pathway and Mast Cell genes. Phase VII presented in Madrid, Spain in June of 2019 research showed how genetic variants in genes related to the production of and utilization of NAD+ and NADPH are creating what is now referred to as the ‘NADPH Steal'. In 2020, he presented his research at the online ILADS conference on genetic mutations in the synthesis and utilization of bile.Bob has created 72 nutritional supplement products exclusively for health professionals for Professional Health Products and Functional Genomic Nutrition through Compounded Nutrients.  The products he formulated are based upon his genetic research and are designed to support function that may be impaired by genetic weakness.Bob is the founder and president of Functional Genomic Analysis, an online software program that organizes and analyzes genetic SNPS for functional health professionals across the world.Memberships:National Association of Certified Natural Health ProfessionalsAmerican Association of Nutritional ConsultantsBoard Certified Naturopath - American Naturopathic Certification & Accreditation BoardBob MillerTree of LifeReferences in This Episode:Rantes Overview PDF - use this to follow along with the discussionWatch the video version of this presentation hereOmegaQuantDr. Jill CarnahanAdditional Resources:Free Resource: 33 Mistakes Most Autism Parents Make and How To Avoid ThemGot a Picky Eater? - this can helpTo learn more about Cass & Len, visit us at www.autismparentingsecrets.comBe sure to follow Cass & Len on InstagramIf you enjoyed this episode, share it with your friends.Don't forget to subscribe to the show on Apple Podcasts to get automatic episode updates for our "Autism Parenting Secrets!"And, finally, please take a minute to leave us an honest review and rating on Apple Podcasts. They really help us out when it comes to the ranking of the show, and we read every single one of the reviews we get. Thanks for listening!

This episode is brought to you by Rupa Health, Levels, and HigherDOSE.I'm willing to bet all of us would feel a whole lot better about aging if it didn't actually mean feeling old. Well, I'm here to tell you it doesn't have to; aging can mean another year of joy, adventure, and spending time with people we love—all while feeling great. Today, as part of my Masterclass series, I am joined by my good friend and podcast host, Dhru Purohit, to answer a question submitted by my community through the video app HiHo about the benefits of hot and cold therapy. We also discuss why adequate protein is vital as we age and how to turn on longevity switches in our bodies to live a longer, healthier life. Find a link below to follow me on HiHo and we may select your question for a future episode!Dhru Purohit is a podcast host, serial entrepreneur, and investor in the health and wellness industry. His podcast, The Dhru Purohit Podcast, is a top 50 global health podcast with over 30 million unique downloads. His interviews focus on the inner workings of the brain and the body and feature the brightest minds in wellness, medicine, and mindset.This episode is brought to you by Rupa Health, Levels, and HigherDOSE. Rupa Health is a place where Functional Medicine practitioners can access more than 2,000 specialty lab tests from over 20 labs like DUTCH, Vibrant America, Genova, and Great Plains. You can check out a free, live demo with a Q&A or create an account at RupaHealth.com. By leveraging biosensors like continuous glucose monitors (CGM), Levels provides real-time feedback on how diet and lifestyle choices impact your metabolic health. Learn more about Levels by going to levels.link/HYMAN. Right now, you can get your own Infrared Sauna Blanket or Infrared PEMF Mat at HigherDOSE.com. Use code FARMACY15 at check out to save 15% off OR just go to higherdose.com/hyman to get your 15% off today. In this episode, we discuss (audio version / Apple Subscriber version):The best way to do hot and cold therapy (4:13 / 00:48) My tips for hot and cold therapy while traveling (18:44 / 15:10) Integrating hot and cold therapy with exercise (19:48 / 16:18) The importance of adequate protein for strength training and healthy muscles as we age (30:14 / 25:00) Activating the mTOR longevity switch in the body (37:30 / 32:34)Using metformin or other drugs to hack longevity (48:37 / 43:20) Follow me on HiHo here! See acast.com/privacy for privacy and opt-out information.

► MTMT Day of Breath: ► https://www.mtmt.life/education/day-of-breath/ Der MTMT Podcast #182 ist Teil II zum Thema Ernährung - wir beantworten eure Fragen rund um das Thema Ernährung.
 Dr. Tilo gibt euch detailliertere Aussagen zu allem was ihr wissen wolltet. Worum geht es euch, wenn ihr auf eure Ernährung achtet? Wie individuell muss unser Essen eigentlich sein? Sind die Glaubenssätze der Fitnessindustrie die Norm, an die wir uns halten sollten oder probieren wir doch lieber, was UNS am besten tut? Es geht um Pizza-Qualitätsmerkmale, Proteineinnahme, Veganismus und Blue Zones und wir geben euch einen Einblick, was für UNS funktioniert. Viel Spaß bei dieser Folge! ► Patreon: https://www.patreon.com/mtmtgym ► (06:30) Was ist das Ziel, wenn man auf die Ernährung achtet? ► (12:00) Individualität beim Essen ► (18:25) Was sind die Indikatoren für eine gute Pizza? ► (23:10) Health-Benefits von Veganismus - overrated oder underrated? ► (25:40) Wie hoch sollte der tägliche Protein-Intake sein? ► (29:30) Wie ernähren sich Menschen in den Blue Zones? ► (32:30) Sind viele kleine oder drei große Mahlzeit besser? ► (42:35) Was soll ich essen, wenn ich mental am Boden bin? ► (47:20) Kalorienüberschuss, hoher Proteingehalt und Körperfettanteil ► (53:35) Insulin ► (55:40) Dauerhaft 16-8 Fasten vs 1 Tag - 3x im Monat ► (58:00) Essen an Trainingstagen vs an Pausentagen ► (01:00:40) AMPK & mTOR ► (01:03:20) Wie wichtig ist das Aminosäurenprofil? Pflanzlich vs Tierisch? ► (01:07:05) Unsere Full Days of Eating ► Instagram: https://www.instagram.com/mtmt.gym ► Online Coaching, Apparel und Personal Training: https://www.mtmt.life/store ► Wenn Ihr Fragen oder Anregungen habt, kontaktiert uns auf unseren Social Media Kanälen oder schreibt uns unter podcast@mtmt.life !! MTMT Gym ist ein Team von Coaches aus München. Seit 10 Jahren begleiten wir ALLE Arten von Menschen auf ihrem persönlichen Weg. In unserer täglichen Arbeit widmen wir uns den Themen Training, Ernährung, Regeneration und Stress-Management. Wir geben bessere Antworten auf die Fragen der Fitnessbranche, mit dem Ziel Athleten und Coaches NACHHALTIG erfolgreich zu machen. MTMT Content ist (meistens) frei von Dogma, Mythen und Bullshit - REAL, TRUE, UNTERHALTSAM und ANWENDBAR.

