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12 episodes with mt1
2 episodes with mt1
2 episodes with mt1
2 episodes with mt1
2 episodes with mt1
MotorTrend's Ed Loh & Jonny Lieberman chat with Founder/CEO, Jason Marks, and Founder/CTO, Forrest North, of TELO! The guys talk all about their TELO MT1 Urban Adventure Vehicle, their battery tech & crash safety innovations, capabilities of the truck, Software Defined Vehicles, autonomy, the current state of electric pickup trucks, EREV (Electric Range Extended Vehicle), and more!0:42 - Scout is back!7:32 - TELO MT1 - Urban Adventure Vehicle!10:06 - Battery tech innovations.16:57 - Crash safety innovations.26:14 - Genesis of the MT1.30:12 - Lack of small trucks.35:04 - Price?37:22 - What is the truck made of?38:55 - Suspension.41:43 - Monster Tunnel & other specs.47:35 - Reservations & delivery.52:10 - Urban Adventurer. 56:27 - Andy Palmer.01:01:18 - What's inside? Software and beyond.01:05:41 - Payload & Towing capabilities.01:08:00 - Lightning Round - Rivian, F-150 Lightning, Scout, and more.01:12:45 - EREV (Electric Range-Extended Vehicle).01:16:10 - Battery tech advancements.01:20:50 - Final thoughts.
Zak Mir spoke to Metals One PLC CEO Jonathan Owen as the company which is advancing strategic minerals projects in Finland and Norway, announces a maiden JORC Inferred Mineral Resource for the P5 area of the Finland - Black Schist Project of 29 Mt1. This brings the total Black Schist Project resource to 57.1 Mt, more than double the previous estimate. Metals One doubles its Black Schist project's resource estimate in Finland to 57.1 million tons, increasing its value to around $3 billion. The company is fast-tracking a Preliminary Economic Assessment, aiming to complete it by the year's end, crucial for development metrics and EU project status. Metals One plans a phased expansion with multiple satellite pits, ensuring low-cost, high-volume mining inspired by successful nearby operations. The interview with Jonathan Owen, CEO of Metals One, conducted by Zak Mir. The discussion focuses on the company's recent progress and strategic plans. Key Points: MRE Upgrade and Doubling Resource: Metals One has announced a significant upgrade, doubling their mineral resource estimate (MRE) for the P5 area of the Finland Black Schist Project to 57.1 Mt. Funding and Strategic Decisions: The company cancelled a farm-in with Gend and directors participated in a subsequent fundraiser. This strategic decision was to ensure immediate cash availability for planned work programs rather than waiting for delayed cash flows. Project Development and Goals: Metals One aims to develop a primary economic assessment this year, supported by the new funding. They have a 93.75% stake in the Black Projects and can reclaim the remaining 6.25% from Gend at a predetermined price. Long-term Target: The company has set a longer-term target of 100 million tons and aims to classify their asset as world-class, aiming for a valuation of around 10 billion in situ value. Critical Mass and Strategic Status: The milestone of reaching 57 million tons allows them to start scoping studies and preliminary economic assessments, which are crucial for project metrics like NPV and IRR. This progress will help them seek EU project financing and grants under the Critical Raw Materials Act. Future Plans and Market Position: Despite a current market cap of 2.9 million, which doesn't reflect recent upgrades and potential EU support, Metals One is actively working on raising its profile. They plan to continue drilling to increase resources and move towards production, either independently or through partnerships. Environmental and Regulatory Preparations: The company is also initiating environmental baseline assessments and other critical path items to reduce project risks, aiming to enhance project attractiveness and feasibility. Conclusion: Metals One is advancing significantly in its mineral resource projects in Finland and Norway, with strategic funding and development plans aimed at achieving world-class asset status and securing critical EU support. The company is positioning itself for significant growth and market recognition in the near future. https://www.share-talk.com/zak-mir-spoke-to-metals-one-plc-aimmet1-ceo-jonathan-owen/
La NAISSANCE DE JESUS CHRIST#1 MT1: 18-25 Haitian Helping Hands is a nonprofit organization that is committed to providing access to education, planting churches, and empowering entrepreneurs in Haiti. We believe that by investing in the education and empowerment of the Haitian people, we can help break the cycle of poverty and build a brighter future for all. Through our programs, we work to provide access to education for children and adults, building schools and providing scholarships to those in need. We also plant churches in communities across Haiti, helping to provide spiritual support and guidance to the people. Furthermore, we empower entrepreneurs by providing training and resources to help them start and grow their own businesses. We believe that by working together, we can make a real difference in the lives of the Haitian people. Join us in our mission and support Haitian Helping Hands today. Dear Sponsor, I hope this message finds you in good health and high spirits in Jesus' name. I am reaching out to you today with an opportunity to make a lasting impact on the lives of some children in need in Haiti. We have launched an initiative called "Education for All," aimed at providing quality education to underprivileged children who are currently unable to attend school due to financial constraints. We firmly believe that education is a powerful tool that can break the cycle of poverty and empower individuals to create a better future for themselves and their communities. Unfortunately, countless bright young minds around us are deprived of this basic right due to their families' limited resources. To address this pressing issue, we are seeking compassionate individuals like yourself to partner with us by contributing $60 per month. Your generous support will go directly towards covering the educational expenses of these children, including tuition fees, school supplies, and other essential resources. By investing in their education, you will not only provide these children with the necessary tools to succeed academically but also instill in them the confidence and motivation to pursue their dreams. Your monthly contribution will make a tangible difference, allowing us to expand our reach and positively impact more lives. As a valued member of our initiative, you will receive regular updates on the progress of the child ren you support. We believe in transparency and accountability, ensuring that t your contribution is being utilized effectively to transform lives and foster a brighter future for these deserving youngsters. Joining our cause is incredibly easy. Simply click on the link provided below to visit our secure donation portal. Once there, you can set up a recurring monthly payment of $60 and become a vital part of our mission: haitianhelpinghands.org (http://haitianhelpinghands.org/) If you are unable to commit to a monthly contribution at this time, any one-time donation you can make would still be immensely valuable in our endeavor to provide education to as many children as possible. Alternatively, if you know someone who may be interested in making a difference, please feel free to forward this message to them. Together, we can create a ripple effect of positive change and uplift the lives of countless children. Thank you for considering this opportunity to make a difference in the lives of these children. Your support can shape their futures and enable them to realize their true potential. If you have any questions or require further information, please don't hesitate to reach out to us at haitianhelpinghands1@gmail.com (mailto:haitianhelpinghands1@gmail.com) Warm regards, CEO EMMANUEL D Chery. haitianhelpinghands.org (http://haitianhelpinghands.org/) HAITIAN HELPING HANDS, INC. ADDRESS P.O.BOX 4564 LYNCHBURG VIRGINIA 24502 --- Support this podcast: https://podcasters.spotify.com/pod/show/haitianhelpinghands/support
Fundada por um ex-engenheiro da Tesla, a Telo Trucks é um novo fabricante americano de pickups 100% elétricas e compactas, com o tamanho de um Mini Cooper.O primeiro modelos desta startup da Califórnia chama-se MT1 e tem capacidade para transportar 5 passageiros. O veículo atinge uma velocidade máxima de 200 km/h e tem autonomia para 550 quilómetros.Saiba mais sobre inovação e nova economia em supertoast.pt.
"Jesus is God in human flesh who alone is worthy of our worship.” ABOUT THIS MESSAGE Christians know that the birth of Jesus fulfilled Isaiah's prophecy about a coming child called Immanuel, but what does it mean. What are we claiming when we say that God is with us in Jesus? This Christmas season, we will examine four claims included in that ancient phrase to see how God with Us leads to worship, provides redemption, enables fellowship, and inspires hope! Download “The Follower's Five,” a weekly discipleship resource, for this message: https://followersfive.s3.us-east-2.amazonaws.com/2022/Fall_22/FF_11.27.22_Mt1.18%E2%80%9325.pdf If want to know and follow Jesus, or have something we can pray for you about please respond HERE: https://go.cbcluling.com/connect —— Stay Connected Website: http://www.cbcluling.com CBC Facebook: https://go.cbcluling.com/fb Scripture References: Matthew 1:18–25 God With Us: Worship | Pastor Brad Mills | CBC Luling
This week, please join author Rod Stables and Associate Editor Nick Mills as they discuss the article "Routine Pressure Wire Assessment Versus Conventional Angiography in the Management of Patients With Coronary Artery Disease: The RIPCORD 2 Trial." Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast, summary and backstage pass through the journal and its editors. We're your co-hosts! I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, Associate Editor, Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Well, Carolyn, this week's feature... Very interesting. There is a lot of information about using fractional flow reserve during contrast coronary angiography. But how does that compare to just reviewing the angiograms when managing patients with coronary artery disease? Well, we are going to hear some results from the RIPCORD 2 trial, and they may surprise you a little bit. But, before we get to that interesting feature discussion with authors and editors, how about we grab a cup of coffee and dive into some of the other articles in the issue? Dr. Carolyn Lam: Yeah, let's do that, Greg. Do you have a paper to share first? Dr. Greg Hundley: Oh, thanks Carolyn. Sure. So Carolyn, as we know, Apolipoprotein B or apoB, provides an integrated measure of atherogenic risk. But whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndromes, beyond that provided by low density, lipoprotein cholesterol, or LDLC, that's uncertain. So Carolyn this study emanates from the Odyssey Outcomes trial, which compared the Proprotein Convertase Subtilisin/Kexin Type 9 inhibitor, Evolocumab with placebo in 18,924 patients with recent ACS and elevated atherogenic lipoproteins despite optimized statin therapy. Now the primary outcome was major adverse cardiovascular events. So MACE was coronary heart disease, death, nonfatal myocardial infarction, fatal non-fatal ischemic stroke, and hospitalization for unstable angina. And associations between baseline ApoB or ApoB at four months and MACE were assessed in adjusted Cox proportional hazards and propensity score matched models over median of 2.8 years. Dr. Carolyn Lam: Oh, right. So what were the results, Greg? Dr. Greg Hundley: Right, Carolyn so impatience with recent ACS and elevated atherogenic lipoproteins, MACE increased across baseline ApoB strata, and now evolocumab reduced MACE across all strata of baseline ApoB, with larger absolute reductions in patients with higher baseline levels. Lower achieved ApoB was associated with lower risk of MACE, even after accounting for achieved LDLC or Non-HDLC indicating that ApoB provides incremental information. And therefore, Carolyn, if it is modified achievement of an ApoB level less than or equal to 35 milligrams per deciliter may reduce lipoprotein attributable residual risk after ACS. Isn't that interesting? Dr. Carolyn Lam: Yes. Very nice, Greg. Thank you. This next paper is a pre-specified analysis of the EMPEROR-Preserved trial, looking at patients with and without diabetes. Dr. Greg Hundley: So remind us, Carolyn, what was the EMPEROR-Preserved trial and what did it show? Dr. Carolyn Lam: Well, in EMPEROR-Preserved Empagliflozin, the SGLT2 inhibitor reduced risk of the composite of cardiovascular death or heart failure hospitalization, as well as first and recurrent heart failure hospitalizations and slowed renal function decline in patients with heart failure and an ejection fraction greater than 40%. So the current paper sought to determine if effects were consistent in patients with, and without diabetes, of the almost 6,000 patients enrolled, 49% had diabetes. The risk of adverse outcomes, first of all, was higher in patients with diabetes. Now the treatment effect of Empagliflozin was however, similar in that Empagliflozin reduced the rate of the primary outcome and total heart failure hospitalization, irrespective of diabetes status. The effect of Empagliflozen falls into attenuate GFR decline, however, was also present in patients with, and without diabetes, although more pronounced in patients with diabetes. Now across all these three endpoints, the effect of Empagliflozen did not differ in patients with prediabetes or normal glycemia. And importantly, there was no increased risk of hypoglycemic events in either subgroup compared with placebo. So a very nice paper there. And that was from Dr. Gerasimos Filippatos from Athens University Hospital Attikon and colleagues. Dr. Greg Hundley: Wow, Carolyn, just really interesting information coming out of the world of SGLT2 innovation. Well, Carolyn, my next paper comes to us from the world of preclinical science and it's from Dr. Kunhua Song from the University of Colorado Anschutz Medical campus. So Carolyn, abnormalities of calcium homeostasis are closely associated with cardiac arrhythmias and heart failure and conditions that cause death of millions of people every year. Now, Carolyn Triadin physically interacts with the Ryanodine receptor 2 and plays an important role in releasing calcium from the sarcoplasmic reticulum to increase the free intracellular calcium concentration in cardiomyocytes. Now alternative splicing of a single Triadin gene produces multiple Triadin isoforms, the predominant cardiac Triadin isoform mouse Mt1 or human Trisk 32 is encoded by Triadin exons from one to eight. In humans, mutations in the Triadin gene that lead to a reduction in Trisk 32 levels in the heart cause cardiac dysfunction, cardiac arrhythmias and sudden death. Decreased levels of Trisk 32, in the heart, are also common in patients with heart failure. However, mechanisms that regulate alternative