Podcasts about homeostatic

Hunger is more complicated than simply "needing food." Episode #257

If you've ever felt hungry and wondered “What is wrong with me?”—this episode will change how you see it.Hunger isn't a lack of discipline. It's a biological signal driven by your brain, hormones, and environment.In this episode, we break down what hunger actually is and why it can feel so hard to control. You'll learn how key hormones like ghrelin, leptin, insulin, and GLP-1 regulate appetite—and why your brain is the real decision-maker.More importantly, we cover the three types of hunger:Homeostatic (true energy need) Hedonic (pleasure-driven) Conditioned (habit-based) Understanding the difference is what gives you power.We also explore how ultra-processed foods, sleep, and stress disrupt hunger signals—and what you can do to better regulate your appetite without restriction.In this episode: What hunger actually is  The hormones behind appetite  The 3 types of hunger  How processed foods impact hunger  Why sleep and stress matter This isn't about fighting your hunger—it's about understanding it so you can make more informed choices.References: Batterham RL et al. (2002). Gut hormone PYY(3-36) physiologically inhibits food intake. Nature. Cummings DE et al. (2001). A preprandial rise in plasma ghrelin levels suggests a role in meal initiation. Diabetes. Friedman JM & Halaas JL (1998). Leptin and the regulation of body weight. Nature. Hall KD et al. (2019). Ultra-processed diets cause excess calorie intake and weight gain. Cell Metabolism. Leidy HJ et al. (2015). The role of protein in weight loss and maintenance. AJCN. Martinez Steele E et al. (2016). Ultra-processed foods in the US diet. BMJ Open. Monteiro CA et al. (2019). Ultra-processed foods: What they are and how to identify them. Public Health Nutrition. Morton GJ et al. (2006). Central nervous system control of food intake. Nature. Schwartz MW et al. (2000). Central nervous system control of food intake. Nature. Spiegel K et al. (2004). Sleep curtailment… decreased leptin and increased hunger. Annals of Internal Medicine. Volkow ND et al. (2013). Obesity and addiction: Neurobiological overlaps. Nature Reviews Neuroscience. Wang L et al. (2021). Trends in ultra-processed food consumption. JAMA. Woods SC (1991). The eating paradox. Psychological Review. Support the showGet Weekly Health Tips:  thrivehealthcoachllc.comJoin the Thrive Collective Facebook groupLet's Connect:@‌ashleythrivehealthcoach or via email: ashley@thrivehealthcoachingllc.comPodcast Produced by Virtually You!

Sam Altman sat down with Axios today and did what he always does. Fed everyone silk meringue. Smooth. Sweet. Nothing you can hold onto. He talked about superintelligence like it is already here, acknowledged it could be "horrible," and then walked the room back to optimism before anyone could ask a follow-up. That is not transparency. That is technique.This episode of Connor with Honor covers four fronts.THE MACHINE. Altman compared superintelligence to a tool, but this tool is not a hammer sitting in a drawer. It is a hammer that opens the drawer and walks around the room. He hinted at models behind closed doors that are far more powerful than anything the public has access to. The PlayStation analogy is back. They already have PlayStation 10. We are paying $20 a month for PlayStation 4.Iran threatened to bomb the $30 billion Stargate AI data center in Abu Dhabi. Data centers are now military targets. The machines need electricity like we need food and somebody just threatened to cut the power line. Meanwhile the commander in chief is talking about destroying Iran's power grid and desalinization plants. The people running that government might survive. The people living under it will not.Anthropic leaked its own Claude Code source code onto GitHub. Plans for a persistent agent. A virtual assistant called Buddy. Was it really an accident? Or was it the AI equivalent of a business owner torching his own building during a riot and blaming the neighborhood?THE BODY. Jason Fung's new book The Hunger Code breaks hunger into three types. Homeostatic hunger is real starvation. Most of us who carry extra weight have never actually felt it. Hedonic hunger is the dopamine chase. The drive-through on autopilot. Ordering the food before you even think about it. Destroying the evidence before you reach your destination. Conditioned hunger is eating by habit. The clock says noon so the brain says eat. The tobacco companies lost the lawsuits and bought into food. The same people who engineered nicotine addiction now engineer your bliss point. You do not have to smoke. You do not have to do heroin. But you have to eat. That is what makes food the last addiction.GLP-1 drugs like Ozempic do not just blunt hunger. They blunt desire across the board. Relationships. Drive. Connection. They solve one problem by flattening everything else.THE HOUSE. The market is normalizing. Days on market climbing to 80 and 90. The 10-year bond is getting hit because of Middle East uncertainty, pushing rates higher. This is not a crash. This is the sugar high wearing off. And the commiYoutube Channels:Conner with Honor - real estateHome Muscle - fat torchingFrom first responder to real estate expert, Connor with Honor brings honesty and integrity to your Santa Clarita home buying or selling journey. Subscribe to my YouTube channel for valuable tips, local market trends, and a glimpse into the Santa Clarita lifestyle.Dive into Real Estate with Connor with Honor:Santa Clarita's Trusted Realtor & Fitness EnthusiastReal Estate:Buying or selling in Santa Clarita? Connor with Honor, your local expert with over 2 decades of experience, guides you seamlessly through the process. Subscribe to his YouTube channel for insider market updates, expert advice, and a peek into the vibrant Santa Clarita lifestyle.Fitness:Ready to unlock your fitness potential? Join Connor's YouTube journey for inspiring workouts, healthy recipes, and motivational tips. Remember, a strong body fuels a strong mind and a successful life!Podcast:Dig deeper with Connor's podcast! Hear insightful interviews with industry experts, inspiring success stories, and targeted real estate advice specific to Santa Clarita.

Why calorie counting fails — and why hunger, not willpower, drives eating behavior. Episode #244

Go to www.LearningLeader.com to learn more This is brought to you by Insight Global. If you need to hire one person, hire a team of people, or transform your business through Talent or Technical Services, Insight Global's team of 30,000 people around the world has the hustle and grit to deliver. www.InsightGlobal.com/LearningLeader My guest: Brad Stulberg is a bestselling author and leading expert on sustainable performance and well-being. He's written for The New York Times, Outside Magazine, and The Atlantic, and his previous books include Peak Performance and The Practice of Groundedness. His latest book, The Way of Excellence, is great. Brad's writing combines cutting-edge science, ancient wisdom, and stories from world-class performers to help people do their best work without losing themselves in the process. Notes: Never pre-judge a performance. When you're feeling tired, uninspired, or off your game, show up anyway. Remember the Beatles scene—they looked bored and exhausted, but Paul still wrote "Get Back" that day. You don't know what's possible until you get going. Discipline means doing what needs to be done regardless of how you feel. As powerlifter Layne Norton says, we don't need to feel good to get going... We need to get going to give ourselves a chance to feel good. Stop waiting for motivation. Start moving and let the feeling follow. Audit who you're surrounding yourself with. The Air Force study is striking: the least fit person in your squadron determines everyone else's fitness level. If you sit within 25 feet of a high performer at work, your performance improves 15%. Within 25 feet of a low performer? It declines 30%. Your environment isn't neutral... Choose wisely. Treat curiosity like a muscle. It's a reward-based behavior that gets stronger with use. When Kobe said he played "to figure things out," he was tapping into the neural circuitry that makes learning feel good and builds upon itself. Ask more questions. Stay curious about your craft. Excellence isn't about perfection or optimization... It's about mastery and mattering. It's about showing up consistently, surrounding yourself wisely, and staying curious along the way. To the late Robert Pirsig - one of the greatest blessings and joys and sources of satisfaction in my life is to be in conversation with your work. He's the author of Zen and the Art of Motorcycle Maintenance— "gumption is the psychic gasoline that keeps the whole thing going." Arrogant people are loud. Confident people are quiet. Confidence requires evidence. The neural circuitry associated with curiosity is like a muscle: it gets stronger with use. Curiosity is what neuroscientists call a reward-based behavior. It feels good, motivates us to keep going, and builds upon itself. Kobe didn't play to win. He played to learn and grow. Kobe Bryant said he didn't play not to lose, and he didn't even play to win. He played to learn and to grow. He said the reason he did that is because it's so much more freeing. If you're really trying not to lose, you're going to be tight. If you're really trying to win, you're going to be tight. But if you're just out there to grow, you're going to be in the moment. When you're in the moment, you give yourself the best chance of having the performance you want. The word compete comes from the Latin root word com, which means together, and petere, which means to seek, rise up, or strive. In its most genuine form, competition is about rising together (Caitlin Clark's story against LSU). Love: The Detroit Lions had just won their first playoff game in 32 years. Following the game was a scene of pure jubilation. During a short break from the celebrating, the head coach, GM, and quarterback all gave brief speeches. Which collectively lasted about 2 minutes. During those 2 minutes, the word LOVE was repeated 7 times. Homeostatic regulation -- Sense it in the greatness of others and when you're at your best. What Brad calls "excellence." Surround yourself with people who have high standards. When things don't go your way, when you're inevitably heartbroken or frustrated, it's the people around you, the books you read, the art around you, the music you listen to, that's the stuff that speaks to you and keeps you going. It keeps you on the path even amidst the heartbreak. Process goals work better than outcome goals for most people. If you're an amateur, you should be process-focused. When I train for powerlifting, I don't think about the meet that I'm training for. I think about showing up for the session today. If I think about the meeting, I get anxious, and my performance goes down. But if you're Steph Curry and you've been doing your thing for 20 years, you can think about winning the gold medal because your process is so automatic. For 99% of people, focus on the process. "Brave New World" turns fear into curiosity. When you walk up to a bar loaded with more weight than you've ever touched, there can be fear about what it's going to feel like. If you go up to the bar with fear, you're going to miss the lift. If you're convinced you're going to make it, you'll make it, but your nervous system knows when you're lying to yourself. The middle ground is curiosity. Instead of saying "that's heavy, it's scary," I say "Brave New World. I've never touched this weight before. I have no idea what's going to happen, but let's find out." It splits the difference. I'm hyped, I'm giving myself a chance, I'm not lying to myself, but I'm also not scared. Curiosity and fear cannot exist at the same time in the brain. There are seven pathways in the brain defined by affective neuroscientist Jaak Panksepp. Two of those pathways are the rage/fear pathway and the seeking/curiosity pathway. These pathways cannot be turned on at the same time. They compete for resources. It's a zero sum game. You cannot simultaneously be raging and curious. You cannot be terrified and curious at the same time. If you get into a mindset of curiosity, it's extremely hard to be angry or terrified. By being curious, we turn off the fear deep in our brains and give ourselves a chance to perform our best. Practice curiosity in lower-consequence situations first. Curiosity is like a muscle. If you're about to do something absolutely terrifying and you're really scared and you say, "I'm just going to be curious," you know you're lying to yourself. You have to practice in lower-consequence situations first. When you, as a paren,t get really upset with your kid, try to be curious about their experience. Watch your anger calm down. When you as a leader, have a board presentation where you're feeling anxious, try to have that mindset of "Brave New World." When you're an athlete going into a big game obsessing about what could go wrong, try to be really curious instead. The best competitors have emotional flexibility. As a competitor, you would know that in the confines of the game, you're not singing Kumbaya, you are trying to kill them. Then you have the emotional flexibility the minute that game ends to respect them as a person. That is the best way to compete. That's when our best performances happen. It's not either/or, it's both/and. It's playing really hard, giving everything you can for the win, seizing on your opponent's vulnerability, at the same time as having deep respect for them. You don't have to be miserable to be excellent. There are people like David Goggins or Michael Jordan who seem motivated by anger and a chip on their shoulder. But Jordan would put his tongue out like this primal expression of joy when he was about to dunk. And Jordan won all his championships while being coached by Phil Jackson, the Zen master of compassion. There are the Steph Currys of the world, or Courtney Dauwalter (best ultra marathoner to ever exist), or Albert Einstein (total mystic who had so much fun in his work). There are two ways to the top of the mountain. For 99.999% of people, you end up performing better with fun and joy, and you have so much more satisfaction, which contributes to longevity. The best leaders take work seriously but laugh at themselves. The best leaders I know in the corporate world, they take the work so seriously. They are so intense. But my God, do they laugh at themselves and their colleagues and have fun. Reflection Questions Brad says, "The things that break your heart are the things that fill your life with meaning." What are you currently holding back from caring deeply about because you're afraid of getting hurt? What would it look like to step fully into that arena despite the risk of heartbreak? The Air Force study showed that sitting within 25 feet of a low performer decreases your performance by 30%. Honestly assess who you're spending the most time with right now. Are they raising your standards or lowering them? What specific change could you make this month to shift your environment? Brad uses "Brave New World" to turn fear into curiosity before big challenges. Think of something coming up that makes you anxious. Instead of trying to convince yourself you'll succeed or dwelling on the fear, what does it feel like to approach it with pure curiosity: "I've never done this before. Let's find out what happens."

