Podcasts about jak stat

Play Episode Listen Later Jun 14, 2022 62:10

Go online to PeerView.com/CCT860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, experts in dermatology discuss the role of the JAK/STAT pathway in psoriasis, as well as treatment with novel kinase inhibitors for the management of patients with psoriasis. Upon completion of this activity, participants should be better able to: Describe and differentiate targeting of the TYK2, JAK1, JAK2, and JAK3 kinases and the correlation to emerging therapies for the treatment of moderate to severe psoriasis, Summarize recent efficacy and safety data for current and emerging therapies for the treatment of moderate to severe psoriasis, Recommend treatment for patients with moderate to severe psoriasis according to the latest guidelines and clinical evidence, particularly as emerging therapies become available.

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244: How Do Biologic Drugs For Chronic Skin Conditions Work? w/ Heather Zwickey, PhD

The Healthy Skin Show

Play Episode Listen Later May 12, 2022 31:57

Are you trying to weigh the pros and cons of possibly using a biologic like Dupixent for your skin condition? Your immune system has such a complex relationship with one another, so it's important to have complete informed consent when starting one. Look into all the side effects- they could be actually helpful, but they could also lead to cancer! My guest today, Heather Zwickey, earned a Ph.D. in Immunology and Microbiology from the University of Colorado and completed a postdoctoral fellowship and taught at Yale University School of Medicine. Dr. Zwickey is recognized internationally as an expert and educator in the fields of integrative medicine, natural therapies and the immune system and has been leading natural medicine research for 20 years. Heather speaks at conferences world-wide, sharing her enthusiasm for naturopathic medicine and science. She currently serves as the Director of Communication and Innovation at Thaena Inc., a microbiome-based company. Join us as we talk about how biologic drugs for chronic skin conditions work. Did you know about the relationship between your immune system and your skin? Let me know in the comments! In this episode: Biologic drugs - what are they, how are they prescribed, and what do they do? Real side effects of biologics - the bad and even the good Breaking down what cytokines are (in layman's terms) Cytokines and the JAK/STAT pathway Discussion of JAK inhibitors (the newest version of biologic drugs for skin issues) Quotes “Back when we used things like methotrexate for skin disorders, we would see that the entire immune system was blocked and as a result, there would be side effects of things like cancer. When we're only blocking one protein, we have much less severe side effects.” [2:59] “If your skin is not in balance with its microbes, it will affect your gut. We really got to address that. That is the root cause, and usually the way that we're going to address that is with eating more plant-based foods and getting some of the toxins out of our system, and letting those microbes grow the way that they were supposed to grow in normal ecosystems.” [17:47] Links Find Dr. Zwickey online here Healthy Skin Show ep. 180: How Hormones Impact Your Immune System + Skin Health w/ Heather Zwickey, PhD Healthy Skin Show ep.157: How Your Immune System Can Trigger Skin Rashes w/ Heather Zwickey, PhD Follow Dr. Zwickey on Instagram

ASH 2021: novel developments in MPNs

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Play Episode Listen Later Mar 11, 2022 27:56

The JAK-STAT pathway plays a pivotal role in the pathogenesis of myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia, and... The post ASH 2021: novel developments in MPNs appeared first on VJHemOnc.

ASH 2021: novel developments in MPNs

ash developments jak stat mpns

Play Episode Listen Later Mar 11, 2022 27:56

The JAK-STAT pathway plays a pivotal role in the pathogenesis of myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia, and... The post ASH 2021: novel developments in MPNs appeared first on VJHemOnc.