splicing of the Triadin gene to maintain levels of cardiac Triadin protein in the heart, remains somewhat elusive. Dr. Carolyn Lam: Wow. I am always learning from these cool papers. Thanks Greg. So what were the results? Dr. Greg Hundley: So Carolyn, the investigators found several things. First, the cardio MyoSite specific long non-encoding RNA or link RNA Triadin AS is essential for maintenance of cardiac function, exercise capacity and normal lifespan and Triadin AS knockout mice were found predisposed to cardiac arrhythmias in response to catecholamine challenge. And finally Carolyn, Triadin AS controls, levels, of cardiac Triadin isoforms, by regulating the splicing of the Triadin gene. Dr. Carolyn Lam: Oh, wow. All right. So could you bring it home for us, Greg? What are the clinical take home messages? Dr. Greg Hundley: Right, Carolyn. So cardiac explants from human heart failure patients as well as patients with cardiac arrhythmias, demonstrate reduced expression of Triadin AS and Triadin. And then next the mechanism of the Triadin AS and Triandin AS mediated alternative splicing of the Triadin gene to specifically control levels of cardiac isoforms of Triadin in the heart, provides a potential strategy for the treatment of cardiac arrhythmias and heart failure. Dr. Carolyn Lam: Wow. Thank you, Greg. Well, let's talk about what else is in today's issue. There's a Research Letter by Dr. Agarwal on Chlorthalidone for resistant hypertension and advanced chronic kidney disease. Dr. Greg Hundley: And Carolyn, I've got a perspective piece by Professor Cowie pertaining to atrial fibrillation entitled, “I'm Sorry, Mrs. Jones, but We Cannot Make You Feel Better Today.” Well, Carolyn, how about we get onto that feature discussion and review the utility of fractional flow reserve measurements, in patients undergoing contrast coronary angiography. Dr. Carolyn Lam: Great, let's go. Dr. Greg Hundley: Welcome listeners to this August 30th feature discussion. And we have with us this afternoon, Dr. Rod Staples from Liverpool and our own associate editor, Dr. Nick Mills from Edinburgh, Scotland. And gentlemen, welcome, Rod we'll start with you. Can you describe for us the background information that went into the preparation of your study and what was the hypothesis that you wanted to address? Dr. Rod Staples: Okay, well thanks very much for hosting today. I'm very grateful to be working circulation on this. I'm working with my co-lead investigator Professor Nick Harrison from Southampton, who's been doing an enormous amount of work on coronary physiology. He actually did the original RIPCORD study, what I suppose we'd now call RIPCORD 1, but it was called RIPCORD in the early days, an observational study that showed that systematic use of fractional flow reserve at the time of diagnostic angiography. Assessing the functional significance measured in each of the major coronary vessels, appeared in an observational study to have a dramatic effect on the subsequent management plans allocated to patients. And we decided to test this in a prospective randomized trial. Dr. Greg Hundley: Very nice. And so the exact hypothesis that you were going to test was what? Dr. Rod Staples: At the time of coronary angiography, a strategy of systematic measurement of fractional flow reserve in each and every coronary vessel, large enough to be considered for revascularization, would improve outcomes compared to a strategy based on angiographic assessments alone. Dr. Greg Hundley: Very nice. And so you mentioned a randomized trial. Can you describe further your study design and then which study population did you include? Dr. Rod Staples: Well, this is a classic multicenter randomized trial performed in the UK. We actually recruited in 17 different UK centers. We asked them to assess patients who were scheduled for invasive, currently angiography for participation against some very minimal inclusion and exclusion criteria, trying to keep the trial generalizable with good external validity. I think one important point to note is that we did allow the inclusion of both patients being assessed with elective angiography for stable symptoms, but in the end half of the population were recruited in the context of a stabilized acute coronary syndrome, a Non-ST-elevation event a day or so down the line. Dr. Greg Hundley: And just a quick breakdown, how many men, how many women? Dr. Rod Staples: Well, it's in that respect, the population is very, very typical for this type of cardiovascular trial. A 70, 30 split an age in the midsixties, a diabetic population in the high teens. So a very typical population we've seen in all this kind of trial environment. Dr. Greg Hundley: Very nice. And so about 1100 patients. And then what were your study results? Dr. Rod Staples: Well, I think there was a very good adherence to the study protocol, very, very few crossovers. And also we were pleased to see that our investigators stayed true to the protocol in that the median number of epicardial vessels assessed by FFR in that randomized arm was four. So there was a good assessment by FFR. The trial was interesting in another respect, in that we assessed an economic outcome based on all NHS hospital costs over the following year and a patient reported outcome based on quality of life using the WHOQOL, and interestingly we found no significant differences either in total subsequent hospital costs from randomization for a year, or indeed in patient reported quality of life by WHOQOL or Angina symptoms by the Canadian Cardiovascular Society classification. Dr. Greg Hundley: Very nice. And then, what about clinical events? Did you examine those as well? Dr. Rod Staples: We did. And again, just a little caveat here, the trial is again interesting in that, what is often in the UK these days called a lean efficient methodology. Whereby, rather than individually contacting individual trial participants or scouring medical records, we interrogated the central national NHS digital repository of all hospital admissions. And we examined electronically a download of every hospitalization event for every patient using algorithms based on diagnostic and procedural codes to define events. And again, we found a very credible representative rate exactly at incidents and events we would've predicted, but again, no difference between the randomized groups. Dr. Greg Hundley: Very nice, well listeners, now we're going to turn to our own Associate Editor, Dr. Nick Mills. And Nick, again, you see many papers come across your desk. What attracted you to this particular manuscript? And it's very interesting study results. Dr. Nick Mills: Thanks, Greg. Firstly, it addresses an important clinical question. Going beyond that, what appealed to me was it was investigator initiated. It was managed by independent trials unit. It recruited a target, it reported the registered outcomes and it was thoughtfully interpreted. And the fact that it didn't prove the hypothesis was irrelevant because it addresses a really important clinical question. And I think it requires some context, and that is that from the previous randomized trials The FAME series, we have been chastised as interventional cardiologists for not using FFR for relatively low use of FFR clinical practice. It's always around one in 20 patients in most series, given the evidence that FFR guided intervention improves outcomes. But actually what FFR is good at is discouraging you from stenting patients with stable Coronary Disease. And so, I think a pragmatic trial that addresses that, the fundamental question, should we be doing more FFR more broadly in both acute and stable disease to guide revascularization with a definitive message that we shouldn't, it doesn't improve quality of life. It doesn't alter costs. Clinical outcomes are similar, but there are more complications associated with routine pressure wire use, gives us a very clear steer for the future. So this is a really important trial addressing a fairly fundamental clinical question. Dr. Greg Hundley: Very interesting. Well, Rod, we're going to turn back to you with Nick's comments and how we're really seeing an evolution in thought processes regarding both diagnostic angiography, and then also the use of functional testing. What do you see is the next study, really in this sphere of research that would be performed? Dr. Rod Staples: Well, I agree with Nick in a way that this raises important philosophical points about the use of intelligence, selective employment of tests or interventions, and that perhaps we need to reflect this in the way we conduct our future studies. I think we're all aware that fractional flow reserve and other measures of functional significance are tremendously valuable in certain clinical settings. And that value's been proven in randomized trials, but in PRECORD 2, for example, if a patient randomized to angiography only was an acute coronary syndrome patient, who had inverted their T waves in their anterior leads, had an associated troponin rise, an echocardiogram had shown some Hypokinesia in the anterior territory. Then I think the potential value of PCI in the LAD does not necessarily require FFR confirmation, and hence that patient will have an equivalent outcome in the angiography group. Similarly, high quality pre-angiography preparation in the elective population with functional testing, stress testing, other forms of imaging mean that we can reserve the use of invasive fractional flow reserve, tight indices to more selective use. Dr. Greg Hundley: And Nick, turning to you, what do you think is the next research study that could be informative in this space? Dr. Nick Mills: I think our whole philosophy by how to manage stable coronary disease is changing. In part because of some other landmark trials that the Ischemia trial and some of the key secondary analyses of the Ischemia trial that tells the Pathoma burden, low attenuation plaque, other aspects of chronic disease are vitally important in predicting major events in the future. And that leaves us with the role for FFR or CT FFR, primarily to manage symptoms. And I think we're getting increasingly good evaluating patients before they get to the Cathflow, optimizing their medical treatment. And so for me, the trial that we really need to help us, is a CT FFR trial to understand the role of Ischemia testing plus anatomical testing and how they dovetail in guiding treatment decisions before they get to the cath lab. I think we need to move this before the lab, always going to be a role for intelligent FFR testing in selected patients once we get to it. But I think that the question probably needs to be addressed before they get to the cath lab. Dr. Greg Hundley: Very nice. Well listeners, we want to thank, Dr. Rod Staples from Liverpool and Dr. Nick Mills from Edinburgh, Scotland for bringing us this very interesting study, highlighting that a strategy of systematic FFR assessment, when compared to angiography alone, did not result in a significant reduction in cost or improvement in quality of life. Well, on behalf of Carolyn and myself, we want to wish you a great week and we will catch you next week On the Run. This program is copyright of the American Heart Association, 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit ahajournals.org.
We are welcoming a special guest to the show this week: Robert Reed of Gin and Truth on YouTube. If you're a fan of a pull-no-punches, take-no-prisoners approach to secular humanism, we think this is probably going to be the show for you. Tune in or call in to talk with our guest at 585-526-8774 or https://tiny.cc/callSG.Find more Robert Reed: Subscribe to his YouTube: https://www.youtube.com/channel/UCLaC... Follow his Twitter: https://twitter.com/RCReed40 Stream his podcast wherever you like to listen! ___________________TIME STAMPS & CALL NOTES 00:00 - Intro04:11 - Robert Gets On the Soapbox 11:39 - Ditch Your Therapist, Come to Church! - Andrew (he/him) - MN20:25 - Ontological Evidence for God... AGAIN - Xeno (he/him) - SK35:10 - Thank You For Speaking Up! - Uncle Beck (he/him) - NM38:26 - Fighting Spiritual Abuse with Skepticism - Tim (he/him) - Czech Republic1:00:15 - Do Debate Bros Actually Deradicalize Anyone? - Garrett (he/him) - MT1:16:50 - You Never Really Believed! - Nick (he/him) - TN1:28:24 - Superchats00:00Intro04:11From taking a leak in peace to preferred pronouns, why does it seem like we aren't ever having the same conversation when it comes to trans rights? Being an ally is more than just recognizing the humanity of our neighbors, it's recognizing that arguments to the contrary make you part of the problem.11:39This caller got to learn about the evils of LGBTQ and poly folks from a religious friend. He also got recommended church instead of actual therapy. We all have a little laugh, but Robert hits the nail on the head when he says, “Make sure you can tell the difference between a doctor and a pastor.”20:25Xeno calls in to make yet another ontological argument for God, and Robert meets his claims with exactly the right reaction: uproarious laughter. Meanwhile, Vi points out the exact reason that Xeno's argument doesn't work using set theory, and Xeno suddenly needs to go… 35:10Uncle Beck wants to shout out just how important it is to have allies that are willing to go to bat. You can find Uncle Beck's channel here: https://www.youtube.com/c/BeNoJustBe 38:26If we need to pick one, should we pick skepticism or critical thinking? This caller thinks that addressing spiritual abuse is an easier pill to swallow if it doesn't include any extra baggage. Our hosts counter that just like leaving any other abusive relationship, recognizing the signs of abuse can prevent those who have suffered abuse from falling into it again in the future.1:00:15Does it really matter if bad reasoning is used to de-radicalize people? Vi shoots back that the problem isn't deradicalization, it's perpetuating bad thinking! If the louder person seems to “win” the debate, it's only a matter of time before listeners are convinced bv a louder person. The better tactic is to place less value on the “debate bro” culture in the first place.For more information about the Federalist Society, check out this article by the Harvard Gazette: https://news.harvard.edu/gazette/stor... 1:16:50Nick has been placed in a church mediation program to determine if he is allowed to communicate with his siblings. During the mediation, he has been told that he was never a true Christian… because he never did miracles! Robert calls it out for the absolute horseshit that it is. We're with you Robert!1:28:24Superchats___________________Skeptic Generation is LIVE every Sunday at 11:30am-1:00pm CTCall on your phone: 585-LA-MURPH (585-526-8774) Call online: https://tiny.cc/callSG Love the show? Become a patron: https://tiny.cc/donatetoSG Buy our new Class of ‘22 merch: tiny.cc/SG22MerchHelp with our studio: https://tiny.cc/SGwishlist Join us after the show on Discord: https://tiny.cc/SGdiscord To find out more, visit https://www.skepticgeneration.com Copyright © 2022 Skeptic Generation. All rights reserved.
