Podcasts about 16S

donaciones por PayPal a yolupor@hotmai.com Grupos de Telegram https://t.me/sanofuerteyfeliz https://t.me/ComparticiondeFluidosHumanos REDES SOCIALES Y PODCAST https://linktr.ee/sanofuertefeliz.com Libro Camino a la Extinción: Microbioma y Disbiosis - autor Sergio Vallejo https://amzn.eu/d/gHHUrqo Un banco internacional de heces para salvar a la humanidad de la extinción masiva https://www.larazon.es/salud/bienestar/banco-internacional-heces-salvar-humanidad_2023042664491be42a35640001e4eb8f.html https://es.wired.com/articulos/microbiota-vault-evitaria-extincion-masiva-del-humano https://pubmed.ncbi.nlm.nih.gov/31852769/ Estudio que asignó al azar a 165 pacientes con síndrome del intestino irritable a placebo, 30 g de FMT o 60 g de FMT en una proporción de 1:1:1. El material para FMT se obtuvo de un donante sano y bien caracterizado, se congeló y se administró a través de un gastroscopio. El resultado primario fue una reducción de los síntomas del SII a los 3 meses después del FMT. El resultado secundario fue una reducción en el índice de disbiosis y un cambio en el perfil bacteriano intestinal, analizado por secuenciación del gen 16S rRNA, 1 mes después de FMT. Resultados: Se produjeron respuestas en el 23,6 %, 76,9 % y 89,1 % de los pacientes que recibieron placebo, 30 g de FMT y 60 g de FMT, respectivamente. Estos estuvieron acompañados de mejoras significativas en la fatiga y la calidad de vida en los pacientes que recibieron FMT. Los perfiles bacterianos intestinales también cambiaron significativamente en los grupos que recibieron FMT. Los eventos adversos de FMT fueron síntomas gastrointestinales autolimitados leves. https://www.sciencedirect.com/science/article/abs/pii/S0016508520349374 En la semana 12, el 56 % de los pacientes que recibieron heces de donantes informaron una mejoría en ambos criterios de valoración primarios en comparación con el 26 % de los pacientes que recibieron placebo. Los pacientes que recibieron heces de donantes tuvieron mejoras significativas en el nivel de malestar. Las muestras fecales de los que respondieron tenían una mayor diversidad de microbiomas antes de la administración del material del donante que las muestras fecales de los que no respondieron y una composición inicial distinta . Después de un solo FMT, el 21 % de los pacientes que recibieron heces de donantes informaron efectos que duraron más de 1 año en comparación con el 5 % de los pacientes que recibieron heces de placebo. Un segundo FMT redujo los síntomas en el 67 % de los pacientes con una respuesta inicial a las heces del donante, pero no en los pacientes sin respuesta previa. Conclusiones En un ensayo aleatorizado de pacientes con SII refractario al tratamiento con hinchazón predominante, el FMT alivió los síntomas en comparación con el placebo (trasplante autólogo), aunque los efectos disminuyeron durante 1 año. Un segundo FMT restableció la respuesta de los pacientes con una respuesta previa. La respuesta se asoció con la composición de los microbiomas fecales antes del FMT; https://www.sciencedirect.com/science/article/pii/S0016508522006254 Se desconoce la eficacia a largo plazo y los posibles eventos adversos del trasplante de microbiota fecal para el síndrome del intestino irritable. Este estudio realizó un seguimiento de 3 años de los pacientes en nuestro ensayo clínico anterior para aclarar estos aspectos. Métodos Este estudio incluyó a 125 pacientes: 38 en un grupo de placebo, 42 que recibieron 30 g de heces de donante y 45 que recibieron 60 g de heces de donante. Las heces se administraron al duodeno. Los pacientes proporcionaron una muestra fecal y completaron 5 cuestionarios al inicio y a los 2 y 3 años después de FMT. Las bacterias fecales y el índice de disbiosis se analizaron utilizando la reacción en cadena de la polimerasa del gen del ARN ribosomal 16S , amplificación de ADN/hibridación de sonda que cubre las regiones V3 a V9. Resultados Las tasas de respuesta fueron del 26,3 %, 69,1 % y 77,8 % en los grupos de placebo, 30 g y 60 g, respectivamente, a los 2 años después del FMT, y del 27,0 %, 64,9 % y 71,8 %, respectivamente, a los 3 años después de FMT. Las tasas de respuesta fueron significativamente más altas en los grupos de 30 gy 60 g que en el grupo de placebo. Los pacientes en los grupos de 30 g y 60 g tenían significativamente menos síntomas de SII y fatiga, y una mejor calidad de vida tanto a los 2 como a los 3 años después del FMT. El índice de disbiosis disminuyó solo en los grupos de tratamiento activo a los 2 y 3 años después de FMT. Las señales fluorescentes de 10 bacterias tenían correlaciones significativas con los síntomas del SII y la fatiga después del FMT en los grupos de 30 g y 60 g. No se registraron eventos adversos a largo plazo.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.21.537874v1?rss=1 Authors: Ontiveros-Angel, P., Vega-Torres, J. D., Simon, T. B., Williams, V., Inostroza-Nives, Y., Alvarado-Crespo, N., Vega Gonzalez, Y., Pompolius, M., Katzka, W., Lou, J., Sharafeddin, F., De La Pena, I., Dong, T., Gupta, A., Viet, C. T., Febo, M., Obenaus, A., Figueroa, J. D. Abstract: Background: Childhood overweight/obesity is associated with the development of stress-related psychopathology. However, the pathways connecting childhood obesity to stress susceptibility remain poorly understood. Here, we used a systems biology approach to determine linkages underlying obesity-induced stress susceptibility. Methods: Sixty-two (62) adolescent Lewis rats (PND21) were fed for four weeks with a Western-like high-saturated fat diet (WD, 41% kcal from fat) or a matched control diet (CD, 13% kcal from fat). Subsequently, a group of rats (n = 32) was exposed to a well-established 31-day model of predator exposures and social instability (PSS). The effects of the WD and PSS were assessed with a comprehensive battery of behavioral tests, DTI (diffusion tensor imaging), NODDI (neurite orientation dispersion and density imaging), high throughput 16S ribosomal RNA gene sequencing for gut microbiome profiling, hippocampal microglia morphological and gene analysis, and gene methylation status of the stress marker, FKBP5. Parallel experiments were performed on human microglial cells (HMC3) to examine molecular mechanisms by which palmitic acid primes these cells to aberrant responses to cortisol. Results: Rats exposed to the WD and PSS exhibited deficits in sociability indices and increased fear and anxiety-like behaviors, food consumption, and body weight. WD and PSS interacted to alter indices of microstructural integrity within the hippocampal formation (subiculum) and subfields (CA1). Microbiome diversity and taxa distribution revealed that WD/PSS exposure caused significant shifts in the diversity of gut dominant bacteria and decreased the abundance of various members of the Firmicutes phylum, including Lachnospiracae NK4A136. Interestingly, the WD and PSS synergized to promote hippocampal microglia morphological and gene signatures implicated in neuroinflammation. These alterations were associated with changes in the microbiome, and in the expression and methylation status of the corticosterone receptor chaperone rat gene Fkbp5. HMC3 responses to cortisol were markedly disrupted after incubating cells in palmitate, shown by morphological changes and pro-inflammatory cytokine expression and release. Notably, these effects were partly mediated by the human FKBP5 gene. Conclusions: The combination of psychosocial stress and poor diet during adolescence has a deleterious synergistic impact on brain health. This study enhances our understanding of mechanisms and adaptations by which obesogenic environments shape the maturational trajectories of common neurobiological correlates of resilience. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Show notes   Principle of Nutrigenomics in Simple Terms You cannot out-supplement a crappy diet. 60% of determinants of health are about diet. 20% is intelligent supplementation. 20% are topicals applied from the outside, to biostimulate the skin. Sugar attaching to collagen in your skin causes fine lines and wrinkles.   Do's and Don'ts for the Skin The closest the food looks to its natural state, the better it is for you. The sad diet is devoid of nutrients, highly processed, and high in sugar and unhealthy oils. Sugar, fats, and dairy (for some people) mostly affect the skin. Essential fatty acids must be balanced. Too much omega 6, and too low omega 3 pushes you to inflammatory pathways. Many people are mineral and vitamin deficient, especially vitamin C, vitamin D, and zinc.   The Gut-Brain-Skin Axis There's chemical information shared in these three all the time. Fiber helps with dysbiosis. Fiber is the preferred food of good bacteria in the gut. Butyrate heals the gut, propionate affects the liver, and acetate goes out to the skin. If you want good skin, start with fiber.    Spore-based probiotics (Bacillus) and diet  The microbiome creates vitamin K, hormones, and other neurotransmitters that are essential for well-being. Gut-produced neurotransmitters don't cross the blood-brain barrier, but it wakes up afferent fibers of the vagus nerve going to the brain which sends information back down to the gut and spleen that regulates inflammation. Most of the probiotics that we take are going to get destroyed in the stomach so they don't really do that much. You need above 2 billion CFU to have much effect.   Nutrients from Plants: The job of the pigments in plants is to protect the plants from UV damage. So when you eat food that is high in these phytonutrients, you get the same skin protection.   When do you need deeper testing? It depends on what your objectives are. 70-80% of our patients will need treatments following the same principle: healing the gut, cutting down things that cause inflammation, and boosting the immune system. But to some people, these things wouldn't be enough, thus, the need for deeper testing. Some useful tests: whole genome sequencing vs 16S, GI tests, organic acids, and other metabolite tests, food sensitivity testing   Sleep, Stress and Skin You absolutely need at least 7 hours of sleep. During this critical time, your body can do its “housekeeping.” Breathing is the first aid for stress   Dr. Tager's Best Medicine: Being married to an amazing woman for 38 years who is as beautiful on the inside as she is on the outside.

Cuántas más válvulas mejor. ¿Seguro? ¿Sabes que ha habido motores de 2, 3, 4, 5 y hasta 8 válvulas por cilindro? ¿Sabes cómo funcionan? Y, sobre todo, ¿sabes porque son mejores? Hoy toca técnica y “Mesa hermética”. Si crees que este vídeo es de muy poco nivel para ti, no te equivoques: Hablaremos del sistema VTEC de Honda, de la distribución variable, de las válvulas rellenas de sodio, de la estructura de una culata, de la distribución desmodrómica… yo creo que habrá nivel… El primer 16v de la historia fue el Peugeot L76 del Gran Premio de 1912 que montaba una culata de 16 válvulas con la cual conseguía un rendimiento impresionante: casi 150 CV de un motor de 7,6 litros… Pero en los años 80, primero a la sombra del turbo, esta técnica comienza a desarrollarse, especialmente en coches de competición. Se habla de 16 válvulas, aunque en realidad habría que hablar de 4 válvulas por cilindro. Pero como la mayor parte de los motores son de 4 cilindros, pues es fácil 4x4=16 y ahí se acuñó el término. Y, como en el caso del turbo, muchos coches presumían de ello con el famoso cartelito de 16V o 16S en el caso de los modelos franceses, porque en francés “válvula” se dice “soupapes”, que suena casi igual que sopapo… También se veían cartelitos de 24V, 32V o 48V en motores de 6, 8 o 12 cilindros, pero la cifra “redonda” eran las 16V, sobre todo porque el mito, el VW Golf, utilizó esta tecnología para potenciar su motor, eludiendo el turbo que en su momento tenía cierta mala fama de “mal carácter”. Seamos honestos, una fama justa. Hoy día la tecnología multiválvulas coexiste con la sobrealimentación… pero ya casi nadie presume de ello… salvo Porsche, que se ha adueñado de la palabra Turbo, más bien diría del concepto: Todo el mundo sabe que todos los Porsche corren mucho, pero los Porsche Turbo, sea cual sea el modelo, más todavía. Incluso hay un Taycan eléctrico con apellido “Turbo”… Para saber por qué son mejores 16 válvulas que 8, hay que saber cómo funciona un motor. Seguro que todos lo sabéis, pero no está de más repasarlo y, sobre todo, centrarnos en la distribución, es decir, las válvulas y todo lo necesario para que funcionen: Arboles de levas, taqués, balancines y correa o cadena de distribución. ¡Vamos a ello! ¿Cómo funciona un motor? Sencillo: Metes aire en un cilindro, lo comprimes, lo inflamas con una chispa y luego expulsas los gases quemados para volver a comenzar. Pero hay detalles que tienes que ver en nuestra Mesa hermética. Os explico los 4 tiempos, pero para preguntaros una cosa: ¿Cómo conseguimos más potencia de un motor? Sólo hay dos vías: Uno, conseguir que la explosión o la combustión si es un Diesel sea lo más eficiente posible, un tema que trataremos en otra ocasión; y, dos, conseguir quemar más gasolina. Y para conseguir quemar más gasolina hay dos formas: Hacer el motor más grande, con cilindros más grandes cabe más gasolina o meter más aire y combustible en el motor. Como funcionan las válvulas. Las válvulas tienen forma de seta, cerradas deben ser completamente estacas y abiertas permitir la mejor salida o entrada de gases. Esto, la “alzada” y como se mueven las válvulas y otros sistemas de distribución lo vemos en nuestra “Mesa Hermética”. Y os cuento como la la distribución variable, el VTEC de Honda y algunas otras cosas. La “respiración” de un motor. Para conseguir que un motor respire mejor, es decir, tenga más fácil introducir el aire en los cilindros y luego sacarlo, cuantos más “agujeros” tenga la culata y más grandes, pues mejor. Lo normal en los comienzos del automóvil fue poner dos válvulas por cilindro, pero luego se vio que con más válvulas se aprovechaba mejor la superficie de la culata… pero esto lo vemos mejor en nuestra “Mesa hermética”. Lo suyo es que en el centro o lo más al centro posible, este la bujía y-o el inyector. Y tratar de aprovechar la superficie al máximo con culatas de 2, 3, 4 y 5 válvulas. Lo cinco válvulas son una excepción, pero no compensa su complejidad. Y decíamos que los cilindros y pistones son siempre redondos, bueno casi siempre, porque hubo una sonada excepción… la Honda NR500 y sus cilindros ovales de 8 válvulas. Las válvulas de admisión y escape no son iguales ni de tamaño ni de composición, porque las de escape trabajan a mayor temperatura. Por eso hay válvulas de escape huecas, ¿por qué? Porque va rellena de sodio para refrigerar… Algún día… … todos los coches se fabricarán así. Esta frase la podían haber dicho los diseñadores del Peugeot de 1912 o del Triumph Dolomite Sprint, el primer coche fabricado en serie con esta tecnología. Nadie la dijo… pero es la verdad. Prácticamente todos los motores modernos de un cierto nivel de prestaciones usan la tecnología multiválvulas y los taqués hidráulicos. Al principio los motores multiválvulas no tenían muchos bajos, pues que respirasen tan bien a alto régimen, impedía que lo hicieran bien a medios y bajos. Ya el motor de Opel a finales de los 80 se encargó de demostrar que no era así. Y ahora muchos usan tecnología multiválvulas y turbo, una tecnología al principio “rival” y luego amiga, porque para meter mucho aire en un motor, nada mejor que el motor tenga “agujeros grandes” y el aire vaya a presión. Conclusión. ¡Cuánto han progresado los motores de combustión interna! Una pena que, con la agenda 2030, este avance tecnológico se va a detener… nunca sabremos hasta dónde se podría haber llegado. Muchos diréis: “Seguro que eso mismo decían en su momento, cuando el motor de combustión sustituyo al de vapor”. Pues sí, pero ese cambio fue sobrevenido por las posibilidades de uno y otro motor, no por las normas de políticos que no saben mucho o nada de coches… no es lo mismo. Coche del día. Podría ser el Kadett, el primer 16V bueno de verdad y popular. Pero confieso tener una debilidad por el Triumph Dolomite Sprint que ya en 1973 usaba las 16 válvulas para obtener de sus motos de 2 litros 127 CV. Y además, era un coche precioso.

Visit our website to learn more about Inside Matters - https://insidematters.health/episodes/dr-richard-hansen   Watch the conversation on our YouTube channel - https://www.youtube.com/watch?v=nZma2Kh-umQ&ab_channel=InsideMattersPodcast   Dr Hansen is a Consultant Paediatric Gastroenterologist at the Royal Hospital for Children in Glasgow and an Honorary Clinical Associate Professor at the University of Glasgow. He is a principal investigator within the Bacteria, Immunology, Gastroenterology and ‘Omics (BINGO) group at the University which developed the CD-TREAT diet for Crohn's disease.   His clinical interests are inflammatory bowel disease (IBD), paediatric endoscopy and Helicobacter pylori. His main research interest is the gastrointestinal mucosal microbiota and its importance in paediatric disease, particularly IBD. He is especially interested in the molecular characterisation of the microbiota and its subsequent modification for the purposes of therapeutic effect via microbial therapeutics.   In this episode, we discuss treating IBD in children, using entirely liquid diets to reduce inflammation, and developing novel strategies that target the microbiome to treat IBD.   1:06 - Intro 1:56 - Interview Starts 2:27 – How to study the microbiome – analytical methods and study types 3:22 - How has microbiome science changed over the last 5 years? 5:13 -  What is Exclusive Enteral Nutrition (EEN)? 7:39 -  What is Inflammatory Bowel Disease (IBD)? 10:18 - Why are people getting IBD earlier in life? 14:54 - Is there different immunology between Crohn's disease and IBD? 17:07 - How has the perceived importance of the microbiome changed in IBD? 21:48 - How did all of this influence your PhD?  26:14 - Are we missing something with the current microbiome studies? 29:17 – The Bristol Stool Score 29:53 - Do you think that the microbiome drives inflammation in the gut? 34:01 – The Appendix  39:15 – Using the microbiome to predict IBD? 46:16 – Faecal microbiota transplantation (FMT) 49:03 – FMT in UC – studies published to date. 52:17 – Super donors in FMT 59:17 – The 16S gene 1:03:06 – The microbiome analytical toolkit 1:07:55 -  AI and large populations 1:09:19 – The implantation of machine learning 1:10:39 - Are clinicians trained in how to use AI 1:13:01 - Discussion on the application of FMT in paediatric populations. 1:14:22 - Infants, diet and gut health. 1:18:01 – Further discussion on FMT in paediatric populations. 1:20:44 - FMT donor screening processes.  1:22:21 – Donor selection for paediatric FMT. 1:26:30 – Potential risks associated with FMT.  1:29:19 - Can FMT or other microbial therapeutics replace immune system dampening therapies? 1:31:13 - When IBD is at its worst, what is it like? 1:36:01 - What do we do about the EEN diet and Crohn's disease? 1:38:20 - Which element of EEN is driving the positive effects in Crohn's? 1:42:27 - How do we create a less socially restrictive diet than EEN but keep the benefits? 1:44:44 - What is the ultimate aim of CDTreat?  1:47:19 - What is the relative importance of bacteria versus other components of the microbiome?   Key takeaways from this episode:   There has been an explosion of interest in the microbiome in recent times as it is becoming it easier and easier to analyse the microbiome through analytical methods that do not involve traditional culture techniques - which are labour intensive and relatively slow.    The field of microbial therapeutics is still in its infancy. There are many ongoing clinical trials into new ideas. Richard is hopeful that these trials will result in new treatment options for patients.    Inflammatory bowel disease is a chronic (long term) condition characterised by inflammation in the gut. There are two main forms of IBD, Crohn's disease and Ulcerative Colitis. Crohn's disease can affect any part of the intestinal tract, from mouth to anus. UC only affects the last part of the gut - the colon.    There is a microbiome that lives within the lumen of the gut and on the surface of the intestine (mucosa). Richard's analogy for this relationship is that they are like a beach and an ocean – they are different but inextricably linked.    The incidence (when the disease first starts) of IBD across the population seems to be occurring earlier and earlier in life. At the start of Richard's career it was rare to see a patient below the age of five presenting to hospital with symptoms, now days it is becoming more common. The environment and its impact on the microbiome may be the key driver for this. There are clear changes that are observed in microbiome studies in patients with reduced IBD, namely: reductions in diversity (how many bacteria are there and how evenly are they spread), and increases / decreases in particular bacteria.    Exclusive internal nutrition (EEN) is a term used to describe a 6-8 week course of an entirely liquid diet. The data suggests 4 out of 5 paediatric patients suffering from Crohn's disease enter remission (where the gut is healed and there is no active disease causing symptoms) after a course of EEN. It thought that the longer the course of EEN the more effective it is.    EEN is becoming much more popular in adult therapy, however its uptake is limited due to social constraints. Richard and a team working at the University of Glasgow are developing a less socially restrictive diet that mimics the effects of EEN. The programme of work is called CD-treat.    Intestinal microbiota transfer (IMT) involves the movement of microorganisms from one person into another with the intention of treating a disease. Six randomised controlled trials have been published in UC so far, with a definite signal towards IMT being effective. Richard is hopeful that these studies will pave the way for new treatment options in IBD. 