This week, Jillian goes over a variety of mistakes people make when trying to lose weight -- from workouts to alcohol, sleep, and hydration -- and what you can do to stay on track. Plus, everything you need to know about protein, mTOR, BCAA's, oxidative stress and more!For 25% off The Fitness App by Jillian Michaels, go to www.thefitnessapp.com/podcastdealFollow us on Instagram @JillianMichaels and @MartiniCindyJillian Michaels Community: https://www.facebook.com/groups/1880466198675549Email your questions to JillianPodcast@gmail.comSee Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Aging is indexed by Web of Science: Science Citation Index Expanded (abbreviated as Aging‑US). As of June 29, 2022, Web of Science (Clarivate Analytics) released their 2021 JCR Impact Factor List. Aging is pleased to report that our 2021 impact factor is 5.955. This number has increased from last year's 5.682. Aging is listed in the Web of Science: Science Citation Index Expanded in two categories: Cell Biology and Geriatrics & Gerontology. According to the Journal Citation Indicator (JCI), Aging is ranked in the Q1 quartile in both categories. Since 2009, Aging has published research papers in all fields of aging research including, but not limited to, aging from yeast to mammals, cellular senescence, age-related diseases such as cancer and Alzheimer's diseases and their prevention and treatment, anti-aging strategies and drug development, and especially the role of signal transduction pathways such as mTOR in aging and potential approaches to modulate these signaling pathways to extend lifespan. This journal aims to promote treatment of age-related diseases by slowing down aging, validation of anti-aging drugs by treating age-related diseases, and prevention of cancer by inhibiting aging. Cancer and COVID-19 are age-related diseases. To learn more about Aging, publication standards, and past or current issues, visit www.aging-us.com. About Aging-US: Launched in 2009, Aging (Aging-US) publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Follow Aging on social media: SoundCloud – https://soundcloud.com/Aging-Us Facebook – https://www.facebook.com/AgingUS/ Twitter – https://twitter.com/AgingJrnl Instagram – https://www.instagram.com/agingjrnl/ YouTube – https://www.youtube.com/agingus​ LinkedIn – https://www.linkedin.com/company/aging/ Pinterest – https://www.pinterest.com/AgingUS/ For media inquiries, please contact media@impactjournals.com. Aging (Aging-US) Journal Office 6666 E. Quaker Str., Suite 1B Orchard Park, NY 14127 Phone: 1-800-922-0957, option 1

Why You Should Listen:  In this episode, you will learn about the mitochondria and The Energy Blueprint. About My Guest: My guest for this episode is Ari Whitten.  Ari Whitten, PhD (Cand), CES, PES is the founder of The Energy Blueprint system, a comprehensive lifestyle and supplement program which has helped more than two million people (and counting) experience optimal health, better performance, and more energy.  He's also the bestselling author of The Ultimate Guide to Red Light Therapy and the host of the popular The Energy Blueprint Podcast which features the world's leading natural health experts.  In 2020, Ari was voted #1 Health Influencer by Mindshare, the largest natural and functional medicine community.  For more than 25 years, Ari has been dedicated to the study of human health science.  He holds a M.S. in Human Nutrition and Functional Medicine, a B.S. in Kinesiology, certifications as a Corrective Exercise Specialist and Performance Enhancement Specialist from the National Academy of Sports Medicine, and he has completed all of the coursework for a Clinical Psychology Ph.D. You can find his podcast, programs, and supplement formulas at TheEnergyBlueprint.com. Key Takeaways: What are the symptoms of mitochondrial dysfunction? What "signals" lead to impairment of the mitochondria? How might supporting the mitochondria need to consider whether or not one is in a Cell Danger Response? What are "zietbegers" and their relevance to brain and body clocks? Can too much protein lead to overactivation of mTOR and potentially be harmful? What role do short-chain fatty acids play in energy production? Can prebiotics and resistant starches be used in those with SIBO? What role might vinegar play in supporting the mitochondria? How might Urolithin A be supportive of the mitochondria? Are niacin derivatives such as NR or NMN proving to be helpful? How might melatonin support the mitochondria? Are the adrenals a key player in fatigue? What role might red light therapy or photobiomodulation have in supporting mitochondria? Connect With My Guest: http://TheEnergyBlueprint.com Related Resources: Book: Eat for Energy: How to Beat Fatigue, Supercharge Your Mitochondria, and Unlock All-Day Energy Breathing for Energy Program The Energy Blueprint Store Interview Date: June 28, 2022 Transcript: To review a transcript of this show, visit https://BetterHealthGuy.com/Episode168. Additional Information: To learn more, visit https://BetterHealthGuy.com. Disclosure: BetterHealthGuy.com is an affiliate of The Energy Blueprint. Disclaimer:  The content of this show is for informational purposes only and is not intended to diagnose, treat, or cure any illness or medical condition. Nothing in today's discussion is meant to serve as medical advice or as information to facilitate self-treatment. As always, please discuss any potential health-related decisions with your own personal medical authority. 

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses. In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today's episode, 4 Cancer.Net Specialty Editors discuss new research in prostate, bladder, kidney, and testicular cancers presented at the 2022 Genitourinary Cancers Symposium and 2022 ASCO Annual Meeting. This episode has been adapted from the recording of a live Cancer.Net webinar held June 15th, 2022, led by Dr. Neeraj Agarwal, Dr. Timothy Gilligan, Dr. Petros Grivas, and Dr. Tian Zhang. Dr. Agarwal directs the Genitourinary Oncology Program at the Huntsman Cancer Institute at the University of Utah. Dr. Gilligan is an Associate Professor and Medical Oncologist at the Cleveland Clinic Taussig (TOSS-ig) Cancer Center. Dr. Grivas is the clinical director of the Genitourinary Cancers Program at University of Washington Medicine. He is also an associate member of the clinical research division at the Fred Hutchinson Cancer Research Center. Dr. Zhang is an Associate Professor of Internal Medicine at UT Southwestern Medical Center and a medical oncologist at the Harold C. Simmons Comprehensive Cancer Center. Full disclosures for Dr. Agarwal, Dr. Gilligan, Dr. Grivas, and Dr. Zhang are available at Cancer.Net. Greg Guthrie: Good afternoon, everyone. I'm Greg Guthrie, and I'm a member of the Cancer.Net content team. I'll be your host for today's Research Round Up webinar focusing on cancers of the genitourinary tract. Cancer.Net is the patient information website of the American Society of Clinical Oncology, known as ASCO. So today, we'll be addressing research from 2 2022 scientific meetings, the ASCO Annual Meeting held in Chicago in June and the Genitourinary Cancers Symposium held in San Francisco in February. Our participants today are all Specialty Editors of the Cancer.Net Editorial Board, and they are Dr. Neeraj Agarwal of the Huntsman Cancer Institute in University of Utah, Dr. Timothy Gilligan of the Cleveland Clinic Taussig Cancer Center, Dr. Petros Grivas of the Fred Hutchinson Cancer Research Center and University of Washington, and Dr. Tian Zhang of the University of Texas Southwestern Medical Center. Thank you, everyone, for joining us today. So starting us off today is Dr. Agarwal who will be talking about research in prostate cancer. Go ahead, Dr. Agarwal. Dr. Agarwal: Hi. Thank you, Greg. So I'd like to start with 2 studies. They both are in prostate cancer which will be followed by my colleagues presenting studies in other cancers in bladder cancer and kidney cancer. So I'll start with this abstract, which was highly discussed by the doctors at the ASCO Annual Meeting a few weeks ago, and it has a lot of relevance in our practice. So this is abstract #5000 presented by Dr. Michael Hofman, and this was the update on a clinical trial which compared lutetium PSMA-617, or lutetium PSMA, to put it simply, with cabazitaxel in patients with metastatic castration-resistant prostate cancer who had disease progression after receiving