"José, hijo de David, no temas recibir a María..." Mt1, 20. --- Send in a voice message: https://anchor.fm/julio-cu00e9sar-ramos9/message
God Will Not Surpass the Name of YeshuaEze36:21-22 ; Mt1:21-23
Annie Mithoefer, B.S.N., is a Registered Nurse living in Asheville, NC. She was co-investigator on two of the MAPS-sponsored Phase 2 clinical trials for individuals with PTSD and a pilot study treating couples combining MDMA-assisted psychotherapy with Cognitive Behavioral Conjoint Therapy for PTSD. She is currently co-investigator in MT1, a protocol allowing MAPS-trained therapists to receive their own MDMA-assisted session, she conducts MAPS Therapist Trainings with her husband, Michael, and is a supervisor for Phase 3 therapists. Annie is a Grof-certified Holotropic Breathwork Practitioner and she is trained in Hakomi Therapy. I met Annie several years ago as a student of hers in the MAPS MDMA training, and I so enjoyed reconnecting in this conversation. What You Will Learn: How MDMA therapy works to heal trauma, and the rich possibilities that exist for MDMA as effective treatment for couples, eating disorders, depression, end of life care, addiction treatment and more The importance of the body and the breath in healing; how Annie has activated both with tools like the Hakomi method, creating deeper presence and safety for patients What makes a good psychedelic therapist or sitter, and why advanced training or education of some type is needed Best practices for Annie’s self care The challenges of the moment with covid-19 and creating clear systems to support new therapists working in this space Resources: MAPS
Mt1:21-23; 28:16-20The One Yeshua Is With
All right. Welcome to the gut check project. I'm here with your host, Dr. Kenneth Brown. I'm Eric Rieger. This is gut check project, Episode Number 26. We're going to wind up 2019 with some awesome info. What's up, Ken?What's going on Eric? How are you doing, man? Episode 26. Unbelievable. I apologize if I'm a little too sexy today because I'm just coming off of a small cold. I think the hottest people are those that are sick.Well, I'm not sick. I'm post sick. Remember, the viral prodrome. The reason why we always like pass so many viruses is that you tend to pass the virus before you even know that you're sick by the time you're actually sick. You're probably okayYeah. At that point you can go back and say I heard you might be sick. I was too back then.Yeah, exactly. Good to see you?Well, today's episode is going to be pretty awesome. We're going to tackle number one, we've received tons of email in your clinic because you also sell the KBMD CBD at your clinic, you get these questions. These have been coming in Fast and Furious over the last little over 14 days. And it's questions about the safety of CBD oil and its application. So we're going to tackle that I do need to tell everyone. Thank you. We're on episode 26 because the first 25 shows were so well supported by all of you who've been keeping up with a gut check project. We grow every single day. Paul, the guy who's helping us put together the production now and helping us spread the word. We just hung up the phone with him. We've gotten more and more downloads each week. So thank thank you every single one of you for liking, sharing, emailing, telling your friends about it. We sincerely appreciate it.We learned so much about it like today we have a new a different guests we do Instead of gutsy our little mascot or green frog, but since we do film on a green screen, he gets blocked out did not know that didn't even realize that. So now we're going to go with a dung beetle, right here? Yeah, yeah, we did. So that's Dilbert, the dung beetle,Dilbert, the dung beetle. So one of my favorite things is whenever we're bringing any patients back and somebody sees you, and they're like, hey, you're Eric, I watch your show that just warms my heart. So if you happen to be a patient and show up and you watch the show, if you say that it just makes us both feel really, really well...needed wanted, appreciated.Yeah. At least outside of me putting you to sleep. Take five or six good deep breaths. Exactly. Today's episode is sponsored by Atrantil. Your bloating relief, it's what we do. So go to Atrantil.com or lovemytummy.com/KBMD. Today it's also sponsored by KBMD CBD oil. You can find your own KBMD CBD oil at kbmdhealth.com which of course, the initials KB, Kenneth Brown, it's endorsed by the guy who's sitting across the table from me. So Ken, why is...What does MD stand for? Well, I'm not really sure.I thought it was your buddy Mike Doyle, but I don't know.Yeah, it's probably. So tell us a little bit about KBMD CBD. Alright, so KBMD CBD oil. I got involved with the science of CBD because I saw the beneficial effect with my patients when we developed Atrantil I then learned that the science of Atrantil the polyphenols in it actually augment CBD. So I'm seeing this combination do incredible things for people. So this particular CBD is one that we have researched, I've seen it work clinically. And we know that it comes with a certificate of analysis. It is organically grown, it is naturally extracted with co2, so it meets all the criteria that you want in your CBD because this is important. The rest of this podcast is going to be all about the dangers of CBD.Definitely and It's really interesting since we do have so many people who have begun to purchase CBD find benefit. It's really kind of weird what's occurred over the last two weeks. And what I would say is a little bit of misinformation. But it's more or less probably just misunderstood information and or or misapplied information. But regardless, the benefits of CBD used correctly, have been undeniable with the people who've come back through the clinic with people that we've scoped, and how well that they are doing. And so, hopefully today, we're going to provide some context on why more or less the dangers that you may or may not have read about in the news recently are really a little concerned. But we'll, we'll see. We'll see how far along we get in at the last. The last thing. Our last sponsor is the KBMD health box. You can find KBMD health box by going to kbmdbox.com. Now last week we did a full unboxing which is something I think we're going to try to do at least once a month. But essentially, if you want almost $300 of physician vetted supplements that can help you benefit your life and get them for only $147 which you would spend, not you would spend more than $147 worth of time driving somewhere to pick them out for yourself and having someone handpick them for you. Go to KBMDbox.com. What was one of the things that we had a patient come through just earlier this week, who showed us his lab results that he took to his primary care physician? So we're starting to make a difference in the landscape of health here in the DFW Metroplex and different places. I've been getting emails and calls from people around the country that will actually hear the podcast and then they'll want to sign up for the box. And what we're seeing is that these vetted supplements actually are making a difference with both subjective how they feel and objective the labs. So the reason why I chose these things is they all have third party analysis. And they all have some scientific background that actually explains how they're going to help you. So much so that I'm thinking of ordering my household, another box. So although it is the KBMD Health box, I actually I love the fact that I can get these things that I'm going to purchase anyways, they come into my house, so my whole family's on it. Now we're running out of stuff. So I'm gonna end up having to double up on everything. So it's one of those things that I feel really good that we can look at different aspects. And when somebody says, Oh, I tried X, Y, and Z, I didn't notice anything. I'm like, oh, did you try one that had a third party analysis? No. And then they do and they're like, Oh my gosh, big difference. Same thing with CBD. I mean, a lot of CBD out there doesn't really have what's on the label. And we're going to get into that because we're going to talk about what the FDA thinks about it. We're going to talk about the different media and what they're doing, and hopefully get into all that but that's the whole point of that box is I want to deliver these vetted things to your house monthly so that you can continue to improve your health. Hundred percent. So without further adieu, be sure to like and share the gut check project. We certainly appreciate all of the support to date. We're going to hop right into it. So what we've received here recently is a lot of speculation and concern from people who have said, Hey, I'm interested in CBD. I know that you and Dr. Brown have heavily studied, been entrenched with CBD and its application over the last few years. I just learned that the FDA is associated or made public a study that says that it may be hepatic toxic or bad for my liver. It's, unfortunately, it's a weird jump off point. So I'm going to kick it to you. Because immediately I had lots of different thoughts and instead of getting emotional, what did we do? We went and tried to find the sources of where this information came from. We want to backtrack on how they got to that conclusion. And I think that we can put a lot of questions at ease and even help people learn how to be a little bit more critical with the data that they receive when they receive it. Because let's face it, lots of stuff that we see on the internet, or that we hear on the news or reading the paper, it's basically clickbait. It's basically things to keep you engaged, whether or not the actual substance is worth the headlines that are written so...So what you're referring to is recently the FDA put out a statement, a consensus statement in the news and it's making all kinds of traction in the news that they're saying that CBD is not as safe as people think not only that it can be harmful. Now this has bled onto TV and my patients have been asking me about this FDA statement. Then there's been other news articles like the one that Forbes published, read said that CBD causes liver failure. Failure. That was the title liver failure caused by CBD. I want to get into all that I wanted to take a really deep dive into the science of all of this as a gastroenterologist, I'm board certified gastroenterologist, which means not only am I a simple country, butt doctor from Texas, but we actually have to learn liver disease, hepatology, I'm not a hepatologist like some of my other friends where I send like really complex things, but we at least have to understand the liver, how it works and what it does. So a lot of these articles discuss this but they don't clarify so many little things. Because and they shouldn't it's a it's a journalist writing an article they want they want it to be shared. And anytime you mentioned CBD, anytime that that is thrown out there, you're going to get some clicks, you're going to get a whole lot more clicks. If you say you're going to die from taking CBD. It reminds me of the I remember Jerry Seinfeld was on Saturday Night Live one time and they were making fun of the nightly news where they always do the promo at like three o'clock. Like five household items that are guaranteed to kill you, tonight at six.You're like what? If it was so important, they probably wouldn't make you wait.No, I'm gonna die before you put this on the air. So what I'd like to do is talk about the briefly the science of the endocannabinoid system and CBD, then do a little bit deeper dive into the liver. So everyone's going to get a primer on the liver 101 here, because these studies don't make sense unless you know, some of this knowledge. It's just sensationalism. For some of it, some of it is a little bit unfair. I think some of it is for what the FDA got, and it's there. But I just want this podcast today to be something that can be useful for industry people that can be useful for patients or people that are thinking about taking CBD and it can be useful for a subset a small subset of people that may be should not consider taking it. Yeah. So all of this is kind of, you know, for the future of this podcast, It's almost going to be a bit of a rebuttal. Not necessarily a defense of hemp derived CBD. But let's just buckle up and kick some science. This might be a little bit I don't know how long we're going to go where we're going to go with this. We're just going to feel it out and see what happens. But I at least want to be able to explain why I still believe that a lot of people should be taking CBD even though Forbes is like you're gonna die from this.Yeah. It's not arsenic people. No it isn't and I think another cool application here is there are people out there who have been on the fence on whether or not I should try CBD or is this something that's good for a family member for me? And unfortunately, there you hit this intersection, where a news headline is written that CBD causes liver failure. Well, if they've been on the fence, that's a pretty big No, no, right? So now you've taken away maybe an avenue that they were considering to help them out. What I hope that we can do with this particular episode is basically let's temper and let's see things in context. I think context is a word that as you get into sensationalism is something that is kind of the rescue item. If I could put something into context, then at least I'm giving someone a fair chance to understand the information that's before them. I don't feel like sensationalized headlines do things like that. Then again, I also don't feel like someone who shakes, hand picked or cherry pick studies is doing that either. So what I think today that we can do is fairly evaluate and talk about the process of how the liver works, and why some of these studies are or are not applicable to the nature they were presented.Absolutely. So the first one we got to discuss is what what what the heck did the FDA say? Sure. So the FDA came out and they mentioned that they've got several issues with the safety of CBD. The two main ones that they're really concerned about are potential for liver injury, and interactions with other drugs. What they actually said is that they're concerned that people may mistakenly believe that trying CBD can't hurt the agency wants to be clear that they have seen only limited data about CBD safety. And these data point to two real risks that need to be considered as part of the drug review and approval process for the prescription drug containing CBD. Interesting. Now, what I say this is because the FDA is referring to the data that was presented to them by GW Pharmaceuticals, who has a epid... eipdi..x you know?E-p-i-d-i-o-l-e-xYes, which is the first FDA approved prescription CBD isolate,Right,for seizure disorders.It's important to point out that is not full spectrum. Correct. That