Episode 96:This week we're continuing Russia in Revolution An Empire in Crisis 1890 - 1928 by S. A. Smith[Part 1]Introduction[Part 2-5]1. Roots of Revolution, 1880s–1905[Part 6-7]2. From Reform to War, 1906-1917Prospects for ReformOn the Eve of WarFirst World War[Part 8 - This Week]2. From Reform to War, 1906–1917Politics and the Economy - 0:40[Part 9 - 11?]3. From February to October 1917[Part 12 - 15?]4. Civil War and Bolshevik Power[Part 16 - 18?]5. War Communism[Part 19 - 21?]6. The New Economic Policy: Politics and the Economy[Part 22 - 25?]7. The New Economic Policy: Society and Culture[Part 26?]ConclusionFootnotes:91) 1:36Kolonitskii, Tragicheskaia erotika, 396.92) 2:17Hubertus Jahn, Patriotic Culture in Russia during World War I (Ithaca, NY: Cornell University Press, 1995).93) 3:03Lohr, Nationalizing the Russian Empire.94) 3:28Jahn, Patriotic Culture.95) 8:51Gatrell, Russia's First World War, 42–3.96) 9:01E. N. Burdzhalov, Russia's Second Revolution: The February 1917 Uprising in Petrograd, trans. and ed. Donald J. Raleigh (Bloomington: Indiana University Press, 1987), 60.97) 9:58Porshneva, Mentalitet, 191.98) 10:28Lewis Siegelbaum, The Politics of Industrial Mobilization in Russia, 1914–1917: A Study of the War Industries Committees (Basingstoke: Macmillan, 1983), 165.99) 10:42David R. Jones, ‘Imperial Russia's Forces at War', in A. R. Millett and W. Murray (eds), Military Effectiveness, vol. 1: The First World War (Boston: Unwyn Hyman, 1988), 249–328 (260).100) 11:05Gatrell, Russia's First World War, 45.101) 11:34Andrei Markevich and Mark Harrison, ‘Great War, Civil War, and Recovery: Russia's National Income, 1913–1928', Journal of Economic History, 71:3 (2011), 672–703.102) 12:35Gatrell, ‘Tsarist Russia at War', 693.103) 12:51Jones, ‘Imperial Russia's Forces', 271.104) 13:08Gatrell, Russia's First World War, 126.105) 13:27Gatrell, Russia's First World War, 136.106) 14:07Jones, ‘Imperial Russia's Forces', 260.107) 14:14Gatrell, ‘Poor Russia', 247.108) 14:26Yanni Kotsonis, States of Obligation: Taxes and Citizenship in the Russian Empire and Early Soviet Republic (Toronto: University of Toronto Press, 2014).109) 15:06Steven G. Marks, ‘War Finance (Russian Empire)', .110) 16:22Marks, ‘War Finance'.111) 17:31M. D. Karpachev, ‘Krizis prodovol'stvennogo snabzheniia v gody pervoi mirovoi voiny (po materialam Voronezhskoi gubernii)', Rossiiskaia istoriiia, 3 (2011), 66–81 (67).112) 19:17M. V. Os'kin, ‘Prodovol'stvennaia politika Rossii nakanune fevral'ia 1917 god: poisk vykhoda iz krizisa', Rossiiskaia istoriia, 3 (2001), 53–66 (55).113) 20:39S. G. Wheatcroft, ‘Agriculture', in Davies (ed.), From Tsarism, 93.114) 21:20I. I. Krott, ‘Sel'skoe khoziaistvo zapadnoi Sibiri, 1914–17gg.', Voprosy istorii, 11 (2011), 103–18.115) 23:01N. F. Ivantsova, Zapadno-sibirskoe krest'ianstvo v 1917—pervoi polovine 1918gg. (Moscow: Prometei, 1993), 71, 75.116) 23:39Mark Baker, ‘Rampaging Soldatki, Cowering Police, Bazaar Riots and Moral Economy: The Social Impact of the Great War in Kharkiv Province', Canadian-American Slavic Studies, 35: 2–3 (2001), 137–55 (141).117) 24:06D. V. Kovalev, Agrarnye preobrazovaniia i krest'ianstvo stolichnogo regiona v pervoi chetverti XX veka (Moscow: Moskovskii pedagogicheskiki gos. Universitet, 2004), 123.118) 24:38Peter Waldron, The End of Imperial Russia, 1855–1917 (Basingstoke: Palgrave, 1997) 155. Tiutukhin states that there were about 800 rural disturbances between July 1914 and March 1917. S. V. Tiutukhin, ‘Pervaia mirovaia voina i revoliutsionnyi protsess v Rossii', in V. L. Mal'kov (ed.), Pervaia mirovaia voina: prolog XX veka (Moscow: Nauka, 1998), 236–49 (245).119) 24:45Shkaratan, Problemy, 219.120) 25:31Porshneva, Mentalitet, 165.121) 26:51Porshneva, Mentalitet, 201.122) 27:34A. S. Sidorov (ed.), Revoliutsionnoe dvizhenie posle sverzheniia samoderzhaviia (27 fevralia–14 aprelia 1917g.) (Moscow: RAN, 1957), 421.123) 28:05Iu. I. Kir'ianov, ‘Massovye vystupleniia na pochve dogorovizny v Rossii (1914–fevral' 1917g.', Otechestvennaia istoriia, 3 (1993), 3–18 (4).124) 28:28Kir'ianov, ‘Massovye', 8.125) 28:41Barbara Alpern Engel, ‘Not by Bread Alone: Subsistence Riots in Russia during World War One', Journal of Modern History, 69 (1997), 696–721.126) 29:03Engel, Women in Russiā, 133.127) 29:50Iu. I. Kir'ianov, Sotsial'no-politicheskii protest rabochikh Rossii v gody Pervoi mirovoi voiny. Iiul' 1914–fevral' 1917 gg. (Moscow: RAN, 2005).128) 30:49Porshneva, Mentalitet, 202.129) 31:02Iu. I. Korablev (ed.), Rabochee dvizhenie v Petrograde v 1912–1917gg. (Leningrad: Lenizdat, 1958), 484.130) 31:30Shkaratan, Problemy, 198, 210.131) 32:08McKean, St Petersburg, 394.132) 32:53Kir'ianov, Sotsial'no-politicheskii protest, 185.133) 33:12Michael Melancon, The Socialist Revolutionaries and the Russian Anti-War Movement, 1914–1917 (Columbus, OH: Ohio State University Press, 1990), 113–14.134) 34:16S. V. Tiutukhin, Men'shevizm: stranitsy istorii (Moscow: ROSSPEN, 2002), 307.135) 36:47Roger W. Pethybridge, Witnesses to the Russian Revolution (London: Allen Unwin, 1964), 76, 78.

In dieser Folge erzählt Lorenz die Geschichte, warum Jonathan Scheiman beim Boston-Marathon 2015 Kot der Läufer:innen einsammelt - wohlgemerkt vor und nach statt während des Rennens. Dabei lernen wir die Unterschiede zwischen 16S- und Shotgun-Sequenzierung kennen, den Cousin von Butyrat, und warum Probiotika von führenden Wissenschaftler:innen zurecht nicht empfohlen werden. Künstliche Intelligenz funktioniert für die Vorhersage von Sportverletzungen ohne den Einbezug der Darmbakterien nicht sonderlich gut, aber woran kann man die Profile von unseriösen Wissenschaftler:innen eigentlich erkennen? Das erfahrt ihr in der Folge genauso, wie die Körperzellen, die Jasmin & Lorenz am liebsten wären. Wir wünschen ein großartiges Hörvergnügen! >> Bugtales auf Steady unterstützen! Material Eine gute Quelle für diese Folge war Spektrum GESUNDHEIT 5.21 (u.a. mit einem Interview mit Alessio Rossi): https://www.spektrum.de/pdf/spektrum-gesundheit-5-2021/1862401 Ein Ausblick im Journal Nature zum Thema Darmbakterien & Athletik: https://www.nature.com/articles/d41586-021-00821-6 Ein Ausblick im Journal Nature zum Thema Vorhersagen von Verletzungen: https://www.nature.com/articles/d41586-021-00818-1 Eine Notiz im Laborjournal zu den Fußball-Genen: https://www.laborjournal.de/editorials/2140.php

Deux amis qui partent en vacances en petit roadster et qui dévient leur route à cause d'un bus. On s'est tous amusés, enfants, à faire des signes aux passants dans un bus. Dingo est allé encore plus loin avec ces trois jeunes femmes très légèrement vêtues à l'arrière de l'autocar. A retrouver sur https://www.histo-auto.com/fr/actualite/422/histoire-de-dingo-les-vacances-en-bus

In this second part of our history of metagenomics with Matthew Schechter, we start with a description of what a metagenome contains and how you analyze this type of data. Matt explains a few high level concepts such as metagenome assembly, metagenomic assembled genomes, contigs, contig binning, and genome completeness. Matt explains how metagenomics can help answer previously unanswered questions and even generate new hypotheses like in the example of the Candidate Phyla Radiation. Matt further explains how metagenomics is unbiased when compared to 16S sequencing and what his vision is for “Metagenomics 3.0.” Further topics discussed include pangenomics, further ways metagenomics can generate new hypotheses, and metapangenomics. Read Matt's full article of the history of metagenomics at https://merenlab.org/2020/07/27/history-of-metagenomics/

In this episode we begin our history of metagenomics with Matthew Schechter. Beginning with highlights like the initial ability to see microbes with a microscope and growing microbial colonies, we work our way through the history of metagenomics leading to modern day sequencing. Matt describes a discrepancy between culturing and what is present in a sample, and how sequencing began to overcome this discrepancy. Matt covers what 16S sequencing is and where it fits in the history of metagenomics. We end with a discussion of a seminal work on reconstructing genomes from sequenced metagenomes. Read Matt's full article of the history of metagenomics at https://merenlab.org/2020/07/27/history-of-metagenomics/