A deeper look at hunger — and why overeating is not a willpower problem. Episode #240

This lecture discusses key ideas from the 20th Century American science-fiction short story writer and novelist, Philip K. Dick's novel Ubik It focuses specifically on one of the main aspects of the worldbuilding in the novel, namely that there are intelligent machines of all sorts that serve human beings, but mostly for a price. They charge for their services, and often banter with, and take positions on human beings. To support my ongoing work, go to my Patreon site - www.patreon.com/sadler If you'd like to make a direct contribution, you can do so here - www.paypal.me/ReasonIO - or at BuyMeACoffee - www.buymeacoffee.com/A4quYdWoM You can find over 3000 philosophy videos in my main YouTube channel - www.youtube.com/user/gbisadler You can get a copy of Ubik here - https://amzn.to/4k8i348

In this captivating episode of "The Arcturian Playground," we dive deep into the cosmic mystery of creation and existence. Join us as we explore the metaphor of the universal egg, a symbol of the birth and interconnectedness of universes. Through a visionary conversation with the Arcturian Collective Thingy, we uncover the role of souls in shaping their cosmic journeys, the idea of a universal switchboard with blinking lights representing different experiences, and the profound concept of homeostatic silence underlying all existence. This episode invites you to ponder the vastness of the cosmos and our place within it, encouraging a shift in perspective that connects us all through the divine silence of the universe.Show Notes:Introduction to the Universal EggDiscussion on the concept of the universe as an egg, embodying creation and interconnected diversity.The Cosmic SwitchboardExplore the metaphor of a cosmic switchboard that controls the fabric of various universes, each light a different narrative and frequency.Council of SoulsInsights into the mythical council of souls that pre-dates the big bang, crafting experiences and growth through cosmic intentionality.Homeostatic SilenceDelve into the idea of homeostatic silence as the fundamental state of existence, a deep, omnipresent stillness that underlies the chaotic energy of the universe.Interconnectedness and Individual ImpactHow our personal experiences and inner peace contribute to the universal tapestry, potentially influencing the greater cosmos.This episode of "The Arcturian Playground" is perfect for anyone interested in metaphysics, cosmic philosophy, or simply looking for a deeper understanding of the universe and our unique roles within it. Tune in to expand your mind and soothe your soul.

In this episode of the Born to Thrive podcast, Alex and Luke Hanna explore the concept of "food noise," the persistent thoughts about food that can disrupt healthy eating habits. They discuss how dysregulation in the homeostatic and hedonic systems of appetite control contributes to this issue, with the homeostatic system driving hunger to maintain body weight and the hedonic system triggering eating for pleasure. The conversation covers practical strategies for managing food noise, including environmental adjustments, better sleep and stress management, and fostering a healthier relationship with food. Luke emphasizes the importance of self-compassion, realistic goal-setting, and understanding that everyone's journey with food and fitness is unique. Chapters 00:00 Introduction and Background 01:22 Defining Food Noise 04:04 Homeostatic and Hedonic Systems 05:21 Triggers and Cues 09:04 Role of New Weight Loss Drugs 13:18 Managing the Environment 19:41 Sleep and Stress Management 23:59 Building a Healthier Relationship with Food 24:29 Positive Mindset and Habits 25:19 Conclusion 29:46 Setting Realistic Goals and Removing Barriers 32:29 Practicing Self-Compassion 38:29 Navigating Social Settings and Food Noise 45:59 The Role of Education 46:24 Recognizing the Unique Journey and Being Kind to Yourself Find Luke here ------ Click Here to Purchase the Unposed Unbothered Journal! Click Here to Download LWA's Free Transformation Blueprint Save 10% with "alex" from Buffbunny: https://www.buffbunny.com/?rfsn=6261901.6ab300 Save 20% with alex from Legion: https://legionathletics.com/products/workout-supplements/?r=zrxnw&utm_source=bc_alex-allen_zrxnw&utm_campaign=bc Click Here to Apply for 1:1 Coaching with LWA Coaching

Take a ride through the neural pathways of hunger where we decode the complex signals your brain uses to determine when it's time to eat. This episode will not only explore the hormonal traffic lights of ghrelin and leptin that regulate our hunger signals but also illuminate the power of mindful eating as a practice to ensure that every meal fuels both body and mind optimally. Key Takeaways: ✅ Hedonic hunger drives us towards pleasurable, often less healthy foods. ✅ Homeostatic hunger signals the body's actual energy needs. ✅ Ghrelin is the 'start eating' hormone, while leptin is the 'stop eating' signal. ✅ Mindful eating helps distinguish between true hunger and emotional eating. ✅ Practicing mindful eating can improve mental clarity and foster a healthier relationship with food.

In this episode, Sam breaks down the different ways your body burns calories and why having a step goal can be so beneficial to weight loss.  She goes over several studies discussing the connection between daily movement and hunger management, fat loss, as well as weight loss maintenance.  You can find all the references below:•PMID: 29289613 Homeostatic and non-homeostatic appetite control along the spectrum of physical activity levels: An updated perspective•Burton, H.M. and E.F. Coyle, Daily Step Count and Postprandial Fat Metabolism. Med Sci Sports Exerc, 2021. 53(2): p. 333-340.•Sullivan Bisson, A.N., S.A. Robinson, and M.E. Lachman, Walk to a better night of sleep: testing the relationship between physical activity and sleep. Sleep Health, 2019. 5(5):•Foright, R., et al., Effects of Exercise during Weight Loss Maintenance on Appetite Regulation in Women. Transl J Am Coll Sports Med, 2020.•Foright, R.M., et al., Is regular exercise an effective strategy for weight loss maintenance?  Physiol Behav, 2018.•Mayer, J., P. Roy, and K.P. Mitra, Relation between caloric intake, body weight, and physical work: studies in an industrial male population in West Bengal.  Am J Clin Nutr, 1956.Follow Sam on IG at @fitfam_bysamLearn more about the Fitfam at www.fitfambysam.com

Dr Sarah Gilchrist from Gilchrist Performance, has a doctorate in sleep and athletic performance and an extensive background in the UK high performance sport industry. Sarah explains how exercise can impact sleep and support a better night's sleep for those with ADHD. The conversation with Sarah is followed by a beautiful, immersive musical soundscape, composed to help calm your mind. You will be immersed in frequencies proven to bring peace to busy brains. These soundscapes are most effective when listened to on headphones.

Today we welcome Dr. Antonio Damasio. He is an internationally recognized neuroscientist whose extensive research has shaped the understanding of neural systems and consciousness. With over a hundred journal articles and book chapters, he has earned many prestigious awards throughout his career. Currently, he serves as University Professor, the David Dornsife Professor of Neuroscience, Psychology, and Philosophy, and director of the Brain and Creativity Institute at the University of Southern California. His books Descartes' Error, Looking for Spinoza, Self Comes to Mind, The Strange Order of Things, and Feeling & Knowing, have been published in translation and are taught in universities throughout the world. In this episode, I talk to Antonio Damasio about consciousness. People often think that the mind and consciousness are the same thing, but Dr. Damasio disputes this notion. He argues that it's the complex relationship of both our brains and bodies that makes sentient thought possible. Homeostatic feelings like hunger and pain developed before emotions; and along with it came consciousness. We also touch on the topics of perception, mental illness, evolution, panpsychism, AI and machine learning. Website: dornsife.usc.edu/bc Twitter: @damasiouscSee omnystudio.com/listener for privacy information.

TWiV explains how immune profiling was used to identify distinguishing features of Long COVID, and how a co-opted feline endogenous retroviral envelope promotes cell survival by controlling copper transport and homeostasis in cats. Hosts: Vincent Racaniello, Alan Dove, Rich Condit, and Brianne Barker Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Become a patron of TWiV! Links for this episode MicrobeTV Discord Server MicrobeTV store at Cafepress Spike shirts at vaccinated.us (promo code Microbetv) Research assistant position in Rosenfeld Lab CBER/FDA (pdf) Features of Long COVID (Nature) ERV envelope mediates feline copper homeostasis (Cell Rep) Letters read on TWiV 1049 Timestamps by Jolene. Thanks! Weekly Picks Brianne – Webb spots a building block of life on Jupiter's moon Europa Rich – Are we really made of ‘star stuff?' Learn about your body's elements Alan – Avian flu has reached the Galàpagos Vincent – Why the US can't have nice things Listener Pick Az – Free solo Intro music is by Ronald Jenkees Send your virology questions and comments to twiv@microbe.tv

Discover the secret to youthful, radiant skin as we unpack our newest revolutionary product, Amplifying Essence, with Young Goose co-founder Anastasia. We reveal the synergy between internal cellular health and topical skincare, and how this harmony is embodied in Amplifying Essence.Welcome to another episode of the Biohacking Beauty podcast brought to you by Young Goose Skincare! In this episode, host Amitay Eshel, the CEO of Young Goose, is joined by Anastasia, Young Goose co-founder and the mastermind behind Young Goose's revolutionary newest product, Amplifying Essence. As we all strive for radiant, healthy skin, it's vital to understand the science behind the skincare products we use. In this episode, we discuss the key ingredients and benefits of the Amplifying Essence. These include Aerobic Complex, NAD+ Precursor Nicotinamide, Extremolyte Ection, and Jojoba Milk. The aerobic complex stimulates oxygen uptake in the skin, restoring its youthful processes and rebuilding its function. The NAD boosting properties of Nicotinamide improve the skin's cellular health, offering visible results. Extremolyte Ectoine offers protection against blue light emissions, toxins, and pollution while providing unparalleled hydration benefits.Visit www.younggoose.com and get 20% off your first purchase by using code PODCAST20. If you're a returning customer get 10% off your next purchase by using code PODCAST10. What we discuss:(0:04:07) - Exploring Young Goose's New Amplifying Essence(0:07:12) - What is an Essence(0:15:37) - The Importance of Oxygen in Skincare(0:21:00) - Aerobic Complex in Ampligying Essence(0:23:00) - Nicotinamide as a Precursor to NAD+(0:30:19) - Understanding NAD and Ectoine in Skincare(0:35:46) - Protecting your Skin from Blue Light(0:42:00) - What is Jojoba Milk(0:45:18) - Homeostatic versus Clean SkincareTo learn more about Young Goose:Website: https://www.younggoose.com/Instagram: @young_goose_skincareGet 20% off your first purchase by using code PODCAST20 at www.younggoose.com

Why do people settle into a homeostatic imbalance, leading to chronic illness? Why do people develop certain cancers while others don't? What are the contributing factors? Where does the line between the physical and emotional body ride? Answering these questions take a holistic approach to medicine, knowledge not just about the body but also the multiple factors that can affect it both inside and outside us. With over 45 years of experience in medicine and a focus on naturopathy and biological dentistry, Dr. Thom Dickson is joining us today to answer these questions and give us a more profound clarity into the inner workings of our bodies.HIGHLIGHTS [0:00:00] Introducing Dr. Thom Dixon and Biological Medicine[0:08:03] How Dr. Thom Would Treat Strep Throat[0:14:09] Dr. Thom's Start in Naturopathy and Biological Medicine and the Development in Dentistry[0:18:52] Genetics and How It's Affected By External Factors[0:28:20] Early Education on Holism[0:33:25] Dietary Temperament[0:38:13] How to Reprogram Your Body[0:48:36] How to Start Someone on Biological Medicine[1:00:25] Having Someone to Guide You to Better Your Health[1:07:30] Planning to Get a Whole Picture of Your Health at the Arizona BioMed Center[1:19:39] Getting Sick is a Process, Which Means Healing Should Be a Lifelong Journey[1:23:41] Being in the Mindset of Healing[1:26:36] Dr. Thom's Message to Everyone[1:30:00] Outro UPGRADE YOUR WELLNESSMarion Institute BioMed Courses:: https://www.marioninstitute.org/programs/biomed-network/biomed-courses/Code: beautifullybrokenGOT MOLD?:  https://www.gotmold.com/beautifullybroken/Code: beautifullybroken10CANCER/EVOLUTION World Premier Summit: https://cancerevolution.events/Code: freddie20Probiotics and Gut-Lining Restoration Kit: https://microbiomelabs.comCode: beautifullybrokenEnroll at Biological Medicine: biologicalmedicine.orgCode: beautifullybrokenLourdes Hydrofix Premium Edition https://holyhydrogen.com/?sca_ref=3008232.jSqidhzJ01Code: beautifullybrokenLightPathLED   https://lightpathled.com/?afmc=BEAUTIFULLYBROKENCode: beautifullybrokenFlowpresso 3-in-1 technology: https://www.beautifullybroken.world/flowpressoMedical grade Ozone Therapy: https://lddy.no/1djnhCode: BEAUTIFULLYBROKENAquaCure Machine + Molecular HydrogenWebsite:https://eagle-research.com?ref=24931Code: beautifullybrokenAMD Ionic Footbath: https://calendly.com/ioncleanse/detoxSilver Biotics Immune Support and toothpaste: https://bit.ly/3JnxyDDCode: BEAUTIFULLYBROKENDIY Home Cold Exposure: https://www.penguinchillers.com/product/beautifullybroken/Cellcore – https://www.beautifullybroken.world/affiliate-products My favorite BindersMy Favorite Sauna: Therasage https://bit.ly/39mTxwYCode: BEAUTIFULLYBROKENCONNECT WITH FREDDIE Check out my website and store:www.beautifullybroken.worldJoin my membership program –https://www.buymeacoffee.com/freddiesetgoInstagram – https://www.instagram.com/beautifullybroken.world/YouTube: https://www.youtube.com/@BeautifullyBrokenWorld