is not full spectrum. And there's some that's important because here later in the podcast, and think we're going to draw some comparisons and just if you're listening, just remember, epidiolex is a CBD Only isolate it is not a full spectrum product.So let's talk about what the FBA what the FDA actually does. So the FDA has a really daunting task. The Food and Drug Administration is responsible for protecting the public health by ensuring the safety, efficacy and security of products. So it is super daunting because there's a lot of products hitting the market, and the FDA has tried keep up with this to try and protect people. And let's be honest, let's look at the elephant in the room. The elephant in the room is that there are a lot of bad CBD products out there. Yep. In fact, in a jam article 2017 showed that 70% of the CBD products that they looked at did not have what was on the label and what was there could be higher levels of CBD could be lower levels of CBD. So it's a gamesmanship that's going on right now. So it is totally true that you need to make sure that you've done your homework on what type of CBD that you're actually taking. There currently is little to no regulation in the CBD industry. There is the President and CEO of Natural Products Association NPA. His name is Daniel Fabricant. He's a PhD. I love this quote. He's quoted as saying it is well past time to bring science into the equation, as federal rules require safety and Consumer Protection must come first. I agree. And we all agree with that. Sure. And I think that all companies that have reputable CBD companies, they all want that. Problem is when you have these different stories leaking out, which gain much more traction, it just starts creating a little bit of confusion misconception, and then people don't really know where to turn. So the feeling is, is that possibly statements by the FDA saying that it creates this narrative that questions the safety of CBD overall, strictly to address a few number of companies which are producing quite frankly, some crap products.What was the number that we learned the last time that we were in Utah at meeting I believe it was one out of every 23 to 24, I could be off it was definitely in the 20s. But every to every 23 or 24,25, CBD labels available for retail purchase. One is seen as a reputable well marketed or correctly labeled product, which means that even if it happens to be off a little bit, you've got 23 or 24 other labels which are just not truthful or probably not correct, don't have a certificate of analysis or are blatantly, just not even what's in the bottle.100%. There's a lot of people out there trying to take advantage of this wave that's coming. So I do not. I believe that the FDA is doing their job by looking at the data that was actually presented to them Agree. So let's take some time and break all this down for the consumers, health care providers, industry personnel. Starting with the question, does CBD cause liver damage? Unfortunately, or fortunately, because I like science we really need to talk about what the endocannabinoid system is. Because if somebody's listening to this, they're like, Well, I was thinking about taking this but I'm worried becasue it can cause liver failure. I don't know why I'm taking it. Why in the world should I be taking it? So let's do a quick one minute discussion of the endocannabinoid system. Let's do it!All right, the endocannabinoid system. The endocannabinoid system is a system which was discovered in the 90s that we now realize it's probably everywhere in the body. There's primarily two different types of receptors, but essentially, the way that I try to explain it to my patients, it's concentrated more so in the neural areas, nerves, brain and the immune areas. Although we now know it's in every single organ, that's where all the original research was. We now realize that its job, the endocannabinoid system is to produce these products called endocannabinoids. Which work as traffic cops. They just kind of get your body to get back to an area of balance. If you've got too much activity, they go Whoa, slow down a little bit. If it's not enough, they go, come on. Let's go ahead and get some more going here. So you have this fantastic system in your body that really just tries to keep balanced. Think of it that way. And you're going to hear a little bit later why I think most of America is out of balance. I think most of America needs some replenishment of their own endocannabinoid system. So that's the important thing is is that there's a dire need to try and get us all back to a certain balance, because the reality is we're getting sicker as a nation. And one of the causes could be that we took hemp derived foods out of our diet and out of our livestock diet. And there's a theory on that, that possibly that's one of the reasons why we're having more autoimmune diseases, why we're having more of the other problems that we're seeing, Well at least contributing factor.Certainly at least a contributing factor. So keep this in mind. So the the primer on the endocannabinoid system is if you're, if you have ears and you're hearing this, you also have an endocannabinoid system, and you have a higher than likely chance that you are out of balance with that. And if you are out of balance with that, then you probably could benefit from some of this. Sure. So right now you're going well, I'm out of balance, I'm going to probably benefit but I'm going to go into liver failure if I do this. So let's talk about what liver failure means. You have a genius living within you. You probably have multiple geniuses living within you.Thank you. That feels great. Sometimes the voices in your head don't say to do bad things.The evil genius. Yeah.Well, one of the geniuses living within you as this beautiful origin called your liver. So you have this and it's amazing. So to understand where they're going with this, let's talk about what the liver actually does. So we all have livers. And they work differently in every single person, and they can continue to adapt, evolve and change. One of the only organs that you can transplant a partial portion of it and it will grow into a full liver. So the nephrologist think that the kidneys, the smartest organ, the neurologists will think that the brain is the smartest organ The cardiologist says if you don't have blood, you can't think so It must be the heart. Yeah, yeah, exactly. I'm gonna say, well, for health span, smartest organ in the body is the endocannabinoid system. So eventually, we're going to have Endocannabinoidologists. Because what ends up turning out is that the endocannabinoid system is in all these different organs.Correct.They're not completely separated. So let's talk about the liver. The liver is responsible if you ever wonder what the liver does. So do you have any idea what the liver does? I've got a little bit of an idea... Little bit of an idea. So the liver is responsible for selective uptake, concentration, metabolism, and excretion of the majority of drugs and toxins, also known as xenobiotics. So let me just say that again. Basically, the liver takes the crap that you bring into the world. And it says, I'm going to convert it to something useful, or I'm gonna get rid of it for you. Yeah, it can detoxify it, or it can say, Oh, you need to be this and then you're useful. That's why I say it's a genius in your body. And it the liver figures this out, it figures out what you need, and it determines if it's a drug, or if it's a toxin, and it can turn into a better form. Now, one of the problems I have with these different articles that I've been reading, is that they discuss that then enzymatic process called the P 450 system, and they just write it like that they're like, CBD has been shown to affect the P 450 system. What doesn't affect the P450? So that's the issue. So let me break that down, I bring up the P 450 because in the lay literature without even describing what it is, it is a complex. It's called a phase one metabolism of the liver. Under p 450. It's an umbrella term that has over 60 different genes, that code for hundreds of enzymes to break down anything that comes your way. So the P 450 enzyme is like saying, Oh, I don't even know an analogy, but it's top of the funnel down. It's like you just so generic, that you can't just say that. So but they write it in the lay literature almost as a sounds sciency so I'm sure that it's, I'm sure that it's right. That's kind of my feeling on I'm like, why would and all these people it's almost like these news articles parrot each other. And nobody's stopping going, wait a minute, because as it turns out, the P450 system, not the P450 enzyme, the system breaks down almost everything that we put in our bodies. Yeah, no joke. So a lot of going back to the pharmaceutical days, I remember that was one of the biggest challenges with with any of the drugs that we detailed a physician on was, how is it affecting the P 450. And that would be something that they would be all salespeople be coached on that before they would go on calling a physician. But the truth is, it doesn't have to be a compound. It doesn't have to be a medical pharmaceutical compound for that to be somewhat important. Something as simple as grapefruit juice. Also, detectibily inhibits the metabolic ability of the P 450. So there's all there's a handful of different drugs that people who are elderly, maybe caution, don't drink grapefruit juice, because it will inhibit your ability for your body to clear this particular drug. And I say that to say this. It's not nothing is inherently just special because it does or does not directly affect the P450, almost everything you take into your body is either cleared quickly or slowly by that same system.Yeah, so they kind of imply like CBD is the only thing that gets...Not even close....that gets processed in the in the P450 system. In fact, we know that there are multiple medications that can be altered by certain foods. Grapefruit is the most common one, and that really affects like immunosuppressants tremendously and that's where it really came up. When they realized, oh my gosh, you have these different drugs, let's say blood thinners and immunosuppressants, which have a very narrow therapeutic window, you have to have these things like right dialed in. Yeah. And then people talk about grapefruit but you know, other things that have actually been shown to do this cranberry juice, black tea, pepper, even chocolate Yep. has been shown to affect drug absorption and they have been shown to affect certain pharmaceuticals. We don't even know the tip of the iceberg on this because you have to do the study on it. You have to do the pharmaco kinetics, the PK is what it's called to actually determine that which is so funny because they say oh CBD is metabolized by the P450 system. That means nothing. And so if you take CBD and or chocolate and or drink tea, be careful. I mean...I think a good analogy a seriously a good analogy is it the P450 being metabolized by the P450. It may be good for base knowledge, but the truth is, is does it overwhelm that, as you put it system, if it is overwhelming that system, chocolate, for instance, for most intents and purposes would be like a single car driving down a six lane highway by itself. It's not really if the highway was a P450 and the car was the chocolate. It doesn't take anything to funnel that that car through.Correct.The problem is is whenever you happen to overwhelm that system. And that is important to know. But I would say in terms of context, kind of the way that we started this discussion in context. It's not my belief through what I've read and seen that CBD inherently overwhelms or becomes more than a single car down that six lane highway.So not only is it just one single car going down the highway, remember that not only foods but drugs, nobody's talking about drug drug interaction.Right.So there's a reason. So I see a lot of patients that one drug may be very effective one thing may be very effective, but there's so many variables like for instance, drugs, the sex of the person plays a role, you may have different levels, the age of the person and any diseases can all affect this whole system called the P 450 which produces enzymes. So not only that, but then genetics play a huge factor, alcohol intake.Alcohol intake, all of that. I mean, genetically, this may be why some drugs work on certain people and why they don't work and others fact there's a whole field of science right now where people are trying to determine the genetics ato go, Oh, you're going to need a higher level of whatever Plavix which is one that they've actually looked at. Or you can, you're going to take less. So we this is a whole field of this beautiful science where we can go Okay, genetically, you're going to be predisposed to need more medications. So when these enzymes get used up, basically if you've got this one chocolate, which is a car, one on six lane highway, and then you add fluconazole, which is an antifungal, that's an but that's not a car, that's a semi now and then you add alcohol, which is a minivan could be ccould be a couple minivansand then you do whatever something else, but you can see that the liver has to try and process this right. So what happens is it becomes this once it becomes a traffic jam. Then people start getting angry, they start honking their horn that is a rise in your what we call lfts liver function panels liver function test Yeah, so AST and ATL are the two ones that we always talk about, that's exactly what the FDA was referencing. So I want everybody hear this. When you overwhelm the liver with multiple cars using your analogy, then honking starts and the honking the warning sign is this rise in AST and ALT. So, for instance, your body can adapt to it. We've seen this all the time. If you drink alcohol on a regular basis. you build more lanes, you build more lanes, you get really good at metabolizing alcohol. Build tollways. I'll use myself as an example.Not with alcohol.With coffee, Okay.I always have to laugh. Whenever I go to the my own doctor. They say how much coffee do you take? I just write obscene amount because I've down regulated by receptors or I've had the ability to ramp up my my livers ability to convert that coffee into an inert thing and there it is. So you see it as an anesthesiologist or as a crna. I mean, describe what your experiences whenever you try and put somebody to sleep using propofols, different medications.Yeah, well, I mean, definitely, if someone says that they happen to be a large consumer of or a consumer of large amounts of alcohol, it generally takes anywhere between 20 and 30% more of an agent to put them to, to sleep safely, say, But back to your point of body habitus, for whatever reason, even just something as simple as someone being a redhead fair