docetaxel chemotherapy. So, who were the patients who were enrolled on the study? These patients had, as I said, metastatic castration-resistant prostate cancer, who had disease progression after docetaxel chemotherapy, and who had to have high PSMA-expressing prostate cancer. And the way they assessed the presence of high PSMA expression was by using a specialized kind of PET scan known as Gallium 68 PSMA-11 PET scan. In addition, they made sure that these patients do not have another type of prostate cancer, also call it dedifferentiated prostate cancer, by making sure that those patients did not have a traditional PET scan-positive disease. So this was a highly selected patient population who were expressing PSMA on their prostate cancer. Prior to this presentation, the earlier presentation had shown that lutetium PSMA was superior to cabazitaxel as far as progression-free survival is concerned and also was associated with lower incidence of grade 3 or 4 side effects. In this update, after a longer follow-up of 3 years, Dr. Hofman and Dr. Davis, who is a senior author, they presented the data on overall survival, which was a secondary analysis, and overall survival was similar with cabazitaxel as well as lutetium PSMA in the range of 19 months. We did not see any new safety signal. So, what does it mean for us? What does this mean for our patients? My key takeaway message here is, lutetium PSMA is a suitable option for men with metastatic castrate-resistant prostate cancer who are expressing high PSMA on their prostate cancer after they had sustained disease progression after docetaxel. However, cabazitaxel is also a valid option in this setting. I would like to add my own view in addition to this because lutetium PSMA was better tolerated and was also associated with better progression-free survival. In my patients who are progressing on docetaxel chemotherapy, I would like to use lutetium PSMA first followed by cabazitaxel chemotherapy. So that would be my key takeaway from this abstract. Now we can move to the next abstract. This was also an update, a much longer update, on ENZAMET trial. If you recall, ENZAMET trial was one of those trials which established that deeper androgen blockade, or deeper androgen signaling inhibitors such as enzalutamide, apalutamide, or abiraterone, these trials were conducted in 2015 onwards, and all these trials showed that upfront using deeper androgen signaling inhibitors at the time of metastatic hormone-sensitive prostate cancer onset improved survival. So ENZAMET trial used enzalutamide, and it showed in the first analysis, which was presented by Dr. Davis and Dr. Sweeney in the 2019 ASCO Meeting Plenary session, that adding enzalutamide to androgen-deprivation therapy in patients with metastatic hormone-sensitive prostate cancer significantly improved survival. In this longer follow-up of 68 months, so we are talking about almost 6 years of follow-up, now, these investigators from ENZAMET trial, as presented by Dr. Davis, showed that the combination of enzalutamide with androgen deprivation therapy or testosterone suppression therapy continues to significantly improve survival in patients with newly diagnosed hormone-sensitive prostate cancer or metastatic prostate cancer. One interesting part of this unique aspect of this trial was that patients were allowed to receive docetaxel chemotherapy concurrently to the protocol treatment. And in this trial, 45% patients actually receive docetaxel chemotherapy. So 503 patients exactly out of 1,000-plus patients. So if you look at the subgroup analysis of those patients who received docetaxel chemotherapy, enzalutamide does not seem to benefit those patients from the overall survival perspective. So on the face of it, it looks like enzalutamide is not helping those patients who are receiving docetaxel concurrently. But there are some caveats with that kind of subgroup analysis. The first one is this is not a randomized assignment of docetaxel chemotherapy. Patients were determined to have docetaxel chemotherapy after discussion with their respective oncologist. This was not a prespecified analysis that so many patients with docetaxel will receive enzalutamide. Also, this was not a randomized assignment of docetaxel. And third, that I don't think this trial had enough power to look for that subgroup analysis. So my take on this trial is that updated results from this trial, almost 6 years of follow-up now show that enzalutamide continues to improve overall survival with a 30% reduction in risk of death in patients with metastatic castration-sensitive or hormone-sensitive prostate cancer. Furthermore, the effect of enzalutamide, in my view, on overall survival is independent of the receipt of docetaxel. If you look at the whole trial population for which the trial was covered for, enzalutamide improved survival for all patients. And based on these results, I feel more confident in saying that upfront intensification of treatment with deeper androgen inhibition remains a standard of care for our patients with metastatic hormone-sensitive prostate cancer and should be offered to all eligible patients with this condition. With that, I would like to wrap up the prostate cancer abstracts. Thank you very much. Greg Guthrie: And thank you, Dr. Agarwal. Next up, we will have Dr. Gilligan, who is going to be discussing testicular cancer. Dr. Gilligan: Thank you very much. So I have 2 studies I want to talk about and then just give a headline of some interesting things that I think are kind of coming down the road. Both of these abstracts have to do with improvement over time in specific patient populations we used to worry about. I'm not saying we don't worry about them anymore, but things are looking better now than they had 1 or 2 decades ago. So the first topic addresses late relapses in testicular cancer. And historically, we have been concerned that these patients did worse and had worse outcomes. And late relapse could variously be described as after 2 years or after 5 years. In the current study, they defined late relapse as being after 2 years and very late relapse as being after 5 years. And what was special about the study was that it captured the entire population of patients with testis cancer in Norway and Sweden so that it wasn't based on a center of excellence that gets selective referrals. It was actually a population-based study. And the key conclusion of the study was one I found, once again, that late relapses are rare. So for stage I patients, 2% of patients will relapse after 2 years, 1% after 5 years, and 0.5%, so 5 out of 1,000 patients, after 10 years. So if you're 2 years out, the likelihood of a relapse is quite low. And if you're 5 years out, it's half of that. In patients with metastatic disease, similarly, 3.6% relapse after 2 years, 1.6% after 5, and 0.8% after 10 years. And what was interesting to me was that if you looked at the more recent patients who were diagnosed after 1995 - I know that doesn't sound very recent, but they had even earlier patients also in the study - the very late relapse rate almost resolved and went away. It went from 2.2% all the way down to 0.8%. So I think with modern imaging, modern care patterns, we're seeing less of this than we used to. But overall, patients were doing better even if they do relapse late. One thing that was interesting in the study to me also was for stage I disease, we typically recommend surveillance rather than active treatment. So active treatment with non-seminomas would be a retroperitoneal lymph node dissection or more surgery or chemotherapy. With seminoma, it would usually be chemotherapy or radiation, although surgery is being investigated there now. And they did find that in men who chose surveillance, which we still recommend, the late relapse rate was a little bit higher, but it was still affecting a small percent of patients. So the relapse rate beyond 2 years was 4% rather than 1%, but out of 4,000 patients, there were only 3 deaths from late relapse. So this isn't changing the recommendation for surveillance, but it is an alert that patients who are on surveillance for stage I disease have a slightly higher risk of late relapse and that may affect how we follow them and specifically how long we follow them. One of the things that was interesting in the study is in the United States, we often stop scans at 5 years, but in the SWENOTECA countries, they continue scans all the way out to 10 