We're so excited to be bringing you today's episode of the SuperFeast podcast; Mason sits down for a chat with the super knowledgable Dr. Jason Hawrelak and delves into the microbiome, gut dysbiosis, disease and, pre-and probiotics. Microbiome health is quite a ubiquitous topic these days and with good reason. Your microbiome is essentially a portal to longevity, and if you want to invest in your future, then it's wise to invest in the health of your gut ecosystem. Dr. Jason Hawrelak is a naturopath (over 21 years of clinical experience) and educator with a passion for gastrointestinal health, the GIT microbiota, pre-and probiotics, and a wealth of knowledge in his field. This episode is full of essential goodness on the gut/vaginal/breast milk microbiome and the importance of the gut ecosystem to all other disease states prevalent in the western world. Dr. Hawrelak touches on the exciting advancements, tools and, technologies that allow us to shift the imbalances in our microbiome, as long as we are willing to make the necessary changes. Make sure you tune in for this one!   Mason and Dr. Jason discuss: What your microbiome says about your health.  Bacterial DNA testing. Stool analysis. Chronic Western diseases and the dysbiotic gut. Probiotics and prebiotics for better health and immunity. Which foods have the best sources of prebiotics? What Dr. Hawrelak recommends for a healthier gut ecosystem. Leaky gut and emulsifiers. Why a diverse diet is essential for a healthy microbiome. Microbiome modification. Depression, anxiety, Alzheimer's, and gut dysbiosis. Optimising the gut ecosystem pre-conception and during pregnancy. The Vaginal microbiome and causes of dysbiosis. The breast milk microbiome. The link between the gut and breast milk microbiota. Who is Dr. Jason Hawrelak? Dr. Jason Hawrelak is a researcher, educator, and naturopath with over 21 years’ clinical experience. He did his PhD examining the capacity of probiotics, prebiotics, and herbal medicines to modify the gastrointestinal tract microbiota and teaches widely, both in Australia and internationally, on these topics. He has published extensively (including 20 textbook chapters) in this field. Dr. Hawrelak is on the Medical Nutrition Council of the American Society for Nutrition and is a Fellow of both the American College of Nutrition and the Naturopaths and Herbalists Association of Australia. He is currently the Senior Lecturer in Complementary and Alternative Medicines at the University of Tasmania’s School of Medicine (Hobart, Tasmania), where he coordinates the Evidence-based Complementary Medicine programmes. He also teaches natural approaches to Gastroenterology within the University of Western States Master of Science in Human Nutrition and Functional Medicine program (Portland, Oregon). Additionally, Dr. Hawrelak is Chief Research Officer at ProbioticAdvisor.com, a searchable database that enables easy, evidence-based prescribing of probiotic products and online resources for clinicians and health-conscious members of the public to learn more about the human microbiome and how they can positively influence these ecosystems.   Resources: ProbioticAdvisor.com Probiotic Advisor Courses Probiotic Advisor Facebook    Q: How Can I Support The SuperFeast Podcast? A: Tell all your friends and family and share online! We’d also love it if you could subscribe and review this podcast on iTunes. Or  check us out on Stitcher, CastBox, iHeart RADIO:)! Plus  we're on Spotify!   Check Out The Transcript Here:   Mason: (00:00) Hey, Jason.   Jason Hawrelak: (00:01) Hey, Mason. How are you going?   Mason: (00:03) Very, very good. It's been great meeting you. I feel like we've talked about your work and you so much on this podcast. It's just so great to tune in. We're really grateful. Everyone loves Dan Sipple, one of your students here on the podcast, and we're really grateful for him opening us up to your work. It's been nice for me to see, because I knew him when I was just at the markets coming up myself before he was a naturopath, so we've had chats for me not in the practitioner realm, kind of going in and out of health circles, him kind of more from a practitioner angle. We've had conversations about all the different types of diets and everything. It's been nice to see him land in one element of his practise here in what we're going to talk today and microbiome and this kind of analysis. It's kind of been, as we were talking about a little bit beforehand, it's nice to not just be hoping that your diet is as good as you think it is.   Jason Hawrelak: (01:09) Yeah. Well, I think we're lucky now that we can more easily assess at least the impact of the diet on the microbiome. That is accessible now, and listen, it wasn't very well accessible 10, 15, 20 years ago. I've been a clinician for 21 years, and the stool tests we had access to 20 years ago gave us a very tiny snapshot of the ecosystem. We know the average person might have 160 species present, and the old stool analysis would tell you four of those and engaged your health on what those four populations were like, which never felt quite right. I think we skip forward in time, we're like, "No, that was not close to it." I know it's the best we had at the time and we're always working with the best tools we have, and again, you skip forward 20 years from now we'll have amazing tools and quick turnaround time for stool tests, et cetera, but I think now we just have that capacity to really see the individual nuanced effect of dietary factors, lifestyle factors, on the microbiome.   Mason: (02:13) Was it like all those years ago, even when you had the four populations you were able to test, did you have the instinct that, all right, well, the gut for you is the foundation? Were you just like, "This is the best we've got and this is what I'm going to have to work with," because this is the foundation of your practise and your treatment?   Jason Hawrelak: (02:30) Yeah. I'm lucky that I did my naturopathy training, I think it started in 1996, and sort of my final fourth year was 1999, and then I moved on to doing my honours degree looking at the gut microbiota or dysbiosis of the ecosystem in irritable bowel syndrome and how we could alter that with prebiotics, probiotics, and herbs. So I went from being a student to when I recently graduated new practitioner seeing patients, but at the same time I was reading research studies that were talking about how to analyse the gut ecosystem, and I could see then that the tools that we had access to were very limited even to the gold standard then.   Jason Hawrelak: (03:06) The gold standard then could find 50, 60 different species in the gut, but it was immensely expensive and not practical in the real world. You had to get stool samples from people and freeze them at minus 40 degrees under a nitrogen atmosphere within moments of them being voided, and then culture that in the lab which is a painstaking, costly experience. So yeah, they can do that in research settings, but it just wasn't possible in clinical reality, so we were stuck with the lactobacilli, E. coli, tetracocci, and bifidobacteria. I think those are the four things they could tell us about, which we know that most of those are tiny players in the healthy gut, but it was what we had access to.   Jason Hawrelak: (03:48) There were some other function markers on those tests, the old comprehensive digestive stool analysis that could help us fill in some of those gaps around short-chain fatty acid production, some of the fat suggestive markers. That would help get us get a feel for someone's gut functionality and gut health, but the ecosystem component was just so tiny, and really, researchers knew it was a tiny amount. Even with what we could do with that recurring gold standard of culturing was what we knew was a tiny amount of what was actually there. There was hints of that.   Jason Hawrelak: (04:20) You look back at that research and you could have people on a mostly meat diet and a vegan diet and you'd look at their ecosystem via culturing and it was no different. It just didn't make sense. It's like, "How the hell could that diet and this diet create the same ecosystem, or changing the diet make no difference to the ecosystem?" That's really the state we were at in the '80s and '90s, is that the technology we were using was just so insensitive we couldn't see these things.   Jason Hawrelak: (04:49) But there was one study that was using a raw food vegan diet to treat rheumatoid arthritis, I think in the early 2000s, that shared a dramatic improvement in rheumatoid arthritis, huge, but the culturing showed no difference in the ecosystem. But they used a different technique which never really caught on and really wasn't great, but it was looking at fatty acid profiles and the cell membrane of cells from memory, and they showed it was dramatically different. And they said, "Something is changing in the gut. We can see it, but this technology [inaudible 00:05:23] is too insensitive. We can't work out what's going on. We really need to develop new techniques. We need to start moving into DNA," and that's where we shifted in the early 2000s is that shift using bacterial DNA as a way of looking at what's there.   Jason Hawrelak: (05:37) That's why everyone is talking about microbiomes now and we weren't so much 20 years ago is because technology has advanced that we can see. We can see the impact of diet. We can see the impact of medications. We can see the impact of environmental chemicals, et cetera, on the ecosystem that we just couldn't see before.   Mason: (05:53) Where do you think we're at in terms of the... We just opened a can of worms with this DNA testing model in terms of just how deep we're going to be able to go with diagnosis and treatment protocols. Are we just scratching the surface, or do you think it's pretty flushed out at this point?   Jason Hawrelak: (06:11) That would depend who you ask and their knowledge of the field. And as someone that's spent 21 years researching this area now I'm pretty comfortable navigating through it, but if you find someone that's just come across the microbiome in the last two years and never heard of it before and then they started reading stuff, they're like, "Whoa." They're looking at it at a different viewpoint, and they might feel that it's insufficient knowledge to make dietary changes or recommendations based on the level of science that there currently is. And I think that yes, science is evolving, yes, we're learning more all the time, but we still know a fair bit. Listen, there's still species in the gut we have no idea what they do. Some of them haven't been named yet. So yes, we know a certain amount and there's a lot more we don't know than what we do know, but as someone that's been in the field to watch it change over that 20 years and being able to work with patients and putting into practise recommendations that change that and see the benefits, I'm pretty confident in that area.   Jason Hawrelak: (07:09) I just look forward to, essentially, probably two things with testing. Perhaps seeing a bit more functionality looking at the genetics, the microbes that are there, but two, just quicker turnaround. At the moment you might be looking at four to six weeks if you're lucky to see what's going... When you sample it, send it off to a lab and get a result back. What I would love is when you can do this on a semi daily basis where you can look at it and even a couple days later you can go, "Okay, what's it like?" You can give a course of antibiotics and then get a result of how disturbed that ecosystem is two days later, not six weeks later, because what are you going to do six weeks later? It's too late to individualise treatment for that patient based on what it was like. You'll still get it to work, but you know what I mean. You can't see the acute damage caused by an event whether that's dietary or medication induced.   Mason: (08:01) That's something I was really thinking about. I haven't really been comfortable doing any tests with naturopaths whether they're mates or not, other than doing heavy metal analysis, looking at long term longevity marks especially, until this came along and it was a really easy, sensible test for me to go forward with. It was based on markers that weren't swinging or weren't volatile. It was something I knew I could invest in long term, and if there was something chronic there, because in my mind it's a long term kind of plan test, and I was looking at all the chronic issues and yeah, it really makes sense in those kinds of treatments settings.   Mason: (08:46) But then I'm looking at just how powerful this could be with acute bacterial and fungal, parasite, viral infections, so on and so forth, that kind of gets me a little bit excited. If I was a practitioner, or we have a huge community and we're able to expose them to awesome practitioners like yourself, it makes me very excited thinking about that kind of progression where again, not taking swings in the dark. You're actually seeing immediately what's happening with the impact of a herbal protocol or an antibiotic protocol. That's really exciting. I've never seen such a potential of like... I'm optimistic, but it would be interesting to hear your two cents on where we are with this information being integrated into the modern medical system. That feels like that's a sensible bridge. That doesn't feel like pie in the sky, like that would be too much to ask. So two questions, the acute, and then that integration. Do you see this being adopted at any point?   Jason Hawrelak: (09:56) Listen, it's happening slowly. And again, back to 20 years when I first started digging into it, there were naturopaths, nutritionists, integrative GPs talking about gut health, dysbiosis, leaky gut, as core contributors to chronic disease, but it was not discussed in the wider medical community. The mainstream media wasn't talking about these issues, but fast forward 15, 20 years, people talking about gut microbiome, people talking about dysbiosis, people talking about leaky gut, so I think that those concepts have reached out to the broader community definitely heaps more in that time period, and I think there's a lot more clinicians aware of it at least to some degree and peripheral degree.   Jason Hawrelak: (10:35) I still don't think that they're core aspects of typical medical training, for example. I think there's probably some discussion now in some medical courses around microbiome, what it is, why it's a little bit important, but just nutrition might take up eight hours of lectures in their five years of clinical study. They do more than that, but you've gone there for five years. The microbiome might take two hours of that, and this is really such a pivotal thing.   Jason Hawrelak: (11:03) What I find fascinating is the microbiome sceptics who say, "I was really sceptical and then I started reading, and now I'm a convert," because they've actually looked into it and spent the time, and I think that sort of proves that there's so much evidence that's built up over time that is enough to get some of these more sceptical people excited if they take the time to look at it. So there's still people that haven't and who are naturally sceptical of anything that feels faddy to them, which for some people this does. For some of us that have been here for 20 years it doesn't feel remotely like a fad. This has been fascinating to watch the growth of that.   Jason Hawrelak: (11:39) There used to be a handful of research teams around the world looking at microbiota health. Now there are thousands, and the number of papers published every year is just huge, not even just on probiotics or prebiotics but just the importance of gut ecosystem health to all these other disease states and how dysbiosis causes or contributes to all these different disease states. I think that's absolutely fascinating, making these broader connections which allow us as clinicians far more tools to treat the cause, other than going, "Okay, I can give you St. John's wort or saffron to treat your depression." Certainly better than giving an SSRI pharmaceutical, for sure. Side effect profile much better. Long-term use not an issue. However, it's still not necessarily getting to the cause, and if that cause is increased permeability and a dysbiotic gut ecosystem, which it often is, it's good to know that we can test for those things and go, "Okay, what's your imbalance like?"   Jason Hawrelak: (12:35) I think that's the other aspect too, is that everyone's ecosystem is so unique, that there are certain patterns we can see associated with disease states, but that doesn't always mean that this individual patient with that disease label is going to fit that pattern that's been found in that research, and that's what I love testing for, going, "Okay, do you? Maybe you do. Great. Maybe you don't, and then all right, we know exactly where it's at. How can we individualise tweaks, make some changes to your diet with prebiotics, probiotics, supplements, to actually get that ecosystem into a healthier state?" Which, to me, probably brings the point of how do you define a healthier state, and to me there's a few things.   Jason Hawrelak: (13:13) One is diversity. You want it to be diverse just like you want the rainforest and coral reef to be diverse. You don't want a forest to be 80% one tree species and then 100 species make up 20%, because it's going to look like a plantation not like a forest. You want it to be a wide number of species present, so species rich and a nice spread, and then you want high levels of beneficial bacteria, low levels of pathobionts and pathogens. Pathobionts are species that are fine in normal amounts, could even be quite helpful, but when they get too high they cause harm, so we want to keep them down to low levels, and that's how we define that and how do we achieve that balance. And I think once you look at their ecosystem, we can generally work out, if you know what you're doing, how to actually change that.   Mason: (14:01) That's what I like as well. I think it's been four months since I had my analysis done and it was super interesting. We did it as a family, and there's a couple of things I'm going to try and fit... As I normally do when I'm in conversations that excite me, I'm going to try to fit too much in at one time, but whatever.   Jason Hawrelak: (14:19) I hear you.   Mason: (14:23) The biggest thing we've talked a lot about, you brought up fads. Most people think this is maybe going to be a fad and then they realise it's not a fad once they start doing a bit of research.   Jason Hawrelak: (14:33) Yeah. That's right.   Mason: (14:36) And in the health world it's been one of those things that's been bandied around for so long like, "You've got to work on your microbiome. How do you do that?" And in the beginning it's like we're just going off kind of body ecology, not to say that these were bad movements, but it's like, "Oh, just cut some sugars, more vegetables, a bit of diversity," and everyone is like, "Oh okay, cool." And then it's like, "All right, but this is going on now. I'm a bit anxious." Skin issues, it's like, "All right, we're going to have to look at the gut," and it became one of those things where everyone is like, "Oh my god. I'm sick of being told it's the gut," and I felt like that was warranted to an extent when you're busy and you don't have anything measurable to know when you are healthy within your gut. Not just go on the raw food vegan diet as you were saying and get some really good lessening of symptoms but then not knowing what's going on long-term and then all of a sudden cracks start showing potentially if it's an extreme diet.   Mason: (15:34) And then being able to finally, for someone who's busy... I think I always think of a mom I knew. She's my prototype when I started my business. I was telling her to go and harvest her own turkey tail in Lane Cove National Park and she's like, "Hey, mate, I've got four kids," and two of her kids were autistic and she works full time, and she's just like, "I don't have bloody time. Give me my mushroom powder." I was like, "All right, I can see the relevance of this business." All of a sudden the, "Well, how is your gut? How does your gut look?" And you're like, "I think it's healthy." Now, bang. You can go and actually, as you said, get an individual approach of what's going on within the diversity and actually start getting a definition of what is healthy. Okay, cool. We can start to kind of actually look at that rather than going, "Trust me."   Mason: (16:22) We talk about a lot of extreme diets here. I'm an extremist, that's why I kind of have a sore spot for talking about them. I throw myself at them and then talk smack at extreme diets, but me and Dan quite often talk how interesting it would be if everyone would present their microbiome profile after they've been on a diet for-   Jason Hawrelak: (16:45) Yeah. That would be fascinating. I agree. For me, sometimes the people who are doing really extreme ones like carnivore diets, I think you can't really assess the impact of that without looking at microbiome, and I think it's skipping a giant component of the potential negative consequences if you're not looking at that, the short and long-term. That's a good example.   Mason: (17:12) Or at least integrate it as a piece of the puzzle. When I was extreme, if someone asked me to test my microbiome I'd be scared because I would have felt like I was about to get called out and possibly I'm going to get shown something that I don't want to see. I get it. I'm empathetic towards folks who are like, "Cool, let's just look at ATP markers," or whatever it is. Metabolic markers or muscle mass or some hormonal... Cherry pick. At least this being slid in there, but it's just nice that's available now instead of four to six weeks. But even then, that's fine if you've got a long-term intention, right?   Jason Hawrelak: (17:55) Yeah, and then the price I think has come down too. Again, if you skip back to early 2000s the best tests we could do was $800 per test and that looked at 12 species of bacteria instead of four. It was like a big step up and used a bit of DNA marker for that, so it's like, "Yes, okay. Evolve with technology, but $800 per patient is like... How often do you do that? How often is that justified? Is it justified at all?" As much as I'd like to see what's going on even in that limited realm, it's like, "That's a lot of money," whereas now, there's a few different types of DNA-based techniques and some of the 16S technique ones are around the 100 US dollar mark per test, and sometimes you get them on special where they can be 50 bucks or something like that, so it means you can really do frequent testing.   Jason Hawrelak: (18:52) To me, that was a game changer when the 16S test came online. It was like, "Oh, gosh. Now we can look at testing these things for $100 a pop and it means we can do repeated tests." Now it's like, "Let's give you stuff for two months and we test, another two months, we test, and you can see dramatic changes from that and see whether your protocols are working or not." And I think obviously this objective is are they feeling better and their disease is getting better. That's the most important thing, for sure. You've got that regardless, but you see that objective change.   Mason: (19:26) [crosstalk 00:19:26] You forget that the symptoms have alleviated to be able to see it.   Jason Hawrelak: (19:30) That's a very good point. It's true, because people, sometimes they're getting better on the slow trajectory and then you look back going... This is where it's nice if you have measures or ways. You could ask them their energy out of 10, and when they first came to see you it's two out of 10. Now it's like seven and they've already forgotten that it used to be two out of 10 because it's taken four months to get there and they just kind of get used to that new normal. But I do think having an objective diet is fantastic and to really gauge treatment effectiveness, because people are unique and their ecosystems are unique, and whilst I'm using research like clinical trial evidence to guide my decision making around what prebiotics to use and what dose et cetera, as well as my clinical experience, it's like someone may... Most people respond as you expect them to and some people respond a bit differently to that, and that's where having that feedback makes a big difference.   Jason Hawrelak: (20:21) I would say I've been working more with autistic kids the last couple of years, and their ecosystems are particularly changeable and flexible and exaggerated responses, so it's been a fascinating learning working with this population. If we weren't doing pre-imposed testing you'd have bloody no idea what's going on, but where you can have a species go from 0.06% of an ecosystem and then four weeks later be 80%. It's just changes that are unheard of in a neurotypical population, but in this population it happens, and it's important that you know that as a clinician and important that you know how to adjust dosages and [inaudible 00:21:03] and things, again, which comes from testing and having the access to these tests at a more affordable price than before.   Jason Hawrelak: (21:10) Some of the other molecular tests or DNA-based test we use are a bit more expensive like shotgun metagenomic sequencing which is more around the $300, $400 mark, so that's another notch up, and again, I've got to consider whether the additional data I get is worth the added cost or whether getting three tests for the same price of the inferior 16S tests would be a better option for this patient.   Mason: (21:40) Lots of questions about that part of the population responding, but I feel like I'm going to open up... That's going to be a big conversation in terms of what's going on there if I go there.   Jason Hawrelak: (21:49) Yeah, it could be.   Mason: (21:55) Straight away, you've brought up depression, and everyone is now at this point of... I'm sure 20 years ago when you talked about a gut-brain connection it's not like today where everyone is just bandying that out there, talking about that access, which is amazing, the gut-brain microbiota. So naturally, I can see your work is with acute and chronic gastrointestinal conditions, but then it just seems like you wouldn't have ever been able to not work in mental health at the same time.   Jason Hawrelak: (22:29) No, and because of that full on link, I see patients with chronic fatigue and patients with depression, anxiety, kids on the spectrum, some of which would have gut symptoms or obvious gut dysfunction and others do not, and we're just looking at how does their gut health or their microbiome composition affect their disease symptoms and how can we then modify it afterwards? So I think that microbiome composition, it's huge for all of those different things that we've just mentioned and more, and really, I don't see it that far in the future where doing a microbiome assessment will be standard because you look at that growing list of diseases associated with dysbiosis, it is growing.   Jason Hawrelak: (23:16) On a monthly basis a new study find a new link between a new disease and dysbiosis, so I don't think it's too far away when this will be part of your annual general checkup. I'd like to see it more common than that, but there'll be awareness around this with all these new disease states and awareness of, "Okay, well, maybe if this practitioner doesn't know how to modify it they can refer to somebody who does," and to people who specialise in microbiome modification to work alongside people who might be prescribing the pharmaceutical that that person might need or the people who are prescribing herbs and nutrients as a way of dealing with that condition.   Mason: (23:52) That's a comforting thought, thinking about that being a part of the regular checkup.   Jason Hawrelak: (23:57) I'd like to think so. I think Western medicine can be slow, cautious, and there's some benefits to caution, but I think sometimes it means things move very slowly. And even, I think of the impact of, to talk about a different ecosystem, but vaginal dysbiosis. This is an area that I'm passionate about because it's just an area that I think doesn't get the attention it deserves, and there's women who are suffering health consequences from having a dysbiotic vaginal ecosystem that no one talks about and no health professionals know about at all. People talk about the gut now, but there's the vaginal ecosystem too and there's a range of increased health risks for women who have a dysbiotic ecosystem, from cervical cancer to a range of STIs, sexually transmitted infections, as well as just symptoms in that area.   Jason Hawrelak: (24:54) I look forward to when that's just part of people's checkup. We look at that and go, "Okay, how is that ecosystem health going? How do we improve that?" We know that vaginal dysbiosis is linked to infertility and poor birth outcomes as well, so to me it's a no brainer that this should be part of a discussion and should be part of a consideration of someone's state of health, but it's just not there in conventional medicine. I don't know how many studies need to be published before it does get there, but I'm hopeful on the other hand that in five or ten years time, which is a long ways away for a lot of people, that some of these cautions will be around this and that care will be far more broad in its scope and some of these areas of dysbiotic ecosystems will be addressed, because I mean the gut was kind of the tip of the iceberg. There's stuff about skin ecosystems that we know so little about, and how do we even modify that? We know so little about it. We know how to kill things, put antibiotics on there, put an antifungal on there, but how do we make the ecosystem on my cheek healthier?   Mason: (25:56) Yeah. Far out.   Jason Hawrelak: (25:57) Nobody even researches that yet. That will change and we're just starting to do that with the gut over the last 20 years, how do we make that ecosystem healthier, but I think there's other broader systems that we are way behind on too.   Mason: (26:10) Yeah. And as we keep saying, it's not just stabbing in the dark. It's nice to have a part of your health protocol or your strategy or your lifestyle or whatever it is, something that you can show, "Actually, how can I increase the diversity in my oral cavity and my skin?" And just talking about UTIs and thrush, I mean that's... What do you get? You get antibiotics or you go and take some cranberry. That's kind of all there is in the awareness around that at the moment, but I think where that's going to start. It's always in preconception. That's where the doors get opened for a lot of the population that do things.   Mason: (26:53) So I think there, just looking at the vaginal cavity and going, "This is going to have a direct link to your gut microbiota," and then, "Okay, cool, so let's..." So now it's nice for me when I have friends who are trying to conceive and we talk. There's a lot of conversation like the Daoistterminology around that, but we always say you've got to make sure you have a nice, healthy gut because that's going to be handed over.   Jason Hawrelak: (27:18) That's right.   Mason: (27:19) All that's in our testing. It was interesting watching at the time our three year old. We were just going, "Yeah, you can see there's the direct... This is what you've given Aiya," which thankfully is pretty good. Just could use some more biodiversity.   Jason Hawrelak: (27:35) That's the cool thing about testing. You can see those things which I think is fantastic too.   Mason: (27:41) Well, I think I see that's where it's really going to. Again, like gastrointestinal microbiota during pregnancy and that handing over the encyclopaedic knowledge, just between that information that's getting handed over to a child and then through breastfeeding, I think this is going to... I'm really excited to be able to give my friends something that's data driven where they can start seeing exactly what they are now handing over to their child versus would have not been.   Jason Hawrelak: (28:14) And by testing that during early pregnancy and working out, "Okay, what's the ecosystem like now?" Ideally before that if you're working with the preconception we can test and look then and then make changes, but how do we optimise the ecosystem during pregnancy so we can pass on the healthiest ecosystem possible? And I think that will be a core part of... I think it is in some people's circles already a core part of that prenatal care, but I think it will become even more so, because you've got that opportunity to... You've only got that one chance of passing on in some ways, one chance of passing on the healthiest ecosystem possible so you do your best. If you know that, you do your best to make it as healthy as possible, but to do that you need to know how healthy that is in the first place, how you can modify that, and then you can follow up and go, "Okay, how is it tracking over time?" And then to ensure the best introduction to the next generation, best seeding and reinoculation to the next generation.   Jason Hawrelak: (29:11) And then we'd expect also that a healthier gut ecosystem will essentially result in a healthier breast milk ecosystem that will be passed on too, because there's certainly a link between the gut microbiota and the breast milk microbiota. The breast milk microbiota is far more complex than just the gut, but there's a sampling going on is what we feel, that bugs are being sampled from the gut, brought up to the breast tissue and fed to the next generation, alongside some amazing, unique prebiotic sugars to feed those microbes.   Mason: (29:48) So cool.   Jason Hawrelak: (29:48) Yeah. It's very cool.   Mason: (29:52) Your mind starts going to fantasy land around this becoming subsidised and us looking at it as a population, because we're walking on eggshells and we've seen that the last year immunologically what's happening. All these symptoms being brought up, all these susceptibilities, seemingly healthy people all of a sudden going down to... That's with the flu or with any virus, but you mentioned data. I didn't want to throw this one out there, but I was just looking, there was a paper that was just starting to look at the diversity of the microbiome. Okay, this is obvious, but it's interesting seeing the papers come around specifically with the... I don't know which strain of COVID they're actually testing it on. Have you seen that data? Have you seen that starting to come out?   Jason Hawrelak: (30:43) I've seen a little bit. I haven't focused too much because I suppose being in Australia, being in this little cocoon, that you're kind of outside the COVID sphere, so you don't actually have patients who are at high risk of getting it and asking questions around it, but I think from my understanding, and I am doing some research with a UK-based practitioner where we're actually treating long COVID patients by changing the microbiota and we're doing pre and follow up testing along the way and we're hoping to get it published to show the improvement in long COVID symptoms associated with microbiota optimization. I'm aware of some of the research around it, but not all the studies are coming out. I wouldn't be surprised if lack of diversity and high levels of pathogens and pathobionts and low levels of beneficial are core risk factors for more severe COVID, given that those are the same risk factors that we would see for most Western diseases that we're dealing with too for that matter.   Mason: (31:44) I guess as you were saying the data is kind of catching up whereas someone would be looking at the data they'd be like, "Okay, maybe this could work," whereas after two decades of clinical practise you know that you're going to see an improvement. It's going to see immunological, a whole physical robustness and basic adaptability and ability to get back to homeo spaces and reduce inflammation, not stay chronically inflamed, is going to be improved. Hormonal functions are going to be improved if you have at least this foundation focused upon as a primary.   Mason: (32:20) This is the first time I've gone, "Yes, here's a test that shows just how much we're walking on eggshells," especially in the Western world and especially on a standard Western diet. It's kind of really going, "All right, guys." I assume the data is going to catch up and be like, "Look at these disease states. Look at the microbiome. Look at the outcomes," and you can start to see various population overgrowths or deficiencies and start going, "Well, how about-"   Jason Hawrelak: (32:51) And similar patterns throughout between a broad range of Western chronic diseases from Alzheimer's and depression [inaudible 00:32:59] I think the similarities between the gut dysbiosis that is showing up in research, which again, is often low diversity, low levels of beneficial species like bifidobacteria or akkermansia or butyrate producing species and high levels of pathobionts like proteobacteria. It's the by parts of some of those bacteria like proteobacteria specifically that are seen as drivers of brain inflammation, changes in neurochemistry, changes in neurotransmitters that occur with things like Alzheimer's as well as depression, anxiety, and I think it's just fantastic that we have the tools available to actually shift that and it's not that... Well, assuming you're willing to change your diet, it's not that challenging to actually make those sort of imbalances and shifts pretty substantial in people's gut ecosystems if they're willing.   Mason: (33:49) We've discussed some of the basic recommendations on the podcast before, but I'm interested in hearing... Obviously, so if we're looking at some serious symptoms you'd want to be getting some testing and formulating I'd assume an individual diet plan, supplement herb plan. Are you most comfortable recommending that? Are there general recommendations at this point you're happy putting out there to take the population in a particular direction?   Jason Hawrelak: (34:22) I think there's different recommendations too. I think the point with individual ecosystems is perhaps just tweaking those to suit this person, giving a little bit more of this, a little bit less of that, because that's what some of the individual nuances are. I think there are some general principles of helping it. How do you get a healthier gut ecosystem, well, that's getting more than seven hours sleep a night. We know that's important, and I didn't always see that. I try. I didn't always.   Jason Hawrelak: (34:50) Point two is moderate amount of exercise. So some of these things aren't mind-blowing, and we've associated with better health for a long time for other reasons too, but moderate amounts of exercise are good. Too much is not so good. Too little not good. Thirdly, probably stuff around diet would be having a greater diversity of plant food stuffs, eating whole unprocessed plant foods, so you're getting lots of fibre, a rainbow of colours. I usually suggest people aim for eating 40 plus different whole plant foods per week. It's not like this is a magic number, but it's an achievable number where people can actually eat 40 plus different food stuffs and that's enough to result in diversity improvements, because essentially in that situation you are not introducing new species into that ecosystem, but you are feeding up species that are there in teeny tiny amounts and allowing them to bloom into larger amounts, to sufficient numbers that they can actually contribute to your ecosystem health and your health. When they're at 0.001% of an ecosystem they're not doing much in terms of contributing much, but when you get them up ten or a hundredfold higher than that, all of a sudden they can.   Jason Hawrelak: (35:58) That's one of the key things associated with health is a more diverse ecosystem, so I think the best way of doing that is feeding the widest number of beneficial microbes possible. I think the key thing there is diversity of diet, as I've said before. That you're having lots of fibres is important but also different shapes and sizes of that fibre, so you're eating 50 grammes of broccoli fibre a day. It's better than no fibre per day, but it's not the same as 50 grammes of fibre from a range of legumes, whole grains, vegetables, fruits, nuts and seeds. You're going to feed a far more diverse ecosystem with a diverseness of food stuffs.   Jason Hawrelak: (36:37) Other things are avoiding processed foods, one because they're often fiberless and don't contain anything really healthy for you anyway, but two, sometimes they contain things like emulsifiers, like polysorbate 80 and carboxymethylcellulose which doesn't really sound like stuff you want to eat, and it's not, but they're things we know now that strip away your protective gut line and it's like, "Do we really want to do this? No, we don't." It needs awareness around that. When people are buying that big tub of home brand ice-cream at the shop, they're not looking at the ingredient so much. There's $2 for that tub. There's a reason why it's two dollars for that tub. It's because it's sugar, water, and heaps of emulsifiers to make that sugar and water and fats all combine together, and oil. Those emulsifiers we know strip away that protective gut lining, make your gut more leaky, and then allow bacterial byproducts to get into your system, and we don't want that.   Jason Hawrelak: (37:34) And choosing organic as much as we can, because we know that certain food chemicals are unhealthy for our human cells but also cause disruptions to the good bacterial populations in our gut as well. And as mentioned before too, a rainbow of colour, because it's the polyphenols in foods like blueberries, eggplant skin, strawberries, raspberries, those colours are generally polyphenols. Not always, like red capsicum isn't polyphenols. It's carotenoids that make that one red, but the multicoloured foods. Most of the polyphenols, in fact probably 90% of the polyphenols are absorbed by gas and they feed the colonic ecosystem, the good guys in the colonic ecosystem, and their populations grow. But as a consequence of eating those polyphenols, they release a smaller compound which we then absorb and we get the health benefit of, and I think it's this great win-win situation that we eat it.   Jason Hawrelak: (38:28) If not for the gut bacteria we would just be pooing it straight out and not getting any health benefit from it, but what we're doing is feeding species who then create an absorbable compound that helps us, plus their population grows, so it's a win-win situation. So we want to have as much colour in our diet as possible, so I always recommend things like red rice and black rice and black beans and adzuki beans to get the different colours. Lots of berries for example, and I think that's one of the other core things we can do.   Jason Hawrelak: (38:57) Things that contain resistant starch, which is a type of starch which is indigestible to us but feeds our microbes, those things are found in legumes, whole grains, root vegetables, but often these things, you get higher amounts when they are less processed i.e. not ground into flour, and secondly when they're cooked a certain way or when they're already processed, so they're cooked and cooled. So if we bake our potatoes and eat them the next day or boil our red and black rice, but then eat it the next day. Some of that starch when it cools gets converted to another type of resistant starch which then feeds our microbes.   Jason Hawrelak: (39:40) Then there are certain foods which contain higher amounts of what we call prebiotics, and prebiotics are the selective fertilisers of supplements, that we take them and we selectively feed the species that are healthy for us to have more of, and I think the key things of that prebiotics is that generally those compounds are indigestible so we can't break them down, and two, it's selective, and I can't reiterate the importance of that as how you define it, because that term prebiotic is thrown around all the time. "Oh, any fibres are prebiotic." It's like, "No."   Jason Hawrelak: (40:13) Fibres are great, and they can feed a whole bunch of different things and that's not a bad thing, but prebiotics are very selective in that I can look at an ecosystem and go, "Okay, your akkermansia population is low. Your bifidobacteria population is low. I'm going to give you some foods or suggest you eat more foods that contain a type of prebiotic called inulin or fructooligosaccharides and that will increase those populations very specifically, and you can see the before and after." You eat those things as a supplement or in those foods, their populations go up very clear.   Jason Hawrelak: (40:43) The research says that. My 20 years of experience says that too. It's not feeding a wide range of microbes. It's really feeding some very specific members of that ecosystem, and we're generally doing that alongside broader dietary principles like diversity and polyphenols that feed a wide diversity of microbes as well, and that way we get that increase in specific beneficial species as well as increased diversity overall.   Mason: (41:07) Have you got any foods currently that are just like, maybe you've read a paper about it recently or a particularly unique pigment or something that you're kind of nerding out on or really enjoying?   Jason Hawrelak: (41:20) Probably, because I'm a bit of a permaculture gardener guy too.   Mason: (41:24) That helps the microbiome.   Jason Hawrelak: (41:25) Ceylon hill gooseberries.   Mason: (41:26) Are you into gooseberries? Yeah. Yum.   Jason Hawrelak: (41:29) The ceylon hill ones, they're these little purple ones that are really high in anthocyanins which are the same compounds in blueberries. They don't grow well down here, sadly, but they grow well up in North New South Wales. They've got beautiful flowers too. They kind of look a little bit like a pink tibouchina. The leaf is a bit tibouchina-like. They're probably some sort of cousin of the melastoma species that also are native to Southeast Queensland or northern New South Wales, but they're more bountiful fruits. Those fruits have been used for centuries in traditional Chinese medicine and Ayurvedic medicine. In fact, the fruit was said to be made by Krishna himself to give to... I can't remember which five brothers it was, but I think when you've got so much historical lore around the fruit, tells you that it's important if it's made by Krishna. It's important food. But it's also very high in polyphenols as well, so that's excited me recently.   Mason: (42:21) I've got a mate who's a permaculturist. I'm going to have to go talk to her. I'm sure she's got some. I'm sure if anyone's going to be like, "Yeah. Yip. Got a couple of trees over there or bushes over there." She'll have the hook up. I guess jaboticaba I think for me at the moment and Brazilian cherries. I guess that's kind of where I'm leaning towards. So are there any herbs or supplements that you are kind of taking or seeing that you're getting most of your clients to take? IS there any kind of just fleshing out what maybe you think they're not going to be able to get in abundance just in an organic diet by getting from the food markets, or are you generally happy with that?   Jason Hawrelak: (43:04) I use lots of prebiotic supplements in practise, and initially, as ways of targeting those species that are deficient in the gut and bringing them up quickly. Yes, eating some more of those foods will help bring that more slowly, but we're often wanting to change things quickly. So I personally don't necessarily take prebiotic supplements so often, although sometimes I do because I like that they taste good. My treat is having a teaspoon of fructooligosaccharides, but I rely mostly on diet. But I'm not unwell and when I'm treating people that have things going on that they need a boost quickly, these things work quickly that a month, two months, you can have a thousandfold increase in bacterial populations from adjusting prebiotic supplements. So for me, they're a core part of my practise and that would be probably three main prebiotics. There's inulin or fructooligosaccharides, oligofructose enriched inulin or inulin-type fructans are all names for compounds in that area. Then there's galactooligosacchardies.   Mason: (44:06) Mm-hmm (affirmative). I like that.   Jason Hawrelak: (44:07) Yeah, which we find naturally in legumes and beets as well, but primarily just amounts on legumes and tiny amounts elsewhere, and then thirdly is lactulose. Now, lactulose isn't found naturally in foods. It is found in tiny amounts of ultra heat-treated milk because lactose when it's boiled converts over to lactulose. Lactose is milk sugar, so I don't suggest people drink UHT milk, but you can find it in there. You essentially bought it in the liquid form from the chemist of all places in the laxative section, because lactulose in large doses, because it's indigestible and it reaches the colon intact and large amounts too much for your bacteria to eat, it draws water to it and you get softer bowel movements that go with it. But in small doses like we use as a prebiotic it just feeds the beneficial bacteria and their populations can expand as I said, hundred, thousandfold in many cases. And things like lactulose is fantastic for lowering levels of things like proteobacteria, species that have really pro-inflammatory endotoxin or lipopolysaccharide into the gut as they live and die. Lactulose is a very effective tool at bringing that population down very quickly.   Mason: (45:25) I thought you were about to say it's in yakult.   Jason Hawrelak: (45:32) Maybe there's a tiny amount because they probably had heat treated milk in there, but I wouldn't recommend it for source of lactulose.   Mason: (45:38) I'm like, "Oh, that's what that crap is." No. You know what I started doing after having my session and just talking about this, the importance of all these pigments, and then just making that natural connection to a diet that was based more on foraging wild foods and just seeing that if you can... For me, I'm starting to really merge these two worlds because after my raw foods days I kind of sat, I guess for lack of a better word, more of that Weston Price ancestral world, but missing the capacity to get biodiversity because I'm not out there foraging, and so I wasn't letting any of those insoluble fibres... I wasn't doing really grains. No lentils, no real beans or anything like that. It was just bad in my mind, and so now I've started really resolving that and merging those two worlds and feeling really fantastic for it.   Mason: (46:38) After that session I was like, "Wow, I've really let go of those wild fruit pigments," and started getting back onto making this big mix of my Kakadu plum, my Davidson plum, really [inaudible 00:46:54] finger lime, native peppers and mixing that up, just getting freeze dried Australian native fruits and just sour, tart, and just...   Jason Hawrelak: (47:03) I love that.   Mason: (47:04) Because we were talking about these other supplements with all the red pigments, it's got beet, and I got one and it was just sweetened with stevia and xylitol. I just couldn't handle it. But then made up that mix, I think, from just Australian Superfood Co is where I bought it from. That made a world of difference for me as well. I'm looking forward to getting that test done.   Jason Hawrelak: (47:25) Yeah. And I think traditionally we would have always eaten things that didn't taste sweet. We'd harvest whatever fruits were growing around that were edible, and certainly some of the Australian ones are not known for their great taste.   Mason: (47:39) Really?   Jason Hawrelak: (47:40) From a traditional Western perspective of just being sweet, you get things like Davidson's plums which is pretty tart, but those colour pigments are absolutely outstanding. Dragon fruit, that one is sweet. The fluorescent pinky red, that's so rich in polyphenols. And we know that those pigments in dragon fruit can feed akkermansia quite well, which is a species that we generally want more of and many Westerns have a deficient population of.   Mason: (48:09) Mm-hmm (affirmative). Yip. More biodiversity. That's going to help. That's true superannuation is go hunt here in the garden. It helps you grow.   Jason Hawrelak: (48:18) Listen, the more you looK at chronic Western diseases that people are dying of in their old age, and slowly dying of too, I should add, the best thing we need to protect against those things is ensure you're looking after your microbes and your gut population now, and that will slow down and prevent that whole process, because Alzheimer's is very much a dysbiotic gut ecosystem and a lot of those chronic Western diseases are really being linked in to dysbiotic ecosystems. We know that Western diet has risk factors for those things and there's probably a number of mechanisms by which it does so, but certainly microbiome modification in a negative way in terms of those diets inducing dysbiosis, which then results in increased inflammatory tone and then that causes a whole range of negative sequelae is key.   Mason: (49:10) Before I let you go, and I think I'm definitely going to have to come back on the podcast and maybe get into some... I can just dive down lots of rabbit holes. I'd really love to talk more about women's health and pregnancy and going into some specific protocols and so much other stuff. Curious in terms of the pigment, have you heard of the blue pigment and have any data on what that's feeding? The phycocyanin that's in the... Have you ever heard of it? That's in the blue green algaes and like...   Jason Hawrelak: (49:41) No. I haven't looked. So some other people may have and there may be research that's looked at that at least in animal or vitro models, maybe even beyond that, but no, I'm not familiar with that research if it has been done.   Mason: (49:52) Just wanted to throw that out there. That's a pigment I haven't been getting lately, is the true blue.   Jason Hawrelak: (50:00) No. Well, true blue is hard. You do find true blue in the... I was going to say clitoris pea. Clitoria ternatea, the butterfly pea. That gives you that beautiful blue. Probably it's a different compound than what you find in that blue green algae, but it is one of the few natural food stuffs that contains such an amazing blue compound.   Mason: (50:26) It's such a vibrant blue as well. Learning that no, actually blueberries aren't blue.   Jason Hawrelak: (50:33) Not compared to that, no. They're like a purpley grey actually compared to that. I remember when I was in Thailand and had the butterfly pea tea for the first time. This is 15 years ago or 16 years ago. I was just amazed because the water was blue and then they gave me some lime juice to put on it and it turned purple. I'm like, "What the hell is this stuff?" It was incredible. It was just very hard to find back then. I remember searching high and low to find a supplier and there was nobody selling it back 15 years, whereas thankfully that's become more available. That grows beautifully up in your area too. You could just have a fence covered with blue butterfly pea.   Mason: (51:11) I hadn't thought of that. Get that growing along the fence. That's a really good idea. Thank you for that. I'll take that gift. I'll let you get on with your day. Thanks so much. Really, really appreciate you coming on. Looking forward to jumping on again. I assume there's going to be a lot of people who want to... You've got so many other podcasts and talks and you've got so many resources on your website. Best place for people to go down the rabbit hole with your work or check out your clinic?   Jason Hawrelak: (51:48) Yeah, so Probiotic Advisor is my broader website and there I've got a database. It's mostly designed for clinicians to teach them about evidence-based use of probiotics and trying to match the best probiotic on the marketplace to whatever you're trying to treat, but then I've got a range of courses as well. Most of my stuff is geared for training practitioners, but there's stuff there for health conscious people who are pretty health literate to gain from as well, courses around treatment of a range of gut conditions and functional testing in terms of what gut tests are the best, what leaky gut tests are the best, things like that. There's a world of information around that, and there's links to a range of my podcasts I think on that site too, so you can click and learn more on a range of different topics.   Jason Hawrelak: (52:35) It's been an amazing journey to be in this field for 21 years and to see the growth of microbiome science in that time and I'm just glad that I chose that topic to do research because it's not often that you spend 20 years doing something and you're just as passionate now as what you were 20 years ago. I'm lucky that that's the case within this area.   Mason: (52:58) Yeah. That's huge. I think because you're not having to pad how effective or how fast it's moving. It's actually been effective more and more and more. That's rewarding in itself. The reward is built into that path that you happened to choose. That's nice. I'm very happy that worked out for you.   Jason Hawrelak: (53:23) Yeah, me too.   Mason: (53:23) I'm just really stoked for... We've kind of always known this, but for the more literal needing data and science part of the population, it's really exciting to see that this is something which like the ecosystem that we can see on the earth is something worth preserving and reseeding and building and nourishing, so it's just really exciting for everyone.   Jason Hawrelak: (53:48) It is, and for me that's a key passion, is that idea of custodianship and that we are gifted our microbes from our previous generation and we've got to give them on to the next generation, and what we do to that ecosystem in the intervening time determines what we pass on and how important that is that just like where we should be caring for custodians of the outer ecosystem and trying to keep it as healthy as possible to pass onto our kids, it's important that we do the same thing for our inner ecosystem as well.   Mason: (54:19) Beautiful. Mate, thank you so much for coming on today. Have an awesome one down there in sunny Hobart.   Jason Hawrelak: (54:27) Not sunny today. It's cloudy and 14, but it will return sunny again another day and two, so I'll enjoy it then.   Mason: (54:35) Awesome. Thanks so much, mate.   Jason Hawrelak: (54:37) Yeah. You're welcome, Mason.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.27.358408v1?rss=1 Authors: Hoffman, C., Siddiqui, N. Y., Fields, I., Gregory, W. T., SImon, H., Mooney, M. A., Wolfe, A. J., Karstens, L. Abstract: The human bladder contains bacteria in the absence of infection. Interest in studying these bacteria and their association with bladder conditions is increasing, but the chosen experimental method can limit the resolution of the taxonomy that can be assigned to the bacteria found in the bladder. 16S rRNA gene sequencing is commonly used to identify bacteria, but is typically restricted to genus-level identification. Our primary aim was to determine if accurate species-level identification of bladder bacteria is possible using 16S rRNA gene sequencing. We evaluated the ability of different classification schemes, each consisting of combinations of a 16S rRNA gene variable region, a reference database, and a taxonomic classification algorithm to correctly classify bladder bacteria. We show that species-level identification is possible, and that the reference database chosen is the most important component, followed by the 16S variable region sequenced. Copy rights belong to original authors. Visit the link for more info