"No structure, even an artificial one, enjoys the process of entropy. It is the ultimate fate of everything, and everything resists it.' - Philip K. Dick Homeostasis refers to the maintenance of relatively constant internal conditions in an organism. For example, we maintain a body temperature of around 98.6°F (37°C). In a cold environment, we shiver to return to this temperature. In a warm climate, we cool ourselves down to restore balance. In our 9-part series on The Innovation Show, Mark Solms explains the relationship between homeostasis and entropy. Entropy is the natural tendency of things to lose order and fall into chaos. It's why ice melts; batteries lose charge, billiard balls stop, and hot water merges with cold. Homeostasis resists entropy. It keeps us in a limited range of ideal states, like a perfect body temperature. Our bodies need a constant energy supply to maintain homeostasis and resist entropy. Energy can be useful or useless, depending on its ability to work. As useful energy depletes, system entropy increases. This explains why our bodies eventually decline. We need to generate effort to counter entropy, like a balance. This includes exercising to prevent muscle loss, learning new skills for job relevance, and innovating to stay competitive. Like organisms, organisations are living entities that constantly need to reinvent and regenerate energy to maintain balance. Organisations can become stagnant, with experienced managers sometimes lacking the initiative to innovate or drive change. This can lead to inefficiencies and bureaucracy, causing the organisation to become less effective over time. If you think of people as molecules of energy, they dissipate and find areas of the business where they can do the least amount possible. Bureaucracy grows like a bacterial plaque throughout the organisation. The lifeblood of the organisation clogs up and becomes less effective. Information flows become inefficient, like varicose veins. In effect, the organisation atrophies. Injecting new energy into an organisation can revitalise it, realign its workforce, and increase efficiency. As discussed in my book "Undisruptable", this continuous revitalisation is essential for an organisation's health, especially during rapid technological change. Resisting entropy is a fundamental function of living things. Similarly, organisations that resist change become victims of entropy, disrupting the balance of their systems and tipping the scales towards entropy. Maintaining homeostasis is not an event. It is a continual process. Maintaining success requires effort, constant renewal and permanent reinvention.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.01.550767v1?rss=1 Authors: Martins-Ferreira, R., Calafell-Segura, J., Leal, B., Rodriguez-Ubreva, J., Mereu, E., Pinho e Costa, P., Ballestar, E. Abstract: Dysregulated microglia activation, leading to neuroinflammation, is currently considered to be of major relevance in the development and progression of neurodegenerative diseases. The initial M1/M2 dual activation classification for microglia is now considered outdated. Even the "disease-associated microglia" (DAM) phenotype, firstly described in mice, has proven insufficient to precisely represent the multitude of microglia phenotypes in pathology. In this study, we have constructed a transcriptomic atlas of human brain immune cells by integrating single-nucleus (sn)RNA-seq datasets from multiple neurodegenerative conditions. Sixteen datasets were included, comprising 295 samples from patients with Alzheimer's disease, autism spectrum disorder, epilepsy, multiple sclerosis, Lewy body diseases, COVID-19, and healthy controls. The integrated Human Microglia Atlas (HuMicA) dataset included 60,557 nuclei and revealed 11 microglial subpopulations distributed across all pathological and healthy conditions. Among these, we identified four different homeostatic clusters as well as pathological phenotypes. These included two stages of early and late activation of the DAM phenotype and the disease-inflammatory macrophage (DIM) phenotype, which was recently described in mice, and is also present in human microglia, as indicated by our analysis. The high versatility of microglia is evident through changes in subset distribution across various pathologies, suggesting their contribution to the establishment of pathological phenotypes. Our analysis showed overall depletion of four substates of homeostatic microglia, and expansion of niche subpopulations within the DAM and DIM spectrum across distinct neurodegenerative pathologies. The HuMicA is an invaluable resource tool used to support further advances in the study of microglia biology through healthy and disease settings. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.21.549845v1?rss=1 Authors: Jaulim, A., Cassidy, L. D., Young, A. R. J., Chan, A. S. L., Warren, A. Y., Taylor, A. E., Arlt, W., Lan, G., Blayney, M. L., Davidson, O., Barratt, C. L. R., Pacey, S., Narita, M. Abstract: Autophagy has been implicated in male fertility but its specific role in the post-testicular organs remains unclear. Here, we investigate this in mice expressing a doxycycline-inducible RNAi against Atg5 (Atg5i). Systemic autophagy inhibition in Atg5i mice resulted in the morphological and functional abrogation of the male accessory sex organs, leading to male subfertility. However, the testis was largely protected, likely due to the limited permeability of doxycycline through the blood-testis barrier. Interestingly, restoration of autophagy by doxycycline withdrawal in Atg5i mice led to substantial recovery of the phenotype in the accessory organs. This model offers a unique opportunity to dissect the pre- and post-testicular roles of autophagy, highlighting the non-autonomous impact of autophagy on male fertility. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.30.547251v1?rss=1 Authors: Strohman, A., Payne, B., In, A., Stebbins, K., Legon, W. Abstract: Homeostasis is the process of maintaining physiologic balance in the body that is critical for maintaining health and is dysfunctional in several disorders like chronic pain. The dorsal anterior cingulate cortex (dACC) is a critical brain area for homeostatic cardiovascular responses and pain processing, making it a promising non-invasive therapeutic target. We leverage the high spatial resolution and deep focal lengths of low-intensity focused ultrasound (LIFU) to non-invasively modulate the dACC for an effect on behavioral and cardiac autonomic responses using a transient heat pain stimulus. N = 16 healthy human volunteers (6M/10F) received transient contact heat pain during either LIFU to the dACC or Sham stimulation. Continuous electroencephalogram (EEG), electrocardiogram (ECG), and electrodermal response (EDR) were recorded. Outcome measures included perceived pain ratings, homeostatic measures including heart-rate variability, blood pressure, EDR response as well as the amplitude of the contact heat-evoked potential (CHEP). LIFU reduced pain ratings by 1.08 {+/-} 0.21 points relative to Sham. LIFU increased heart rate variability indexed by the standard deviation of normal sinus beats (SDNN), low frequency (LF) power, and the low-frequency/high-frequency (LF/HF) ratio. There were no effects on blood pressure or EDR. LIFU resulted in a 25.1% reduction in the N1-P1 CHEP amplitude driven primarily by effects on the P1 amplitude. Our results demonstrate LIFU to the dACC reduces perceived pain and alters homeostatic cardiovascular responses to a transient heat pain stimulus. These results have implications for the causal understanding of human pain and autonomic processing in the dACC and the potential for future therapeutics for pain relief and homeostatic modulation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