years. I don't know that U.S. guidelines are going to change, but it was a provocative finding. The key thing, as I alluded to at the beginning, was that 61% of patients with late relapse were alive 10 years later, and while we would like that number to be higher, it used to be around 50% in older studies. So it's a significant improvement from where we were before. A particularly interesting thing to me was that patients relapsing 2 to 5 years out actually had the best prognosis. Patients who relapsed in years 1 to 2 had a worse prognosis and patients relapsing after 5 years had a worse prognosis, whereas the patients relapsing 2 to 5 years had a better prognosis. In the end, I think what this means for us is that patients are doing better. It's not going to really change our treatment patterns, but it's reassuring that we shouldn't be pessimistic about late relapses, and we still have a solid chance of curing them. So again, bottom line, most men with late relapse is cured and late relapse is less common now than it was earlier, particularly in non-seminomas. Let's go to the next study. So this is a different group of patients who had a particularly ominous prognosis historically and still we have a lot of room for improvement. These are patients with non-seminomas that start in the mediastinum. So in the chest, under the breastbone, under the sternum typically. And patients are treated aggressively upfront, they are considered poor risk at the initial time of diagnosis, and they're treated aggressively at the time with 4 cycles of BEP or 4 cycles of VIP chemotherapy. And then they go for surgery to remove any residual disease. And the hope is they're cured at that point because historically, if there was a relapse after chemotherapy and surgery, it was almost impossible to cure them. Indiana University published their results using high-dose chemotherapy in this population, and they reported that 30% of men who were treated with high-dose chemotherapy had no evidence of cancer after 2 years, and 35% were still alive. Obviously, we need longer follow-up, but most of the relapses you're going to see are going to be in the first 2 years. So while again, there is significant room for improvement here, this indicates that high-dose chemotherapy is a good option, and that has been a question. So this is reassuring in that regard. But it is a good option for men with relapsed mediastinal non-seminomas of the germ cell tumors. So there's hope there where in the past, this has felt a little bit helpless. The thing I wanted to also highlight was that there are 3 things I think are going to be interesting to keep an eye on over the next year. One is the use of surgery for early-stage seminomas. There are a number of papers out about that. I still think this is an investigational approach, and so I didn't want to go into great detail about it, but it is looking like that RPLND, or retroperitoneal lymph node dissection, will likely or may be an option for stage I and stage II seminoma in the future. We are getting more evidence for that. It's not quite as promising as we had hoped until there's more data that's needed, but it's looking like that will become an option. So for men with early-stage seminoma, at least raising the question whether surgery is an alternative to chemotherapy or radiation, is an important discussion to have with your oncologist. Secondly, MRI rather than CT scans for surveillance. So to keep an eye on men who have been treated or men who are just stage I and are being followed and typically come in routinely for CT scans, which expose people to ionizing radiation, which theoretically has a risk of causing cancer, there's more and more data that MRI is just as good as CT, and MRI does not use ionizing radiation. So there's probably going to be an expanding role for MRI as an alternative to CT scans. And lastly, the use of microRNA rather than just depending on serum tumor markers. So right now, we use the blood tests alpha-fetoprotein, beta hCG, extensively to monitor for relapse, and there's more and more evidence for using what we call microRNAs instead. It may be more accurate in multiple different settings. So it'll be interesting to see how that evolves and that's what I wanted to cover today. Thank you very much. Greg Guthrie: Thank you, Dr. Gilligan. And now we have Dr. Grivas, who's going to discuss some research in bladder cancer. Dr. Grivas: Thank you so much, Greg, and thanks Cancer.Net for the great opportunity to discuss this for our patients. We're very excited about the data from the ASCO Annual Meeting, and I would encourage the audience to review as possible other presentations as well. I'm going to cover 3 highlights. I'm going to start with the QUILT-3.032 study. This trial reported the final results of a clinical trial that took place in different centers and involved patients with what we used to call “superficial bladder cancer.” And the modern term is “non-muscle-invasive bladder cancer.” Bladder cancer that does not involve the muscle layers, not that deep in the bladder wall. Non-muscle-invasive bladder cancer is usually treated by our colleagues in urology with installation inside the bladder with an older form of immunotherapy which is BCG. And that's the most common way we treat this disease. And proportion of patients may have tumors that may not respond to BCG that may come back or persist despite the installation of the BCG in the bladder. And these patients usually have a standard of care of getting what we call radical cystectomy, meaning, removal of the bladder and the lymph nodes around the bladder, radical cystectomy and lymph node dissection. However, many patients may not have, I would say, the opportunity to get the surgery because the body may not be that strong to undergo that significant procedure. Very few patients may have that challenge because of other medical conditions or what we call poor performance status. Or some patients for quality-of-life reasons may try to keep their bladder as long as possible. And for some of those patients, that might be an option. And we have been looking for those options in the last few years. Intravesical, inside the bladder, installations of chemotherapy have been used with some positive results in some other studies. So that's an opportunity. We call this intravesical, inside the bladder, installations of chemotherapy, and the other option is an FDA-approved agent given intravenously inside the vein called pembrolizumab, which is in the form of immunotherapy. Of course, research continues. And this study I'm showing here from Dr. Chamie and colleagues, looked at this combination of BCG plus this molecule called N-803. This is another form of immunotherapy, and this was tested in patients who have this BCG-unresponsive, as we called it, non-muscle-invasive bladder cancer. The results were very promising. I would say impressive that it was a high response rate if we focus our attention on patients who had the superficial form carcinoma in situ, about 70% had no evidence of cancer upon further evaluation of the bladder. And in many of those patients that this response lasted for more than 2 years. 96% of patients avoided to have worsening of the bladder cancer in 2 years for those who had a response, and about 9 out of 10 avoided cystectomy again from those patients who had received the response. So it was 70% of all the population. And as you see, all patients, 100% were alive without dying from bladder cancer after 2 years, which again is a very promising finding. This combination, to conclude, this inside the bladder installations of BCG plus the N-803, looks very promising. For those patients with BCG-unresponsive non-muscle-invasive bladder cancer, that might be an option down the road, we have to see. Now I'm going to shift my attention to patients with metastatic or spread urothelial cancer. I want to point out that I'm a co-author in this abstract and I participated in that survey I will show you the results from. This is a population of patients who have spread cancer from the urinary tract, either the bladder was the most common origin or other parts of the urinary tract, for example, what we call kidney, pelvis and ureter, or rarely the urethra. The urothelial cancer that starts from those areas, again more commonly bladder, if it spreads, if it goes outside the urinary tract system, usually those patients get chemotherapy, what we call with an agent called cisplatin