44: Approach to Critical Iron Deficiency Anemia

PICU Doc On Call

Play Episode Listen Later Mar 6, 2022 19:56

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists. I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine. Welcome to our Episode a 2-year-old with severe pallor and O2 desaturation. Here's the case presented by Rahul: A two-year-old presents to the PICU with severe pallor + O2 requirement. The patient went for a routine check with her primary care who noted the patient appeared severely pale. He sent the patient to the ED. An initial Hgb check revealed a Hgb of 1.5gm/dL. Per mother, she is otherwise healthy but a very picky eater. She also reports the patient drinks milk as a soothing adjunct at night, consuming between 12 - 36oz a day. No family h/o of anemia or any other blood disorders. No h/o recent illness. Mother had a normal spontaneous full-term delivery. The patient is up to date on her immunizations. Per mother, developmental milestones are normal. The mother also denies any history of decreased activity in the child. Given the low Hgb, the patient was admitted to the PICU. Let's transition into some history and physical exam components of this case? What are key history features in this child? Severe pallor in a 2-year-old H/o being a picky eater H/o excessive milk consumption Pertinent negatives include: No obvious blood loss, No petechia, bruising, or jaundice What did the physical exam show? The patient was hypertensive, tachycardic to the 140s, and 10th% weight for growth percentiles On physical exam, the patient was in no acute distress. Her lips, gums, and conjunctiva were pale. She had a systolic ejection murmur. As a pertinent negative, she had no hepatosplenomegaly. She also has no rash, bruising, or petechiae. The lack of hepatosplenomegaly may indicate that the patient has no signs of extramedullary hematopoiesis. Patients with hemolytic processes resulting in anemia may present with signs of scleral icterus, jaundice, and hepatosplenomegaly resulting from increased red cell destruction. In fact, in an emergency department setting, the clinical detection of jaundice was found to have sensitivity and specificity of only approximately 70 percent. To continue with our case, then what were the patient's labs consistent with: Initial CBC showed: WBC 8.5K, RBC 1.14 (L), Hgb 1.5gm/dL; Hct 6.1, MCV 53.5, and an elevated RDW 37.7. Initial platelet count was 50K, reticulocyte count 1.1% Peripheral smear revealed no blasts, thrombocytopenia - with occasional medium-sized platelets - ghost cells and anisocytosis/poikilocytosis- which appears most consistent with iron deficiency. It was interesting that the patient had thrombocytopenia Absolutely, typically with Iron deficiency, there is thrombocytosis (erythropoietin is increased which closely mimics thrombopoietin stimulates platelets). In fact, both act via the non-TK, JAK-STAT pathway. OK, to summarize, we have: Two year old with severe anemia most likely secondary to iron deficiency. As you think about our case, what would be your differential? For any patient with acute severe anemia presenting to the PICU- One has to think in terms of blood loss, decreased or impaired production (i.e bone marrow failure), or peripheral blood destruction (i.e hemolysis). Here would be the organizations: Blood loss Decreased or impaired production Increased destruction Let's go into detail for each: Blood loss can be internal or external (due to trauma, excessive blood draws, due to surgery)-typically gives rise to normochromic normocytic anemia. Decreased or impaired production: Deficiency of substances needed for Hgb & RBC production such as iron Vit B12 etc. Depression of BM due to infection (parvo B), chemicals, pharmacologic agents or immune mechanisms. Bone marrow aplasia can be idiopathic with or without congenital anomalies. Infiltration of BM due to malignancies such as leukemia, Hodgkin disease,...

CRISPR cure for XMEN disease?, JAK inhibition in T-cell lymphomas, and intracranial hemorrhage in hemophilia

Blood Podcast

Play Episode Listen Later Dec 30, 2021 19:39

In this week's episode, we'll review a research article that provides the first description of a targeted gene insertion approach to correct the genetic mutation underlying XMEN disease. Next, we'll cover results of a phase 2 study that provides proof-of-principle that the JAK/STAT pathway is a promising target for the treatment of peripheral T-cell lymphomas. We'll close with a study providing precise and up-to-date estimates on the incidence of intracranial hemorrhage in patients with hemophilia that could have important implications for preventive strategies.