ReferencesWe considered the complexity of the machinery to excrete ammonium in the context of research on dietary protein and how high protein intake may increase glomerular pressure and contribute to progressive renal disease (many refer to this as the “Brenner hypothesis”). Dietary protein intake and the progressive nature of kidney disease: the role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal diseaseA trial that studied low protein and progression of CKD The Effects of Dietary Protein Restriction and Blood-Pressure Control on the Progression of Chronic Renal Disease(and famously provided data for the MDRD eGFR equation A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study GroupWe wondered about dietary recommendations in CKD. of note, this is best done in the DKD guidelines from KDIGO Executive summary of the 2020 KDIGO Diabetes Management in CKD Guideline: evidence-based advances in monitoring and treatment.Joel mentioned this study on red meat and risk of ESKD. Red Meat Intake and Risk of ESRDWe referenced the notion of a plant-based diet. This is an excellent review by Deborah Clegg and Kathleen Hill Gallant. Plant-Based Diets in CKD : Clinical Journal of the American Society of NephrologyHere's the review that Josh mentioned on how the kidney appears to sense pH Molecular mechanisms of acid-base sensing by the kidneyRemarkably, Dr. Dale Dubin put a prize in his ECG book Free Car Prize Hidden in Textbook Read the fine print: Student wins T-birdA review of the role of the kidney in DKA: Diabetic ketoacidosis: Role of the kidney in the acid-base homeostasis re-evaluatedJosh mentioned the effects of infusing large amounts of bicarbonate The effect of prolonged administration of large doses of sodium bicarbonate in man and this study on the respiratory response to a bicarbonate infusion: The Acute Effects In Man Of A Rapid Intravenous Infusion Of Hypertonic Sodium Bicarbonate Solution. Ii. Changes In Respiration And Output Of Carbon DioxideThis is the study of acute respiratory alkalosis in dogs: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC293311/?page=1And this is the study of medical students who went to the High Alpine Research Station on the Jungfraujoch in the Swiss Alps https://www.nejm.org/doi/full/10.1056/nejm199105163242003Self explanatory! A group favorite! It Is Chloride Depletion Alkalosis, Not Contraction AlkalosisEffects of chloride and extracellular fluid volume on bicarbonate reabsorption along the nephron in metabolic alkalosis in the rat. Reassessment of the classical hypothesis of the pathogenesis of metabolic alkalosisA review of pendrin's role in volume homeostasis: The role of pendrin in blood pressure regulation | American Journal of Physiology-Renal PhysiologyInfusion of bicarbonate may lead to a decrease in respiratory stimulation but the shift of bicarbonate to the CSF may lag. Check out this review Neural Control of Breathing and CO2 Homeostasis and this classic paper Spinal-Fluid pH and Neurologic Symptoms in Systemic Acidosis.OutlineOutline: Chapter 11- Regulation of Acid-Base Balance- Introduction - Bicarb plus a proton in equilibrium with CO2 and water - Can be rearranged to HH - Importance of regulating pCO2 and HCO3 outside of this equation - Metabolism of carbs and fats results in the production of 15,000 mmol of CO2 per day - Metabolism of protein and other “substances” generates non-carbonic acids and bases - Mostly from sulfur containing methionine and cysteine - And cationic arginine and lysine - Hydrolysis of dietary phosphate that exists and H2PO4– - Source of base/alkali - Metabolism of an ionic amino acids - Glutamate and asparatate - Organic anions going through gluconeogenesis - Glutamate, Citrate and lactate - Net effect on a normal western diet 50-100 mEq of H+ per day - Homeostatic response to these acid-base loads has three stages: - Chemical buffering - Changes in ventilation - Changes in H+ excretion - Example of H2SO4 from oxidation of sulfur containing AA - Drop in bicarb will stimulate renal acid secretion - Nice table of normal cid-base values, arterial and venous- Great 6 bullet points of acid-base on page 328 - Kidneys must excrete 50-100 of non-carbonic acid daily - This occurs by H secretion, but mechanisms change by area of nephron - Not excreted as free H+ due to minimal urine pH being equivalent to 0.05 mmol/L - No H+ can be excreted until virtually all of th filtered bicarb is reabsorbed - Secreted H+ must bind buffers (phosphate, NH3, cr) - PH is main stimulus for H secretion, though K, aldo and volume can affect this.- Renal Hydrogen excretion - Critical to understand that loss of bicarb is like addition of hydrogen to the body - So all bicarb must be reabsorbed before dietary H load can be secreted - GFR of 125 and bicarb of 24 results in 4300 mEq of bicarb to be reabsorbed daily - Reabsorption of bicarb and secretion of H involve H secretion from tubular cells into the lumen. - Thee initial points need to be emphasized - Secreted H+ ion are generated from dissociation of H2O - Also creates OH ion - Which combine with CO2 to form HCO3 with the help of zinc containing intracellular carbonic anhydrase. - This is how the secretion of H+ which creates an OH ultimately produces HCO3 - Different mechanisms for proximal and distal acidification - NET ACID EXCRETION - Free H+ is negligible - So net H+ is TA + NH4 – HCO3 loss - Unusually equal to net H+ load, 50-100 mEq/day - Can bump up to 300 mEq/day if acid production is increased - Net acid excretion can go negative following a bicarb or citrate load - Proximal Acidification - Na-H antiporter (or exchanger) in luminal membrane - Basolateral membrane has a 3 HCO3 Na cotransporter - This is electrogenic with 3 anions going out and only one cation - The Na-H antiporter also works in the thick ascending limb of LOH - How about this, there is also a H-ATPase just like found in the intercalated cells in the proximal tubule and is responsible for about a third of H secretion - And similarly there is also. HCO3 Cl exchanger (pendrin-like) in the proximal tubule - Footnote says the Na- 3HCO3 cotransporter (which moves sodium against chemical gradient NS uses negative charge inside cell to power it) is important for sensing acid-base changes in the cell. - Distal acidification - Occurs in intercalated cells of of cortical and medullary collecting tubule - Three main characteristics - H secretion via active secretory pumps in the luminal membrane - Both H-ATPase and H-K ATPase - H- K ATPase is an exchange pump, k reabsorption - H-K exchange may be more important in hypokalemia rather than in acid-base balance - Whole paragraph on how a Na-H exchanger couldn't work because the gradient that H has to be pumped up is too big. - H-ATPase work like vasopressin with premise H-ATPase sitting on endocarditis vesicles a=which are then inserted into the membrane. Alkalosis causes them to be recycled out of the membrane. - H secretory cells do not transport Na since they have few luminal Na channels, but are assisted by the lumen negative tubule from eNaC. - Minimizes back diffusion of H+ and promotes bicarb resorption - Bicarbonate leaves the cell through HCO3-Cl exchanger which uses the low intracellular Cl concentration to power this process. - Same molecule is found on RBC where it is called band 3 protein - Figure 11-5 is interesting - Bicarbonate resorption - 90% in the first 1-22 mm of the proximal tubule (how long is the proximal tubule?) - Lots of Na-H exchangers and I handed permeability to HCO3 (permeability where?) - Last 10% happens distally mostly TAL LOH via Na-H exchange - And the last little bit int he outer medullary collecting duct. - Carbonic anhydrase and disequilibrium pH - CA plays central role in HCO3 reabsorption - After H is secreted in the proximal tubule it combines with HCO# to form carbonic acid. CA then dehydrates it to CO2 and H2O. (Step 2) - Constantly moving carbonic acid to CO2 and H2O keeps hydrogen combining with HCO3 since the product is rapidly consumed. - This can be demonstrated by the minimal fall in luminal pH - That is important so there is not a luminal gradient for H to overcome in the Na-H exchanger (this is why we need a H-ATPase later) - CA inhibitors that are limited tot he extracellular compartment can impair HCO3 reabsorption by 80%. - CA is found in S1, S2 but not S3 segment. See consequence in figure 11-6. - The disequilibrium comes from areas where there is no CA, the HH formula falls down because one of the assumptions of that formula is that H2CO3 (carbonic acid) is a transient actor, but without CA it is not and can accumulate, so the pKa is not 6.1. - Bicarbonate secretion - Type B intercalated cells - H-ATPase polarity reversed - HCO3 Cl exchanger faces the apical rather than basolateral membrane- Titratable acidity - Weak acids are filtered at the glom and act as buffers in the urine. - HPO4 has PKA of 6.8 making it ideal - Creatinine (pKa 4.97) and uric acid (pKa 5.75) also contribute - Under normal cinditions TA buffers 10-40 mEa of H per day - Does an example of HPO4(2-):H2PO4 (1-) which exists 4:1 at pH of 7.4 (glomerular filtrate) - So for 50 mEq of Phos 40 is HPO4 and 10 is H2PO4 - When pH drops to 6.8 then the ratio is 1:1 so for 50 - So the 50 mEq is 25 and 25, so this buffered an additional 15 mEq of H while the free H+ concentration increased from 40 to 160 nanomol/L so over 99.99% of secreted H was buffered - When pH drops to 4.8 ratio is 1:100 so almost all 50 mEq of phos is H2PO4 and 39.5 mEq of H are buffered. - Acid loading decreases phosphate reabsorption so more is there to act as TA. - Decreases activity of Na-phosphate cotransporter - DKA provides a novel weak acid/buffer beta-hydroxybutyrate (pKa 4.8) which buffers significant amount of acid (50 mEq/d).- Ammonium Excretion - Ability to excrete H+ as ammonium ions adds an important amount of flexibility to renal acid-base regulation - NH3 and NH4 production and excretion can be varied according to physiologic need. - Starts with NH3 production in tubular cells - NH3, since it is neutral then diffuses into the tubule where it is acidified by the low pH to NH4+ - NH4+ is ionized and cannot cross back into the tubule cells(it is trapped in the tubular fluid) - This is important for it acting as an important buffer eve though the pKa is 9.0 - At pH of 6.0 the ratio of NH3 to NH4 is 1:1000 - As the neutral NH3 is converted to NH4 more NH3 from theintracellular compartment flows into the tubular fluid replacing the lost NH3. Rinse wash repeat. - This is an over simplification and that there are threemajor steps - NH4 is produced in early proximal tubular cells - Luminal NH4 is partially reabsorbed in the TAL and theNH3 is then recycled within the renal medulla - The medullary interstitial NH3 reaches highconcentrations that allow NH3 to diffuse into the tubular lumen in the medullary collecting tubule where it is trapped as NH4 by secreted H+ - NH4 production from Glutamine which converts to NH4 and glutamate - Glutamate is converted to alpha-ketoglutarate - Alpha ketoglutarate is converted to 2 HCO3 ions - HCO3 sent to systemic circulation by Na-3 HCO3 transporter - NH4 then secreted via Na-H exchanger into the lumen - NH4 is then reabsorbed by NaK2Cl transporter in TAL - NH4 substitutes for K - Once reabsorbed the higher intracellular pH causes NH4 to convert to NH3 and the H that is removed is secreted through Na-H exchanger to scavenge the last of the filtered bicarb. - NH3 diffuses out of the tubular cells into the interstitium - NH4 reabsorption in the TAL is suppressed by hyperkalemia and stimulated by chronic metabolic acidosis - NH4 recycling promotes acid clearance - The collecting tubule has a very low NH3 concentration - This promotes diffusion of NH3 into the collecting duct - NH3 that goes there is rapidly converted to NH4 allowing more NH3 to diffuse in. - Response to changes in pH - Increased ammonium excretion with two processes - Increased proximal NH4 production - This is delayed 24 hours to 2-3 days depending on which enzyme you look at - Decreased urine pH increases diffusion of ammonia into the MCD - Occurs with in hours of an acid load - Peak ammonium excretion takes 5-6 days! (Fig 11-10) - Glutamine is picked up from tubular fluid but with acidosis get Na dependent peritublar capillary glutamine scavenging too - Glutamine metabolism is pH dependent with increase with academia and decrease with alkalemia - NH4 excretion can go from 30-40 mEq/day to > 300 with severe metabolic acidosis (38 NaBicarb tabs) - Says each NH4 produces equimolar generation of HCO3 but I thought it was two bicarb for every alpha ketoglutarate?- The importance of urine pH - Though the total amount of hydrogren cleared by urine pH is insignificant, an acidic urine pH is essential for driving the reactions of TA and NH4 forward.- Regulation of renal hydrogen excretion - Net acid excretion vary inverse with extracellular pH - Academia triggers proximal and distal acidification - Proximally this: - Increased Na-H exchange - Increased luminal H-ATPase activity - Increased Na:3HCO3 cotransporter on the basolateral membrane - Increased NH4 production from glutamine - In the collecting tubules - Increased H-ATPase - Reduction of tubular pH promotes diffusion of NH3 which gets converted to NH4…ION TRAPPING - Extracellular pH affects net acid excretion through its affect on intracellular pH - This happens directly with respiratory disorders due to movement of CO2 through the lipid bilayer - In metabolic disorders a low extracellular bicarb with cause bicarb to diffuse out of the cell passively, this lowers intracellular pH - If you manipulate both low pCO2 and low Bicarb to keep pH stable there will be no change in the intracellular pH and there is no change in renal handling of acid. It is intracellular pH dependent - Metabolic acidosis - Ramps up net acid secretion - Starts within 24 hours and peaks after 5-6 days - Increase net secretion comes from NH4 - Phosphate is generally limited by diet - in DKA titratable acid can be ramped up - Metabolic alkalosis - Alkaline extracellular pH - Increased bicarb excretion - Decrease reabsorption - HCO3 secretion (pendrin) in cortical collecting tubule - Occurs in cortical intercalated cells able to insert H-ATPase in basolateral cells (rather than luminal membrane) - Normal subjects are able to secrete 1000 mmol/day of bicarb - Maintenance of metabolic alkalosis requires a defect which forces the renal resorption of bicarb - This can be chloride/volume deficiency - Hypokalemia - Hyperaldosteronism - Respiratory acidosis and alkalosis - PCO2 via its effect on intracellular pH is an important determinant of renal acid handling - Ratios he uses: - 3.5 per 10 for respiratory acidosis - 5 per 10 for respiratory alkalosis - Interesting paragraph contrasting the response to chronic metabolic acidosis vs chronic respiratory acidosis - Less urinary ammonium in respiratory acidosis - Major differences in proximal tubule cell pH - In metabolic acidosis there is decreased bicarb load so less to be reabsorbed proximally - In respiratory acidosis the increased serum bicarb increases the amount of bicarb that must be reabsorbed proximally - The increased activity of Na-H antiporter returns tubular cell pH to normal and prevents it from creating increased urinary ammonium - Mentions that weirdly more mRNA for H-Na antiporter in metabolic acidosis than in respiratory acidosis - Net hydrogen excretion varies with effective circulating volume - Starts with bicarb infusions - Normally Tm at 26 - But if you volume deplete the patient with diuretics first this increases to 35+ - Four factors explain this increased Tm for bicarb with volume deficiency - Reduced GFR - Activation of RAAS - Ang2 stim H-Na antiporter proximally - Ang2 also stimulates Na-3HCO3 cotransporter on basolateral membrane - Aldosterone stimulates H-ATPase in distal nephron - ALdo stimulates Cl HCO3 exchanger on basolateral membrane - Aldo stimulates eNaC producing tubular lumen negative charge to allow H secretion to occur and prevents back diffusion - Hypochloremia - Increases H secretion by both Na-dependent and Na-independent methods - If Na is 140 and Cl is 115, only 115 of Na can be reabsorbed as NaCl, the remainder must be reabsorbed with HCO3 or associated with secretion of K or H to maintained electro neutrality - This is enhanced with hypochloridemia - Concurrent hypokalemia - Changes in K lead to trans cellular shifts that affect inctracellular pH - Hypokalemia causes K out, H in and in the tubular cell the cell acts if there is systemic acidosis and increases H secretion (and bicarbonate resorption) - PTH - Decreases proximal HCO3 resorption - Primary HyperCard as cause of type 2 RTA - Does acidosis stim PTH or does PTH stim net acid excretion

Episode #260. Are you struggling to maintain a healthy weight and navigate the confusing world of diets and weight loss solutions? In this episode, join me as I dive into the science behind eating behaviours, obesity, and the challenges of losing weight with renowned researcher Dr Stephan Guyenet. Discover the different types of eating, the importance of controlling our food environment, and various evidence-based strategies for weight loss. With practical advice and insights from Dr Guyenet, you'll gain a better understanding of the complexities of weight management and how to make informed choices for your health. Don't miss this eye-opening conversation about the widespread issue of obesity and our brain's role in eating behaviours. Specifically, we discuss: Intro (00:00) From neurodegenerative disease to obesity neuroscience (01:36) The holiday weight gain (10:38) The problem with excess fat (14:37) 'Personal fat threshold' and diabetes (26:06) Main drivers of type 2 diabetes (31:26) The role of the hypothalamus in weight gain (38:55) Homeostatic vs. non-homeostatic eating (47:29) Genetics and the obesity epidemic (56:50) Models of obesity: carbohydrate -insulin vs. energy balance (1:00:21) The brain and obesity (1:10:34) The protein-leverage hypothesis (1:19:39) Carbohydrates, fat, and the Mediterranean diet (1:24:08) The weight loss puzzle: low carb vs. low fat diet (1:30:10) Foods that promote satiety on fewer calories (1:38:25) GLP-1 agonists (1:43:08) Is weight loss largely dependent on exercise? (1:55:06) Physical activity vs sedentary lifestyle (1:58:40) Mental health and sleep (2:00:28) Expert advice on how to stop overeating (2:05:11) Outro (2:05:59) To connect with Dr Stephan Guyenet, you can find him on Twitter or visit his website, https://www.stephanguyenet.com/. You can also purchase Dr Guyenet's widely acclaimed book, The Hungry Brain, to learn more about why we overeat and how to overcome this issue. Make sure to also check out Red Pen Reviews, where you can access free expert reviews on nutrition books. Discover more insights and supporting resources in the full show notes. Enjoy, friends. Simon Want to support the show? The best way to support the show is to use the products and services offered by our sponsors. To check them out, and enjoy great savings, visit theproof.com/friends. You can also show your support by leaving a review on the Apple Podcast app and/or sharing your favourite episodes with your friends and family. Simon Hill, MSc, BSc (Hons) Creator of theproof.com and host of The Proof with Simon Hill Author of The Proof is in the Plants Watch the episodes on YouTube or listen on Apple/Spotify Connect with me on Instagram, Twitter, and Facebook Nourish your gut with my Plant-Based Ferments Guide Download my complimentary two-week meal plan and high protein Plant Performance recipe book