if they can tolerate that chemotherapy drug or carboplatin if they cannot tolerate the cisplatin drug. And usually either of these, cisplatin or carboplatin, is combined with a drug called gemcitabine. That's the most common chemotherapy used as initial therapy for patients with spread metastatic urothelial cancer. In this abstract, Dr. Gupta and colleagues tried to survey 60 medical oncologists, including myself, who treat urothelial cancer that considered experts in this disease type, to see if there are any features that could deter us from using chemotherapy in those patients. In other words, are there any features that may make us think that chemotherapy may be too risky for our patients and we should not do it? We should give immunotherapy instead. This is probably a small proportion of our patients, maybe 10 to 20% in our practice, may not be able tolerate that chemotherapy. And which are those features? Poor performance status, meaning the body is very tired and the patient is not moving too much, is confined in the chair or the bed most of the day, and rely on others on daily activities. This is what defines the performance status of ECOG 3. Peripheral neuropathy, meaning that there is numbness or tingling or weakness in the hands or the feet that impact the quality of life. And patients may have trouble buttoning buttons or tying laces, so impacting the quality of life. That's grade 2 neuropathy. Symptomatic severe heart failure, there is a grading system, like New York Heart Association Class III or IV that is significant, notable heart failure symptoms. And also, patients with kidney failure with what we call creatinine clearance below 30 cc per minute. That's a marker how we measure kidney function and the creatinine clearance more than 60 is usually close to normal. As the creatinine clearance drops and goes below 30, chemotherapy with these platinum agents may become a challenge by itself or if it's combined with the ECOG performance status of 2, which means more patients are not moving most of the day. So those features again have to do with the functionality of the day-to-day life. The presence of significant neuropathy, heart failure, and poor kidney function may potentially make the oncologist recommend immunotherapy versus the standard of care, which is chemotherapy, in those patients. And I would say if someone gets chemotherapy, which is the majority of patients, usually they may get immunotherapy later. So pretty much I would say discuss with the medical oncologist what is the right treatment for you. Most patients get chemotherapy up front, followed by immunotherapy. Some others may need to get immunotherapy, and those criteria help us make that patient selection for the right treatment at the right time. So I just alluded to you that most patients with spread or metastatic urothelial cancer, most of them receive chemotherapy. We discussed some criteria in the previous studies that we may use immunotherapy upfront instead of chemo, but for the vast majority of patients, chemotherapy is used upfront and that was based on the results of phase 3 clinical trial called JAVELIN Bladder 100. This was presented at the ASCO Annual Meeting in 2020 about 2 years ago, and it was published in a big journal. And that study showed that if you give chemotherapy upfront, those patients who can tolerate the chemotherapy, of course, who do not have the previously listed criteria, those patients benefit and live longer, so longer overall survival, meaning they live longer, and they have longer progression-free survival, meaning they live longer without worsening of the cancer if they get immunotherapy with, immunotherapy drug is given through the vein, called avelumab. If that is given after the end of chemotherapy for patients who have a response or stable disease, meaning no progression on chemotherapy. So if you get a complete response, meaning that the CAT scans look normal after chemotherapy as at least we can tell visually. Partial response, meaning that the CAT scans look better, but still we can see some cancer spots. Stable disease, meaning that the scans look stable compared to the beginning before we start chemotherapy. If someone has worsening of the cancer in chemotherapy, then the concept of maintenance therapy doesn't apply. So it's only for patients with complete response, partial response, or stable disease, SD. And the poster we had, and I can tell you - I was a co-author in the abstract and co-investigator in the trial, as a disclosure - was sort of the benefit of the patient with avelumab as maintenance therapy after chemotherapy was notable in patients with complete response, partial response, and stable disease. So in any of these 3 categories, avelumab immunotherapy should be offered as level 1 evidence and benefit patients in terms of overall survival and progression-free survival as long as there's no progression to the upfront initial chemotherapy of the patient with metastatic urothelial cancer received. Many other abstracts on these cancers were presented, and I would encourage you to look at them. Thank you so much for the opportunity today. Greg Guthrie: And thank you, Dr. Grivas. Next, we have Dr. Zhang who will discuss some research in kidney cancer. Dr. Zhang: Hi everyone, glad to be here today. I'll be discussing 2 highlights from ASCO 2022 in kidney cancer. The first one we wanted to highlight was a trial called EVEREST: everolimus for renal cancer ensuing surgical therapy, a phase 3 study. And in context, this study is a trial of evaluating everolimus, an mTOR inhibitor, in the post-surgical context. And we do have in the landscape 2 approved therapies, sunitinib and pembrolizumab. And as we have seen, some effective therapies in the refractory setting, many of these therapies are being tested in this postoperative space. So this particular study of EVEREST looked at patients with renal cell carcinoma who underwent resection for their primary nephrectomy and looking to evaluate postsurgical treatment. So everolimus has been approved as a treatment on its own in the refractory setting as well as in combination with lenvatinib. And so this question of whether everolimus alone could delay or prevent disease recurrence in the postoperative setting was tested in this EVEREST trial. The study ultimately enrolled more than 1,500 patients and assigned them to receiving either everolimus or placebo in the postoperative setting. Of these patients, 83% had clear cell kidney cancer and the remaining had non-clear cell kidney cancer. And the follow-up was quite long, over 5 years, and actually over 6 years, and the researchers looked at time until disease recurrence. And risk of recurrence was actually decreased by 15% in patients who were treated with everolimus compared to placebo. But the prespecified cut-off for a statistical significance was not quite reached, and the researchers took a specific look at a group of very high-risk patients defined by larger tumors, invasion of the perinephric fat in renal veins or invasion of nearby organs or known positive disease. And those patients with very high-risk disease had more benefit from everolimus compared to placebo. Of note, 37% of patients who were treated with everolimus had to stop treatment due to their side effects, and the most common severe side effects included mouth ulcers, high triglyceride levels, and high blood sugars. So ultimately this particular study did not show sufficient benefit of everolimus given the toxicity and lack of statistical significance. And so this is a balance between potential benefit in delaying recurrence versus treatment toxicities that we must have in this adjuvant setting. So what does this particular study mean for patients? Well, it was certainly a large phase 3 trial performed in the cooperative group setting and through the generosity of 1,500 patients and the principal investigators on the study, we learned this answer for a very important question of whether everolimus makes a difference in this postoperative setting. I think we're not using this in clinical context currently, but in this postoperative setting, we are always balancing this risk of toxicity with the potential for benefit and discussing the potential treatment options. I do not think this particular trial changes the standard of care in this adjuvant setting. And then I think finally for today's prepared talks, this abstract on depth of response and association with clinical