This month on Episode 15 of the Discover CircRes podcast, host Cindy St. Hilaire highlights three featured articles from the July 31 and August 14 issues of Circulation Research. This episode features an in-depth conversation with Drs Venu Venna and Juneyoung Lee from the Department of Neurology at the McGovern Medical School at the University of Texas Health Science Center at Houston regarding their study Gut Microbiota-Derived Short-Chain Fatty Acids Promote Post-Stroke Recovery in Aged Mice. This episode also includes a brief discussion with BCVS Outstanding Early Career Investigator Award competition finalists, Drs Shyam Bansal from Ohio State University, Emmanouil Tampakakis from Johns Hopkins University, and Yang Zhou from the University of Alabama, Birmingham.   Article highlights:   Veys, et al. GLUT1 in Angiogenesis and BBB Integrity   Zhang, et al. Self-Renewal of Local Macrophages Attenuates DiCM   Lerchenmüller, et al.  CITED4 in Cardiac Remodeling     Dr Cindy St. Hilaire:        Hi. Welcome to Discover CircRes, the podcast of the American Heart Association's journal, Circulation Research. I'm your host, Dr Cindy St. Hilaire from the Vascular Medicine Institute at the University of Pittsburgh. Today I'm going to share with you three articles selected from the late July and early August issues of Circulation Research. I'm also excited to share with you my discussions with Drs Venugopal Venna and Juneyoung Lee, who are from the group of Louise McCullough at the University of Texas Health Science Center, regarding their study Gut Microbiota-Derived Short-Chain Fatty Acids Promote Post-Stroke Recovery in Aged Mice. I also speak with the finalists of the BCVS Outstanding Early Career Investigator Award, Shyam Bansal from Ohio State University, Emmanouil Tampakakis from Johns Hopkins University, and Yang Zhou from the University of Alabama, Birmingham. So first the highlights. The first article I'm sharing with you is titled Role of the GLUT1 Glucose Transporter in Postnatal CNS Angiogenesis and Blood-Brain Barrier Integrity. The first author is Koen Veys and the corresponding author is Katrin De Bock from ETH Zurich. The primary energy source for the brain is glucose and the blood vessel endothelial cells which from the blood-brain barrier supplied glucose to the brain via the glucose transporter protein GLUT1. Patients with genetic mutations in GLUT1 have neurological problems, including seizures, movement disorders, and delayed neurological development. Low GLUT1 levels in the blood-brain barrier have also been linked to Alzheimer's disease in humans and have been known to exacerbate the disease in a mouse model. In this study, the group examined the role of GLUT1 in blood-brain barrier endothelial cells in more detail. They found that while structural integrity of the blood-brain barrier remained intact, inhibiting the activity of GLUT1 in newborn mice impaired aspects of normal blood vessel growth in the brain, and inhibiting GLUT1 in adult mice led to progressive neuron loss, behavioral abnormalities, reduced movement, seizures, and signs of inflammation. The results highlight GLUT1's importance in the brain endothelial cells, and the role of GLUT1 in glucose utilization in overall brain function. The second article I want to share with you is titled Self-Maintenance of Cardiac Resident Reparative Macrophages Attenuates Doxorubicin-induced Cardiomyopathy Through the SR-A1-c-Myc Axis. The first authors are Hanwen Zhang, Andi Xu, Xuan Sun, and the corresponding author is Qi Chen and the work was completed at Nanjing Medical University in China. Doxorubicin and it's analogues are commonly used chemotherapeutic agents. However, the use of these drugs is limited by dose-dependent cardiotoxicity. Doxorubicin-induced cardiomyopathy presents with dilated and poorly functioning left ventricle in the absence of abnormal loading conditions. This may induce cardiac systolic dysfunction. Accumulating clinical evidence suggests that inflammation contributes to doxorubicin-induced cardiomyopathy pathogenesis. Several studies suggest that the inhibition of cardiac inflammation can improve cardiac function; however, the underlying mechanisms remain unclear. This group wanted to explore the role of cardiac resident macrophages during doxorubicin-induced cardiomyopathy progression. They found that cardiac resident macrophages were vulnerable to doxorubicin insult but that monocyte-derived macrophages survived. Further, these surviving monocyte-derived macrophages exhibited a proinflammatory phenotype which contributed to impaired cardiac function. Scavenger receptors are expressed on macrophages and help to modulate their inflammatory response. Global, or myeloid-specific deletion of class A1 scavenger receptor, also called SR-A1, inhibited proliferation of resident reparative macrophages and this inhibition exacerbated cardiomyopathy. At the mechanistic level, this group identified that the transcription factor c-Myc mediated the effect of SR-A1 in reparative macrophage proliferation in doxorubicin-induced cardiomyopathy. The last article I want to share with you before we switch to our interviews is titled CITED4 Protects Against Adverse Remodeling in Response to Physiological and Pathological Stress. The first author is Carolin Lerchenmüller and the corresponding author is Anthony Rosenzweig, and they're from Massachusetts General Hospital. Exercise is good for the heart. It increases cardiac mass which is called physiological hypertrophy, which appears to induce cardiac benefits. However, pathological stimuli, such as hypertension and aortic stenosis, can lead to pathological hypertrophy which is associated with adverse outcomes and can lead to heart failure. Cardiac CITED4 is a protein that is induced by exercise and is sufficient to cause physiological hypertrophy and mitigate adverse ventricular remodeling after ischemic injury. However, the role of endogenous CITED4 in response to physiological or pathological stress is unknown. To understand the role of endogenous cardiomyocyte CITED4, this groups generated cardiomyocyte specific knockouts of CITED4. These mice were analyzed at baseline. They were subjected to a swimming protocol which provided physiological stimuli or they underwent transverse aortic constriction, also called TAC, which causes pressure overload and served as the pathological stimulus for heart remodeling. CITED4 knockout mice developed modest cardiac dysfunction and dilation in response to exercise. After TAC, these knockouts developed severe heart failure with left ventricular dilation and impaired cardiomyocyte growth. The study goes on to show that CITED4 protects against pathological cardiac remodeling by regulating mTOR activity and also a network of microRNAs which control cardiomyocyte to fibroblast crosstalk. So for our interview of this episode, I have with me Drs Venugopal Venna and Juneyoung Lee from the Department of Neurology at the McGovern Medical School at the University of Texas Health Science Center at Houston. Today we're going to be discussing their manuscript titled Gut Microbiota-Derived Short-Chain Fatty Acids Promote Post-Stroke Recovery in Aged Mice. Thank you both very much for joining me today. Dr Venu Venna: Thank you Cindy for having us. It's a pleasure. Dr Juneyoung Lee: Yeah, thank you for the opportunity. Dr Cindy St. Hilaire: It's a wonderful paper. Actually I really enjoyed the nice graphical abstract, that really made a good visual of what this papers about, so I encourage everyone to go take a peek at that. Could you introduce yourselves and tell us a little bit about your lab group? Dr Venu Venna: Yeah, sure, I'm Venu Venna, it's my third year at McGovern Medical School UT Health, and we are a part of a large research group in the Department of Neurology here. This is headed by Dr Louise McCullough. She's also a co-corresponding author on this paper. Unfortunately she's not here today, but it's basically her idea and her initiative that led us to drive this huge project. We are very excited to share with you more details today. Dr Juneyoung Lee: Hi, my name is Juneyoung Lee. I'm postdoctoral fellow here and I'm working with Dr McCullough and Dr Venna. Dr Cindy St. Hilaire: So this manuscript is testing the general hypothesis that the gut microbiome can influence stroke recovery but before we dig into the details of your study, can you give us a little bit of background about what the microbiota gut brain axis is? Dr Venu Venna: That's a great question. Thank you for asking that. So recent advances in 16S sequencing, metagenomics, and metabolic analysis lead us to specifically identify the role of gut microbiota. We have... Everybody consists of large number of microbiota in the gut, so particularly the microbiota's role is largely remains unknown, as of now. The recent advances helped us to understand whether it's for communication of the microbiome, how it actually influences our health, and how the metabolites that are released by the microbiota can actually influence the brain-gut. So this is where the concept of microbiota gut-brain axis continues to evolve and we rely on 16S metagenomics, as well as metabolomics to understand if the microbiome itself has a specific role in the stroke recovery and stroke in this paper. Dr Cindy St. Hilaire: Great, so I know that previous research by you specifically, and also you mentioned your fellow corresponding author, Dr Louise McCullough, your prior work has shown that stroke can cause aberrant changes in the gut regarding things like motility, permeability, activation of gut-immune cells. So this to me suggested that aberrant signaling can come from the brain and affect the gut, but your study is kind of now flipping that. You want to ask the question is changing the gut microbiome after the stroke also beneficial? So there's kind of a chicken and egg type conundrum going on. Is there a preceding event, is it the stroke that alters the gut microbiome primarily, or is the gut microbiome maybe deficient in different people and therefore their stroke outcomes are different? Dr Venu Venna: Yeah, I mean this is a very new emerging field and what's very interesting about this is the brain gut microbiota axis, it's a bi-directional axis. In this case, what we think is if we have a stroke, it may actually directly influence the gut. There is a brain-gut axis. At the same time, the changes in the microbiome can actually trigger an inflammatory state where it can actually contribute to the worst stroke outcomes. It's a chicken and egg relationship as you rightly mentioned, but at the same time what is not known is whether if we can simply manipulate the microbiota, can you actually improve the stroke outcomes or can you improve the age associated outcomes? Because what we found in previous studies is age itself causes changes in the microbiome. Dr Cindy St. Hilaire: Interesting, so just being young or old, if you were to compare those microbiomes of old individuals and young individuals, you see differences that are I guess negatively impactful on things like stroke and disease? Dr Venu Venna: That's exactly right, so the more imaging data coming out from the literature, not just our group, but all other groups, on humans and animal studies, do suggest that age itself is associated with changes in the gut microbiome. Dr Cindy St. Hilaire: So the overall goal of this specific study was to determine if replacing the gut microbiota of an older mouse with the microbiota from a younger mouse would help in the recovery after an ischemic stroke. Can you talk about the design of that study and the different aspects that you had to consider when designing these experiments? Dr Venu Venna: Yeah, absolutely. This was a great question. The initial experiments, like what we were trying to do before, was whether we can actually even manipulate the microbiome in an aged animal. In our previous study, what we did is we took a young animal and we transplanted the biome from an aged animal. We used a combination of antibiotics to actually deplete the existing biome and that's what gave us susceptibility to transplant. Once you transplant the biome into a donor from a host, so the biome can actually sustain for quite a bit of time. This gave us an opportunity to study the direct role of microbiome. Later, what we did was we subjected these animals to the stroke and then what we found is when we induced this stroke in an animal that received aged biome, despite being young, the animal that received aged biome, can itself contribute to the worst stroke outcomes and increased mortality. In this follow-up study, what we decided to do was can we even manipulate the microbiome after stroke? So this is particularly important because most of the clinical patients don't come into medical attention until after stroke. Transplanting the microbiome or even manipulating the microbiome after stroke can have a broader clinical relevance. In this particular study we decided to see if we can actually manipulate the microbiome after several days or several hours after the stroke happens. We decided to test if we can wait for three days. This is a particular time where we can actually see the infarcts get mature and all the injury in all groups of animals are same, and then we transplanted the aged animals with the young microbiome. So this gives us an opportunity to actually study the role of microbiome, independent of infarct. Meaning, all animals have a similar degree of injury, so now whatever the beneficial affects you are seeing because of the microbiome transplant, are potentially due to, not because of the size of the injury, because they have a smaller injury they have better recovery, but it's basically because their infarcts are the same and whatever you're seeing is because of the manipulation of the microbiome. Dr Cindy St. Hilaire: Interesting. Juneyoung, would you like to tell me a little bit about what you found then? Using these interesting fecal transplant models, what are the key results that you found in this study? Dr Juneyoung Lee: Great question. As Dr Venna explained, we treated young biome to aged stroke mice, after stroke. We found that young biome contributes to better behavior outcomes and they regulate the immune system in the brain and the gut and increase the short term brain-gut axis in the aged stroke recipient mice. One interesting finding is that we found dominant T-cells, which are very small number of T-cells in the host, but they secrete proinflammatory cytokines which is IL-17. Cytokines exacerbate new inflammation in the brain so if we treat the young biome, we found that the level of proinflammatory cytokine IL-17 decrease cytokines compared to aged biome. Dr Cindy St. Hilaire: You also focused on short-chain fatty acids, SCFA producing bacteria. What is it about these short-chain fatty acids that are beneficial and what are the signaling pathways that you found to be activated or things that were present that helped to promote better stroke recovery? Dr Juneyoung Lee: Short-chain fatty acids are key metabolites produced by bacterial fermentation of dietary fiber in the gut. These are suspected to play an important role in microbiota gut-brain crosstalk. Also, in our previous study we found that young fecal biome has higher levels of short-chain fatty acid compared to aged biome so we think that the short-chain fatty acid has a beneficial role in our mild level stroke. Dr Cindy St. Hilaire: So are you focusing more on identifying the metabolites or trying to move into humans? What do you think the next step of this vein of research is? Dr Venu Venna: So what we think is right now, this is a very interesting and fascinating finding, even for us. We're trying to understanding what other metabolites could be involved and what other ways as you previously asked, what other pathways these bacteria itself are triggering or contributing to actually enhance this recovery, that's what we are seeing from the young microbiome. As a future direction, we are also seeing if this transplant of biome can have a broader therapeutic relevance, meaning is it only specific to the stroke related outcomes or can it be beneficial in large settings of other age relate diseases like what we are seeing, again as I mentioned before like age related diseases such as... Many age related diseases like cognitive dementia, or Parkinson's disease, any neurodegenerative disease. Dr Cindy St. Hilaire: Well thank you, Drs Venu Venna and Juneyoung Lee for joining me today. I really appreciate it and congratulations again on this wonderful story. Dr Venu Venna: Thank you very much for having us, Cindy, and for this work I would like to acknowledge the funding agency. This work is funded by NIH and also the American Heart Association, both for my Scientist Development Grant and also as well as for Juneyoung Lee's postdoctoral fellowship. This funding helped us to perform these highly innovative studies in gut microbiome axis. Dr Cindy St. Hilaire: Wonderful. Yes, well, we love seeing AHA funded research published in AHA journals, so thank you. Right so now we're going to have our interview with the BCVS Outstanding Early Career Investigator Award competition finalists. I have with me today, Shyam Bansal from Ohio State University, Emmanouil Tampakakis from Johns Hopkins University, and Yang Zhou from the University of Alabama, Birmingham. So congratulations to all of you for being recognized for your outstanding science. These topics are great. The timing of T-cells activity in chronic heart failure, sympathetic neuron signaling, circadian genes and cardiomyocyte proliferation, and the identification of a transcription factor that helps promote maturation of reprogrammed cardiomyocytes. So, Dr Bansal, your abstract that's recognized, is titled Novel Inhibitors For Temporal Modulation Of T-lymphocytes During Chronic Heart Failure. Where was this study conducted and where are you now? Dr Shyam Bansal: Right now I'm at Ohio State University. I joined here in July 2019 and I've been setting up my lab. While doing that, we conducted all this work. This work, most of it is done here, and we have been looking to identify certain inhibitors that can be used for T-cell modulation. Dr Cindy St. Hilaire: Excellent so why should I care about T-cells in the heart? And what did you all find in this paper? Dr Shyam Bansal: The right question is why shouldn't you? T-cells are coming out to be involved in almost every chronic disease. We have heard about CAR T-cell therapy. Recently it revolutionized the whole cancer research field. The heart failure and cardiovascular diseases has also been realizing the importance of T-cells. They're important in a way because they are kind of a two-edged blade. They are protective because we need them to initiate those wound healing cascades so the tissue can regain its original function. But then, too much activation of T-cells can be injurious and lead to autoimmune reactions. In 2017 I published a paper during my postdoc with Dr Sumanth Prabhu at UAB where we showed that these T-cells get activated during chronic heart failure. It's a double-sided activation to get activated immediately after injury but then they go down and they come back again, during chronic heart failure. That's where the two-edged blade comes into picture. If you alter these T-cells during this acute phase, during the cardiac infarction, the animals always do worse, right? They are protective because they are needed for wound healing pathways. Dr Cindy St. Hilaire: We can't just stop them at the start, we need to fine tune. Dr Shyam Bansal: Yes. Dr Cindy St. Hilaire: So what's this temporal aspect you looked at? Dr Shyam Bansal: So that's what we found in my postdoc in 2017 paper. If you inhibit these during the chronic phase, in mouse, in rodents, it was whole weeks after infarction, then you can actually stop maladaptive remodeling. You can complete shut it down, it doesn't get better but you at least shut it down completely. We did those studies by using some antibodies, again CD4+ T-cells, and using genetic mouse models. Dr Cindy St. Hilaire: So do you think anything that you found can quickly or soon translate to humans? Dr Shyam Bansal: That's exactly what we did after we came here, right? So we compared what happens during this chronic heart failure, what happens to these T-cells. We identified one molecular pathway that's associated with receptor signaling, being activated in these T-cells. The interesting thing is, these T-cells came from male mice, not from females. Still, they had strong activation of the surge in receptor signaling. We found a drug molecule that can activate another pathway that inhibits this pathway, so indirectly we're able to inhibit this pathway. We did those studies and found that we can actually stop T-cells from getting activated during chronic heart failure and when we do that, this drug can actually, again, inhibit left ventricular remodeling significantly. Dr Cindy St. Hilaire: Wow. Dr Shyam Bansal: And if you give this drug early in myocardial infarction, again, animals died. Dr Cindy St. Hilaire: It's going to be very important to fine tune when that drug could potentially be administered to humans. Dr Shyam Bansal: Yes, and that's the first drug in our knowledge that can actually target specific antigen activated T-cells. Dr Cindy St. Hilaire: Super exciting, well congratulations again. Well done and well earned. Dr Tampakakis, your study is titled Sympathetic Innervation Negatively Regulates Postnatal Cardiomyocyte Proliferation Through Circadian Genes. So where was this conducted and what position are you in now? Dr Emmanouil Tampakakis: This research was conducted at Johns Hopkins University and I'm currently part of the... I'm Assistant Professor within the Division of Cardiology in the School of Medicine. Pretty much for my curiosity and the fact that we know a lot about the role of neurons for adult heart disease but we really don't know what much about neurons are doing at the neonatal stages in heart development. We know at least in preterm babies where the innervation is really affected, some of them do develop changes in their heart geometry, and there might be a role there, plus there is some data to suggest that the autonomic nervous system does manipulate or does affect the neonatal heart regeneration. The role of neurons to me was really intriguing. Dr Cindy St. Hilaire: So this is linking together sympathetic nervous signaling, circadian genes, and postnatal cardiomyocyte proliferation. Why do I care about all these things fitting together? Dr Emmanouil Tampakakis: Yes, so apart from the fact that it's fascinating knowing that each individual organ has in their body its own circadian genes that regulate actually, several functions. Without being affected by the central nervous system and what's happening in the hypothalamus, which to me is really fascinating, is we really don't know much about what actually regulates and synchronizes the circadian cycle of the heart. We, in this study, showing that actually the innervation that happens in neonatal stages, already aaffects how certain genes are circulating within the heart. That appears to be through one of the adrenergic pseudoephedrine way that the sympathetic nerves are secreted. Again, by affecting this, we are showing that there is more proliferation of neonatal cardiomyocytes which can be important for disease at later time points, and we're also showing that if you mess up two specific circadian genes, Period 1 and Period 2, that are transcription regulators, and are some of the masterminds of this phenomenon, you can actually still affect neonatal cardiomyocyte proliferation which can be important for diseases like heart degeneration and whether we're thinking about manipulating other pathways to induce more regeneration and induce healing in the heart. The novelty of our work is we see that there's a link between that cell cycle and the circadian genes, at least at neonatal time points when myocytes proliferate a little more. Dr Cindy St. Hilaire: So neat. Congratulations again, it's a wonderful story and I'm really happy it's being recognized. And Dr Zhou, you're being recognized for your work that's titled TBX20 Activates Cardiac Maturation Gene Programs Promoting Direct Human Cardiac Reprogramming. So where was this study started and where are you now? Dr Yang Zhou: So I started as an Assistant Professor of Biomedical Engineering at UAB in January 2019. Before I moved to Birmingham, I did my postdoc training at the University of North Carolina at Chapel Hill in Dr Li Qian's lab. I basically studied direct cardiac programming which directly convert non-myocyte cell type to the functional cardiomyocytes. I did a lot of work and found the epigenetic barriers and I find that the features of these direct programming cells and almost in the mouse cells, but we know that we have to move that to the human cells, so then when I moved to Birmingham and then I studied the cardio programming from the cells. Dr Cindy St. Hilaire: Excellent, so your study is looking for ways to really kind of push the direct conversion of cardiomyocytes into a more fully differentiated state. Why is that an important question and what did you find in this study? Dr Yang Zhou: Yeah, it is still challenging to gather a functional beating cardiomyocytes from human fibroblast by the direct reprogramming method. We want to get the functional cardiomyocytes to do the cell therapy. Also this method has promise to do the in situ heart regeneration because we use the transcription factors we can inject these factors to the injured heart then directly convert those cardiac fibroblasts into the cardiomyocytes. So we have to study, we have to know how to get the functional work that cardiomyocytes. Dr Cindy St. Hilaire: That is so neat. So really you're hoping to harness those fibroblasts in the heart that everyone kind of ignores because they're not contractile and you're hoping to really take them and transition them to these fully functioning beating cardiomyocytes. Dr Yang Zhou: Right, so we know that the stuff we are coding are very important for the contractility, the myocyte contractility, so we find that a lot of missing protein expression in the current direct programming cells, so my hypothesis is they might be missing key regulators and can promote expression of those coding in the genes. My computational analysis of the transcription data, I find that this T-box, transcription factor Tbx20, that can highly promote those unexpressed genes in the reprogrammed human cardiomyocyte. Dr Cindy St. Hilaire: That's wonderful. Well congratulations again on some excellent work. So I want to ask you all, early career question, you're all within I think the first couple years of starting up your lab, and we're in the midst of a pandemic which means none of us are in the labs. Maybe staff is at reduced numbers, but first, how's it going? And second is, you're kind of still fresh in terms of transitioning. So I'm wondering if there's any one piece of advice that you'd like to share with maybe someone who's in the middle of transitioning or just about to. Or if there's something you wish you knew ahead of time that you'd love to tell your pre-faculty self? Dr Emmanouil Tampakakis: Yeah, I don't know if I can give advice, already I think I'm too junior to do this. I would say that- Dr Cindy St. Hilaire: What, too traumatized? Dr Emmanouil Tampakakis: Maybe. Probably, or will be traumatized, but I would say for me at least, the things that kept me sane during this is my son, who's three and a half years old and lives in a complete different world, so that helps me balance what's happening out there. Dr Cindy St. Hilaire: That's so important. Dr Emmanouil Tampakakis: Probably some good alcohol at the end of the day but both those two things combined actually helped me maintain my sanity. In terms of advice, I would say to try to enjoy science. Try to stay focused and productive and at the end of the day, enjoy what you do. I think that if you are creative and if you like what you do, find the right people to collaborate and work with and you can hope that you will do well. Dr Cindy St. Hilaire: I agree. Excellent advice. Dr Shyam Bansal: I also have two kids, three years and eight years old, so we were at home for two and a half months or so. I think those kids were really helpful in keeping my sanity because the weather was getting better so we had to put in a swing set for them, get some play items and stuff, so they kept me busy. That was good that way. The advice that I will have for junior investigators is be collaborative. Try to see how you can help others because when you help others, others are ready to help you as well. Remember science is a collaborative field, the more you collaborate with people, the more you get to know many more stuff. Dr Cindy St. Hilaire: I think that's so important. Dr Shyam Bansal: I was able to get done a lot of whatever work we presented. I was able to set up my lab, get some work done, and be at a position that I was able to summit my first abstract to BCVS for my independent own work, just because I had good collaborations here. I had good people who helped me stand on my feet and obviously I was working and helping them also. Dr Cindy St. Hilaire: Yeah, and it also sounds like you have good colleagues so that's another key to it. Dr Shyam Bansal: Yeah, I'm really lucky that way. Our whole department is really great. We have several senior faculty who are always ready to help us out in whatever issues we have, personal, professional, scientific, they're always here for us. Dr Cindy St. Hilaire: That's great. Yang, how about you? Dr Yang Zhou: I think the pandemic is very challenging for our junior faculty and for research and career developments but we have to balance between the work and the family, like kids. You might have an issue because we have two PIs in our lab. Dr Cindy St. Hilaire: Oh gosh. Dr Yang Zhou: Yeah, but I learned a lot these two years before this position. I think the most important thing I feel like is you have to talk to people. You always can find people that can help you to find answers. You need a mentor because they are more senior, they have more experience, even in this pandemic, if you find someone to share even just your feelings, that's very helpful. Dr Cindy St. Hilaire: We're almost lucky that this happened now where we can have platforms like Zoom, and Adobe Connect, where we can have these virtual conferences because at least on all the different committees I'm on, ATVB and BCVS, we can have these discussions and break-out sessions, so I think it's really... We're lucky it's happening now and not 1997 when there's no video. Dr Yang Zhou: Concerns... We all feel that the University and the Department, they all responded very quickly and they have much more support here than before. Dr Emmanouil Tampakakis: As a more senior, what advice can you give us as a more senior person? Dr Cindy St. Hilaire: Oh gosh, more senior? Well thank you. My advice? I definitely agree on the collaboration, I think that's key. Finding sponsors is equally important, someone who's going to go to bat for you. Finding a safety net where you can send someone a half-baked game page and have them tell you just how bad it is and be honest and be willing to give you that kind of critical feedback is really important. Building your network is key, and getting involved in societies and getting people to know you independently from your former mentor, I think is really critical. Yes, you want to collaborate but you also got to make sure that you have your own path in the sand, to make sure you can move forward independently, and have fun while you're doing it, like you said. Great, well I wish you all the best of luck. Congratulations again on being recognized and I'll see you on the BCVS webinar. That's it for our highlights from the late July and early August issues from Circulation Research. Thank you for listening. Please check out the Circulation Research Facebook page and follow us on Twitter and on Instagram with the handle @CircRes and #discoverCircRes. Thank you to our guests, Drs Venu Venna and Juneyoung Lee, and to the BCVS Outstanding Early Career Investigator Finalists, Shyam Bansal, Emmanouil Tampakakis, and Yang Zhou. This podcast is produced by Rebecca McTavish and Ishara Ratnayake, edited by Melissa Stoner, and supported by the editorial team at Circulation Research. Some of the copy text for the highlighted articles is provided by Ruth Williams. I'm your host, Dr Cindy St. Hilaire and this is Discover CircRes, your on-the-go source for the most exciting discoveries in basic cardiovascular research.  