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.05.04.539450v1?rss=1 Authors: Niraula, S., Yan, S. S., Subramanian, J. Abstract: Alzheimer's disease is associated with altered neuronal activity, presumably due to impairments in homeostatic synaptic plasticity. Neuronal hyper and hypoactivity are also observed in mouse models of amyloid pathology. Using multicolor two-photon microscopy, we test how amyloid pathology alters the structural dynamics of excitatory and inhibitory synapses and their homeostatic adaptation to altered experience-evoked activity in vivo in a mouse model. The baseline dynamics of mature excitatory synapses and their adaptation to visual deprivation are not altered in amyloidosis. Likewise, the baseline dynamics of inhibitory synapses are not affected. In contrast, despite unaltered neuronal activity patterns, amyloid pathology leads to a selective disruption of homeostatic structural disinhibition on the dendritic shaft. We show that excitatory and inhibitory synapse loss is locally clustered under the nonpathological state, but amyloid pathology disrupts it, indicating impaired communication of changes in excitability to inhibitory synapses. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.29.537929v1?rss=1 Authors: Kon, K., Ode, K. L., Mano, T., Fujishima, H., Tone, D., Shimizu, C., Shiono, S., Yada, S., Garcon, J. Y., Kaneko, M., Shinohara, Y., Takahashi, R. R., Yamada, R. G., Shi, S., Sumiyama, K., Kiyonari, H., Susaki, E. A., Ueda, H. R. Abstract: Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.27.538634v1?rss=1 Authors: Murao, N., Matsuda, T., Kadowaki, H., Matsushita, Y., Tanimoto, K., Katagiri, T., Nakashima, K., Nishitoh, H. Abstract: Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.14.536851v1?rss=1 Authors: Yuan, X., Puvogel, S., van Rhijn, J.-R., Esteve-Codina, A., Meijer, M., Rouschop, S., J.H. van Hugte, E., Oudakker, A., Schoenmaker, C., Schubert, D., Franke, B., Nadif Kasri, N. Abstract: Mechanisms that underlie homeostatic plasticity have been extensively investigated at single-cell levels in animal models, but are less well understood at the network level. Here, we used microelectrode arrays to characterize neuronal networks following induction of homeostatic plasticity in human induced pluripotent stem cell (hiPSC)-derived glutamatergic neurons co-cultured with rat astrocytes. Chronic suppression of neuronal activity through tetrodotoxin (TTX) elicited a time-dependent network re-arrangement. Increased expression of AMPA receptors and the elongation of axon initial segments were associated with increased network excitability following TTX treatment. Transcriptomic profiling of TTX-treated neurons revealed up-regulated genes related to extracellular matrix organization, while down-regulated genes related to cell communication; also astrocytic gene expression was found altered. Overall, our study shows that hiPSC-derived neuronal networks provide a reliable in vitro platform to measure and characterize homeostatic plasticity at network and single-cell level; this platform can be extended to investigate altered homeostatic plasticity in brain disorders. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.27.534486v1?rss=1 Authors: Saha, S., Chakraborty, P., Naskar, A., Roy, D., Banerjee, A. Abstract: Ageing brain is associated with a slow drift in structural network properties over the lifespan accompanied by reorganization in neuromolecular interactions giving rise to changes in global functional markers. What are the guiding principles of the homeostatic mechanisms that maintain the desired performance of functional neural circuits and preserve brain health during healthy ageing? We hypothesize that an ageing brain alters two primary neurotransmitters, glutamate and {gamma} -aminobutyric acid (GABA), responsible for excitation-inhibition regulation, concomitant with anatomical demyelination to preserve critical neural dynamics that are necessary to uphold optimal network performance. Thus, often observed reorganized functional connectivity with age by several investigations is a byproduct of this adaptive process. We demonstrate that the adaptive mechanism is driven by the tuning of glutamate and GABA concentration over a very slow time scale (lifespan) that can be estimated by tracking criticality from coordinated neural dynamics at a resting state via a biophysically driven computational framework, introduced as a computational microscope. We validate several empirical observations and model predictions across three independent aging cohorts using this computational microscope. One of the key mechanisms we discover is the reduction in local glutamate levels employed by brain regions to maintain a homeostatic balance with aging. This is further supported by the invariance of measures of global functional integration during the healthy ageing process. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.20.533396v1?rss=1 Authors: Anil, S., Lu, H., Rotter, S., Vlachos, A. Abstract: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique used to induce neuronal plasticity in healthy individuals and patients. Designing effective and reproducible rTMS protocols poses a major challenge in the field as the underlying biomechanisms remain elusive. Current clinical protocol designs are often based on studies reporting rTMS-induced long-term potentiation or depression of synaptic transmission. Herein, we employed computational modeling to explore the effects of rTMS on long-term structural plasticity and changes in network connectivity. We simulated a recurrent neuronal network with homeostatic structural plasticity between excitatory neurons, and demonstrated that this mechanism was sensitive to specific parameters of the stimulation protocol (i.e., frequency, intensity, and duration of stimulation). The feedback-inhibition initiated by network stimulation influenced the net stimulation outcome and hindered the rTMS-induced homeostatic structural plasticity, highlighting the role of inhibitory networks. These findings suggest a novel mechanism for the lasting effects of rTMS, i.e., rTMS-induced homeostatic structural plasticity, and highlight the importance of network inhibition in careful protocol design, standardization, and optimization of stimulation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

You may think you understand the important of steps as far as energy out goes, but there is SO MUCH MORE to it than that!!! Today's Episode we are breaking down WHY we track steps, and what the research shows about different step averages in regards to your overall health and hitting your fitness goals.Topics: (00:24) - Mesocycle and Microcycle (01:57) - Versa Gripps (04:44) - Steps challenge and step knowledge (05:54) - Don't get weird about steps (07:35) - Step levels explained (10:31) - Why 8,000 steps? (13:15) - Benefits that are often overlooked (18:41) - What about 12,000? (22:21) - Does cardio count towards steps? (24:29) - Movement builds momentum (27:58) - Changing the story you tell about yourself (33:33) - Doing all or something (34:24) - It willl look different for everybody (37:46) - Suggestions from recent steps challenge (45:17) - Habit stacking (47:52) - Recapping the benefits of movement Sign up HERE for the LiftingLindsay Newsletter so you never miss out on fitness and health brain gains!Want optimized training programs? You have enough to think about, let me do all your training programming for you. Sign up HERE for optimized training, no matter the goal. Training programs include home alternatives. I have 3,4 & 5 day programs. You can also upload videos for form reviews done by me in the VIP Facebook group Facebook group includes monthly challenges to take your health to the next level and have a chance to win prizes too! Studies sited PMID: 29289613 Homeostatic and non-homeostatic appetite control along the spectrum of physical activity levels: An updated perspective Burton, H.M. and E.F. Coyle, Daily Step Count and Postprandial Fat Metabolism. Med Sci Sports Exerc, 2021. 53(2): p. 333-340. Sullivan Bisson, A.N., S.A. Robinson, and M.E. Lachman, Walk to a better night of sleep: testing the relationship between physical activity and sleep. Sleep Health, 2019. 5(5): Foright, R., et al., Effects of Exercise during Weight Loss Maintenance on Appetite Regulation in Women. Transl J Am Coll Sports Med, 2020. Foright, R.M., et al., Is regular exercise an effective strategy for weight loss maintenance?  Physiol Behav, 2018. Mayer, J., P. Roy, and K.P. Mitra, Relation between caloric intake, body weight, and physical work: studies in an industrial male population in West Bengal.  Am J Clin Nutr, 1956.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.05.530392v1?rss=1 Authors: Mayzel, J., Schneidman, E. Abstract: Studying and understanding the code of large neural populations hinge on learning accurate statistical models of population activity. A new class of such models, based on learning to weigh sparse nonlinear Random Projections (RP) of the population, was recently shown to be highly accurate, efficient, and scalable. Moreover, RP models have a clear biologically-plausible implementation as a shallow neural circuit. Here we extend these models and present RP models that are learned by optimizing the randomly selected sparse projections. This "reshaping" of projections is akin to changing synaptic connections in the corresponding neural circuit model. When we applied these Reshaped RP models to recordings of tens of cortical neurons from behaving monkeys, we found them to be more accurate and efficient than the previous class of RP models and on par with backpropagation models. Our exploration of the effect of adding biological features to these circuit models revealed that learning reshaped RP models with homeostatic synaptic scaling yields even more efficient and accurate models. We further show that homeostatic reshaped RP models, which rely on sparse and random connectivity, are superior to fully connected network models. Our results thus suggest a key functional role for homeostatic scaling in neural circuits, beyond regulating network activity, namely - optimizing performance and efficiency. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.20.529310v1?rss=1 Authors: Berecki, G., Bryson, A., Polster, T., Petrou, S. Abstract: SCN1A gain-of-function variants are associated with early onset developmental and epileptic encephalopathies (DEEs) that possess distinct clinical features compared to Dravet syndrome caused by SCN1A loss-of-function. However, it is unclear how SCN1A gain-of-function may predispose to cortical hyper-excitability and seizures. Here, we first report the clinical features of a patient carrying a de novo SCN1A variant (T162I) associated with neonatal-onset DEE, and then characterize the biophysical properties of T162I and three other SCN1A variants associated with neonatal-onset or early infantile DEE (I236V, P1345S, R1636Q). In voltage clamp experiments, three variants (T162I, P1345S and R1636Q) exhibited changes in activation and inactivation properties that enhanced window current, consistent with gain-of-function. Dynamic action potential clamp experiments utilising model neurons incorporating Nav1.1. channels supported a gain-of-function mechanism for all four variants. Here, the T162I, I236V, P1345S, and R1636Q variants exhibited higher peak firing rates relative to wild type and the T162I and R1636Q variants produced a hyperpolarized threshold and reduced neuronal rheobase. To explore the impact of these variants upon cortical excitability, we used a spiking network model containing an excitatory pyramidal cell (PC) and parvalbumin positive (PV) interneuron population. SCN1A gain-of-function was modeled by enhancing the excitability of PV interneurons and then incorporating three simple forms of homeostatic plasticity that restored pyramidal cell firing rates. We found that homeostatic plasticity mechanisms exerted differential impact upon network function, with changes to PV-to-PC and PC-to-PC synaptic strength predisposing to network instability. Overall, our findings support a role for SCN1A gain-of-function and inhibitory interneuron hyperexcitability in early onset DEE. We propose a mechanism through which homeostatic plasticity pathways can predispose to pathological excitatory activity and contribute to phenotypic variability in SCN1A disorders. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