skinned, those people generally take more agent to make them go to sleep. Yeah, let's go ahead and clarify this. This is a well known thing in anesthesia. You're not being prejudiced? No, not at all. No, they literally just for whatever reason, the metabolism rate of someone who's fair skinned with red hair is typically higher than the average calculation and you can go through any types of weight based medications that we use to bring sedation to someone and generally fair skin redhead folks just take more. Is that interesting?Yeah, it is. So that is more than just anecdotal like they've actually done some studies on this and they've actually shown probably because whatever lineage, they come from Scotland, Ireland, they have a higher P450 to metabolize that particular or a higher subset of the P450 systems. So just keep that in mind. So when you take certain foods or drugs, everything's competing for your liver, to do to just say, hey, fix me, you know, figure out what's going on. Fortunately, it is a badass organ and the liver is tough and it can handle a lot, the largest solid organ that we have in the body. So usually it can handle everything. Now the most common example like we've talked about, if you take grapefruit juice with certain immunosuppressants and things then that particular combo because those drugs need exact or how they were manufactured need exact metabolism numbers. Not only that, did you know that like nutrition plays a big role. So, high protein diet will actually affect your P 450 and malnutrition will affect it. of course it will. So those are all of our paleo friends over at paleo FX and such those guys have revved up p 450s. Eating a lot of protein working out a whole lot, they're able to do this. Unfortunately, malnourished people probably can't tolerate as muchNo and they aren't they aren't they honestly they don't have the supply to rebuild the enzymes that are that are used within the P 450 I mean it's just malnutrition is going to deplete all different types of systems, not just the liver.So in the intro, I kind of mentioned that we're getting sicker. And so let's use nutrition as an example. federal policies tightened by the controlled substance act of 1970 essentially banned the production of industrial hemp during the war on drugs effectively we made hemp CBD illegal and put it under the umbrella of cannabis cultivation. Now what were we were talking with Will Clyden of O-hi energetics right, who actually discussed this and he said some cool stuff on this. He back before this when they were they were using hemp and hemp has been used for ever like since we landed in America, hemp has been using hemp has been used in China for thousands of years and all this other stuff that we were feeding because it's a fantastic crop. It's it detoxifies the soil. And it actually works. It grows quick. It's a great crop industrial. What were we thinking making it a banned substance, I don't know, separate discussion. But they've got data to show that when they were feeding chickens, so for everybody out there I had a patient today who said I said Oh, she was suffering from some things and I think CBD would help with and I mentioned Hey, have you ever considered CBD Oh, I would never ever, ever, ever do anything like that. I am not like that. I said, Okay, that's cool. said hey, let me tell you something. Do you know that before 1970 we were actually feeding animals like chickens and cattle. One of the primary things that we would feed them would be hemp, and it's been shown that you can take a chicken egg and it had over 250 milligrams of CBD, right so right now if you're somebody that just spent $200 on your CBD that has 300 milligrams in 1968 you could've just had an egg.A three cent egg.I know 3 cent egg. And I looked at the literature and I and I could not find anything that said death by egg otoxicity. It didn't so everybody that's sitting there thinking oh my gosh, no. I'm not going to do CBD. We were having CBD in our diet. A great Great example, to learn a lot more about this and do a deep dive. Our friend Chris kresser had Will Clyden and the CEO of O-hi, O-hi energetics on and he went into this tremendously. It was so cool. It was just like I just it's crazy that we stopped like, and I as a physician have seen that we are getting sicker as a country. So in 1970, we've got since 1970. We've got more chronic disease, we've got more dementia, we've got more autoimmune disease. coincidence, like we said in the intro, maybe it's at least a contributing factor. And now we have the FDA saying that CBD can be harmful yet it was in our food supply up until 1970.That's nuts, dude.It is nuts. And it doesn't make sense and if you look at mean hemp seed, birds eat seeds, birds consume seeds, they do all kinds of things where they can they take in product, What's the matter? No, I'm just looking at I'm trying to make sure we get through everything.Okay good, but I mean they eat everything and people have been consuming eggs from not just chickens they've been consuming eggs from all different birds on the planet for that long. The fact that we've restricted hemp growth etc has only taken away one of the natural things that birds were eating.If you're if you're really interested in this like I said go to Chris Cressors podcast where he's got Will Clyden on there is really cool wills smart dude Chris is super smart dude. So those guys those guys kick some crazy knowledge.Right?So that is it's weird that we're talking on this episode about CBD causing hepatotoxicity. And we've already shown that the liver's pretty badass, right? It can do a whole lot and we've already shown that the endocannabinoid system is necessary and since 1970, or up until 1970. We are taking in significant amounts of CBD in our dietRight.Weird.It is weird, but it's not so weird when we get down to why everyone's alarmed. So you want to get into a...Now let's go ahead and look at the studies. So that is sort of the phase one of this podcast because now we're going to start geeking out a lot. So I hope I didn't hope I didn't lose everybody with a but you kind of need that background to understand what we're going to talk about next.Sure, you definitely that background.Alright. So what they're talking about is the FDA published this revised consumer update. So this is the consumer update that they put out there for everybody detailing the safety concerns about CBD products. Now, this was based on the studies provided by GW Pharmaceuticals, GW Pharmaceuticals has done multiple different studies looking at different things to get their FDA approval. And I'm going to say right now, that kudos to GW for being the first company to step up and really try and make something for a group of people with intractable seizures have an alternative. Kudos to the FDA for doing their job and looking at the data that was presented to them. What I'm going to do is go next level and say, Well, you didn't look at everything. That's the bottom line here. So I'm not bashing anybody. Let's make let's make certain of this. Sure. So there have been several randomized, controlled and open label trials that studied the effects of epidolex, I'm going to call it epidolex from now on it's just easier, which is a 99% pure oral CBD extract on patients with refractory epilepsy. So this in turn led to the FDA approval for two diseases, dravet syndrome and Lennox-Gestaut syndrome. So if you recognize those names, bless you, because you're dealing with some serious stuff, It's a serious seizure issue. If you don't know those. Count your blessings. It's one of those times to go well, no matter where you're at in life. It's like well, thank goodness that I don't have to Deal with a child that has this because that's, that's a really big deal. These are intractable seizures. So they looked at the data on that. And in these studies, the kicker here is I'm going to say it again, getting back to the lane highway, the patients maintained on their stable drug regimen with a median of three anticonvulsant drugs. That's important. It's super important. Three anticonvulsant drugs. So when we use the analogy of the car on the road, imagine a six lane road. And three of those roads. Three of those lanes are double semis.Yeah, that are closed construction... Or closed, Yeah, that's more likely or closed. So let's talk about that. So when we're talking about three different agents used to control seizures, some of those agents would be and I'm assuming here, but probably Depakote, probably Dilantin, also known as phenytoin, or fosphenytoin, which is seravex. There's a handful of anti seizure medications and through my knowledge, all of them, all of them have been recorded as raising the enzyme levels used by the liver which of course would lead to ALT and AST elevation, showing that the liver is essentially working overtime to long term process these drugs right or wrong?Correct. Correct, which is exactly what the FDA is supposed to do. They're supposed to look at this data and go Okay, so let's just look at the study that they're talking about. So the FDA accumulated this data, and they looked at what GW presented GW presented in isolette of CBD, not a full spectrum. And the dose they ramped up to 20 mg's per kick 20 mg's per kick. What that means is a guy like me would take 1954 milligrams a day.That's a lot more...of CBD isolate. Now I see the effects, beneficial effects of taking KBMD health CBD 15 milligrams twice a day,that's 30 milligrams,that's 30 milligrams.The exact dose of what makes people feel better is very argued because all the data coming out of Israel shows that a lot higher doses, but I'm seeing effects at these doses So let's be real quick let's stop for context. So right now at this intersection what we're what you're saying is with a full spectrum and we said this at the beginning of the podcast that what GW Pharmaceuticals has with epidiolex is a CBD isolate and what they've done...You're saying epidiolex now that's funny. Yeah, whatever it is, Well, because I started with that. Then you told me no, that's not how you say it.I think we should switch it up the whole time. EPA max the way it was edimax. What they did is they were able to establish that almost 2000 milligrams for you would be the ideal dosage however, you...isn't that correct? That's the dosage that they went for or the dosage that they felt was safe, Safe. Okay, I'm sorry. So but but on the upper end of... That was what they were aiming for on everybody. In essence, though, from where you have had beneficial effects, you're talking 60 times that amount, two months worth, is what they are saying the safe level would be in one day where you're finding the beneficial spectrum. So just just in terms of context, full spectrum, CBD, one 60th of the dose that they're saying it's a it's a safe level is really all that you need from our experience.Yeah. Now in GW's defense, let's look at the data. So in dravet syndrome, seizures dropped 39% and in Lennox-Gestaut 42%. So... that's good. So they probably did their homework and said, well, we need to get up that high to actually help that so I don't know anything about that. I'm not a neurologist. That's where it's at. But I'm just saying that when we look at that dose, no average consumer is going to be able to consume that Much CBD in a single day, unless it comes through this 2 full grams a day is more than most take Yes,yeah. Now here's the problem 94% of the people had side effects. Okay 94% at the highest dose compared to 75% placebo, kind of weird. So there's just a huge placebo side effect profile that doesn't get discussed at all.Did they say what it just had a curiosity do they state with the placebo was for the control,They did not stay with the placebo was oh, I take that back. I don't know what they use, but basically they left people on the same medications. So, essentially, let's just look at this and say okay, but the good news is, most of it was not a big deal. Most of it was what the FDA also discussed beyond the liver tests and beyond the drug metabolism. They also said Oh, CBD can cause nausea. It can cause drowsiness. It can cause all these other kind of nuisance things. That's what they're referring to right here. It's interesting though, that have a side effect profile assigned to a placebo that's that exceeds around the 30% range, because that's generally the throwaway number. Yeah. So we've gone twice away from the throwaway number. And they've had they've had reported side effects, which I'm not trying to over draw conclusions here, but it could at least indicate that side effect profiles assigned to CBD in this study probably weren't solely to CBD, Well, you're dealing with one of the highest risk populations you can get your hands on, when I did clinical research and when we would do a moderate to severe Chron's study. The placebo arm would have tons of side effects because the disease is bad. That's what's going on here also. So most was not a big deal, upper respiratory tract infection, somnolence, decreased appetite, diarrhea, blah, blah, blah, blah, blah. But the one that they focused on is the increase in amino transferase concentrations. This once again was a revised consumer update, they put this out to the public and their statement is increase in liver amino transferase concentrations when I just got done explaining what the liver does. Did I ever say amino transferase concentrations? No. I said liver enzymes. right? frickin talk to the public if you're going to release a consumer paper. yeah, liver enzymes. AST ALT. This is hiding behind scientific garbaly goop. It's like you're doing half science half anyway. But but whatever. So a patient show up and they're like, I need you to check my amino transferase concentrations. I'm like, Whoa, why? They Hand me this, this, this news article. Right? This is what we're trying to address right here. So what they found is that in the higher dose, 20 mgs per kg, there was a rise in some patients in three times the level which is significant, so if your normal is 20. You can be 60 if your normal is 40 it can be 120. When patients come into me and it's three times the level it sounds alarming. Do you know what happens when somebody gets hepatitis A acute infection? It's way more than that thousands of times the level when somebody goes into foaming at failure there AST and ALT will go from 40 to 10,000.AST and ALT have risen for almost everyone who's listened here, way more than three times throughout their lifetime multiple times in acute or in very isolated settings. It happens with illness.So getting back to your highway analogy, which I think is really cool analogy. I'm glad you came up with that. Thank you .Getting back to the highway analogy. 