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.18.101147v1?rss=1 Authors: Bermudez-Martin, P., Becker, J. J., Fernandez, S. P., Costa-Campos, R., Barbosa, S., Martinez Gili, L., Myridakis, A., Dumas, M. E., Bruneau, A., Cherbuy, C., Langella, P., Chabry, J., Barik, J., Le Merrer, J., Glaichenhaus, N., Davidovic, L. Abstract: Background: Perturbations of the microbiota-gut-brain axis have been identified in autism spectrum disorders (ASD), suggesting that the microbiota could be involved in the development or maintenance of abnormal social and stereotyped behaviors in ASD patients. Yet, the underlying mediators and mechanisms remain unclear. We hypothesized that microbial metabolites produced by the gut microbiota contribute to behavioral deficits in ASD. We focused on p-Cresol, a microbial metabolite previously described as abnormally elevated in ASD patients. Methods: Wild-type mice were chronically treated with p-Cresol in drinking water to mimic intestinal exposure. We combined behavioral phenotyping, electrophysiology, microbiota 16S sequencing and fecal microbiota transplantations to decipher the consequences of p-Cresol exposure. Results: We showed that p-Cresol selectively induced behavioral alterations reminiscent of ASD core symptoms: social behavior deficits, stereotypies and perseverative behaviors, but no changes in anxiety, locomotion or cognition. We further showed that p-Cresol decreases the activity of dopamine neurons in the ventral tegmental area (VTA), a key brain region for social reward processing. In addition, we reveal that p-Cresol remodels the intestinal microbiome, impacting specific bacterial taxa associated with social behavior deficits and stereotypies. We further demonstrated that social behavior deficits are transferred to control mice after transplantation of microbiota from p-Cresol-treated mice. Finally, both social interactions and VTA dopamine neurons activity were normalized in p-Cresol treated mice after transplant of microbiota from control mice. Conclusions: Our study suggests that the microbial metabolite p-Cresol could be involved in the development of autistic behaviors through remodeling of the gut microbiota. Copy rights belong to original authors. Visit the link for more info

Interview with Robin Patel, M.D., and Justin Kreuter, M.D. This episode discusses a “universal” gene in all bacteria,16S ribosomal RNA gene. It has regions of high conservation and areas of variability. It can be targeted by PCR in such a way that any bacterium’s 16S ribosomal RNA gene is amplified and then the amplified product can be sequenced to identify the source bacterium.