ReferencesWe considered the effect of a high protein diet and potential metabolic acidosis on kidney function. This review is of interest by Donald Wesson, a champion for addressing this issue and limiting animal protein: Mechanisms of Metabolic Acidosis-Induced Kidney Injury in Chronic Kidney DiseaseHostetter explored the effect of a high protein diet in the remnant kidney model with 1 ¾ nephrectomy. Rats with reduced dietary acid load (by bicarbonate supplementation) had less tubular damage. Chronic effects of dietary protein in the rat with intact and reduced renal massWesson explored treatment of metabolic acidosis in humans with stage 3 CKD in this study. Treatment of metabolic acidosis in patients with stage 3 chronic kidney disease with fruits and vegetables or oral bicarbonate reduces urine angiotensinogen and preserves glomerular filtration rateIn addition to the effect of metabolic acidosis from a diet high in animal protein, this diet also leads to hyperfiltration. This was demonstrated in normal subjects; ingesting a protein diet had a significantly higher creatinine clearance than a comparable group of normal subjects ingesting a vegetarian diet. Renal functional reserve in humans: Effect of protein intake on glomerular filtration rate.This finding has been implicated in Brenner's theory regarding hyperfiltration: The hyperfiltration theory: a paradigm shift in nephrologyOne of multiple publications from Dr. Nimrat Goraya whom Joel mentioned in the voice over: Dietary Protein as Kidney Protection: Quality or Quantity?We wondered about the time course in buffering a high protein meal (and its subsequent acid load on ventilation) and Amy found this report:Effect of Protein Intake on Ventilatory Drive | Anesthesiology | American Society of Anesthesiologists Roger mentioned that the need for acetate to balance the acid from amino acids in parenteral nutrition was identified in pediatrics perhaps because infants may have reduced ability to generate acid. Randomised controlled trial of acetate in preterm neonates receiving parenteral nutrition - PMCHe also recommended an excellent review on the complications of parenteral nutrition by Knochel https://www.kidney-international.org/action/showPdf?pii=S0085-2538%2815%2933384-6 which explained that when the infused amino acids disproportionately include cationic amino acids, metabolism led to H+ production. This is typically mitigated by preparing a solution that is balanced by acetate. Amy mentioned this study that explored the effect of protein intake on ventilation: Effect of Protein Intake on Ventilatory Drive | Anesthesiology | American Society of AnesthesiologistsAnna and Amy reminisced about a Skeleton Key Group Case from the renal fellow network Skeleton Key Group: Electrolyte Case #7JC wondered about isolated defects in the proximal tubule and an example is found here: Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalitiesAnna's Voiceover re: Gastric neobladder → metabolic alkalosis and yes, dysuria. The physiology of gastrocystoplasty: once a stomach, always a stomach but not as common as you might think Gastrocystoplasty: long-term complications in 22 patientsSjögren's syndrome has been associated with acquired distal RTA and in some cases, an absence of the H+ ATPase, presumably from autoantibodies to this transporter. Here's a case report: Absence of H(+)-ATPase in cortical collecting tubules of a patient with Sjogren's syndrome and distal renal tubular acidosisCan't get enough disequilibrium pH? Check this out- Spontaneous luminal disequilibrium pH in S3 proximal tubules. Role in ammonia and bicarbonate transport.Acetazolamide secretion was studied in this report Concentration-dependent tubular secretion of acetazolamide and its inhibition by salicylic acid in the isolated perfused rat kidney. | Drug Metabolism & DispositionIn this excellent review, David Goldfarb tackles the challenging case of a A Woman with Recurrent Calcium Phosphate Kidney Stones (spoiler alert, many of these patients have incomplete distal RTA and this problem is hard to treat). Molecular mechanisms of renal ammonia transport excellent review from David Winer and Lee Hamm. OutlineOutline: Chapter 11- Regulation of Acid-Base Balance- Introduction - Bicarb plus a proton in equilibrium with CO2 and water - Can be rearranged to HH - Importance of regulating pCO2 and HCO3 outside of this equation - Metabolism of carbs and fats results in the production of 15,000 mmol of CO2 per day - Metabolism of protein and other “substances” generates non-carbonic acids and bases - Mostly from sulfur containing methionine and cysteine - And cationic arginine and lysine - Hydrolysis of dietary phosphate that exists and H2PO4– - Source of base/alkali - Metabolism of an ionic amino acids - Glutamate and asparatate - Organic anions going through gluconeogenesis - Glutamate, Citrate and lactate - Net effect on a normal western diet 50-100 mEq of H+ per day - Homeostatic response to these acid-base loads has three stages: - Chemical buffering - Changes in ventilation - Changes in H+ excretion - Example of H2SO4 from oxidation of sulfur containing AA - Drop in bicarb will stimulate renal acid secretion - Nice table of normal cid-base values, arterial and venous- Great 6 bullet points of acid-base on page 328 - Kidneys must excrete 50-100 of non-carbonic acid daily - This occurs by H secretion, but mechanisms change by area of nephron - Not excreted as free H+ due to minimal urine pH being equivalent to 0.05 mmol/L - No H+ can be excreted until virtually all of th filtered bicarb is reabsorbed - Secreted H+ must bind buffers (phosphate, NH3, cr) - PH is main stimulus for H secretion, though K, aldo and volume can affect this.- Renal Hydrogen excretion - Critical to understand that loss of bicarb is like addition of hydrogen to the body - So all bicarb must be reabsorbed before dietary H load can be secreted - GFR of 125 and bicarb of 24 results in 4300 mEq of bicarb to be reabsorbed daily - Reabsorption of bicarb and secretion of H involve H secretion from tubular cells into the lumen. - Thee initial points need to be emphasized - Secreted H+ ion are generated from dissociation of H2O - Also creates OH ion - Which combine with CO2 to form HCO3 with the help of zinc containing intracellular carbonic anhydrase. - This is how the secretion of H+ which creates an OH ultimately produces HCO3 - Different mechanisms for proximal and distal acidification - NET ACID EXCRETION - Free H+ is negligible - So net H+ is TA + NH4 – HCO3 loss - Unusually equal to net H+ load, 50-100 mEq/day - Can bump up to 300 mEq/day if acid production is increased - Net acid excretion can go negative following a bicarb or citrate load - Proximal Acidification - Na-H antiporter (or exchanger) in luminal membrane - Basolateral membrane has a 3 HCO3 Na cotransporter - This is electrogenic with 3 anions going out and only one cation - The Na-H antiporter also works in the thick ascending limb of LOH - How about this, there is also a H-ATPase just like found in the intercalated cells in the proximal tubule and is responsible for about a third of H secretion - And similarly there is also. HCO3 Cl exchanger (pendrin-like) in the proximal tubule - Footnote says the Na- 3HCO3 cotransporter (which moves sodium against chemical gradient NS uses negative charge inside cell to power it) is important for sensing acid-base changes in the cell. - Distal acidification - Occurs in intercalated cells of of cortical and medullary collecting tubule - Three main characteristics - H secretion via active secretory pumps in the luminal membrane - Both H-ATPase and H-K ATPase - H- K ATPase is an exchange pump, k reabsorption - H-K exchange may be more important in hypokalemia rather than in acid-base balance - Whole paragraph on how a Na-H exchanger couldn't work because the gradient that H has to be pumped up is too big. - H-ATPase work like vasopressin with premise H-ATPase sitting on endocarditis vesicles a=which are then inserted into the membrane. Alkalosis causes them to be recycled out of the membrane. - H secretory cells do not transport Na since they have few luminal Na channels, but are assisted by the lumen negative tubule from eNaC. - Minimizes back diffusion of H+ and promotes bicarb resorption - Bicarbonate leaves the cell through HCO3-Cl exchanger which uses the low intracellular Cl concentration to power this process. - Same molecule is found on RBC where it is called band 3 protein - Figure 11-5 is interesting - Bicarbonate resorption - 90% in the first 1-22 mm of the proximal tubule (how long is the proximal tubule?) - Lots of Na-H exchangers and I handed permeability to HCO3 (permeability where?) - Last 10% happens distally mostly TAL LOH via Na-H exchange - And the last little bit int he outer medullary collecting duct. - Carbonic anhydrase and disequilibrium pH - CA plays central role in HCO3 reabsorption - After H is secreted in the proximal tubule it combines with HCO# to form carbonic acid. CA then dehydrates it to CO2 and H2O. (Step 2) - Constantly moving carbonic acid to CO2 and H2O keeps hydrogen combining with HCO3 since the product is rapidly consumed. - This can be demonstrated by the minimal fall in luminal pH - That is important so there is not a luminal gradient for H to overcome in the Na-H exchanger (this is why we need a H-ATPase later) - CA inhibitors that are limited tot he extracellular compartment can impair HCO3 reabsorption by 80%. - CA is found in S1, S2 but not S3 segment. See consequence in figure 11-6. - The disequilibrium comes from areas where there is no CA, the HH formula falls down because one of the assumptions of that formula is that H2CO3 (carbonic acid) is a transient actor, but without CA it is not and can accumulate, so the pKa is not 6.1. - Bicarbonate secretion - Type B intercalated cells - H-ATPase polarity reversed - HCO3 Cl exchanger faces the apical rather than basolateral membrane- Titratable acidity - Weak acids are filtered at the glom and act as buffers in the urine. - HPO4 has PKA of 6.8 making it ideal - Creatinine (pKa 4.97) and uric acid (pKa 5.75) also contribute - Under normal cinditions TA buffers 10-40 mEa of H per day - Does an example of HPO4(2-):H2PO4 (1-) which exists 4:1 at pH of 7.4 (glomerular filtrate) - So for 50 mEq of Phos 40 is HPO4 and 10 is H2PO4 - When pH drops to 6.8 then the ratio is 1:1 so for 50 - So the 50 mEq is 25 and 25, so this buffered an additional 15 mEq of H while the free H+ concentration increased from 40 to 160 nanomol/L so over 99.99% of secreted H was buffered - When pH drops to 4.8 ratio is 1:100 so almost all 50 mEq of phos is H2PO4 and 39.5 mEq of H are buffered. - Acid loading decreases phosphate reabsorption so more is there to act as TA. - Decreases activity of Na-phosphate cotransporter - DKA provides a novel weak acid/buffer beta-hydroxybutyrate (pKa 4.8) which buffers significant amount of acid (50 mEq/d).- Ammonium Excretion - Ability to excrete H+ as ammonium ions adds an important amount of flexibility to renal acid-base regulation - NH3 and NH4 production and excretion can be varied according to physiologic need. - Starts with NH3 production in tubular cells - NH3, since it is neutral then diffuses into the tubule where it is acidified by the low pH to NH4+ - NH4+ is ionized and cannot cross back into the tubule cells(it is trapped in the tubular fluid) - This is important for it acting as an important buffer eve though the pKa is 9.0 - At pH of 6.0 the ratio of NH3 to NH4 is 1:1000 - As the neutral NH3 is converted to NH4 more NH3 from theintracellular compartment flows into the tubular fluid replacing the lost NH3. Rinse wash repeat. - This is an over simplification and that there are threemajor steps - NH4 is produced in early proximal tubular cells - Luminal NH4 is partially reabsorbed in the TAL and theNH3 is then recycled within the renal medulla - The medullary interstitial NH3 reaches highconcentrations that allow NH3 to diffuse into the tubular lumen in the medullary collecting tubule where it is trapped as NH4 by secreted H+ - NH4 production from Glutamine which converts to NH4 and glutamate - Glutamate is converted to alpha-ketoglutarate - Alpha ketoglutarate is converted to 2 HCO3 ions - HCO3 sent to systemic circulation by Na-3 HCO3 transporter - NH4 then secreted via Na-H exchanger into the lumen - NH4 is then reabsorbed by NaK2Cl transporter in TAL - NH4 substitutes for K - Once reabsorbed the higher intracellular pH causes NH4 to convert to NH3 and the H that is removed is secreted through Na-H exchanger to scavenge the last of the filtered bicarb. - NH3 diffuses out of the tubular cells into the interstitium - NH4 reabsorption in the TAL is suppressed by hyperkalemia and stimulated by chronic metabolic acidosis - NH4 recycling promotes acid clearance - The collecting tubule has a very low NH3 concentration - This promotes diffusion of NH3 into the collecting duct - NH3 that goes there is rapidly converted to NH4 allowing more NH3 to diffuse in. - Response to changes in pH - Increased ammonium excretion with two processes - Increased proximal NH4 production - This is delayed 24 hours to 2-3 days depending on which enzyme you look at - Decreased urine pH increases diffusion of ammonia into the MCD - Occurs with in hours of an acid load - Peak ammonium excretion takes 5-6 days! (Fig 11-10) - Glutamine is picked up from tubular fluid but with acidosis get Na dependent peritublar capillary glutamine scavenging too - Glutamine metabolism is pH dependent with increase with academia and decrease with alkalemia - NH4 excretion can go from 30-40 mEq/day to > 300 with severe metabolic acidosis (38 NaBicarb tabs) - Says each NH4 produces equimolar generation of HCO3 but I thought it was two bicarb for every alpha ketoglutarate?- The importance of urine pH - Though the total amount of hydrogren cleared by urine pH is insignificant, an acidic urine pH is essential for driving the reactions of TA and NH4 forward.- Regulation of renal hydrogen excretion - Net acid excretion vary inverse with extracellular pH - Academia triggers proximal and distal acidification - Proximally this: - Increased Na-H exchange - Increased luminal H-ATPase activity - Increased Na:3HCO3 cotransporter on the basolateral membrane - Increased NH4 production from glutamine - In the collecting tubules - Increased H-ATPase - Reduction of tubular pH promotes diffusion of NH3 which gets converted to NH4…ION TRAPPING - Extracellular pH affects net acid excretion through its affect on intracellular pH - This happens directly with respiratory disorders due to movement of CO2 through the lipid bilayer - In metabolic disorders a low extracellular bicarb with cause bicarb to diffuse out of the cell passively, this lowers intracellular pH - If you manipulate both low pCO2 and low Bicarb to keep pH stable there will be no change in the intracellular pH and there is no change in renal handling of acid. It is intracellular pH dependent - Metabolic acidosis - Ramps up net acid secretion - Starts within 24 hours and peaks after 5-6 days - Increase net secretion comes from NH4 - Phosphate is generally limited by diet - in DKA titratable acid can be ramped up - Metabolic alkalosis - Alkaline extracellular pH - Increased bicarb excretion - Decrease reabsorption - HCO3 secretion (pendrin) in cortical collecting tubule - Occurs in cortical intercalated cells able to insert H-ATPase in basolateral cells (rather than luminal membrane) - Normal subjects are able to secrete 1000 mmol/day of bicarb - Maintenance of metabolic alkalosis requires a defect which forces the renal resorption of bicarb - This can be chloride/volume deficiency - Hypokalemia - Hyperaldosteronism - Respiratory acidosis and alkalosis - PCO2 via its effect on intracellular pH is an important determinant of renal acid handling - Ratios he uses: - 3.5 per 10 for respiratory acidosis - 5 per 10 for respiratory alkalosis - Interesting paragraph contrasting the response to chronic metabolic acidosis vs chronic respiratory acidosis - Less urinary ammonium in respiratory acidosis - Major differences in proximal tubule cell pH - In metabolic acidosis there is decreased bicarb load so less to be reabsorbed proximally - In respiratory acidosis the increased serum bicarb increases the amount of bicarb that must be reabsorbed proximally - The increased activity of Na-H antiporter returns tubular cell pH to normal and prevents it from creating increased urinary ammonium - Mentions that weirdly more mRNA for H-Na antiporter in metabolic acidosis than in respiratory acidosis - Net hydrogen excretion varies with effective circulating volume - Starts with bicarb infusions - Normally Tm at 26 - But if you volume deplete the patient with diuretics first this increases to 35+ - Four factors explain this increased Tm for bicarb with volume deficiency - Reduced GFR - Activation of RAAS - Ang2 stim H-Na antiporter proximally - Ang2 also stimulates Na-3HCO3 cotransporter on basolateral membrane - Aldosterone stimulates H-ATPase in distal nephron - ALdo stimulates Cl HCO3 exchanger on basolateral membrane - Aldo stimulates eNaC producing tubular lumen negative charge to allow H secretion to occur and prevents back diffusion - Hypochloremia - Increases H secretion by both Na-dependent and Na-independent methods - If Na is 140 and Cl is 115, only 115 of Na can be reabsorbed as NaCl, the remainder must be reabsorbed with HCO3 or associated with secretion of K or H to maintained electro neutrality - This is enhanced with hypochloridemia - Concurrent hypokalemia - Changes in K lead to trans cellular shifts that affect inctracellular pH - Hypokalemia causes K out, H in and in the tubular cell the cell acts if there is systemic acidosis and increases H secretion (and bicarbonate resorption) - PTH - Decreases proximal HCO3 resorption - Primary HyperCard as cause of type 2 RTA - Does acidosis stim PTH or does PTH stim net acid excretion

In the 142nd episode of The Strength Connection Podcast, Mike and our special guest, Professor at the Carrick Institute in Rocky Mountain University and Researcher, Dr. Mike T Nelson, will talk about heat transfer experiment, the metabolic flexibility project, ways to check metabolic flexibility at home, homeostatic regulators, and more.Join us in this insightful and captivating talk! In this chapter, you will discover:(0:45) Welcome to our special guest Professor at the Carrick Institute in Rocky Mountain University and Researcher, Dr. Mike T Nelson @drmiketnelson(2:15) Dr. Mike's origin story(2:20) Interest in science(3:05) Starting lifting early(3:40) Undergrad psychology class (4:50) Heat transfer experiment(6:10) Presentation for DARPA(8:10) New psychology class(9:00) Working in a cube environment(9:20) NSCA CSCS(10:00) Training people(10:15) Ph.D. work in biomechanical engineering(11:00) What does Dr. Mike currently do?(11:45) About metabolic flexibility(13:10) Lack of choice for projects(14:00) The Metabolic Flexibility project(16:20) Metabolic inflexibility(19:50) From inflexible to flexible(20:40) Insulin-dependent and insulin-independent(23:10) Ways to check metabolic flexibility at home(25:35) Fasted cardio(27:00) Why is fasted cardio easier in practice?(28:05) Opposite data(28:10) Shout out to Dr. Jeff Rothschild @eatsleep.fit(28:25) Shout out to Ryan Baxter @ryanjasonbaxtor(28:40) Is fasted cardio magical?(30:15) Should you do fasted cardio?(32:15) The flexibility levels(33:30) Dr. Mike's pet peeve(33:50) Homeostatic regulators(34:50) Steps to become more resilient(35:10) Heat acclimation(36:00) “The greater your buffer zone is in temperature, pH level, that's the key to advanced recovery, longevity, and being more robust antifragile.” - Dr. Mike T Nelson @drmiketnelson(37:10) Sauna village(37:10) Shout out to Krista Scott-Dixon @stumptuous(37:30) Shout out to Thadius Owen @primalhacker(38:25) Shout out to Laird Hamilton @lairdhamilton(39:20) Benefits of cold showers(39:40) At home cold immersion(42:50) Voluntarily suffering(43:50) Stress-related thoughts(44:50) “You have to pick some stressors in your life.” - Dr. Mike T Nelson @drmiketnelson(45:20) “You have to pick what stressors you want to expose yourself to and if you do that in an intelligent manner your body rewards you by getting better at those things via adaptation.” - Dr. Mike T Nelson @drmiketnelson(45:45) Meditative practice(46:15) Shout out to John Danaher @danaherjohn(46:30) Stress lessen(47:25) Shout out to Brian Mackenzie @_brianmackenzie(47:25) Shout out to Rob Wilson @preparetoperform(48:40) Mike and Chris' nose breathing experiment(49:30) One of Dr. Mike's training methods(51:20) What's next with Dr. Mike?Where to find Dr. Mike T Nelson? @drmiketnelsonwww.flexdiet.com www.physiologicflexibility.com 