80% of them were taking a drug called valproic it matters Depakote Yeah, that matters. That matters a lot.It's when you take these medications, which is why at the beginning of the show, I said you're more likely don't have to worry about it. But if you're on certain medications, keep it in mind. Now that being said at the lower dose didn't see this stuff. So there is a dose dependent usage of the P450 enzyme you can if I give you one drink, or if I give you a bottle of tequila 512 which in my opinion is really one of the tastiest, most fantastic tequilas you can ever get your hands on. It is delicious. It's delicious. I'm gonna I'm gonna digress right here. Oh my God, Tequila 512... Also sponsored by Tequila 512Tt was really good seriously, ummm in every single person with liver test rose.They went back to normal if they decreased the anticonvulsant or decreased the CBD. So either one it went back to normal. So it wasn't number one, it wasn't permanent liver damage. More than likely correct they were able to return back to normal. And number two, it was simply A case of an overwhelmed P450 pathway more more than likely.So you want to get really confusing? Not really but we might as well try. I don't want to but here's what's really interesting, then they kind of get a little geeky. So GW presented their their stuff and then they showed that the P450 in this enzymes and they went into will, the CYP to, 2c19 CYP three a four can inhibit the CYP blah, blah, blah. Those are all just cytochromes people. Those are all just cytochromes It's under the umbrella of P 450. That's how complex this is. Yeah,It is nuts how complex. The highest plasma concentration to CBD occurs within two to three hours after exposure to the Epidolex. With medication, so timing of these medications going to play a role, which actually got me down a weird rabbit hole where i started thinking. We haven't done this much analysis on what happens if you take your Ace inhibiter and you take your cholesterol medicine, timing wise PK analysis on different people and everything. Because when they do these pharmacokinetics, they do it to get the FDA approval, they do it on people that are healthy, that they can understand it. Let's put this into context again, if you're listening to this you've ever taken tagamet. Have you ever thought about when you take your tagamet, you probably only take it whenever you're afraid that you're going to have acid problems, right? Cimetidine?Yeah, guess what? It's also known as a high level p 450 inhibitor if it's over consumed. So I guess what I'm saying here is, there's probably way more alarms being driven over something that yes, is handled by the P 450 system, but is far less invasive or it's much it's a much smaller vehicle on this highway than some of the other things that the alarms are not sounding over.And then surprise surprise after I just got done talking about the liver and the genetic variability and all these other things. When they looked at the pharmacokinetics there was tremendous variation. Hmm. Weird. Yeah. Odd, right? So and anybody that's listening to this that is a, a pharmacist or is a scientist or like Well, yeah, duh. Like I know, duh. But why put out such an alarming statement? Yeah. Without context.Yeah, yeah, you're right. So it for Okay, so it's a little bit of clickbait stuff, right. And so maybe even the journalist who wrote it doesn't understand specifically, the implication, they may have only seen P450, written somewhere turned to a health care provider and said, What is this? Well, that's indicating that things are rising up, they freak out. They write a headline that says CBD causes liver failure. I just learned that from this health care provider. So I'm going to write this piece.Well, that we're going to get into that. The liver failure. This is still just the FDA. Oh, yeah. To the consumer. So I hope that the FDA looks at this and says, You know what? That's right. All that stuff that was just being said it's right. But we didn't have the time to do it. We couldn't sit there put that on paper, we'd lose everybody. I get it. It's quite true. We all we all but we all have a responsibility, much like any doctor to try and explain. You and I have this ability to have this forum to reach hundreds of trillions of people.Yeah. It eflects in our subscriptions on YouTube. They so many trillions of people subscribed, they started his back over to about 200. Yeah, so every time we got trillions, they start back over. Yeah. So So anyways, so what what you're realizing here is exactly what we're talking about. When you put stress on the liver. The liver honks its horn and does a little rise and the lfts goes, Well, hey, guys, maybe not so much. Can we just back off the traffic a little bit and see what's happening here. So additional studies have shown that levels of the anticonvulsant drugs actually caused the daily effects. So now we start wondering that the that the CBD may actually rise some of the anticonvulsants and then you have more side effects from that comes down to the same thing we're talking about how many things do you want to tax your liver, that's the bottom line. To summarize high dose of a pure CBD isolate, not full spectrum, while using a mean of three other anticonvulsants can cause temporary rise in liver tests and affect the metabolism slightly of the anticonvulsant. Of note, it did not happen at lower doses. So one more time, if you are on an anticonvulsant discuss with your doctor and make sure that you stay well below the 2000 milligrams a day. Yep. So this whole thing of Oh We're going to block the P 450 the P450 is So frickin complex, it is nuts. So anything you want to add to that, because I'm going to move on to the thing that I really want to, like kind of make fun of No, not really, I just want to say that I think that the FDA, unfortunately, is a very important and serious organization within our government. And I think that for all of the flack that they take their, unfortunately, with any other entity, there are limitations on what it is that they can do. And I do believe that they try their best to fairly ascertain and address situations as they are presented to them. Regardless of how frustrated that one of this may get is we don't get a result from them. A lot of it is just simply because there's not enough manpower. Oh, absolutely. They get thrown everything think about, think if you're in an organization where you know that 70% of the crap that's out there needs to be pulled off the shelves and you're limited. It's a government organization. These people making these statements are MD's. I'm really limited fortunately, I have well, we have the show where I kind of enjoy looking up some of this stuff. Fortunately, we have some friends of ours that are that work in the nutrition industry that are fantastic at researching articles. And some of that gets gets brought to me I want to make sure that we all get better this is the whole purpose of this.Hundred percent.I want to help the FDA and help GW I want to help the CBD industry. I want to help all of it. But let's just talk about this because something super weird happened. And this is the one that got the most press A Forbes article came out that promoted a mouse study and made the sensational claim that CBD causes liver failure.Yeah, that's kind of what I was referencing earlier. I may steal the thunder but yeah, you're right.Yeah, so this is you're exactly right. In the intro, you said it was clickbait. I really after looking at this study after pulling the study, because how many people read that article are actually going to pull the study.Well is the is the person who wrote this study that well versed in reading studies like that. I mean, that's that's an important thing. I mean, they I think that probably even the author of the article feels like that they are doing a service to the reader, but probably doesn't understand. And if they do, then shame on them, but if they don't, I think that would be a better explanation doesn't fully understand how to read the study and the quality and the qualifications of that study to make a statement like that.Yeah. And you know, this, this could be an arguable point, I'm sure that the person that that wrote this feels very strongly that what they said was right, the bottom line is the goal of this study was to investigate CBD cannabidiol hepatic toxicity, meaning liver issues in an eight week old male mouse. So they they took a group of eight week old male mice, and then they gave them a CBD that they produced. The CBD that they produced and Will Clyden will just jump up and down when he hears this because he decided Is this on Chris Cresser's podcast. The CBD that they produced was used to extract using hexane, which is a molecule that is known to be hepatotoxic. Yeah, you're not supposed to have heaxane. Don't do that! Will Clyden talked about the fact that if you find a CBD with an outrageously high amount of of CB, if you find a full spectrum CBD with an outrageously high amount of CBD more so and the price ranges, okay? Because what they did is they extracted that with hexane in a cheap way and threw it in their bottle and said, there you go. Now you can check that's got 10,000 milligrams of CBD or whatever. And it's really interesting because there's so much going on in the industry like this. So this particular study out of the University of Arkansas, took the CBD, or they made their own CBD using hexane which is a hepatotoxic in itself and in their certificate of analysis. It was there and then they gave it to these mice. Second thing neatI don't even know there has to be a second but we can hear it. Because I mean seriously, that's, that's like saying, I know your stomach hurts. You should take this Pepto bismol. And then I don't tell you that I've broken up some glass shards and have you drink it and you're like i'm bleeding now! What's going on? I'm like, I don't know. Yeah, but you only paid half the price.I made it myself.Which, by the way, that last batch of propophol that you did in your bathtub is working phenomenally. I'm sure it is. Now we do not make propophol in our bathtubs.Alright, so the second issue. If we have any mice that are subscribers to our show, or listening, I would like you to have your children removed from the room at this moment. Because they took these poor mice, and they gavaged to them. Would you mind defining what gavaged is? I think it's when you kind of force feed somebody I don't think it's willing. That's your I think gavaged something you kind of threw one at me there I think to gavaged someone you basically introduce a funnel to the esophagus and well you kind of get after it, don't you? Yes, I'm currently gavaging my mic right now trying to figure it out. I just undid everything. You're gavaging our ears with your, your microphone adjustments?All right, so gavage is they forcibly give these mice?The CBD extract? Yeah, I don't think it's comfortable nor pleasant.No typically through a tube feeding or down the throat to the stomach is how they generally gavage things. A quick side note, now because I'm now all of a sudden I feel like I'm living in a glass house when I was an undergraduate student. I actually did my first surgery on a rat and we took out their adrenal glands. And I'm just saying that so I don't want to sit there and pretend like I'm not done mean things to an animal. But that was when I knew immediately I could not be a bench researcher. I did not like that. At all, now I was like, I need to, I want to heal. I want to heal. I don't want to hurt these animals, but it's it's a whole separate discussion. So anyways, so they gavage these animals with different doses, and it's really interesting. Now in what they call their defense, they call it allometric dosing, which means they're trying to get the body weight to human weight ratio appropriate. I've read some rebuttals of this article where it is a joke, you just can't do that. And when I read vitamin weed Michelle Ross? Michelle Ross, when I read vitamin weed she dis... she specifically discusses why research on CBD versus mice is very difficult to do because the weight basing the endocannabinoid system is different, all these other things. So allometric dosing being said, assuming that they're saying it's right, so the dose would be the equivalent of what they gave and What a human would give So I'm doing the allometric dosing, which I think is actually higher than what it actually is separate thing. They took mice and they gavaged them with zero milligrams of hexane derived CBD 246 milligrams per kilogram 738 milligrams per kilogram or 2460 milligrams per kilogram of dirty CBD. It doesn't make sense dirty CBD isolate. So for instance, in a horrible alternate universe where humans are now the test subjects and we have large mice which are running tests on us, and they decided to gavage me with the same thing. That would be the equivalent at the highest dose of 241,080 milligrams of hexane derived CBD isolate. I'm not even sure what the hexane would do it 240,000 milligrams 242,000 milligrams.No I mean that being the more or less than now at this point, it's just an additive. It's just I mean it's it's not an excipient It's a straight up additive. That would not make sense at all. Oh, it's crazy.It's poison.This article came out in Forbes and said CBD causes hepatotoxicity. Also hexane causes hepatotoxicity.It is nuts. Alright, spoiler alert. The mice suffered hepatic toxicity and death at the highest dose. Shocking... You know what? I also hear it's bad to have breakfast cereal with not milk but drain-o. Just something that I'm gonna go out on a whim. Don't think you're supposed to do that. It just doesn't make sense. It's It's It's not. That is not an apples to apples comparison if you're talking Okay, so we talked about it earlier. reputable CBD source there is no reputable CBD producer that's going to have and Will special shout out to you it's going to have hexane as a byproduct or an excipient in their full spectrum COA approved which is also why KBMD Health with powered by olyxenol hundred percent is does not have that. I mean they do co2 extraction, which is the important thing which is a reason why we partnered with them to make that product. So we are the one out of the 23 or 24 that is the safe and trusted COA back no hexane etc etc. Doing this study is not an apples to apples comparison on what would happen because who knows? Who Okay, I don't get it because GW we already did that study. They determined that 20 Meg's per kg which is still a shit ton. It's a lot. It's a lot. Yeahis the safe maximum dose. These guys went times it by 100.Yeah, they did.And see what happens? Yeah, it's it's a bad it's a bad comparison. I mean, yeah, honestly, if you wanted to find out if CBD plus hexane causes liver toxicity at a ridiculous amount, top to bottom, then that's a great study outside of that, since nobody does it, I would say it's a bad study. Speaking of road, that's a road to