outcomes with CheckMate 9ER patients treated with cabozantinib and nivolumab. So this was a post-trial analysis of patients who had kidney cancer with disease spread and treated with cabozantinib and nivolumab compared with sunitinib in the CheckMate 9ER study. And the context, this was the phase 3 trial in which the benefit of cabozantinib and nivolumab was established in the first-line setting and gained the registration and approval of this combination in the first-line treatment of metastatic kidney cancer. This particular analysis, presented at ASCO this year, was a post-trial prespecified analysis evaluating this depth of partial responses and associating those with clinical outcomes of time until disease progression as well as time until death. These depth of responses were defined as 80 to 100% for PR-1, 60 to 80% for PR-2, and then 30 to 60% as PR-3. And as we saw in this analysis, the deeper the responses on cabozantinib and nivolumab, the more correspondence with higher 12-month rates of disease-free progression compared with those same depths of responses from sunitinib. And there were similar 12-month overall survival rates for patients with similar depth of responses for either the cabozantinib and nivolumab combination compared with sunitinib. So I do think the degree of partial response in these settings is productive of time until progression and establishes further the efficacy and benefit of cabozantinib and nivolumab compared with sunitinib. And what does this trial mean for our patients? I think that early on, as we're looking for responses and radiographic changes for our patients on cabozantinib, nivolumab in the first-line setting, these deeper responses are associated with longer time until disease progression, and we can counsel patients, to discuss whether cabozantinib and nivolumab is working for them. This could be an early indicator for how patients will do overall on this combination. So with that I'd love to wrap up and turn it back over to you, Greg. Greg Guthrie: Thanks so much Dr. Zhang. And now it's time to move on into our Q&A session. This is for you, Dr. Agarwal. So the question is utility of triple therapy, ADT plus docetaxel plus ASI and metastatic hormone-sensitive prostate cancer given ENZAMET was inconsistent with PEACE-1 and ARASENS. Would you give ASI concurrent or sequential after chemotherapy for tolerability? I'm assuming ASI here is androgen suppression, correct? Dr. Agarwal: Yes. Great question. There are 2 questions here. Number 1, if I would use triplet therapy given the negative subgroup analysis of the ENZAMET trial, and number 2, what is the role of triplet therapy in general? The answer to the first question is ENZAMET trial, subgroup analysis is very different from preplanned, prespecified, well-powered analysis from PEACE-1 and the ARASENS trial. So yes, we saw discrepant results, but my impression from ENZAMET trial is enzalutamide is an effective option for all patients regardless of the receipt of docetaxel chemotherapy because that was a subgroup analysis. So I don't think it really affects negatively the results of the ARASENS and the PEACE-1 trial. But a bigger question here is triplet therapy versus doublet therapy? Is triplet therapy for all or doublet therapy for all? Answer is no. Triplet therapy trials only showed that adding a novel hormonal therapy or deeper androgen blockade to the backbone of ADT plus docetaxel improves survival. These trials did not answer the question, if adding docetaxel chemotherapy to ADT plus, for example, enzalutamide or darolutamide or apalutamide, will improve survival. We do not have that question answered by any of the trials and unlikely any other trial will answer that question. So my take ADT plus docetaxel is replaced by ADT plus docetaxel plus these deeper androgen blocker therapy. So wherever I was going to use docetaxel chemotherapy, so those are the patients with visceral metastases or in my practice, when I do comprehensive genomic profiling, I see those molecular aberrations which predict lack of response to deeper androgen blockade such as baseline AR variants. Or if I see 2 out of 3 mutations of p53, RB loss, p10 loss, if I see 2 out of these 3, I tend to think about docetaxel chemotherapy. So in those patients where I'm using ADT plus docetaxel, I would add another androgen receptor blocker such as abiraterone and darolutamide. But when I'm using enzalutamide or apalutamide which I use for majority of those patients, my patients with metastatic hormone-sensitive prostate cancer, I do not think about triplet therapy. Greg Guthrie: Thanks, Dr. Agarwal. We actually have a follow-up question, and this is, what is the role of oncology in low-stage early prostate cancer? Can neoadjuvant chemotherapy reduce the number of people who end up with metastatic prostate cancer? Dr. Agarwal: This answer is very simple. There is no role of neoadjuvant chemotherapy in high-risk localized prostate cancer or any localized prostate cancer setting. Greg Guthrie: Great. Thank you. Next question. I believe that this is for everybody. How long will it be until the information from the trials discussed will be used in the community clinics? What can patients do to bring this information to their less experienced doctors? Dr. Grivas: So, Greg, just to clarify the question, is it about the translation of the results of the clinic from ASCO to clinical practice, generically speaking, or any particular tumor type or any particular data results? Greg Guthrie: The way I read this question, it's more just kind of a broader scope question about just like, how long does the results of clinical trials make it to community practice, and what role can patients have in perhaps fostering this transmission of information? Dr. Grivas: Of course, I can start briefly, and then my colleagues can add. I would say the world we live in right now, the information travels very quickly. It's much faster compared to the past. And I think there is much more alignment, in my opinion, in terms of information access between academic oncologists and community oncologists. If, for example, a trial result comes at ASCO being presented, and then there's a follow-up approval authority from a regulatory agency, this agent may be accessible to both community and academic practices. Of course, there are always opportunities for education, and Dr. Agarwal is the director of the ASCO Daily News, and he knows that well to disseminate the information well, broadly, in an equitable manner across academic oncologist providers and community providers. And I think CME, continued medical education practices, can help in that regard. And obviously, the other aspect of that is the ongoing clinical trials and how we can do a better job disseminating the opportunity for equitable participation in clinical trials across racial groups, ethnicity groups, minority groups, to give them the chance to participate in ongoing clinical trials that may change the practice down the road, which are just early thoughts. But other colleagues can comment. Dr. Zhang: Yeah, if I could chime in. I think these continuing medical education programs, particularly in the context after large symposia like the ASCO Annual Meeting we just had, are particularly important. And the Best of ASCO series, as well as ASCO Direct Highlight series - I believe Dr. Grivas and I are hosting 2 of these - are very helpful, I think, to bring the latest findings from the ASCO Annual Meeting to our community colleagues. And they really are our colleagues. We work together with our oncologists within the community to take care of our patients, oftentimes for standard of care treatments. Patients can access them more in their backyards. And I think from a patient standpoint on the second part of the question, they're able to hear these from patient-friendly platforms and to bring that to the attention of their oncologist, wherever that may be. It all helps in the grand context of clinical care. So I hope that these trial results and the latest findings from ASCO can get inseminated very quickly.   