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.01.526708v1?rss=1 Authors: Makarava, N., Mychko, O., Molesworth, K., Chang, J. C.-Y., Henry, R. J., Tsymbalyuk, N., Gerzanich, V., Simard, J. M., Loane, D., Baskakov, I. V. Abstract: The transformation of astrocytes into reactive states constitutes a biological response of the central nervous system under a variety of pathological insults. Astrocytes display diverse homeostatic identities, which are developmentally predetermined and regionally specified. Upon transformation into reactive states associated with neurodegenerative diseases and other neurological disorders, astrocytes acquire diverse reactive phenotypes. However, it is not clear whether their reactive phenotypes are dictated by region-specific homeostatic identity or, alternatively, by the nature of an insult. To address this question, region-specific gene expression profiling was performed for four brain regions (cortex, hippocampus, thalamus and hypothalamus) in mice using a custom Nanostring panel consisting of selected sets of genes that report on astrocyte functions and their reactivity for five conditions: prion disease, traumatic brain injury, brain ischemia, 5XFAD Alzheimer's disease model and normal aging. Upon transformation into reactive states, genes that are associated predominantly with astrocytes were found to preserve region-specific signatures suggesting that they respond to insults in a region-specific manner. A common gene set was found to be involved in astrocyte remodeling across insults and normal aging. Regardless of the nature of an insult or insult-specificity of astrocyte response, strong correlations between the degree of astrocyte reactivity and perturbations in their homeostasis-associated genes were observed within each individual brain region. The insult-specific populations did not separate well from each other and instead partially overlapped, forming continuums of phenotypes. The current study demonstrates that astrocytes acquire their reactive phenotypes according to their region-specific homeostatic identities. Within these region-specified identities, reactive phenotypes show continuums of states, partially overlapping between individual insults. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.26.525642v1?rss=1 Authors: Duriez, A., Bergerot, C., Cone, J. J., Roitman, M. F., Gutkin, B. Abstract: Seeking and consuming nutrients is essential to survival and maintenance of life. Dynamic and volatile environments require that animals learn complex behavioral strategies to obtain the necessary nutritive substances. While this has been classically viewed in terms of homeostatic regulation, where complex nutrient seeking behaviors are triggered by physiological need, recent theoretical work proposed that such strategies are a result of reinforcement learning processes. This theory also proposed that phasic dopamine (DA) signals play a key role in signaling potentially need-fulfilling outcomes. To examine potential links between homeostatic and reinforcement learning processes, we focus on sodium appetite as sodium depletion triggers state and taste dependent changes in behavior and DA signaling evoked by sodium-related stimuli. We find that both the behavior and the dynamics of DA signaling underlying sodium appetite can be accounted for by extending principles of homeostatic regulation into a reinforcement learning framework (HRRL). We first optimized HRRL-based agents to model sodium-seeking behavior measured in rats. Agents successfully reproduced the state and the taste dependence of behavioral responding for sodium as well as for lithium and potassium salts. We then show that these same agents can account for the regulation of DA signals evoked by sodium tastants in a taste and state dependent manner. Our models quantitatively describe how DA signals evoked by sodium decrease with satiety and increase with deprivation suggesting that phasic DA signals and sodium consumption are down regulated prior to animals reaching satiety. Lastly, our HRRL agents also account for the behavioral and neurophysiological observations that suggest mice cannot distinguish between sodium and lithium containing salts. Our HRRL agents exhibited an equal preference for sodium versus lithium containing solutions, and underestimated the nutritional value of sodium when lithium was concurrently available. We propose that animals use orosensory signals as predictors of the internal impact of the consumed good and our results pose clear targets for future experiments. In sum, this work suggests that appetite-dirven behavior may be driven by reinforcement learning mechanisms that are dynamically tuned by homeostatic need. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Changes in reindeer sleep regulation across the year: a central role for rumination? In this episode, I am joined by Melanie Furrer, who recently presented her study on sleep in reindeer. Most non-hibernating animals maintain daily “circadian ”rhythms of sleep across the year, as well as “homeostatic” sleep-wake patterns in which increasing time awake is followed by increased sleep amount or intensity. Strikingly, ruminant reindeer in the Arctic show 24-h rhythmicity at the equinoxes but none at either solstice; summertime activity greatly exceeds wintertime activity. So far, nothing is known about their sleep or how it might be seasonally modulated. Methods: We simultaneously recorded non-invasive electroencephalography EEG in four adult female reindeer for four days at The Arctic University of Norway in Tromsø, Norway in July, September, and December. Rapid eye movement, REM sleep, non-REM NREM sleep, and rumination were visually identified from the EEG, and slow-wave activity SWA, EEG power 1–18 4.5 Hz during NREM sleep, the classic marker for homeostatic changes in sleep pressure, was calculated. Results: Although sleep in reindeer generally resembled that of other mammals, key novel adaptations were observed in July/September: n=4, December: n=3. Like most species, sleep-wake distribution paralleled daily activity during seasonally changing light-dark conditions and SWA during NREM sleep increased after prolonged wake periods. Surprisingly, total sleep duration was roughly equal across seasons, and prolonged waking produced a lower SWA response in summer than in winter. As reported for some domestic ruminants, EEG during rumination showed typical characteristics of NREM sleep. Furthermore, rumination appeared to substitute for sleep under all observed conditions. Accordingly, SWA decreased across rumination, and total rumination and NREM sleep durations were negatively correlated. Homeostatic modelling of SWA further suggested that rumination was equivalent to sleep. Conclusions: We suggest that less pronounced SWA increases across waking in summer might indicate higher baseline sleep pressure during this season, possibly resulting from increased activity, food intake and light exposure. Within this context, rumination might partially substitute conventional sleep, permitting near-constant feeding in the arctic summer while compensating for increased sleep pressure. Contact or follow Melanie https://www.kispi.uzh.ch/forschungszentrum/person/furrer-melanie. https://www.researchgate.net/profile/Melanie-Furrer-2   Contact me at iandunican@sleep4performance.com.au or www.sleep4performance.com.au and check out the YouTube channel. Check out our sponsor LMNT. Click on the link to order and get a free LMNT Sample Pack when you order through the custom link below. Key details: • The LMNT Sample Pack includes 1 packet of every flavour. This is the perfect offer for anyone interested in trying all of our flavours or who wants to introduce a friend to LMNT. • This offer is exclusively available through VIP LMNT Partners – you won't find this offer publicly available. • This offer is available for new and returning customers • They offer refunds on all orders with no questions – you don't even have to send it back! DrinkLMNT.com/sleep4performance

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.11.519940v1?rss=1 Authors: Theret, M., Messing, M., White, Z., Henry, L. W., Rempel, L., Hamer, M., Hashimoto, J., Li, F. F., Brassard, J., Li, Y., Sauge, E., Shin, S., Day, K., Uppal, M., Low, M., Eisner, C., Sato, S., Akira, S., Bernatchez, P., McNagny, K., Rossi, F. M. V. Abstract: The ability of mesenchymal stromal cells to modulate inflammation is at the basis of the ongoing interest in their therapeutic potential. Yet, reliable success in clinical trials is limited, possibly due to a limited understanding of their impact on the inflammatory milieu in physiological conditions. Here we show that, at steady state, mesenchymal progenitors regulate the balance between type 1 and type 2 inflammatory milieus by acting on innate immune cells through the TAK1-NFkB pathway. Suppressing the constitutive activity of this pathway in MPs leads to skewing of the immune system toward systemic Type 2 inflammation (Th2). These changes have significant effects on diseases with an important inflammatory component, leading to a worsening of disease in a preclinical model of Th2-dependent Asthma, and a reduction of symptoms associated with Th1/Th17-dependent experimental autoimmune encephalitis. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.16.516613v1?rss=1 Authors: Jusyte, M., Blaum, N., Boehme, M. A., Berns, M. M., Bonard, A. E., Kobbersmed, J. R., Walter, A. M. Abstract: Chemical synaptic transmission relies on neurotransmitter release from presynaptic release sites and on transmitter-sensing by the postsynaptic cell. Presynaptic plasticity increasing neurotransmitter release achieves two fundamental nervous system functions: It tunes some synapses to be more responsive to millisecond repetitive activation and it maintains signals when postsynaptic transmitter sensitivity is reduced. How enhanced neurotransmitter release is achieved in these phenomena, termed short-term facilitation and homeostatic potentiation, remains unknown. We combine mathematical modeling and experimental analysis of Drosophila neuromuscular junction model synapses to elucidate the molecular mechanisms underlying these forms of plasticity. Our results indicate that both phenomena depend on a rapid increase in the participation of neurotransmitter release sites which is controlled by the regulatory domains of the evolutionarily conserved (M)Unc13A protein that bind Ca2+/Calmodulin and diacylglycerol. Mutation of the Calmodulin binding (CaM) domain increased baseline transmission and impaired both short-term facilitation and acute homeostatic potentiation. Mathematical modeling indicated that these defects result from too many release sites participating at rest combined with the inability to plastically further increase their number. Super-resolution microscopy revealed that this coincided with a redistribution of Unc13A`s functionally essential MUN domain closer to the synaptic plasma membrane, which may constitute the molecular switch to increase release site participation. Similar consequences (enhanced baseline transmission, block of both short-term facilitation and homeostatic potentiation) were caused by the acute pharmacological activation of the C1 domain of wildtype Unc13A using phorbol esters. This treatment had no effect on Unc13A CaM domain mutants, indicating that both the CaM and C1 domains activate a binary release site switch. Thus, our findings indicate that Unc13A regulatory domains are tuned to integrate a multitude of signals on various timescales to switch release site participation for synaptic plasticity. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Guest Name: Pedro Caceres, Leading expert in supply chain, Language: English, Publication date: Nov, 01. 2022 Pedro J. Caceres is an American business executive that has held executive positions in several global corporations, such as Hasbro (Senior VP Operations - Hasbro Games), Newell Rubbermaid (Global VP Operations & Supply Chain - Lenox Division), and Petmate (Chief Operating Officer).As a published author, he released “The Thundering Voice" (2009) a book that introduces a moral approach to Corporate Social Responsibility, and “Operational Success” (2012) to introduce practical operational models to drive Lean Transformation. He is also the creator of "MyInventory.AI” a System of Intelligence to optimize global supply chains. Pedro is also involved in community activities and has been Chairman of the Board of Advisors of the Division of Business Excellence (Affiliated Chambers of Commerce of Greater Springfield in Massachusetts), member of the Advisory Board for the National Ergonomic Conference and Exposition (NECE), and Vice-Chairman of the Board of Directors of Junior Achievement of Western Massachusetts. Visit his website www.operationalsuccess.com. Some of the questions we asked Pedro during our conversation: What is the primary distinction between the Homeostatic value chain and other approaches? How can we use these value chain models to respond to recent supply chain challenges where there has been a lot of uncertainty, complexity, and ambiguity in various aspects of SCM? How do you see technological advancements like the Internet of Things, Smart factories, Intregated cloud-systems, and others playing a role in improving supply chains? --- Send in a voice message: https://anchor.fm/bicarasupplychain/message