Home health testing is all the rage. But which one of the many services available provides the most accurate results? And is there a platform with more to offer than information? A platform that delivers actionable advice for solving your health challenges or improving your performance? Dr. Christopher Mason is an Associate Professor at Weill Cornell Medicine and Cofounder of Onegevity Health, a platform designed to empower individuals to maintain optimal health by democratizing access to actionable information from leading-edge biomedical research. Dr. Chris earned his BS in Genetics and Biochemistry from the University of Wisconsin-Madison and his PhD in Genetics from Yale. On this episode of Ali Fitness, Dr. Chris joins us to discuss what differentiates Onegevity from other genetic testing services. He explains why the team started with Gutbio and walks us through the process of testing your gut microbiome with a Onegevity kit. Dr. Chris also offers insight around Onegevity’s products in development, including Performbio for athletes and Fembio for women. Listen in to understand who can benefit from using their health intelligence platform and learn what Onegevity has to offer in terms of genetically tailored products and actionable results! Topics Covered [1:13] The fundamentals of Onegevity Health Health intelligence platform Measure, monitor and act on info re: molecular profile Microbiome, genetics/DNA + blood [3:07] What differentiates Onegevity from other genetic testing Actionable and specific, customized plan for individual Uses more precise shotgun sequencing (vs. 16S) and AI [9:22] Why Onegevity Health started with Gutbio Easy to collect sample, know system well Plastic part of biology (modify + improve) [10:22] Who should use Onegevity Health testing Healthy and curious, want to improve performance Suffer from dysbiosis, IBS or IBD Recovering from recent traumatic condition [12:10] The Onegevity Health results report Reviewed by physician but anyone can understand Suggests genetically tailored products to resolve issues [13:13] Onegevity Health’s partnership with Thorne supplements Trusted by physicians, professional athletes Systematic research to quantify what works [17:30] Onegevity’s forthcoming Performbio for athletes Look at nutrition, training load, stress and sleep Incorporate data from wearables (e.g.: Fitbit) [20:22] Where Onegevity Health is available Expanding network of physicians in 42 states Partnership with Kirin for Japanese market [22:04] Onegevity’s OneDraw blood collection device Must be supervised by healthcare professional [22:30] What’s next for Onegevity Health Fembio for issues specific to women’s health [25:23] How to test your gut microbiome with Onegevity Order kit online (routed through physician) Collect and send stool sample Receive report via email or app [29:46] Dr. Chris’ insight around food sensitivities Low-level exposure reduces risk of allergy later In early days of predicting and understanding [32:19] How to measure quality in at-home health testing ‘Proof is in the phenotype’ (how people feel) Use tool like Lab100 to quantify what works [34:22] Why Dr. Chris believes Onegevity is the best Use cutting-edge, modern methods Most extensive phenotyping platform that exists Learn More About Dr. Christopher Mason Onegevity Health Dr. Chris on LinkedIn Resources Dr. Joel Dudley Thorne Supplements Oura Ring Fitbit Kirin Onegevity + Kirin Press Release Dr. Theresa Hardy Onegevity on the App Store Onegevity on Google Play ‘Randomized Trial of Peanut Consumption in Infants at Risk for Peanut Allergy’ in The New England Journal of Medicine ‘The Rise of Food Allergy: Environmental Factors and Emerging Treatments’ in EBioMedicine EverlyWell Lab100

Lucy Mailing is an MD/PhD student at the University of Illinois. She recently completed her PhD in Nutritional Sciences and continues to perform research on the impact of diet and exercise on the gut microbiome in states of health and disease. She has authored several peer-reviewed journal articles related to the microbiome and health and was recently named an Emerging Leader in Nutritional Sciences by the American Society for Nutrition. Lucy has also been a staff research associate for the Kresser Institute for four years and writes about evidence-based gut health on her blog. She plans to begin medical school at the University of Illinois in 2020 after a year dedicated to writing and the launch of a gut-related startup. In this podcast, Lucy discusses the most promising trends and research in gut health. She talks about the best and worst ways to test for GI problems and the effects of exercise intensity and diet change on the gut microbiota. She also challenges the notion that ketogenic and high-fat diets are bad for the gut, and explains why your SIBO breath test results might be inaccurate.  Lucy is a fine example of one of the many wonderful experts who have shaped NBT into what it is today—an online clinic helping athletes and likeminded people overcome chronic health complaints and improve performance. If you’re an athlete and you’ve been listening to the podcast for a while and you’re still struggling with your gut health, feel free to come to the front page where you’ll find a button to book a free starter session. During the session, we’ll take a look at your history and share how we’d work with you. We now have a variety of billing options, one of which will make sense for you. Here’s the outline of this interview with Lucy Mailing: [00:00:21] Ancestral Health Symposium; Lucy’s presentation slides; Look for the video from Lucy’s 2019 presentations to be posted on the AHS YouTube channel in the upcoming months.  [00:01:17] Becoming interested in the microbiome. [00:03:01] Working with Chris Kresser; ADAPT Health Coach Training. [00:07:49] Why the focus on the microbiome? [00:08:25] Transplanted human microbiome into sterile mice, mice take on phenotype of donor; Study: Zheng, P., et al. "Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism." Molecular psychiatry 21.6 (2016): 786. [00:09:30] What does a healthy microbiome look like? [00:13:09] Viome; metatranscriptomics. [00:14:37] 16S testing; uBiome. [00:15:06] Proteobacteria as a red flag that colonic epithelial cells are starving for energy. Study: Hughes, Elizabeth R., et al. "Microbial respiration and formate oxidation as metabolic signatures of inflammation-associated dysbiosis." Cell host & microbe 21.2 (2017): 208-219. [00:16:24] Jason Hawrelak; Podcast: How to Use Probiotics to Improve Your Health. [00:17:29] Butyrate; Is supplementing a good idea? Tesseract, ProButyrate. [00:21:17] Dietary recommendations: Microbiota accessible carbohydrates (term from Justin Sonnenberg). [00:22:37] Preliminary evidence that reduced carbohydrate diet may be beneficial for people with inflammatory bowel disease; Study: Suskind, David L., et al. "Clinical and fecal microbial changes with diet therapy in active inflammatory bowel disease." Journal of clinical gastroenterology 52.2 (2018): 155. 00:23:42] Carnivore diet. [00:25:01] Dr. Michael Mosley; Robb Wolf. [00:27:59] Fecal microbiota transplant (FMT) from ketogenic mice; Study: Olson, Christine A., et al. "The gut microbiota mediates the anti-seizure effects of the ketogenic diet." Cell 173.7 (2018): 1728-1741. [00:29:54] Autologous FMT restores the ecosystem after antibiotics: Study: Taur, Ying, et al. "Reconstitution of the gut microbiota of antibiotic-treated patients by autologous fecal microbiota transplant." Science translational medicine 10.460 (2018): eaap9489. [00:31:17] Mike T Nelson; Podcasts: 1. High Ketones and Carbs at the Same Time? Great Performance Tip or Horrible Idea…, 2. The Importance of Strength Training for Endurance Athletes, 3. How to Assess an Athlete: The Best Principles, Methods, and Devices to Use. [00:33:35] Taymount Clinic for FMT. [00:34:11] Recent FDA report on risks of infection related to FMT. [00:34:49] Doctor's Data stool testing; PCR sequence-based testing. [00:35:40] Culture vs PCR. [00:39:27] Diagnostic Solutions GI-MAP as a PCR DNA stool test. [00:41:04] Metagenomics; Onegevity, Sun Genomics, DayTwo. [00:42:37] Small Intestinal Bowel Overgrowth (SIBO) breath testing; Mark Pimentel, MD. [00:42:57] Dr. Bryan Walsh. [00:43:33] Lucy's blog posts on SIBO breath testing: All about SIBO: Small Intestinal Bacterial Overgrowth, and What the latest research reveals about SIBO. [00:43:41] A positive breath test may not be due to SIBO; Study: Connolly, Lynn, and Lin Chang. "Combined orocecal scintigraphy and lactulose hydrogen breath testing demonstrate that breath testing detects orocecal transit, not small intestinal bacterial overgrowth in patients with irritable bowel syndrome." Gastroenterology 141.3 (2011): 1118-1121. [00:46:11] Individuals with SIBO may in fact have small intestinal dysbiosis; Study: Saffouri, George B., et al. "Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders." Nature communications 10.1 (2019): 2012. [00:48:00] What you can learn from a uBiome Explorer 16S test. [00:54:17] Probiotics, prebiotics; Pomegranate husk powder. [00:58:02] Response to prebiotics is highly individualized; Study: Venkataraman, A., et al. "Variable responses of human microbiomes to dietary supplementation with resistant starch." Microbiome 4.1 (2016): 33. [00:59:50] Effects of exercise on the microbiome; Studies: 1. Allen, Jacob M., et al. "Exercise alters gut microbiota composition and function in lean and obese humans." Med Sci Sports Exerc 50.4 (2018): 747-757; 2. Allen, Jacob M., et al. "Voluntary and forced exercise differentially alters the gut microbiome in C57BL/6J mice." Journal of applied physiology118.8 (2015): 1059-1066; 3. Allen, J. M., et al. "Exercise training-induced modification of the gut microbiota persists after microbiota colonization and attenuates the response to chemically-induced colitis in gnotobiotic mice." Gut Microbes 9.2 (2018): 115-130. [01:02:26] Research on the microbiome of marathoners; Study: 1. Zhao, Xia, et al. "Response of gut microbiota to metabolite changes induced by endurance exercise." Frontiers in microbiology 9 (2018): 765; 2. Scheiman, Jonathan, et al. "Meta-omics analysis of elite athletes identifies a performance-enhancing microbe that functions via lactate metabolism." Nature Medicine (2019): 1. [01:02:39] Lauren Petersen; Study: Petersen, Lauren M., et al. "Community characteristics of the gut microbiomes of competitive cyclists." Microbiome 5.1 (2017): 98. Our 2016 podcast with Lauren: The Athlete Microbiome Project: The Search for the Golden Microbiome. [01:05:51] Find Lucy: NextGen Medicine. [01:07:04] Dr. Josh Turknett’s Migraine Miracle. Our podcast with Josh: The Migraine Miracle.

I skrivelsen de sände honom stod:”Var hälsad, konung Dareios! 8Må det bli känt för konungen att vi for till provinsen Juda och såg att den store Gudens tempel byggs upp i huggen sten, med trävirke i väggarna. Arbetet görs grundligt och går stadigt framåt. 9Vi förhörde de äldste och frågade vem som hade gett dem befallning att bygga och inreda templet. 10Vi frågade dem också vad de hette för att skriva upp namnen på deras ledare och kunna underrätta dig. 11Vi fick detta svar:Vi tjänar himlens och jordens Gud. Vi bygger upp det tempel som en gång för många år sedan uppfördes här. En stor konung i Israel byggde och färdigställde det. 12Men eftersom våra fäder gjorde himlens Gud vred utlämnade han dem åt kaldén Nebukadnessar, den babyloniske konungen. Och han förstörde detta hus och förde bort folket till Babylonien. 13Men under sitt första regeringsår gav konung Kyros av Babylonien befallning att detta tempel skulle återuppbyggas. 14Och de kärl av guld och silver som tillhört Guds hus, men som Nebukadnessar hade tagit från Jerusalems tempel och fört till templet i Babylon, hämtade nu konung Kyros därifrån och överlämnade åt en man vid namn Sheshbassar, som han hade utnämnt till ståthållare. 15Han sade: ’Ta dessa kärl och för dem till templet i Jerusalem, ty Guds hus skall byggas upp på sin gamla plats.’ 16Så kom Sheshbassar hit och lade grunden till Guds hus i Jerusalem. Och från den tiden tills i dag har man byggt, och det är ännu inte färdigt. 17Om det behagar konungen må man efterforska i den kungliga skattkammaren i Babylon om konung Kyros verkligen gav befallning att bygga detta tempel i Jerusalem. Låt sedan meddela oss konungens beslut i denna fråga.”Esra 5:7-17 (Bibel 2000)Marie Ek Lipanovskahttp://www.marieeklipanovska.se