Dr. Grivas: And to also add very briefly, the role of patient advocacy groups, and in the bladder cancer work, there are many, for example, the Bladder Cancer Advocacy Network, World Bladder Cancer Coalition, and many others can help also in that regard and teaming up with all of us to disseminate information and also clinical trial access. Greg Guthrie: Great. Thank you, everyone. We have a question for Dr. Grivas. After the survey results in the study you described, is there any plan to make a guideline or tool to make sure we standardize the definition of cisplatin/platinum ineligibility? Dr. Grivas: Great question. Just 1 more thing on my prior answer, kudos to Cancer.Net for serving that mission, Greg and Claire in that-- or the previous question to have a complete answer. Answering this new question here, which is very important. I think the next step is to try to publish the results of the survey. The survey like the previous one done by Dr. Galski about 10 years ago-- it's a survey on expert oncologists, and it's a consensus-based definition. It's criteria that we came up with together. And I think the next step here is to publish this in a peer-review process. And our hope is by publishing these results, we can have a more formal definition to help guide our practices in academia, but also in the community oncology practices and make sure that we have a standardized way that we approach this therapy selection and of course, to help design clinical trials that for this particular patient population in order to improve outcomes in this setting. So hopefully publication will come soon. Greg Guthrie: Thanks, Dr. Grivas. I'll just drop a really quick pitch there. Here at Cancer.Net, we do have a very broad array of information on clinical trials. And patients can come visit us at Cancer.Net and learn about clinical trials, what they mean, and how they help advance cancer research. We now have a question for Dr. Zhang. Based on the results of EVEREST and other trials approved systemic therapies in the adjuvant setting like sunitinib and pembrolizumab, are there ongoing other trials in this setting and is risk stratification used? Dr. Zhang: The short answer is yes. There are ongoing adjuvant trials that build on pembrolizumab in the adjuvant setting. There's one that is looking at the addition of belzutifan with pembrolizumab in the adjuvant setting. So that trial is a global trial which is about to get started, if not enrolling already. And in the context of adding on in the adjuvant setting, I do think we really need to discuss with our patients how much of a benefit the treatment will have versus the real toxicity in the postoperative setting, many patients will not have symptoms from their cancer, so they may have some pain or healing side effects from surgery, but they won't have symptoms from cancer. So any toxicities from medications can be further amplified, so are we truly giving a lot of benefit in that context or not. So that's an individualized decision, and I do think conversations must be had to make that decision together. Greg Guthrie: Thanks, Dr. Zhang. I want to ask a question myself of Dr. Gilligan. You had mentioned that microRNA is an emerging field of study, and I've heard about this in other types of cancer as well. I wonder if you could discuss that a little bit more. Dr. Gilligan: Yeah, microRNA, the promise that holds is being a more accurate detector, specifically of testicular cancer. So the problem we have with alpha fetoprotein and beta HCG is half of the testicular cancers may not make 1 or both of those markers. So people can relapse without the markers going up, even though markers are most commonly what we see, there are a couple of different scenarios. Someone has stage I testicular cancer, which means their testicles removed and all their scans show no evidence of cancer. We know that 25% or so of non-seminomas and 20% or so of seminomas will relapse, even though we can't see what the cancer is, and the markers are negative in that situation. MicroRNA may be able to detect those people who still have cancer much, much earlier. So we know that they're, in fact, not stage I and that they need active treatment right away. So that's one place. Another place that we're seeing evidence is that men who've had metastatic testicular cancer. They go through chemotherapy, and they have residual masses. And we're wondering if there's cancer in those masses or is it all dead scar tissue or is it teratoma? MicroRNAs may be able to allow us to determine who needs additional treatment, who needs surgery without having it. Right now, we typically go in and operate just to figure that out. So there are a number of situations in which we could more accurately stage patients and figure out who's cured and who's not cured much earlier in the course of disease. And for a patient, this would be fantastic, because right now, if you've got stage I disease with non-seminomas and you go on surveillance and somebody says you have a 25% risk the cancer is going to come back, that's a 1 in 4 chance that at some point in the next 2 years, most likely, or longer, you're going to have to suddenly drop everything and go through months of chemotherapy. If we knew on day 1, it looks like you're cured, but in fact, there's cancer hiding there somewhere, and we need to treat you now, that would be helpful to know so they can get it over with. And the other men, we could say we're really extremely confident that there's not a 25% risk, it's a 5% risk or something much lower. So there are a number of ways, if this really gets proven and there's emerging data that's promising, I think we could reassure men, treat them more appropriately, spare them unnecessary treatment, and give them more peace of mind. Greg Guthrie: Great. Thanks, Dr. Gilligan. I think we have a question from Dr. Grivas now. Dr. Grivas: Thank you, Greg. This is a great panel. I like to learn from my colleagues here. One question for Dr. Zhang, you have done so much work in the field, leading the field there, Dr. Zhang. Any comments about the ideal end points in the adjuvant setting in kidney cancer, urothelial cancer, disease-free survival or overall survival? Would you comment about how we design trials, and what will be an acceptable benchmark? And what is meaningful for patients, too, in the adjuvant treatment after radical surgery for kidney cancer and urothelial cancer? Dr. Zhang: Oh, that's a great question, Petros. Thank you so much for asking. We have discussed this many times together because you and bladder cancer and myself and kidney cancer, we're thinking a lot along the same lines right as new immunotherapies get approved in the postoperative setting, so disease-free survival as an endpoint and recurrence-free survival as an endpoint is a valid endpoint. It's a direct result of the randomized treatment on the trial, so I do think that is the valid endpoint, and it's an endpoint that the FDA has approved the sunitinib and pembrolizumab indications in kidney cancer, nivolumab and bladder cancer. So I think it's certainly a valid endpoint to delay disease recurrence. How much of that is meaningful degree of improvement for an individual patient? Their own measure of recurrence is either yes or no. It's much more binary than population effects. So how much does that translate into benefits for the patient? I think that warrants deeper individualized discussion. But these disease-free survival endpoints in all of these studies is a valid endpoint to see whether the treatment is worthy in delaying disease recurrence in each of these disease types. Greg Guthrie: Thanks, Dr. Zhang. We have one last question here, and I believe this is a follow-up for Dr. Gilligan. And what is the time frame for the rollout of microRNA 371 to the community? Dr. Gilligan: I don't know the answer to that. I'm not sure that we have enough data right now that it's going to get approved. I think we're headed in the right direction, but it's very hard to know what the timing of that is. There are trials going on, so I don't know at the moment of exactly what the scenarios are in which people are going to be, which patient populations are going to be eligible, but there are trials going on. I think I'm hoping within the next 2 years or so, but I really don't know what the time frame is, unfortunately. Dr. Grivas: And if I may add a more generic comment to Dr. Gilligan's wonderful answer is that when we have what we call biomarkers that are like metrics that can give us information about how the patient does over time, it's important to tease out what we call prognostic, meaning how can this biomarker give us a sense of the chance of recurrence, as Dr. Gilligan said, or death from the cancer. But also, the bigger question is, is it going to give us information to predict benefit from an