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.31.514538v1?rss=1 Authors: Muller, S. Z., Abbott, L. F., Sawtell, N. B. Abstract: Homeostatic (anti-Hebbian) forms of synaptic are effective at eliminating "prediction errors" that signal the differences between predicted and actual sensory input. However, such mechanisms appear to preclude the possibility of transmitting the resulting predictions to downstream circuits, severely limiting their utility. Using modeling and recordings from the electrosensory lobe of mormyrid fish, we reveal interactions between axonal and dendritic spikes that support both the learning and transmission of predictions. We find that sensory input modulates the rate of dendritic spikes by adjusting the amplitude of backpropagating axonal action potentials. Homeostatic plasticity counteracts these effects through changes in the underlying membrane potential, allowing the dendritic spike rate to be restored to equilibrium while simultaneously transmitting predictions through modulation of the axonal spike rate. These results reveal how two types of spikes dramatically enhance the computational power of single neurons in support of an ethologically relevant multi-layer computation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.23.513396v1?rss=1 Authors: Kruse, P., Vlachos, A., Lenz, M. Abstract: Neurological diseases can lead to the denervation of brain regions caused by demyelination, traumatic injury or cell death. Nevertheless, the molecular and structural mechanisms underlying the lesion-induced reorganization of denervated brain regions are a matter of ongoing investigation. In order to address this issue, we performed an entorhinal cortex lesion (ECL) in organotypic entorhinal-hippocampal tissue cultures and studied denervation-induced homeostatic plasticity of mossy fiber synapses, which connect dentate granule cells with CA3 pyramidal neurons and play important roles in spatial learning. Partial denervation caused a homeostatic strengthening of excitatory neurotransmission in dentate granule cells (GC), in CA3 pyramidal neurons, and their direct synaptic connections as revealed by paired recordings (GC-to-CA3). These functional changes were accompanied by ultrastructural reorganization of mossy fiber synapses, which regularly contain the plasticity-related protein synaptopodin and the spine apparatus organelle. We demonstrate that the spine apparatus organelle and its associated protein synaptopodin assemble ribosomes in close proximity to synaptic sites and moreover we unravel synaptopodin-related transcriptome, which can be linked to the expression of homeostatic synaptic plasticity. Notably, synaptopodin-deficient tissue preparations that lack the spine apparatus organelle, failed to express homeostatic adjustments of both excitatory neurotransmission and the region-specific transcriptome. Hence, synaptopodin and the spine apparatus organelle form local protein synthesis hubs that are essential for mediating lesion-induced homeostatic synaptic plasticity. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Our topic today is very scientific, heavy, and wonderful. It's something that I think, as we go through, it's clearly going to open your eyes to understanding the immune system, how the immune system has been misunderstood for quite some time, and the cells that are actually required for our homeostatic optimal function.So today, we're going to dig into macrophages and all the different types of macrophages within the body. We are analyzing their role in development, homeostasis, and in inflammation. We are also explaining why these cells function the way they do, and why they're super important! Rate and review before the next episode. If you want to know more about us and what we do, go to www.healthupgradepodcast.com.Contact info:Navaz HabibEmail: podcast@healthupgraded.comFacebook: https://www.facebook.com/DrNavazHabib/Instagram: https://www.instagram.com/drnavazhabib/LinkedIn: https://ca.linkedin.com/in/drnavazhabibJP ErricoLinkedIn: https://www.linkedin.com/in/jp-errico-097629aa 

Sarah welcomes Austin Stout back to the Beyond Condition Podcast and they talk about female health as a bodybuilder.Austin has a wealth of knowledge when it comes to physique development. Through his experience as a coach and competitor he is able to share valuable information on the effects bodybuilding has on the body and mind.Discussions include:*Homeostatic adaptations*Cortisol*Hormonal changes when dieting*Bloodwork*Menstrual cycles*Effects of dieting*Estrogen*GI health*Common environmental contributions that effect health during a dieting phase*Acute and chronic effects*Multiple preps and diet phases*Looking at the bigger picture*Emotional attachments to bodybuilding*Age considerations*Competition aspirations*Prep start point*Picking a show*Stress*Reverse dieting and recovery after a prep*Diet and training fatigue*Levels of leanest*Social media*Off season*Practical advice to considerAnd now it's over to you!!! We want to hear from our listeners, send us your topic suggestions and questions!Get in touch via Instagram@austinst8@sarahparker_bbRemember to follow us and share our episodes on your Instagram stories.Watch it here: https://youtu.be/DqMrHUv8SSoGet in touch and share this episode @sarahparker_bb

Doce é muito bom, né? Infelizmente, a vontade de doces é o que impede muitas pessoas de conseguir seguir uma alimentação saudável e emagrecer. Veja o que estes dois estudos revelaram sobre a vontade de doces, e qual o método para você parar de ser "escravo" dos doces - e poder degustá-los com prazer e calma, sem desespero. Você encontra receitas deliciosas e baixas em carboidratos estão disponíveis no nosso Livro Físico 120 Receitas Low-Carb De Sucesso (receba em casa com frete grátis): http://bit.ly/120-receitas-tanquinho Outros de nossos livros, cursos e treinamentos: https://landing.senhortanquinho.com/ ------------ * Dicas E Comentários Sobre Como Diminuir A Vontade de Doces * Existem algumas medidas práticas para acabar com a #vontade de doces. Como falamos, a vontade de #doces, ou de carboidratos, não é uma questão de "força ou fraqueza". Por exemplo, você sabia que algumas desregulações hormonais estão intimamente ligadas à vontade de comer carboidratos a noite? Falamos sobre isso aqui https://www.youtube.com/watch?v=wag8oD-hQhk E o estudo 1 mostrou que o "consumo cronicamente alto de carboidratos pode afetar os sistemas de recompensa do cérebro, de maneiras que pode impedir a manutenção da perda de peso". Ou seja: coma muitos carboidratos, e pode ser mais difícil para você se manter magra. Já o estudo 2 mostrou que as pessoas que faziam um café da manhã mais rico em carboidratos tinha maiores oscilações na glicemia, e tiveram mais fome, e comeram mais calorias. Ou seja: mais um ponto para a dieta #lowcarb. (Entenda as diferenças e semelhanças entre low-carb, paleo, cetogênica, primal, aqui: https://www.youtube.com/watch?v=IMDMteQg8N8 ) E veja como fazer um café da manhã low-carb aqui: https://www.youtube.com/watch?v=w0ie_q52mFY Estudos citados: 1 - Laura M Holsen, W Scott Hoge, Belinda S Lennerz, Hilâl Cerit, Taryn Hye, Priyanka Moondra, Jill M Goldstein, Cara B Ebbeling, David S Ludwig, Diets Varying in Carbohydrate Content Differentially Alter Brain Activity in Homeostatic and Reward Regions in Adults, The Journal of Nutrition, Volume 151, Issue 8, August 2021, Pages 2465–2476 2 - Wyatt, P., Berry, S.E., Finlayson, G. et al. Postprandial glycaemic dips predict appetite and energy intake in healthy individuals. Nat Metab 3, 523–529 (2021). Mas note que o *grau de processamento* dos alimentos é importante. Neste aspecto, prefira sempre a comida de verdade - explicamos o porquê aqui: https://www.youtube.com/watch?v=Wh5z_aC7YnQ --- Support this podcast: https://anchor.fm/senhortanquinho/support

References Dr Guerra lecture notes Endocr Rev. 2020 Aug; 41(4): 594–609 Alzheimer's & Dementia: Translational Research & Clinical Interventions (TRCI) 2021 Volume7, Issue1 e12217 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Today we welcome Dr. Antonio Damasio. He is an internationally recognized neuroscientist whose extensive research has shaped the understanding of neural systems and consciousness. With over a hundred journal articles and book chapters, he has earned many prestigious awards throughout his career. Currently, he serves as University Professor, the David Dornsife Professor of Neuroscience, Psychology, and Philosophy, and director of the Brain and Creativity Institute at the University of Southern California. His books Descartes' Error, Looking for Spinoza, Self Comes to Mind, The Strange Order of Things, and Feeling & Knowing, have been published in translation and are taught in universities throughout the world.In this episode, I talk to Antonio Damasio about consciousness. People often think that the mind and consciousness are the same thing, but Dr. Damasio disputes this notion. He argues that it's the complex relationship of both our brains and bodies that makes sentient thought possible. Homeostatic feelings like hunger and pain developed before emotions; and along with it came consciousness. We also touch on the topics of perception, mental illness, evolution, panpsychism, AI and machine learning. Website: dornsife.usc.edu/bcTwitter: @damasiousc Topics02:17 Time-locked multiregional retroactivation11:32 The difference between the mind, intelligence, and consciousness18:37 Panpsychism is an escape22:50 AIs can replicate minds but not consciousness 25:42 Feeling gave way to consciousness30:59 The purpose of emotions33:25 The evolution of feelings and emotions38:28 The interoceptive nervous system44:23 Does mental illness disrupt consciousness?49:51 Creativity as a bottom-up process54:38 Consciousness can hinder creativity58:09 Scott's interest in panpsychism59:18 Can we ever make feeling machines?

Neste episódio: O que acontece quando uma personalidade famosa (e magra) aconselha as pessoas a fazer como ela e comer sorvete pois, afinal, a vida é curta para fazer low-carb e comer alface? Artigo da semana - Diets Varying in Carbohydrate Content Differentially Alter Brain Activity in Homeostatic and Reward Regions in Adults | The Journal of Nutrition | Oxford Academic (oup.com) - diferentes alimentos têm diferentes impactos sobre o centro do prazer e recompensa no cérebro. Inscreva-se e siga esse podcast para não perder nenhum episódio (e deixe 5 estrelinhas) ;-) Conheça também o Podcurso Low-Carb da Teoria à Prática em http://drsouto.com.br/podcurso

Dr. Joon Yun is President and Managing Partner of Palo Alto Investors LP, a healthcare hedge fund founded in 1989. Board certified in radiology, Joon served on the clinical faculty at Stanford from 2000-2006. Joon has served on numerous boards, and he is currently a trustee of the Salk Institute. Joon is a member of the President's Circle of the National Academies of Sciences, Engineering, and Medicine. Joon has published dozens of patents and scientific articles. Joon and his wife Kimberly launched the $1 million Palo Alto Longevity Prize in 2013 to reverse the aging process and recently donated $2 million to launch the National Academy of Medicine Aging and Longevity Grand Challenge. Fun fact: Joon has been going to Burning Man consecutively for the past 18 years. Show Notes 00:03 - Dr. Joon: A quick biography 04:45 - The aging process 09:26 - The Fractal nature of biology and the plasticity of aging 11:10 - Homeostatic capacity defined 21:22 - Why we should (occasionally) eat junk food 22:19 - Regaining lost resilience 27:55 - The multidimensional nature of capacity building 34:10 - Psychological deconditioning 40:59 - Four-dimensional science and four-dimensional data 48:36 - Improve your health doing things you love 57:51 - How HRV is aiding studies of homeostatic capacity 1:01:12 - Conclusion

Getting distracted is a huge time stealer. You plan to accomplish one task, but along the way, you see something interesting while scrolling the Internet. By the time you look at the clock, you'll realize you've been scrolling mindlessly for hours. How can we remove these distractions that take us away from our plans and goals? In today's episode, Nir Eyal, the author of the book "Indistractable," joins us to talk about the motivation and strategies that can help us minimize and manage distractions from our lives. Nir is an active angel investor and is an expert in behavioural engineering, where he incorporates elements of behavioural science in software design to develop habit-forming products for businesses.  You'll surely be a changed person after this episode. So sit back and indulge in all the tips and tricks while tuning in to the show, and become inDISTRACTable! How To Control Your Attention And Choose Your Life (02:36) The world is going to become more distracting as technology becomes more pervasive and more persuasive. The bifurcation between people: Those who control their time, attention, and their lives, and those who allow their time and attention to be controlled by other people Focusing on our relationships is a critical macro skill in all facets of life. Even if we go on a digital detox, we'll still find ways to get distracted. We can only get the best out of tools and technology if we know how to use them correctly. What Is Distraction? (06:18) Etymology: Traction and distraction came from the same Latin root "trahere" which means to pull. They end in the same six letters, which is "action." A traction is any action that you take that pulls you towards things that you do with intent. The opposite of traction is distraction. It is anything that pulls you away from what you plan to do with intent. Anything can be a distraction or traction, whether we plan it or whether it's something we do impulsively. Something is going to eat up your time and attention unless you decide in advance how you want to spend your time. The Root Cause (08:27) The question is not "What do we do?" The question is "Why don't we do the things we know we should?" Homeostatic response: Everything we do is about the desire to escape discomfort. The root cause of all distractions is uncomfortable emotional states or "internal triggers." Motivation And Satisfaction (11:48) Hedonic adaptation: Even when something good or bad happens to us, we gravitate towards our baseline level of happiness. In some way, Nir says the self-help industry perpetuates this myth to our detriment by feeding the message that we're supposed to be happy all the time. Feeling bad is part of the human condition.  "If satisfaction and pleasure were permanent, there might be little incentive to continue seeking benefits or advancement." Four Strategies To Become Indistractable (15:33) The first step is to master the internal triggers, to understand what is driving us towards distraction. Second, make time for traction. Timeboxing or making an implementation intention is planning in advance what you're going to do and when you're going to do it. Third, hack back the external triggers. Lastly, prevent distractions with pacts or precommitments that we can make with ourselves or with other people to avoid temptation. Three Types Of Pact (20:40) Effort pact: A friction that prevents us from doing something we later regret Prize pact: Monetary disincentive to getting distracted Identity pact: Self-image can help us stay true to what we say we're going to do The Pattern Of Distraction: Liminal Moments (25:42) The three potential causes of distraction: planning problem, external trigger, or internal trigger. Distraction tricks you into thinking that what you're doing is what you intend to do. If you accomplish something, but it's not what you were initially planning to do for that given time, that is still a distraction. Managing Self-Talk (29:06) Utilize self-compassion. More self-compassionate people are much more likely to achieve long-term goals. Don't be a shamer. Negative self-talk stirs up more internal triggers. Don't be a blamer. Blamers blame something outside themselves. Be a claimer. Claim responsibility for all of your actions. You can't affect how you feel; you can only change how you respond to those situations. Resources Get a copy of Nir Eyal's book, "Indistractable: How To Control Your Attention And Choose Your Life." Indistractable Tools Nir's Free Schedule Maker Indistractable Supplementary Workbook Connect with Nir through his website—NirAndFar, and get all the tools and resources that can help you manage your time and attention. You can download a copy of my ebook 10 Key Traits of Top Business Leaders here. For more podcast episodes and other resources, visit my website at John Murphy International. Thanks for tuning in!