荣耀赵明回应挖孔发黄问题，V20渲染图参数曝光 黄章表示无刘海才是王道，魅族16S将因成本涨价……

Dr Carolyn Lam:                Welcome to Circulation on The Run, your weekly podcast summary and backstage pass to the journal and it's editors. I'm Dr Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. We will be discussing accelerated diagnostic protocols for chest pain, a very, very important issue in Cardiology with very important new safety and effectiveness data on one such protocol provided in our feature paper this week. Coming right up after these summaries.                                                 Our first original paper this week identifies a new link between specific gut bacteria and atherosclerosis. Co-First authors, Dr Yoshida and Emoto, corresponding author, Dr Yamashita, from Kobe University Graduate School of Medicine, and colleagues recruited patients with coronary artery disease and controls without coronary artery disease but with coronary risk factors. They then compared gut microbial composition using 16S ribosomal RNA gene sequencing in fecal samples. Subsequently, they used atherosclerosis prone mice to study the mechanisms underlying the relationship between such species and atherosclerosis. Their analysis of gut microbial profile in patients with coronary artery disease showed a relative depletion of bacteroides vulgatus and bacteroides dorei compared to controls with coronary risk factors. Gavage with live bacteroides vulgatus and bacteroides dorei decreased fecal and plasma lipopolysaccharide levels and protected against atherosclerosis in apoE deficient mice. Fecal lipopolysaccharide levels in patients with coronary artery disease were significantly higher compared to controls. These findings suggest that bacteroides treatment may serve as a novel and effective therapeutic strategy for suppressing lipopolysaccharide-induced inflammatory response in coronary artery disease.                                                 The next paper identified a potential novel molecular target in the treatment of myocarditis. Co-First authors, Dr Chen and Zeng, Co-Corresponding authors, Dr Song from Fuwai Hospital in Beijing, and Dr Yang from Shenzhen University School of Medicine, and their colleagues aim to elucidate the role of BCL2 Like protein 12 in the pathogenesis of biased T Helper-2 response in myocarditis. Using a combination of mouse models of myocardial inflammation and human hearts from patients undergoing heart transplantation, the authors found that CD4 positive T-cells isolated from hearts in myocarditis at the end stage of heart failure expressed high levels of BCL2 Like protein 12, which was required for the development of aberrant T Helper 2 polarization in the heart. Thus, BCL2 Like protein 12 may be a novel target in the treatment of myocarditis, as well as other T Helper 2 biased inflammatory processes.                                                 Could vaccination against LDL be a way to prevent atherosclerosis? Well, the next paper brings us one step closer to this dream. First author, Dr Gisterå, corresponding author, Dr Hansson from Karolinska School University Hospital and colleagues developed T-cell receptor transgenic mice to study LDL autoimmunity in a humanized hypercholesterolemic mouse model of atherosclerosis. A strong T-cell dependent E-cell response was induced by ODL leading to production of anti-LDL IgG antibodies that enhanced LDL clearance and ameliorated atherosclerosis. Results show that anti-LDL immuno-reactivity evoked three atheroprotective mechanisms, namely 1) antibody-dependent LDL clearance, 2) increased cholesterol excretion, and 3) reduced vascular inflammation, thus targeting LDL-reactive T cells may enhance atheroprotective immunity, and vaccination against LDL components may be an attractive way to prevent atherosclerosis.                                                 MicroRNAs regulate nearly all biological pathways and dysregulation of MicroRNAs is known to lead to disease progression. However, are there cell type specific effects of MicroRNAs in the heart? Co-First authors, Drs Rogg and Abplanalp, corresponding author, Dr Dimmeler from Goethe University Frankfurt, and colleagues assessed MicroRNA target regulation using MicroRNA 92a3p as an example. Their data showed that MicroRNAs have cell type specific effects in vivo which would be overlooked in bulk RNA sequencing. Analysis of MicroRNA targets in cell subsets disclosed a novel function of MicroRNA 92a3p in endothelial cell autophagy and cardiomyocyte metabolism. These findings may have clinical applications for the fine tuning of autophagy and metabolism to mitigate tissue damage in patients with cardiac disease.                                                 The next paper establishes a mechanism by which cardiac inflammation may be initiated in response to hemodynamic stress, but in the absence of significant cardiomyocyte cell death. Co-First authors, Drs Suetomi and Willeford, Co-Corresponding authors, Drs Brown and Miyamoto from University of California San Diego, and their colleagues used conditional cardiomyocyte-specific calcium calmodulin-regulated kinase Delta all CaM kinase II Delta knockout mice to demonstrate that cardiomyocytes generate inflammatory chemokines and cytokines and are the initial site of NLRP3 inflammasome activation. They further identified a causal role for CaM-Kinase II Delta-mediated activation of NLRP3 inflammasome and inflammatory responses in macrophage recruitment, cardiac fibrosis, and development of heart failure induced by pressure overload. Their elegant mouse experiments revealed sites and mechanisms of proinflammatory gene and inflammasome activation within cardiomyocytes which could serve as targets for early intervention or disease prevention.                                                 Are there different metabolomic effects between PCSK9 inhibitors and statins? First author, Dr Sliz, Corresponding Author, Dr Würtz from Nightingale Health Limited in Helsinki, Finland, and their colleagues quantify 228 circulating metabolic measures by Nuclear Magnetic Resonance Spectroscopy for over 5300 individuals in the PROSPER Trial at six months post randomization. The corresponding metabolic measures were also analyzed in eight population cohorts, including more than 72,000 individuals using a specific PCSK9 inhibitor SNP as an unfounded proxy to mimic the therapeutic effects of PCSK9 inhibitors. Scaled to an equivalent lowering of LDL cholesterol the effects of genetic inhibition of PCSK9 on these 228 metabolic markers were generally consistent with those of statin therapy. Alterations of lipoprotein lipid composition and fatty acid distributions were also similar. However, discrepancies were observed for very low-density lipoprotein or VLDL lipid measures where genetic inhibition of PCSK9 had weaker effects on lowering VLDL cholesterol compared with statin therapy. Genetic inhibition of PCSK9 showed no significant effects on amino acids, ketones, or a marker of inflammation, where a statin treatment weekly lowered this marker of inflammation. Thus, if VLDL lipids have an independent causal effect on cardiovascular disease risk, the observed discrepancy on VLDL lipid lowering could contribute to differences in cardiovascular risk reduction between statins and PCSK9 inhibitors for an equivalent reduction in LDL cholesterol. Moreover, these results exemplify the utility of large-scale metabolomic profiling with genetics and randomized trial data to uncover potential molecular differences between related therapeutics.                                                 The final original paper this week demonstrates a novel biomarker discovery paradigm to identify candidate biomarkers of cardiovascular and other diseases. Co-First authors, Dr Mosley and Benson, co-corresponding authors, Dr Wang from Vanderbilt University Medical Center and Gerszten from Beth Israel Deaconess Medical Center, and their colleagues employed a virtual proteomic approach linking genetically-predicted protein levels to clinical diagnosis in more than 40,000 individuals. They used genome-wide association data from the Framingham Heart Study to construct genetic predictors for more than 1100 plasma protein levels. They validated the genetic predictors for 268 proteins and used them to compute predicted protein levels in more than 41,000 genotyped individuals in the eMerge Cohort. They tested associations for each predicted protein with more than 1100 clinical phenotypes. These associations were validated using directly-measured protein levels and either LDL cholesterol or subclinical atherosclerosis in the Malmo Diet and Cancer study. Using this virtual biomarker strategy the authors identified CLC1B and PDGFR Beta as potential circulating biomarkers of atherosclerosis and validated them in an epidemiologic cohort. Thus, these results demonstrate that a virtual biomarker study may efficiently identify potential biomarker disease associations, and that wraps it up for our summaries. Now for our feature discussion.                                                 Accelerated diagnostic protocols for testing are used everywhere. They're designed to improve the quality and value of chest pain risk stratification. However, many of them lack sufficient prospective safety and effectiveness data. We're so pleased to have a paper today that provides such important data on one of these accelerated diagnostic protocols for chest pain, and it's the HEART Pathway. To discuss this, I've got the corresponding author of today's featured paper, Dr Simon Mahler from Wake Forest School of Medicine, as well as our Associate Editor, Dr Deb Diercks from UT Southwestern. Simon, could you start by just telling us, what is the HEART Pathway? Dr Simon Mahler:             Sure. Yeah, it's an accelerated diagnostic protocol. It's based on an accelerated diagnostic protocol called the HEART Score. We use a modified version of the Heart Score. We actually use a HEAR score, and that stands for the history, EKG, Age, and risk factors. That is combined with two troponin measures at 0 and 3 hours. We also factor in whether or not the patient has had prior coronary artery disease or has an acute ischemic EKG. So, to be low-risk you have to have a HEAR score of 0-3. HEAR is an acronym. You get points for each of those categories. If you have less than 3 points that's a low score. You have to have a low score, a non-ischemic EKG, no history of prior coronary disease, and two troponins less than a 99th percentile at 0 and 3 hours to be considered low risk and recommended for early discharge. If you don't meet any of those criteria then you are considered non-low risk and appropriate for further in-hospital evaluation. Dr Carolyn Lam:                That's great. Could you just tell us what you did to give us some real-world safety and effectiveness data on this. Dr Simon Mahler:             Yeah, so we had done a single-site randomized controlled trial. That was published in 2015 in Circulation: Quality and Outcomes, and really showed some promising results. We received some funding to do an implementation trial. So, this is the results of our implementation study. It's a before and after study. What we did was we sought to implement a HEART Pathway as a clinical decision support tool, integrated fully into our electronic medical record so that when providers see the patient with chest pain and order a troponin they interact with a HEART Pathway tool that guides them through the HEART Pathway risk assessment and then provides real-time decision support regarding their treatment and disposition decisions based on whether or not the patient has a low-risk assessment or a non-low-risk assessment. The design of the study was we collected data on all patients with chest pain and troponin order for one year while we worked on how we were gonna build this tool and embed it, and then we had three month watching period where we built the tool into the electronic health record across our three sites. Then, we had one year where we were post implementation where we collected data and looking at the difference in outcomes, particularly looking at both safety and utilization outcomes before and after use of the HEART Pathway. Dr Carolyn Lam:                That's just such a clever design. Just give us a summary of the results before I ask Deb to chime in here. Dr Simon Mahler:             There's a few really important things that we found. Probably the most important thing was the safety data that came out of this study. We had some good safety signals on prior studies. They didn't have enough sample size to really have a good precision around the safety point estimate, so in this study we had over 4000 patients in our post-implementation cohort, and about 31%, 30.7%, of those patients were classified as low-risk by the HEART Pathway. Among those patients that were classified by low-risk, the rate of death and MI, the composite outcome at 30 days, was 0.4%. Typically for these accelerated diagnostic protocols we want them to have an adverse cardiac event rate less than 1%, so a finding of 0.4% with a confidence in our role that doesn't extend beyond 1% that was a really important finding that really confirms the safety of this strategy.                                                 The other thing that we found which was interesting was that the use of the HEART Pathway was actually associated with detecting more myocardial infarctions during the index visit, which means that possibly the HEART Pathway use improved the recognition of those patients that were presenting with MIs. It's possible that without using the HEART Pathway some of those cases may have been missed. Finally, we were able to demonstrate that use of the HEART Pathway as a clinical decision support tool was able to decrease hospitalizations and some other utilization metrics such as stress testing and possible length of stay. Dr Carolyn Lam:                Oh, that's awesome, Simon. I said it earlier. I'm gonna say it again. Thank you so much for publishing this wonderful work with Circulation. I really think that implementation, science, and decision support tools you've got that all in this paper, just beyond even the actual topic. Deb, take us behind the scenes a little bit with how we reacted as editors to this paper, please. Dr Deb Diercks:                 Well, I think that overall, we were really excited about this paper. It really does add a real, real context to something we were really discussing and wondering about. I think one of the great things about the implementation, and Simon, please comment on this, is the diversity of the places that you actually used this in. I mean, most of us when we look at papers there's always a fear that it won't be able to be generalized to real-world practices. Correct me if I'm wrong, but you really applied it to just a wide variety of Emergency Departments that really support that this could be used anywhere. Dr Simon Mahler:             Yeah, I think that's a really important point, that we did this across our system so that included a large academic busy Emergency Department that sees over 100,000 patients per year, all the way, basically to a smaller 12,000 per year, essentially almost a free-standing Emergency Department at the time that we started our study; it now has inpatient bed capacity, and then a suburban/rural hospital, as well, with about 30,000 patient visits per year. We extended beyond kind of the typical kind of comfort zone of large academic centers and into smaller community Emergency Departments as well. Dr Deb Diercks:                 One of the things that this manuscript nicely articulated is that you kind of break it into the HEAR and then the troponin. Dr Simon Mahler:             Right. Dr Deb Diercks:                 Things change in the US with troponin. How do you think that's gonna impact how you guys apply this Pathway in the future? Dr Simon Mahler:             It's a big topic of discussion right now, what to do with these Pathways. Are these Pathways still needed with the availability now of high-sensitivity troponins in the United States? I think that for many years as we've kind of followed data coming out of Europe we've been anxiously awaiting the arrival of these tests in the U.S., and there's a lot we can learn from the European data so far. Most of that data suggests that the high-density troponins are best used still in the context of a Pathway or an accelerated diagnostic protocol.                                                 I think that this particular study was conducted just using contemporary troponins, particularly given the time frame of the study in which we were accruing patients from 2013 through 2016, but I think it's still gonna be highly relevant, because I think that best practices are gonna still require us to use some sort of structured framework with high-sensitivity troponins. Now, it does remain to be seen a little bit what the best Pathway is gonna be to incorporate that. My take on this is that I believe that clinical decisions support tools or decision aids integrated with high-sensitivity troponins is going to be the best way to go. I'm a little bit skeptical about troponin-only approaches. Dr Deb Diercks:                 That's a great summary. I don't think it's time to throw out all the value of that risk stratification tool, and I think your study showed that how it can easily be incorporated into what we do in a manner that doesn't really negatively impact the work flow, which I think is so important. Dr Simon Mahler:             You know, we did a smaller study where we looked at the performance of the HEART Pathway with high-sensitivity assays. We studied it with both the Roche troponin high-sensitivity troponin T and the Abbott high-sensitivity I, and at the 99th percentile it actually made very little difference in terms of the performance of the HEART Pathway. What the potential advantages of incorporating high-sensitivity assays is that you probably no longer need a 0 and 3 hours, evaluation can be condensed. I think there's a lot of really interesting questions that availability of high-sensitivity troponins has created, and I think that there's gonna be a lot of emerging evidence over the next few years about new Pathways, and what are the best ways to fully take advantage of these higher-sensitive assays because, frankly, most of the decision aids that are currently in use they were developed using contemporary troponins, and they may not fully take advantage of high-sensitivity troponins. We may see modifications of our Pathway, and it will interesting to see kind of how things evolve as we study the impact of high-sensitivity troponin. Dr Carolyn Lam:                Wow, exciting work ahead. Just one last question regarding the future. So, you followed up the patients in your study for 30 days. Am I wrong? Any plans to follow them up longer, and do you think such data are needed? Dr Simon Mahler:             Yeah, we actually followed them for a year. Our primary analysis was through 30 days, and so we do have one-year data on all of our patients, and so we'll be doing a secondary analysis looking out to a year. Yeah, you can look forward to that coming up hopefully in the next six months or so. Dr Carolyn Lam:                That is awesome. Thank you so much, Simon. Thank you so much, Deb. Thank you, listeners, for joining us today. You've been listening to Circulation on the Run. Don't forget to tune in again next week. This program is copyright American Heart Association 2018.

Robin Patel discusses her work on prosthetic joint infections and how metagenomics is changing infectious disease diagnostic procedures. Take the listener survey: asm.org/mtmpoll Julie’s Biggest Takeaways: The term antimicrobial resistance can mean many things. Although acquisition of genetic elements can lead to drug resistance, so can different growth lifestyles of bacteria; the same bacteria growing in liquid culture may be more susceptible to a drug than those bacteria growing on a biofilm. Lifestyle and genetics can intertwine, however, when bacteria growing as a biofilm exchange resistance genes through horizontal gene transfer. How do bacteria reach an implanted surface, such as on a prosthetic joint, to cause infection? It may rarely occur during surgery, if even a single bacterium reaches the joint surface despite the sterile conditions; alternatively, it could occur through hematogenous spread (through the blood) after the surgery is over. Most infections are believed to be seeded at the time of implantation. While scientists don’t perform teeny, tiny implants in animal models of infection, the materials are placed in animal bone to mimic as similar an immune response as possible. Targeted metagenomics and shotgun metagenomics are both being developed clinically. Targeted metagenomics looks at one specific gene found in a number of species, such as the 16S ribosomal RNA gene. Shotgun metagenomic looks at all DNA present, and requires a lot more cleaning up to eliminate human genomic material, which is the major sequence of any human-derived sample.  

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Lynn Nichols Federal Tax Update Podcast April 16, 2018, edition   Listen as Lynn Nichols provides commentary on 6 Items pertaining to current developments in U.S. tax law. This week’s topics include: OUR PROGRAM THIS WEEK INCLUDES . . . . . . IRS Fact Sheet Outlines Options for Taxpayers Who Can't Pay What's Owed The IRS has advised individuals who can't pay all of their tax bill to file their return on time and pay as much as possible, which will help reduce penalties and interest, and to seek options provided by the IRS if they can't pay at all. [FS-2018-8; 4/13/2018]                                                                                                                                                                                                        Student Loan Repayments to Doctors Are Excludable From Income In a legal memorandum, the IRS concluded that cash awards made under a state’s student loan repayment program are excludable from the recipients’ gross income under section 108(f)(4) and that the state isn’t required to file or provide any information returns regarding those payments. [ ILM 201815016; 1/8/2018, rel. 4/16/2018] Extension Granted to Adjust Basis of Partnership Property The IRS granted a partnership an extension of time to file an election under section 754 to adjust the basis of partnership property. [LTR 201815002; 11/30/2017; rel/ 4/13/2018     PRACTITONER ALERT ! ! ! Questions Loom Over Repeal of Alimony Tax Provisions Upcoming IRS guidance on the repeal of alimony tax provisions is unlikely to answer some of the more pressing questions in the area that practitioners are wrestling with. [Tax Notes Today Article; 4/17/2018; by Eric Yauch     Individual Fails to Establish Entitlement to Innocent Spouse Relief The Tax Court, in a summary opinion, denied an individual innocent spouse relief from joint tax liabilities with her former husband, finding that there was no evidence that she would suffer economic hardship if held liable, that she had reason to know the tax liability wouldn’t be paid, and that she benefited from the underpayment. [ Suwareh, Chinelo Nwankwo et al. v. Commissioner; No. 7233-16S; T.C. Summ. Op. 2018-23; 4/16/2018]     Engineer Can’t Deduct Many Expenses He Claimed for Music Activities The Tax Court, in a summary opinion sustaining accuracy-related penalties, held that an engineer wasn’t entitled to many of the loss deductions he claimed for his music activities, finding that, while he substantiated most of his expenses, many of them were nondeductible personal, living, or family expenses under section 262(a). [Nicholson, Aaron Keith v. Commissioner; No. 17625-16S; T.C. Summ. Op. 2018-24; 4/18/2018]

Lynn Nichols Federal Tax Update Podcast April 16, 2018, edition   Listen as Lynn Nichols provides commentary on 6 Items pertaining to current developments in U.S. tax law. This week’s topics include: OUR PROGRAM THIS WEEK INCLUDES . . . . . . Partnership Denied $1.8 Million Deduction for Easement Donation The Tax Court, declining to impose a penalty, held that a land development partnership wasn’t entitled to a $1.8 million charitable contribution deduction for the donation of a conservation easement, finding that the easement was donated with the expectation of receiving a substantial benefit and that the value of the easement was zero. [Wendell Falls Development LLC et al. v. Commissioner; No. 3494-14; T.C. Memo. 2018-45, 4/4/2018]   Reconstruction of Mileage Logs Falls Short of Substantiation Rules The Tax Court, sustaining an accuracy-related penalty, held that an attorney with multiple law offices wasn’t entitled to a deduction for his business-related vehicle expenses, finding that his attempt to reconstruct the expenses failed to satisfy section 274(d)’s strict substantiation requirements. [Velez, Alavaro G. v. Commissioner; No. 23718-15; T.C. Memo. 2018-46, 4/5/2018] Individual's Questionable Mileage Summary Wrecks Deduction Claims The Tax Court, in a summary opinion imposing accuracy-related penalties, held that an individual failed to properly substantiate his Schedule C car expenses for two tax years, finding that his estimated mileage summary contained “far too many . . . irregularities, errors, and questionable and improbable entries to be considered reliable."   Restless Retiree’s Costs to Remodel House Are Capital Expenditures The Tax Court, in a summary opinion, held that a couple may not deduct expenses related to a house remodeling project meant to occupy the husband’s time during retirement, finding that his activity was not a trade or business and that expenses incurred to improve the house, a capital asset, may only be treated as capital expenditures. [Havener, Shane et ux. v. Commissioner; No. 4506-16S; T.C. Summ. Op. 2018-17; 4/4/2018]   Wrong Year on Tentative Claim Results in Denial of $3 Million Refund A U.S. district court denied an investment holding company’s refund of $3 million for its 2005 tax year stemming from the carry back of losses for 2008, finding that the company failed to file a timely formal or informal refund claim because the form it filed for a tentative refund was for the wrong tax year and the court lacked jurisdiction. [UPK Holdings Inc. v. United States; USDC E NY; No. 1:15-cv-06431, 4/6/2018]   Individual Can’t Seek Damages for False Corporate Information Return The Eleventh Circuit, in an unpublished per curiam opinion, affirmed a district court’s dismissal of an individual’s suit against a couple and their company seeking damages under section 7434 for the filing of a false information return, finding that he failed to state a claim because the information return was issued for his corporation. [Baker, James v. James Batmasian et al.;  CA 11; No. 17-12830; 4/9/2018]   IRS Issues Transitional Guidance on Treatment of Advance Payments The IRS has issued transitional guidance allowing taxpayers, with or without applicable financial statements, to continue to rely on Rev. Proc. 2004-34 for the treatment of advance payments until coming guidance implementing legislative changes to section 451 is effective. [Notice 2018-35; 2018-18 IRB 1; 4/12/2018

Lynn Nichols Federal Tax Update Podcast April 2, 2018, edition   Listen as Lynn Nichols provides commentary on 10 Items pertaining to current developments in U.S. tax law. This week’s topics include: OUR PROGRAM THIS WEEK INCLUDES . . . . . . Economic Analysis: A Spreadsheet to Calculate the New Passthrough Deduction In economic analysis, Martin A. Sullivan discusses the difficulties new section 199A presents to owners of passthrough businesses. [Tax Notes Today; 4/2/2018; Article by Martin A. Sullivan]   Interest Deductibility Guidance Settles Unanswered Questions The IRS released expected initial guidance on business interest expense limitations that address several questions for which practitioners had been clamoring for answers since the new tax law was enacted, but they yearn for more. [Tax Notes Today; 4/3/2018; Article by Emily Foster] IRS Issues Guidance on Business Interest Expense Limitations The IRS has issued guidance describing regulations that it intends to issue to help taxpayers comply with section 163(j), which was amended by the Tax Cuts and Jobs Act to provide new rules limiting the deduction of business interest expense for tax years beginning after December 31, 2017. [Notice 2018-28; 2018-16 IRB 1; 4/2/2018]   IRS Announces Guidance on Business Interest Expense Limitation The IRS has announced the release of guidance for computing the business interest expense limitation under section 163(j), as amended by Tax Cuts and Jobs Act. [IR-2018-82; 4/2/2018]   Tax Court Upholds Disallowance of Alimony Deduction The Tax Court held that the IRS properly disallowed an attorney's alimony deduction because under Arkansas law his obligation to pay his former wife’s share of their 2009 federal income tax, joint credit card debt, and property taxes survives her death and therefore does not meet all the requirements to qualify as alimony. [Davidson v. Commissioner; No. 24619-15; T.C. Memo. 2018-38; 4/2/2018]   Business Owner’s Loans Flunk the Bad Debt Test The Tax Court, sustaining some accuracy-related penalties but not others, held that an individual used one of his real estate business’s funds to pay another of his companies’ debts, finding that these purported loans weren’t deductible as bad debts but instead were taxable distributions and wages. [Povolny Group Inc. et al v. Commissioner; No. 5935-14; No. 5936-14; T.C. Memo. 2018-37; 4/2/2018]   Tax Court Finds Retirement Benefits Subject to Self-Employment Tax The Tax Court, in a summary opinion, held that retirement benefits received by a businesswoman from a cosmetics company are deferred compensation subject to self-employment tax under section 1401 because they were "derived by an individual from any trade or business carried on by that individual." [Sherman v. Commissioner; No. 13052-16S; T.C. Summ. Op. 2018-15;4/2/2018]   Responsible Person’ Dispute Keeps Payroll Tax Case Alive A U.S. district court, denying summary judgment to the government in a trust fund recovery penalty case, found genuine issues of material fact over whether an individual was a responsible person under section 6672 who willfully failed to pay a company’s payroll taxes. [Ireland, Mike L. v. United States; No. 2:17-cv-02014; 4/2/2018]   Tax Court Upholds Disallowance of Passthrough Loss Deduction The Tax Court held that the IRS properly disallowed a couple’s passthrough loss deduction, finding that their real estate activities could not be grouped with their aircraft chartering activities to determine whether they materially participated in the latter, and that the loss from the chartering activities was a passive loss because they did not materially participate. [Brumbaugh, Charles and C.E. Holifield v. Commissioner; No. 9161-14; T.C. Memo. 2018-40; 4/3/2018]   Partnership Denied $1.8 Million Deduction for Easement Donation The Tax Court, declining to impose a penalty, held that a land development partnership wasn’t entitled to a $1.8 million charitable contribution deduction for the donation of a conservation easement, finding that the easement was donated with the expectation of receiving a substantial benefit and that the value of the easement was zero. [Wendell Falls Development LLC et al. v. Commissioner; No. 3494-14; T.C. Memo. 2018-45, 4/4/2018]   Restless Retiree’s Costs to Remodel House Are Capital Expenditures The Tax Court, in a summary opinion, held that a couple may not deduct expenses related to a house remodeling project meant to occupy the husband’s time during retirement, finding that his activity was not a trade or business and that expenses incurred to improve the house, a capital asset, may only be treated as capital expenditures. [Havener, Shane et ux. v. Commissioner; No. 4506-16S; T.C. Summ. Op. 2018-17; 4/4/2018]   Reconstruction of Mileage Logs Falls Short of Substantiation Rules The Tax Court, sustaining an accuracy-related penalty, held that an attorney with multiple law offices wasn’t entitled to a deduction for his business-related vehicle expenses, finding that his attempt to reconstruct the expenses failed to satisfy section 274(d)’s strict substantiation requirements. [Velez, Alavaro G. v. Commissioner; No. 23718-15; T.C. Memo. 2018-46, 4/5/2018]