individual therapy? And that's a bigger question in oncology that is a harder one. This predictive question and try to identify biomarkers and validate them to make sure they have, they're clinically useful. They can help us make treatment decisions in the clinic. And I'm very excited about what Dr. Gilligan discussed about the promise in the future. But more trials are needed for many biomarkers. Dr. Gilligan: I think when we do this update next year, we'll have significantly more data then, I'm hopeful. Greg Guthrie: Thank you to you all. Thank you, Dr. Agarwal. Thank you, Dr. Grivas. Thank you, Dr. Gilligan. Thank you, Dr. Zhang, for sharing this great research with us, as well as your expertise. It's been a real pleasure this afternoon. And to all of our viewers, thank you for joining us. You can find more coverage of the research from ASCO Annual Meeting and other scientific meetings at the Cancer.Net blog, which is at www.cancer.net/blog. And if you're interested in more Cancer.Net content, please sign up for a monthly Inside Cancer.Net newsletter or follow us on social media. We're on Facebook, Twitter, and YouTube where our handle is always @CancerDotNet, with dot spelled out. Thank you all, and be well. Thanks. ASCO: Thank you, Dr. Agarwal, Dr. Gilligan, Dr. Grivas, and Dr. Zhang. You can find more research from recent scientific meetings at www.cancer.net. Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care. And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

Dr. James DiNicolantonio shares amazing tips about how salt, hydration and sauna strategies can help improve strength and exercise performance.  Support your Exercise Performance with the new Electrolyte Stix by MYOXCIENCE Nutrition: Save with code podcast at checkout Get Jame's New book Win: Time Stamps 03:15 Maintain your muscle and cardiovascular health through exercise. Reduce the risk of sarcopenia with resistance training, 30 – 60 min 3 – 4 times per week. Running at 60 – 70% of your max heartrate boosts your endurance. HIIT or super maximal interval training 2 – 3 times per week helps your cardiovascular system. 07:10 Preloading with salt and fluids is 10 to 20 times better than other supplements. Dosing salt correctly, allows you to exercise up to 20 minutes longer. Beta alanine allow you to vigorously exercise 1 to 2 minutes longer. 07:40 The main benefit from preloading with salt and fluids is from the boost in blood volume prior to vigorous exercise. You have an 8 to 10% drop in blood volume within 5 minutes of vigorous exercise.  The biggest adaptation during vigorous endurance exercise is the attempt to increase baseline blood volume. 08:54 Elite athletes have a 40% increase in blood volume over typical males and females. High doses of salt and fluids should be reserved for just prior to competition. 10:32 Dehydration acclimation, inducing mild amounts of dehydration multiple times, can help build blood volume. 12:05 Before a typical workout, you can ingest 1,000 mg of sodium and 10 to 16 ounces of fluid. High levels used for competition would be 3,000 to 4,300 mg of sodium and about 26 ounces to 33.8 ounces of fluid. This matches to saltiness of your blood. 13:40 Increased blood volume increases cardiac output, decreases oxygen demand on the heart and gives you a larger volume to dissipate heat. We lose blood volume to sweat. You can better pull waste from your cells and better deliver nutrients. 15:30 Sauna therapy is similar in metabolic adaptations to dehydration therapy. When you become heat activated, your baseline core body temperature becomes lower. You have a larger pool to soak up heat. You can train and perform longer before the enzymes that produce ATP start shutting down. 16:05 When you are heat activated, your sweat becomes more dilute. You lose fewer electrolytes. The diluted sweat evaporates faster, so your cool faster. 16:34 To become heat activated, you need to do a sauna session every day for 2 weeks or so, raising your core body temperature to 101.3 and maintain it for 20 to 30 minutes. You can go as few as 4 days per week, but it will take you longer to achieve being heat activated. The benefits of doing this will last as long as 2 weeks, as long as you maintain a good exercise program. 18:57 Endurance exercisers with large blood volumes typically have good blood pressure. As long as your arteries vasodilate well, and you do not have increased vasoconstriction with increased blood volume, you should not see an increase in blood pressure. 20:07 Body temperature is highly influenced by circadian biology. Post exercise sauna for 13 sessions, improves performance by about 10%. 23:28 Postpone your cold plunge for 2 to 4 hours after exercise, if your goal is hypertrophy. Sooner than that inhibits some of your muscle size and strength gains from exercise. Elite athletes plunge directly after exercise to limit inflammation and accelerate recovery. 26:55 Exercise timing is individual and depends upon whether you are a morning person or a night owl. About 8 hours after you wake up is typically when you perform at your best. Your cognition is shot for a few hours after vigorous exercise. Exercise close to bedtime impacts your ability to go to sleep. 29:20 Avoid caffeine at least 6 hours before bedtime. 31:48 If you are a vegetarian, you are not getting many nutrients found in red meat. Carnitine is important for fat oxidation for fuel. Carnosine is an advanced glycation end product inhibitor and buffers acid produced during exercise. Beta alanine boosts carnosine levels. Taurine is an amino acid that helps with blood pressure, blood flow, antioxidant status in the central nervous system.  33:45 Red meat is more nutrient dense than chicken. Pork is 10 times higher in thiamine (vitamin B1). Consume liver (for vitamin A and copper) and heart (for coQ10) on a fairly consistent basis.  Many of us are deficient in vitamin A and copper and anemia is driven by this. 35:10 Creatine improves cognition. 50% of methylation is for the creation of creatine in your body. Supplementing frees up that effort for you body. 36:35 Supplementing 3 to 5 grams of creatine per day brings most benefits. Eating red meat may not get you to that level. 37:20 The more hydrated your muscle is, the better blood flow, oxygen delivery and pump you get. Your muscle is about 75% water. Creatine enhances cell hydration. 38:40 Supplementing with creatine at doses of 5 grams per day is completely safe. 39:40 To induce hypertrophy, the key is to go near or to failure. Heavy weight is not necessary. Inositol helps to improve insulin sensitivity, thus preserving muscle mass. 41:51 For prolonged vigorous explosive activity, preloading with carbs improves performance. It helps you to tap your muscle glycogen reserves. There are benefits to training fasted. Metabolic flexibility is when you can burn either fats or carbs. 42:50 It is taxing to force your body to make glucose, rather than ingesting exogenous glucose. 45:00 Longevity populations are generally smaller and have less muscle mass than Americans, so they can get away with lower protein intake. Our needs are higher. 46:42 Exercise improves insulin sensitivity. Insulin resistance chronically elevates mTOR. 48:40 Elevated LDL (outside of genetic influences) is not a risk factor for increasing heart disease, in the face of good insulin sensitivity, low triglycerides, and good HDL. 49:30 Oxidized LDL is a contributor to heart disease. The amount of linoleic acid in LDL influences oxidation. Eating heart for ubiquinol and eating high quality meat for carotenoids, helps to protect LDL from oxidation. Increasing olive oil consumption increases monounsaturated fats in LDL, decreasing susceptibility to oxidation. 51:30 When you replace animal fats with vegetable oils, there is an increase in all-cause mortality. LPa is a functional marker of oxidation, with elevated LDL. 55:05 Salt intake recommendations are based upon expert opinion, not clinical evidence, or meta-analysis. Lowering salt intake barely lowers blood pressure. Some may have an increase in blood pressure with the decrease of salt intake. Decreases in blood pressure from reducing salt is from depleting blood volume. Stress hormones increase. 56:00 When you go below 3000 mg of sodium, all the stress hormones increase. Insulin resistance increases as well. 3000 to 5000 mg of sodium is associated with the least amount of rise in stress hormones and the lowest amount of risk of cardiovascular disease.