nowhere.Yeah. And so study like this, uh, like you had mentioned is essentially it's not science. It's clickbait. Yeah. And right now that that author, that journalist is just kind of laughing. He's like, I know, and now you're bringing it up, and I'm going to get another whatever, because that's what people are trying to do. They're trying to get attention at this point.So at that point, good for you, you got to click but I would be truly interested if possibly that particular journalists would say, you know what, I didn't fully understand it. I mean, that's okay. Let's look reading studies, right? There's there's a study to reading studies. I mean, we heard that we heard the breakdown that kresser did on Joe Rogan is he Twice had to address his approach to completely different topic about the the plant based diet and then how he had to re approach that with the rebuttal. All that just simply to say, there is a science to reading studies and being really good at understanding what is and is not applicable and then how to find studies that you can compare to each other for good meta analyses. So what we're doing right now is I'm telling you that maybe sometimes there aren't studies, but my anecdotal evidence, I have a busy practice, you hear the patients, we hear them talk I listen to them, when they say that doesn't work. I go, Okay, I'm not publishing it. I don't have time to do that. I wish I did. If I published everything that we're gathering data on, if we're looking at, you know, just so many different things, CBD is just one of them. We've got I love I'm a huge fan of brain.FM for the ability to use sound to change your mood. I Would love to they're unpublished, a lot of studies on stuff like that. There's, there's tons of stuff. So when people go, oh, the studies aren't out there, there is something to be said about the Socratic method, or I'm sorry, the paternalistic method, the way that medicine used to be where the guy in front of you that saw thousands of patients, this is the method that he has. You see me scope, I mean, there's a difference in scope techniques.So they, although some may even still say it qualifies as anecdotal, I will say that there's objective data in both in a scope, somebody can't just come, anybody can come to you say I feel better. Anybody can even if they don't mean it. But they can't make the disease disappear from the imaging that we see in their colonoscopy, or the the mucosal samples that you take. And that's something that's completely objective data. That we see. So those are the everyday results that we see from these types of applications where you just, look it's not made up whenever we okay full pleasure when we first started looking at CBD, I thought was bullshit. Who you looking at?Just anybody who's out there. But when we first started talking about it, I didn't believe it. I was like, man, let's see, because we've been down this road before but we tried new, new without throwing a bunch of things under the bus. We tried new or innovative different things and high hopes. And unfortunately, low expectations and the expectations get met and the hopes are never never realized. The opposite for me personally occurred with CBD over the last three and a half years. And that is it actually stinking works.Dude, I knew that we were onto something with Atrantil, because after we did the initial studies, everybody came back and said, I want more. I knew that I was onto something or I was not on something. I knew that CBD had a viable place in my practice, because I bought and the story goes all the way back which is why we work with which is why it's powered by elyxenol right now, when we went to paleo FX, and I ordered a couple cases and I just gave them away to patients. That was not cheap. Not because I was sitting there trying to be altruistic, not because I was doing charity. I'm like, I don't know. I didn't. And I told everybody, I don't have a clue. I haven't even looked at this yet. All I know is try this. Tell me what happens. And when about 80% of them came back said I want more. And I went, Okay, we're onto something. And that's when I took my clothes off the deep dive into the science and went, holy cow. Yeah,this is crazyUp until that point, I just didn't know there was a whole lot to it. I mean, it really didn't. And then the fact is, oh, and to clarify, it's not like Brown just handed out CBD to just anybody who came to the clinic. You literally just like we did with Atrantil you found very diseased patients to say and who had gone through a gamut of different pharmaceuticals and weren't finding relief, and suddenly they're like, this is working for me. Tell me more about it. And I was, I was blown away.So let's talk a little bit. So we're I'm over here going well studies I haven't published and everything. Let's talk about a few studies. So I've got a Mendeley account, I know how to look at PubMed. I know how to get a Google Scholar, I just want to talk about a couple studies have come out recently. And let's kind of compare it and see if it still makes people concerned that they're going to die of liver failure.Sure. Alright. So in the Journal of Clinical Pharmacology published in 2019, the this was actually a study, also sponsored by GW Pharmaceuticals, as part of the process of getting the FDA approval that the FDA did not reference the best I can tell they did not reference this. This is way more complex and it gets super cool, because what they're looking at is the pharmacokinetics or how CBD is actually metabolized by that beautiful genius called a liver. In high doses in people with liver disease. Yeah, they went through the trouble to take high doses of CBD and give it to people People that did not have liver disease had mild liver disease moderate and severe. This was ballsy to say the least, because using a product like this in somebody with liver disease is is risky. This thing could backfire and it could shut down the whole process. Here's what's nuts, the pharmacologic and safety of a single oral dose of 200 milligrams of epidolex, which is the CBD isolate. They were assessed in subjects they had eight people with moderate or with mild disease, six people with moderate and eight people with severe and then they had this collection of normal people. Blood samples were collected to check for the pharmacokinetics This is how drugs are looked at. They give you a drug and then they check your levels. Basically, the blood concentration was higher in the hepatic impairment and they describe it in nanograms. So the nanogram comparison is that it's a little bit higher in those with severe hepatic impairment. But this is what's nuts there was no increase in adverse reactions. There was no change in blood levels. So basically, the only adverse reaction that they found was a little bit of diarrhea. And it all happened in the mild hepatic impairment. So the FDA had mentioned Oh, studies have shown that it causes diarrhea. What was really funny about
The BHaash Bros--Tyler and Petey--drop in (virtually) to beg for mercy in their semi-final matchup with the one true MT1 and talk all things future league scoring, league weekend 2019, and what makes Petey more of a Joey than a Jesse. This one has that...inferior-sound-quality-sizzle.
text :: Matthew 1: 18 – 25 theme verse :: But just when he had resolved to do this, an angel of the Lord appeared to him in a dream … (Mt1:20) // It would have been so easy, perhaps even reasonable and likely, for Joseph to give a ‘hard pass’ to the massive assignment […]
text :: Matthew 1: 1 – 17 theme verse :: “An account of the genealogy of Jesus the Messiah, the son of David, the son of Abraham.” (Mt1:1) // It’s a text that we skip quite often because it’s hard to read, but it’s here that we see just what it meant for the Divine […]
Annie Mithoefer, B.S.N., is a Registered Nurse living in Asheville, NC. She was co-investigator on two of the MAPS-sponsored Phase 2 clinical trials for individuals with PTSD and a pilot study treating couples combining MDMA-assisted psychotherapy with Cognitive Behavioral Conjoint Therapy for PTSD. She is currently co-investigator in MT1, a protocol allowing MAPS-trained therapists to receive their own MDMA-assisted session, she conducts MAPS Therapist Trainings with her husband, Michael, and is a supervisor for Phase 3 therapists. She is a Grof-certified Holotropic Breathwork Practitioner and is trained in Hakomi Therapy. Michael Mithoefer, M.D., is a psychiatrist living in Asheville, NC. He was co-investigator on two of the MAPS-sponsored Phase 2 clinical trials for individuals with PTSD and a pilot study treating couples combining MDMA-assisted psychotherapy with Cognitive Behavioral Conjoint Therapy for PTSD. He is the lead author of the MAPS Manual for MDMA-assisted Psychotherapy in the Treatment of Post-traumatic Stress Disorder. He is currently co-investigator in MT1, a protocol allowing MAPS-trained therapists to receive their own MDMA-assisted session, he conducts MAPS Therapist Trainings with his wife Annie, and is a supervisor for Phase 3 therapists. He is also the lead Medical Monitor for ongoing Phase 3 trials, is a supervisor for Phase 3 therapists, and participates in new MPBC protocol development. He is a Grof-certified Holotropic Breathwork Facilitator and is trained in EMDR and Internal Family Systems Therapy. He is clinical assistant professor in the Department of Psychiatry and Behavioral Sciences at the Medical University of South Carolina, and has been board certified in Internal Medicine, Emergency Medicine and Psychiatry and is a Fellow of the American Psychiatric Association.
In dieser Folge hört ihr Mt1,16.18-21.24a, Die Liebe macht uns eins und ein Gebet von Peter Dyckhoff
I'm in the process of recording audio book versions of both volumes of Musical Truth. I've decided to offer the final two chapters of MT1 for free, given that they contain the most important information of all, which needs to be freely communicated as widely as possible. Here they are, offered with benevolent wishes to all.
I'm in the process of recording audio book versions of both volumes of Musical Truth. I've decided to offer the final two chapters of MT1 for free, given that they contain the most important information of all, which needs to be freely communicated as widely as possible. Here they are, offered with benevolent wishes to all.
Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Ticagrelor has shown superior efficacy to clopidogrel in the management of acute coronary syndromes. But what about in patients undergoing PCI for stable coronary artery disease? Well, our feature paper this week gives us answers to this question but you're going to have to wait to the feature discussion to hear these answers. That's coming up right after these summaries. Our first original paper this week shows that RBM20 mutation carriers have an increased risk of arrhythmias. You may recognize RBM20 as that splicing factor which targets multiple pivotal cardiac genes such as Titin and Calcium/Calmodulin-Dependent Kinase 2 Delta or CAMK2D. In today's paper first author Dr van den Hoogenhof and co-corresponding authors Dr Pinto and Creemers from Academic Medical Center Amsterdam, compared the clinical characteristics of RBM20 and Titin mutation carriers and used RBM20 knock out mice to investigate the downstream effects of RBM20 dependent splicing. They showed that loss of RBM20 disturbed calcium handling and led to more pro-arrhythmic calcium releases from the sarcoplasmic reticulum. Patients that carried a pathogenic RBM20 mutation had more ventricular arrhythmias despite a similarly depressed left ventricular function compared to patients with a Titin mutation. Targets of RBM20 splicing were enriched for calcium and ion handling genes, most notably CAMK2D and type 2 Ryanodine receptor. Loss of RMB20 induced an increased L-Type Calcium current density, intracellular calcium overload, increased sarcoplasmic reticulum calcium content and increased spontaneous calcium releases which all could be attenuated with treatment with an L-type calcium channel blocker. Furthermore, these results suggest that RBM20 mutation carriers should be closely monitored for potential electrical disturbances and cardiac arrhythmias even in the early stages of disease. Echocardiographic quantitation of degenerated mitral regurgitation is recommended in clinical guidelines but is it really scalable to routine clinical practice? First author Antoine, corresponding author Sorano from Mayo Clinic Rochester Minnesota and their colleagues looked at more than 3900 patients diagnosed with isolated mitral valve prolapse between 2003 and 2011 and to any degree of mitral regurgitation quantified by any physician or sonographer in routine clinical practice. They found that in multi-variable analysis routinely measured effective regurgitant orifice area was associated with mortality independent of left ventricular ejection fraction and systolic diameter symptoms or age and comorbidities. Furthermore, compared with general population mortality excess mortality appeared for moderate mitral regurgitation with an effective regurgitant orifice area above 20 squared millimeters and became notable with an effective regurgitant orifice area above 30 squared millimeters which then steadily increased with even higher levels of above 40. Thus, quantitation of degenerative mitral regurgitation is scalable to routine clinical practice with strong independent prognostic power when performed routinely by multiple practitioners. The next study identifies a novel mechanism of lipid homeostasis that is linked to a pseudo gene associated with the recently discovered apolipoprotein known as APOO. Co-first authors Montasser and O'Hare, corresponding author Dr Mitchell from University of Maryland School of Medicine in Baltimore, performed an array based association analysis in more than 1100 Amish subjects and identified a variant strongly associated with LDL cholesterol levels. They identified a founder haplotype on chromosome 5 which was associated with a 15 mg/dl increase in LDL cholesterol after recombination mapping, the associated region contained eight candidate genes. Using a zebra fish model to evaluate the relevance of these genes to cholesterol metabolism they found that the expression of the transcribed pseudo gene APOOP1 increased LDL cholesterol and vascular plaque formation. Thus, based on these data the authors proposed that APOOP1 regulates levels of LDL cholesterol in humans and represents a novel mechanism of lipid homeostasis. The Orion-1 trial demonstrated that inclisiran which is a small interfering RNA therapeutic that targets PCSK9 MRNA with [inaudible 00:05:42] produces significant LDL reduction. In today's study from Dr Ray from Imperial College London and colleagues, the authors described in detail the effect of inclisiran on prespecified secondary lipid