Lynn Nichols Federal Tax Update Podcast March 26, 2018, edition   Listen as Lynn Nichols provides commentary on 5 Items pertaining to current developments in U.S. tax law. This week’s topics include: Plastic Surgeon’s Fraud, Tax Evasion Conviction Affirmed   A divided Third Circuit upheld a plastic surgeon’s conviction for fraud and tax evasion stemming from his participation in a tax fraud scheme, finding that the district court didn’t abuse its discretion by excluding evidence that he paid his taxes after discovering he was being investigated or by allowing allegedly unfair comments by the government. [Evdokimow, David v. United States; CA 3; No. 15-3876; 3/19/2018]   IRS Says Vasectomy Decision Could Be Reversible The IRS could revisit its recent decision that male sterilization doesn’t qualify as preventive care under some health plans, but first the agency needs a workable standard for determining what is preventive. (Speech at Employers Council on Flexible Compensation) [Tax Notes Today; 3/20/2018]      Tax Court Determines Tax Home, Denies Travel Expense Deductions The Tax Court, in a summary opinion, sustained the IRS’s disallowance of a couple’s unreimbursed employee business expense deductions for the husband’s travel expenses in the 2013 tax year, finding that his tax home was in Oklahoma where he had been working since 2010 and not in California. [Jahangirian, Hamid et ux. v. Commissioner; No. 25916-16S; T.C. Summ. Op. 2018-14, 3/20/2018]       IRS Urges Tax Professionals to Protect Taxpayer Data The IRS, state tax agencies, and the tax industry have advised tax professionals to beware of taxpayer data theft as the April 17 return filing deadline approaches, urging them to enhance their data safeguards and alerting them to a spear phishing scheme in the form of a new client email scam that has recently reemerged. [IR-2018-68; 3/22/2018]        Tax Court Upholds Levy to Collect LLC’s Late-Filing Penalties The Tax Court held that the IRS didn’t abuse its discretion by sustaining a levy to collect penalties assessed against a limited liability company for the late filing of partnership returns; the court found that the LLC had represented itself as a partnership on returns and rejected its claim that it was not a partnership but a single-member LLC. [ Argosy Technologies LLC v. Commissioner; No. 29856-14L; T.C. Memo. 2018-35; 3/22/2018] 

Lynn Nichols Federal Tax Update Podcast March 19, 2018, edition   Listen as Lynn Nichols provides commentary on 8 Items pertaining to current developments in U.S. tax law. This week’s topics include: IRS Publishes List of Practitioners Subject to Disciplinary Action The IRS has published a list of attorneys, CPAs, enrolled agents, enrolled actuaries, enrolled retirement plan agents, and appraisers who have received disciplinary sanctions for violating the regulations governing practice before the IRS. [Announcement 2018-4; 2018-10 IRB 401; 3/5/2018]   Business Network Loses Exemption The IRS revoked the tax-exempt status of an organization described in section 501(c)(3) because its primary activity is operating a networking event for business owners and investors, which is not an exempt purpose. [LTR 201809011; 9/21/2017]   Tax Court Invalidates Scheme to Bypass Roth IRA Limits A group of taxpayers is on the hook for excise taxes after the Tax Court invalidated their scheme to contribute funds to a foreign sales corporation and then Roth IRAs. [Tax Notes Today; 3/5/2018; Article by Velarde and Madara]      Family Directly Contributed to Roth IRAs, Liable for Excise Taxes The Tax Court, declining to sustain additions to tax, held that funds a couple and their daughter routed from their business through a Bermuda-based foreign sales corporation to their Roth IRAs were contributions from the individuals and held them liable for excise taxes under section 4973 for excess contributions to the retirement accounts.                                                                                                            [Mazzei, Celia et al. v. Commissioner; No. 16702-09; No. 16779-09; 150 T.C. No. 7; 3/5/2018] Architect Was Real Estate Professional, Allowed Rental Loss Deduction The Tax Court, in a summary opinion, held that an architect qualified as a real estate professional during the 2013 tax year and the IRS improperly disallowed a loss deduction for his rental real estate activities under the passive activity loss limitations in section 469. [Franco, Jose et ux. v. Commissioner; No. 22469-16S; T.C. Summ. Op. 2018-9; 3/6/2018]   Company Co-Owner Liable for Trust Fund Recovery Penalties A U.S. district court held that one of the owners of a construction contracting company was a responsible person who willfully failed to pay the company’s employment tax liabilities; the court granted the government a nearly $1 million judgment against him for trust fund recovery penalties. [Davis, Kelly D. v. United States; USSDC CO; No. 1:13-cv-00450; 3/6/2018]   Wife Wasn’t a Real Estate Professional, Losses Limited The Tax Court, sustaining accuracy-related penalties, held that a couple’s rental real estate activities were passive and their losses for those activities were limited under section 469(i), finding that the wife didn’t spend the required time participating in real estate activities to qualify as a real estate professional. [Farrokh E. Pourmirzaie et ux. v. Commissioner; No. 25558-14; T.C. Memo. 2018-26; 3/8/2018]   Lawyer’s Losses From Real Estate Activities Were Capital The Tax Court, in a summary opinion, held that a practicing attorney wasn’t engaged in the trade or business of buying and selling real estate, so his losses from his real estate activities were not subject to ordinary loss treatment, but deductible as capital losses. [Bruce Joseph Levitz v. Commissioner; No. 15393-14S; T.C. Summ. Op. 2018-10; 3/8/2018]   IRS Releases Practice Unit on Shareholder Debt Owed by S Corp The IRS released a practice unit on debt basis for an S corporation shareholder, addressing what qualifies as bona fide debt and whether that debt is owed directly to the shareholder creating debt basis. [SCO/C/53_04_02_01-04 (2016); updated 1/19/2018; 3/8/2018]

Lynn Nichols Federal Tax Update Podcast Feb. 19, 2018, edition   Listen as Lynn Nichols provides commentary on 10 Items pertaining to current developments in U.S. tax law. This week’s topics include:   Partnership Audit Push-Out Election Comes With Strict Timeline Partnerships pushing out adjustments to partners under the new centralized partnership audit regime must do so within 45 days of receiving a final partnership adjustment, even if they are seeking judicial review. [Tax Notes 2/5/2018, Article by Matthew Madara]     IRS Releases Practice Unit on S Corp Debt Basis Adjustments The IRS released a practice unit on adjustments to an S corporation shareholder’s debt basis in various circumstances, explaining why shareholders must track stock basis and debt basis separately. [SCO/C/53_4_2_2-05 (2016)]     S Corp Shareholder Cannot Skip Bona Fide Indebtedness Test The Tax Court rejected an S corporation shareholder’s argument that the section 1366 back-to-back loan rules eliminated the requirement to demonstrate an actual economic outlay, concluding that proving bona fide indebtedness is essential.   Back-to-Back Loan Regs Do Not Alter Bona Fide Indebtedness Test The Tax Court determined that the IRS properly reduced an S corporation owner’s allowable net operating loss carryback, finding that the controlling test still requires the basis in an S corporation’s debt to have “bona fide indebtedness . . . that runs directly to the shareholder”; the court held that the S corporation’s debt was not bona fide. [Meruelo, Homero F. v. Commissioner; No. 1795-13; T.C. Memo. 2018-16; 2/5/2018]     Corporation Can't Deduct Expenses for Purported Home Office Rental The Tax Court held that a corporation whose sole shareholder and employee was a physician can’t deduct expenses for the purported rental of part of the physician’s home, finding that the corporation failed to prove that it had a bona fide rental arrangement rather than an arrangement to make mortgage payments on the physician’s behalf for his home. [Christopher C.L. Ng MD Inc. APC v. Commissioner; No. 13696-16; T.C. Memo. 2018-14]       Rental Property Expenses Were Not Deductible as Business Expenses The Tax Court, in a summary opinion, sustained the IRS’s determination that a couple’s business expense deductions for expenses incurred to repair their commercial rental property were depreciable capital expenditures, finding that they failed to prove the disputed expenses were for deductible repairs. [Brown, Brandon et ux. v. Commissioner; No. 2809-16S; T.C. Summ Op. 2018-6, 2/5/2018]     Treasury Lists 18 New Priorities to Put Tax Law in Motion Treasury is prioritizing 18 guidance projects, including new rules on passthroughs and electing small business trusts, as part of its plans to implement the Tax Cuts and Jobs Act.  [Tax Notes 2/8/2018; Article by Matthew Madara and Fred Stokeld]     Government Says Reliance on CPA Doesn’t Negate Late-Filing Penalties In a brief for the Fifth Circuit, the government argued that a district court correctly followed the Supreme Court’s decision in United States v. Boyle, 469 U.S. 241 (1985), and held that a couple’s reliance on their CPA to timely e-file their return did not excuse them from late-filing penalties.   Couple Argues They Reasonably Relied on CPA to E-File Return A couple argued in a brief for the Fifth Circuit that they reasonably relied on their CPA to e-file their return so late-filing penalties shouldn’t apply and that the holding in United States v. Boyle, 469 U.S. 241 (1985), that a taxpayer can’t rely on an accountant to timely file a paper return should not be extended to e-filed returns. [Christopher A. Haynes et ux. v. United States; No. 17-50816; 2/18/2018]     W&M Committee Publishes Summary of Budget Bill’s Tax Provisions On February 8 the House Ways and Means Committee released a summary of the tax provisions in the Bipartisan Budget Act of 2018, which include tax relief for victims of hurricanes Harvey, Irma, and Maria and the California wildfires, and extensions of expiring tax provisions. [Summary of Tax Provisions in Bipartisan Budget Act of 2018; 2/9/2018]

Jennifer Martiny describes the incredible microbial biodiversity of natural ecosystems such as soils and waterways. She explains how to add a bit of control in experiments with so many variables, and why categorizing microbial types is important for quantifying patterns. Host: Julie Wolf Subscribe (free) on iPhone, Android, RSS, or by email. You can also listen on your mobile device with the ASM Podcast app. Julie's biggest takeaways: Studying microbial community functions in their natural environment are harder to understand, but help us to parse the complexity of the natural world, in part because these experiments also include local flora and fauna that are often omitted in the controlled lab environment. Microbial cages - an actual physical barrier that contains a soil-based community - can help to disentangle the effects of the microbial community from those of the surrounding environment by adding a level of control by limiting interaction of microbes inside the nylon mesh cage with those outside of it. Are microbial functions redundant? It depends on what function you look at - respiration is a very common function, so it’s less likely to be affected by a change in microbiome composition. Other functions, such as degrading particular compounds, may have a stronger relationship between the microbes present and those functions. Microbes are hugely diverse! Jennifer’s comparison of all the diversity of the birds on Earth to a single bacterial taxon is mind-blowing! Microbial categorization may be hard, but the ability to group similar organisms is necessary to formulate hypotheses and conduct experiments. It’s important to remember the groupings are manmade and sometimes have to be reconstructed!   Featured Quotes (in order of appearance) “One of the hardest things we study is not on the microbiology side but is on the ecosystem side, measuring those biochemical functions in the environment.” (10:05) “It’s not as if we are ever going to be able to study every particular organism out there and build a model with thousands of equations; instead what we really need to do is go after trade-offs and overall relationships that may hold across large groups, and in that way have some simple rules under different conditions like drought or temperature.” (16:45) "Modern birds evolved about 100, 125 million years ago. Two sequences that share the 16S gene, if it’s roughly 97% identical, probably diverged 150 million years ago. That means we are lumping in all the diversity within the bacteria group within one taxon, calling it a species, which is the equivalent of lumping all birds together!" (18:47) “It’s a bit overwhelming to imagine that for each 16S rRNA taxon, you could have as much functional, morphological, and behavioral diversity as what we see in all of birds!” (19:39) “In biology, we’re always using an operational definition but we don’t want to get too hung up on the definition and miss all the interesting patterns going on!” (20:49) “If you can start to quantify patterns, then you can start to ask ecological and even evolutionary questions about why we see those patterns.” (33:04)   Links for this episode Jennifer Martiny Lab Home Page University of California Irvine Microbiome Initiative HOM Tidbit: TWIM 50: These things aren’t even bacteria! Carl Woese Obituary (New York Times) Carl Woese 1996 Feature (New York Times) Send your stories about our guests and/or your comments to jwolf@asmusa.org.

Michael Tessler and Christopher Mason join me to talk about their comparison of 16S amplicon sequencing and shotgun sequencing for quantifying microbial diversity. Links: The 2017 Nature paper that we discuss: Large-scale differences in microbial biodiversity discovery between 16S amplicon and shotgun sequencing Michael’s et al. 2016 paper that describes their original 16S study: A Global eDNA Comparison of Freshwater Bacterioplankton Assemblages Focusing on Large-River Floodplain Lakes of Brazil The sequencing data for these studies is available from NCBI: PRJNA310230 (16S), PRJNA389803 (shotgun) Michael’s website Christopher’s lab website The Integrative Biology & Medicine conference, featuring the talk on Postmodern Synthesis by Eugene Koonin

Lauren Petersen, PhD, is a postdoctoral associate investigating the microbiome and she’s back on the podcast to update us on her research. Be sure to listen to our first interview first! I sent Lauren some of the probiotics we use in our practice, and she said, “they look great!” Lauren did some calculations for the number of CFUs, and she got pretty much exactly what the bottle claims for live organisms, with growth on both Lactobacillus-selective and Bifidobacterium-selective medias. The same was not true for Renew probiotics where her qPCR analysis showed that Bifidobacterium was pretty much all dead. Here are some photos of the Lactobacillus-selective and Bifidobacterium-selective plates that Lauren used to grow the probiotics. She shot for 250 CFUs per plate (based on if all the organisms per gramme probiotic were alive) and that's pretty much what she got! Sign up for our Highlights email and every week we’ll send you a short (but sweet) email containing the following: One piece of simple, actionable advice to improve your health and performance, including the reference(s) to back it up. One item we read or saw in the health and fitness world recently that we would like to give a different perspective on, and why. One awesome thing that we think you’ll enjoy! Here’s the outline of this interview with Lauren Petersen, PhD: [00:00:32] Previous episode: The Athlete Microbiome Project: The Search for the Golden Microbiome. [00:03:10] Prevotella. [00:04:42] uBiome and The American Gut Project. [00:05:25] Scher, Jose U., et al. "Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis." Elife 2 (2013): e01202. [00:06:33] Probiotics: S. boulardii. [00:08:48] Bifidobacteria. [00:09:54] Testing probiotics: Renew Life. [00:12:06] D-Lactate Free Bifido Probiotic. [00:12:28] Sign up for our highlights email. [00:14:44] qPCR analysis definitely picked up lactobacillus. [00:15:33] 16S vs qPCR. [00:16:03] RNA-Seq. [00:17:20] Whole-genome shotgun. [00:18:26] 60-day Bionic Fiber Program. [00:19:11] Brummel & Brown 35% Vegetable Oil Spread with Yogurt + bananas. I’m not linking to this rubbish because it’s not fit for human consumption. [00:21:25] Akkamansia. [00:21:49] Remely, Marlene, et al. "Increased gut microbiota diversity and abundance of Faecalibacterium prausnitzii and Akkermansia after fasting: a pilot study." Wiener klinische Wochenschrift 127.9-10 (2015): 394-398. [00:24:41] Tolerating inulin. [00:25:22] Celeriac root. [00:26:19] Where do the microbes come from? [00:28:33] Antibiotics. [00:29:09] Cephalexin antibiotic. [00:29:56] Clindamycin antibiotic. [00:32:08] Amoxicillin antibiotic. [00:33:54] Metabolic endotoxaemia. [00:39:28] Mother Dirt. [00:41:42] FMT and the Taymount Clinic. [00:42:17] 4-Cresol Vancomycin.

Dr. Dawn Kernagis is a Research Scientist in the area of human performance optimization and risk mitigation for operators in extreme environments, such as those working in undersea diving, high altitude aviation, and space. Dr. Kernagis came to IHMC from Duke University Medical Center, where her postdoctoral research was funded by the Office of Naval Research and the American Heart Association to identify pathophysiological mechanisms and potential therapeutic targets in multiple forms of acute brain injury. Here’s the outline of this interview with Dr. Dawn Kernagis [00:00:20] STEM-Talk podcast. [00:01:35] Ken Ford. [00:03:44] Keto Summit. [00:04:06] Outside Magazine: Is the High-Fat, Low-Carb Ketogenic Diet Right for You? [00:04:22] NEEMO expedition. [00:08:30] The Twins Study was the first study of its kind to compare molecular profiles of identical twin astronauts with one in space and another on Earth. [00:12:04] Apolipoprotein E (APOE). [00:12:13] STEM-Talk Episode 12: Dale Bredesen Discusses The Metabolic Factors Underlying Alzheimer’s Disease. [00:16:28] Apolipoprotein E4 protective against malaria? [00:19:14] AHS 16 - Steven Gundry - Dietary Management of the Apo E4. [00:20:37] STEM-Talk Episode 14: Dominic D'Agostino. [00:21:28] Lauren Petersen: The Athlete Microbiome Project: The Search for the Golden Microbiome. [00:22:55] A combination of 16S, metagenomic shotgun, and metatranscriptomic sequencing. [00:29:48] Estrogen receptor (ER), progesterone receptor (PR), and HER2 expression. [00:31:16] Python, scikit-learn, TensorFlow. [00:31:32] The R Project for Statistical Computing. [00:33:15] MATLAB. [00:34:10] STEM-TALK Episode 1: Peter Attia On How To Live Longer And Better. [00:35:23] Swiss cheese model, Gareth Lock. [00:40:48] Duke University. [00:41:04] Richard Moon. [00:42:59] NEEMO blog.

Lauren Petersen, PhD, is a postdoctoral associate working for Dr. George Weinstock and investigating the microbiome. Our knowledge of the 100 trillion microorganisms that inhabit the human body is still very limited, but the advent of next-generation sequencing technology has allowed researchers to start understanding what kind of microorganisms inhabit the human body and identifying the types of genes these organisms carry. As part of the NIH-funded Human Microbiome Project, her lab is focused on developing and applying the latest technologies to characterize the microbiome and its impact on human health. One of her main projects is metatranscriptomic analysis whereby they are attempting to characterize gene expression of an entire community from human samples such as stool and saliva. Gaining information on what signals or environmental factors can trigger changes in global gene expression of an entire microbial community may provide us with the tools to better treat certain types of diseases in humans. Lauren is currently working on the Athlete Microbiome Project. By collecting stool and saliva samples from a cohort of highly fit professional cyclists, she will make an attempt to understand how their microbiomes may differ from those of the general population. The goal is to characterize the species present, the genes they carry, and how gene expression is modulated in athletes who push their bodies to the limit. Here’s the outline of this interview with Lauren Petersen: [00:00:28] George Weinstock, PhD. [00:01:27] Jeremy Powers interview. [00:01:43] Jeff Kendall-Weed. [00:02:15] Why care about the gut microbiome? [00:03:32] Metabolic functions. [00:03:51] NIH Human Microbiome Project. [00:04:39] Phase II longitudinal study. [00:06:01] Microbial diversity. [00:07:33] Lyme and antibiotics. [00:08:15] Chronic Fatigue Syndrome. [00:09:35] Gordon conferences - Rob Knight. [00:10:27] American Gut Project. [00:10:48] Firmicutes and Bacteroidetes. [00:11:05] Enterobacteriaceae. [00:11:59] Fecal transplant. [00:13:16] Screening donors. [00:13:32] DIY. [00:13:52] C. diff. [00:14:14] Transplants started in the 50s. [00:14:47] IBS. [00:16:12] Healthy donor. [00:17:43] Within a month, Lauren was feeling a lot better. [00:18:13] Instantaneous improvement on the bike. [00:19:22] No more stomach issues, "more energy than I knew what to do with". [00:19:54] Retest data showed perfect match with donor. [00:20:56] Sequencing large vs. small intestinal microbes. [00:21:28] FDA has no idea what to do. [00:23:02] Strategies for maintaining a healthy gut microbiome. [00:23:31] Whole foods, lots of fruit and vegetables. [00:23:48] No gels. [00:24:26] Athlete Microbiome Project. [00:26:34] Microbiome doping? [00:27:05] Ruminococcus - starch digester. [00:28:26] Enterotype - the dominate species in the gut. [00:28:56] Prevotella. [00:30:14] Teasing apart the cause and the effect. [00:32:28] Endotoxins released during intense exercise. [00:32:49] 25 participants at the time of recording, I'm number 26! [00:33:29] Matching cohort of healthy controls. [00:34:28] Ibis World Cup racer. [00:35:01] uBiome. [00:35:08] My app. [00:35:54] The problem with 16S sequencing. [00:36:16] Missing bifidobacteria. [00:37:05] A combination of methods is required for accurate testing. [00:38:30] New commercially available test? [00:39:11] Probiotic quality. [00:40:04] Testing probiotics. [00:41:37] Bifido doesn't like oxygen (or your stomach). [00:42:02] Lactobacillus is more resilient. [00:42:50] Bifido love fructooligosaccharides. [00:43:36] Lack of association with dietary restrictions. [00:44:53] Feed your microbiome!

Hosts: Vincent Racaniello, Alan Dove, and Rich Condit Vincent, Alan and Rich explain how to make a functional ribosome with tethered subunits, and review the results of a phase III VSV-vectored Ebolavirus vaccine trial in Guinea.   Links for this episode Social media specialist position at ASM WHO dismisses Catholic church on vaccine safety U of T Dean resigns over anti-vaccine course (Tor Star) Vaccine Adverse Event Reporting System (VAERS) Countering anti-vaccination attitudes (PNAS) Designer ribosome (Nature) rVSV-EBOV preliminary report (NEJM) rVSV-EBOV phase III interim report (pdf, Lancet) World on verge of Ebolavirus vaccine (WHO) Ebolavirus vaccine in Africa (virology blog) Letters read on TWiV 349 11:55 This episode is sponsored by ASM GAP Weekly Science Picks Alan - Above and BeyondRich - DSCOVR (Dark moon side crossing Earth)Vincent - Stuxnet virus (Wired, YouTube) Listener Pick of the Week Konrad - Stated Clearly Send your virology questions and comments (email or mp3 file) to twiv@twiv.tv