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Circulation December 14, 2021 Issue

Circulation on the Run

Play Episode Listen Later Dec 13, 2021 25:48

Please join Guest Host Mercedes Carnethon, author Jason Roberts, and Associate Editor Vlad Zaha as they discuss the article "Epigenetic Age and the Risk of Incident Atrial Fibrillation." Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. We're your co-host, I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center in 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 we're going to learn more about the risk of incident atrial fibrillation, but as that pertains to epigenetics. But before we get to that feature, how about we grab a cup of coffee and get started on some of the other articles in the issue. Would you like to go first? Dr. Carolyn Lam: I would love to. And the first paper I want to highlight asks the question, are social economic variables associated with 30 day survival after out of hospital cardiac arrest. And this comes from Dr. Jonsson from Karolinska Institute in Stockholm, Sweden, and colleagues. They linked data from the Swedish Registry of Cardiopulmonary Resuscitation with individual level data on social economic factors. In other words, educational level and disposable income, all from statistics, Sweden. And what they found was that both higher disposable income and higher educational level independently associated with better 30 day survival following out of hospital cardiac arrest. The relationship between disposable income and 30 day survival was more robust for mediating factors compared to educational level. Dr. Greg Hundley: Oh, wow Carolyn. Really interesting in a very, what I would call hot topic these days. So what are the clinical implications of this particular study? Dr. Carolyn Lam: Well, the results really highlight the importance of preventive efforts aimed at patients with lower social economic status. And these preventive actions could include both early recognition and warning signs and for example, CPR and AED training. So very lovely paper there. Dr. Greg Hundley: Absolutely. Very nice Carolyn. Well, my first paper comes to us from Dr. Nan Wang from Columbia University Medical Center. And Carolyn this paper focuses on a common genetic variant called link RS 3184504, and it is associated with increased platelet and neutrophil counts, coronary artery disease, thrombotic stroke, and autoimmune diseases. And so this research group previously has shown that hematopoietic link deficiency synergizes with hyperlipidemia to promote platelet production and activation, neutrophilia, platelet neutrophil aggregates, atherosclerosis and arterial thrombosis, all of those things. So platelet activation and platelet neutrophil interactions have been shown to promote neutrophil extracellular traps or net formations. So nets are formed when neutrophils release their contents leading to the formation web-like structures made of DNA, myeloperoxidase, citrullinated histone and proteases that entrap and kill bacteria. Now, while nets may help to suppress infection, the formation of nets called NETosis in blood vessels can promote atherosclerosis and thrombosis. And so this study was undertaken to investigate the hypothesis that linked deficiency might promote NETosis leading to formation of unstable atherosclerotic plaques, and arterial thrombosis. Dr. Carolyn Lam: Wow. What a really neat hypothesis and NETosis. I learn new things all the time. So what do they find? Dr. Greg Hundley: Right Carolyn. First of all, hypercholesterolemic mice with hematopoietic link deficiency displayed accelerated arterial thrombosis with nets in thrombi and these changes were reversed by PAD4 deficiency or OxPL antibodies. Second, linked deficient platelet from hyperlipidemic mice expose and release increased OxPL when activated promoting NETosis, when incubated with link deficient neutrophils. Third, an AntiOxPL antibody reduced OxPL levels, NETosis and arterial thrombosis specifically in link deficient mice, and finally Carolyn targeting atherothrombotic risk using OxPL antibodies might be particularly effective in genetically defined populations with reduced link function or increased JAK-STAT signaling. Dr. Carolyn Lam: Wow. Okay. So they proved their hypothesis. Could you sum it up for us, Greg? Dr. Greg Hundley: You bet Carolyn. So this foundational work suggests that perhaps future studies targeting NETosis and OxPL in patients carrying the common link loss of function variant, could reduce atherothrombotic risk. Dr. Carolyn Lam: Wow. Thanks, Greg. My next paper is super interesting in its approach. Listen up. Now the assessment of the relationship between myocardial ATP production and cardiac workload. We know is important for better understand disease development and choice of nutritional or pharmacological treatment strategies. So what Dr. Berndt from Charity University and colleagues did, was they developed a comprehensive physiology based mathematical