and lipoprotein outcomes over time for up to 210 days and also described the individual variation and response in these measures. They found that a single 300 milligram dose of inclisiran lowered non-HDL cholesterol at day 180 by 35% and a second dose at day 90 resulted in a 46% reduction at day 180. Similarly a single dose of 300 milligrams of inclisiran reduced apolipoprotein B by 31% at day 180 and a second dose of 300 milligrams administered in day 90 reduced apolipoprotein B by 41%. Significant reductions in all atherogenic lipoproteins measured were sustained through today 210. Furthermore, every individual had a reduction of apolipoprotein B and non-HDL cholesterol at 180 days with the 300 milligram two-dose regimen of inclisiran. Thus, inhibiting the synthesis of PCSK9 through small interfering RNA may be a viable alternative to monoclonal antibodies with respect to effects on atherogenic lipoproteins and that brings us to the end of our summaries. Now for our feature discussion. Ticagrelor has superior efficacy to clopidogrel in the management of acute coronary syndrome but it has not really been assessed in patients undergoing PCI for stable coronary artery disease. For our feature paper today it's going to shed some light and help us with this question and these are the results of the STEEL-PC trial. I'm so pleased to have with me right now the corresponding author Dr Robert Storey from University of Sheffield in the UK as well as our associate editor who managed this none other than Dr Stefan James from Uppsala University. Thank you. Rob, could you tell us what is the issue you tried to address and because your study is not that simple, we're not used to thinking about these pharmacodynamic and kinetic studies so could you explain a bit of what you did? Rob Storey: Well it's quite a few concepts that we assessed in this study. We've got data from a number of studies showing that Ticagrelor both at doses of 90 mg twice daily and 60 mg twice daily is more reliable and superior P2Y12 inhibitor compared to clopidogrel. We've got this issue of very variable response to clopidogrel with some poor responders and some high responders and a range in between. That's fairly well established and part of this study was to get more data on the 60 mg dose of Ticagrelor in these stable CAD patients undergoing PCI and get some pilot data on clinical efficacy obviously this study was not part of clinical outcomes. But, there's another issue in terms of adenosine uptake so Ticagrelor has a relatively weak effect on adenosine uptake into red cells and other cells and this may or may not explain some of its clinical effects including some adverse effects such as dyspnea. We wanted to get a better idea of the impact of Ticagrelor at both these doses on adenosine uptake. Dr Carolyn Lam: Could I ask ... Okay this may be naïve. I'm not an interventional cardiologist but why would you expect something different in an acute coronary syndrome compared to stable coronary artery disease? Is there an underlying hypothesis there? Rob Storey: Well there can be changes to their differences in platelet reactivity although those aren't particularly great and overwhelmed really by P2Y12 inhibitor like Ticagrelor which gives such reliable inhibition of the P2Y12 receptor. But, there have been a limited number of groups that have looked at adenosine uptake and so we wanted to get independent confirmation or not of whether Ticagrelor therapeutic concentrations impacting on adenosine uptake and get some ideas of whether it's affecting circulating adenosine levels. That's an important question in terms of understanding the mechanisms and actions of Ticagrelor. Dr Carolyn Lam: Got it. Thanks for breaking it down so nicely. So what did you find? Rob Storey: What we found was surprisingly that we saw no impact of Ticagrelor at either dose and at any time point within a month after PCI on adenosine uptake. That is the circulating levels of adenosine and the rate at which adenosine is taken up by cells in the blood mainly red blood cells. The explanation for that really is that the therapeutic levels of Ticagrelor that you see are not sufficient to impact on adenosine uptake because it's a very weak inhibitor of the adenosine uptake pathway known as the MT1. The therapeutic levels are just not getting up to a high enough concentration to have a significant impact on that. Dr Carolyn Lam: Stefan, you've thought a lot about this. What did you think of the findings? Stefan James: I think it's very interesting. Of course, the pharmacodynamic effects that you can measure by pretty simple means, the level of platelet inhibition, it should be similar in ACS and stable coronary artery disease and I think it's sort of confirming what Rob has been showing in other populations with ACS ... we have been very interested in trying to understand the additional mechanisms of action of Ticagrelor... try to understand the mortality rate without the benefit for Plato, for example. Was it only -- platelet inhibition or were there other mechanisms? And, there is a specific Ticagrelor related side effect, dyspnea, which we would have been interested in understanding... is this a mechanism of action? We can't really explain that. There are other mechanisms and other effects that we have seen can also be explained by adenosine, so I thought it was very interesting and important to understand more about these mechanisms. Dr Carolyn Lam: Yeah. Stefan James: But I would like to ask you, Rob. Do you think this adenosine hypothesis now, is dead, or should we still try to explore this? Rob Storey: Well of course in this study what we didn't look at was the adenosine kinetics in the tissue level which is where we hypothesize the dyspnea may arise from stimulation of C5 is in the lung tissue so we're missing that piece of information. It's still conceivable that very weak levels of ENT-1 inhibition may impact from adenosine levels in the tissue. We're not seeing a strong ENT-1 inhibition sufficient to raise circulating levels or something that we can pick up on this in vitro assay. I think it still remains an open question. We've got this sort of contradictory information from drugs like cangrelor and other drugs in development like Elinogrel where we don't see an impact on adenosine but they still may cause dyspnea. So I think it's a very open question still. Stefan James: Do you think that your paper gives us additional strength to the hypothesis that the mortality benefit for ticagrelor as seen in Plato is explained by the platelet inhibition and the balance between the reduction in ... Rob Storey: Well I think what we see really in all these studies is that Ticagrelor is a fantastically effective PTY12 inhibitor. It gives you the best level of platelet inhibition during maintenance therapy out of all the available PTY12 inhibitors. And clearly having such more reliable PTY12 inhibition than clopidogrel could still be driving a mortality benefit in high risk patients so we can't exclude the adenosine pathway contributing to some of the clinical effects but I think this sways me a little bit more to the position of thinking this is most of the benefits through platelet inhibition. Dr Carolyn Lam: Interesting. So you're on the cutting edge of this. What's the next step then? Rob Storey: Clearly we can see that very effective and reliable P2Y12 inhibition is important and leads to clinical benefits and I think we need to implement that wherever we're using P2Y12 inhibitors. We need to take that message and use a more consistent therapy rather among those with associated with variable response which doesn't seem to make sense. I think this stable PCI population, their risk has fallen. And we see that in this study, quite a number of patients report a response to clopidogrel but no stent thrombosis. That really reflects, I think improvements in stent design and implantation techniques, so the implication is that maybe aspirin alone is enough to prevent stent thrombosis with modern techniques if you get a good result but in the higher risk patients particularly the ACS patients it's likely you need much more reliable platelet inhibition and that's why Ticagrelor really provides this security. Dr Carolyn Lam: So, Rob there is one thing you tested two doses and they seemed to be equivalent at least in antiplatelet inhibition, right? So what does this mean? Should we maybe preferentially use the lower dose from now on, is there still room for the higher dose? Could you share some insights there? Rob Storey: Well I think one has to be cautious in not jumping to adopt a dose just on the basis of pharmacodynamic data but clearly what we show is that the 60 mg dose of Ticagrelor offers a very reliable and consistent level of PTY12 inhibition and that's likely to be very effective in preventing stent thrombosis in combination with aspirin. We also show signals that were also shown in the Pegasus study that the 60 mg dose may be better tolerated such as with lower levels of dyspnea. So, there is the option for off label use of the lower dose of Ticagrelor in those who cannot tolerate the high dose due to dyspnea because certainly they'll have better platelet inhibition down titrating from 90 to 60 and if they were to switch to Clopidogrel. So I think our study offers some comfort in terms of that aspect. The only caveat is that you have to be careful not to use strong CYP3A inducers such as some epilepsy drugs with Ticagrelor cause that can increase the metabolism and we did have one case of high platelet reactivity with strong CYP3A inducers so using a higher dose initially I think is a good idea. The label says 90 mg for 1 year following ACS and the 6 is licensed beyond one year as a down titration predominantly. Our study certainly gives some comfort that down titrating earlier if a patient can't tolerate the 90 for whatever reason, seems to be a justifiable thing. And the other thing is the European guidelines support the use of Ticagrelor off label in elective PCI and our study certainly gives some comfort that off label use and the low risk elective PCI patients of the 60 mg dose can be justified at least from a pharmacodynamic point of view. Dr Carolyn Lam: Well, thank you because that's exactly what our audience is loving to hear. How do these findings translate into the clinical practice - Would you have any other take home messages for the clinicians listening in? Rob Storey: Well I think one thing we looked at also was troponin release which is very common after PCI. We didn't see an impact of PTY12 inhibition high levels on troponin release and I think that sort of caveat in terms of that's not going to be the best measure in terms of surrogate for efficacy in the PCI population. The other question really is, how much of the platelet inhibition and how much of the adenosine effects of Ticagrelor influence the clinical outcomes and clearly the studies sways towards the platelet inhibition very consistent high level of platelet inhibition explaining most of the benefits. Carolyn Lam: You've been listening to circulation on the run, don't forget to tune in again next week.
Igerész: Máté1,18-25 Lelkész: Kuti József Lejátszás közvetlen fájlból (hiba esetén): https://krek.hu/media/files/igehirdetesek/20171224_1530h_KJ_karácsonyi ünnepély_Mt1,18-25.mp3 Becsült hossz: 2585 mp Generálta: ScrapeCast by Fodor Benedek UUID: 814676ba-c44a-4e1c-b39f-2bf49bdbc3c4
Behavioral endophenotypes are determined by a multitude of counteracting but precisely balanced molecular and physiological mechanisms. In this study, we aim to identify potential novel molecular targets that contribute to the multigenic trait "anxiety". We used microarrays to investigate the gene expression profiles of different brain regions within the limbic system of mice which were selectively bred for either high (HAB) or low (LAB) anxiety-related behavior, and also show signs of comorbid depression-like behavior. We identified and confirmed sex-independent differences in the basal expression of 13 candidate genes, using tissue from the entire brain, including coronin 7 (Coro7), cathepsin B (Ctsb), muscleblind-like 1 (Mbnl1), metallothionein 1 (Mt1), solute carrier family 25 member 17 (Slc25a17), tribbles homolog 2 (Trib2), zinc finger protein 672 (Zfp672), syntaxin 3 (Stx3), ATP-binding cassette, sub-family A member 2 (Abca2), ectonucleotide pyrophosphatase/phosphodiesterase 5 (Enpp5), high mobility group nucleosomal binding domain 3 (Hmgn3) and pyruvate dehydrogenase beta (Pdhb). Additionally, we confirmed brain region-specific differences in the expression of synaptotagmin 4 (Syt4).Our identification of about 90 polymorphisms in Ctsb suggested that this gene might play a critical role in shaping our mouse model's behavioral endophenotypes. Indeed, the assessment of anxiety-related and depression-like behaviors of Ctsb knock-out mice revealed an increase in depression-like behavior in females. Altogether, our results suggest that Ctsb has significant effects on emotionality, irrespective of the tested mouse strain, making it a promising target for future pharmacotherapy.
Perform at least one act of kindness every day. Callers to my show share their kindness experiences (giving or receiving) creating a "kindness consciousness" that can truly change the world. Be kind - and call.
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Perform at least one act of kindness every day. Callers to my show share their kindness experiences (giving or receiving) creating a "kindness consciousness" that can truly change the world. Be kind - and call.
Perform at least one act of kindness every day. Callers to my show share their kindness experiences (giving or receiving) creating a "kindness consciousness" that can truly change the world. Be kind - and call.
Perform at least one act of kindness every day. Callers to my show share their kindness experiences (giving or receiving) creating a "kindness consciousness" that can truly change the world. Be kind - and call.
Perform at least one act of kindness every day. Callers to my show share their kindness experiences (giving or receiving) creating a "kindness consciousness" that can truly change the world. Be kind - and call.
Perform at least one act of kindness every day. Callers to my show share their kindness experiences (giving or receiving) creating a "kindness consciousness" that can truly change the world. Be kind - and call.
Perform at least one act of kindness every day. Callers to my show share their kindness experiences (giving or receiving) creating a "kindness consciousness" that can truly change the world. Be kind - and call.
Perform at least one act of kindness every day. Callers to my show share their kindness experiences (giving or receiving) creating a "kindness consciousness" that can truly change the world. Be kind - and call.
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