model of cardiac energy metabolism. And this model is called cardiokine one. And what it does is it recapitulates numerous experimental findings on cardiac metabolism obtained with isolated cardiomyocytes, perfused animal hearts and in vivo studies with humans. The model encompassed all pathways along, which the possible energy delivering substrates like glucose, long chain fatty acids, keto bodies, acetate, branch chain, amino acids are utilized. Dr. Carolyn Lam: They use the proteomic space, the abundance of metabolic enzymes and cardiac tissue to generate individualized metabolic models of cardiac energy metabolism. And so to prove their case, they further applied this approach to the left ventricles of controls in patients with mitral insufficiency and aortic stenosis, and showed that despite overall preserved systolic function, the ATP producing capacity of these left ventricles of patients with valvular dysfunction was generally diminished and correlated positively with mechanical energy demand and cardiac output. Dr. Greg Hundley: So Carolyn really interesting findings. Sort of linking metabolism them with ventricular dysfunction in those with valvular heart disease. So what were the clinical implications here? What's the take home? Dr. Carolyn Lam: Well, this methodology is just awesome, but what they also found I think is a very important physiological principle. And that is, while metabolic capacity have a significant correlation with biomechanical properties like myocardial power and cardiac output, they can also vary considerably between individual patients and therefore help us to understand in future perhaps why some patients develop heart failure over time while others with similar hemodynamic conditions do not. So just interesting. I think it just opens the space to a lot more. Dr. Greg Hundley: Absolutely beautiful summary there Carolyn. Well, in the rest of the mailbag for this issue, we have an exchange of letters between Professors Hu and Trifon on the previously published paper, entitled “Short Term Treatment with Aspirin plus Clopidogrel Compared to Monotherapy of Aspirin May Not Significantly Decrease the Risk of Stroke Recurrence.” Also, there's a Research Letter from Professor Catalucci entitled, “Nano miR-133A Replacement Therapy, Blunts Pressure Overloaded Induced Heart Failure.” And then finally Carolyn, there's an In-Depth article from Professor Aengevaeren entitled, “Exercise-Induced Cardiac Troponin Elevations From Underlying Mechanisms to Clinical Science.” Well Carolyn, how about we get onto that feature discussion and learn more about incident atrial fibrillation and the age of epigenetics. Dr. Carolyn Lam: Let's go. Dr. Mercedes Carnethon: Welcome to this episode of Circulation on the Run, where we're going to have a very exciting discussion about a paper on epigenetic age and the risk of incident atrial fibrillation. We're extremely excited to have the lead author here with us, Dr. Jason Roberts from the Population Health Research Institute, McMaster University and Hamilton Health Sciences in Ontario Canada. And I am really excited to host this episode alongside the handling editor. My name is Mercedes Carnethon and I'm the professor and vice chair of Preventive Medicine at the Northwestern University School of Medicine. And I'm pleased to be hosting this with Dr. Vlad Zaha from UT Southwestern Medical School, who was the associate editor who handled the piece. So I'm really excited to jump right into this because I think there's a lot that we can all learn from this. So welcome Jason, and thank you so much, Vlad. Dr. Jason Roberts: Thank you so much for having me, it's a delight to be here. Dr. Mercedes Carnethon: So Jason, tell us a little bit about the rationale for this study, what you found and what it means. Dr. Jason Roberts: Absolutely. So as a cardiac arrhythmia specialist, I see a lot of patients with atrial fibrillation. And in 2021, our understanding of its underlying pathophysiology still remains modest. Our treatment strategies for the condition are also somewhat modest, although catheter ablation and antiarrhythmic drugs can potentially be very effective. In the context of these limitations, they're also exacerbated to some extent by the prevalence of atrial fibrillation, increasing dramatically in developed countries. Part of this is related to the obesity epidemic. Things like hypertension increasing becoming more common, but because atrial fibrillation is age dependent and because of our aging populations in developed countries, this is felt to have a major contribution to the growing prevalence of atrial fibrillation. Unlike obesity and hypertension and other risk factors, which are potentially modifiable, chronological aging is viewed as non-modifiable. It's not something that we can tackle. That said, we know within the population and just from personal experience that people age at different rates. There are some people that are 65 who behave more like they're 50, other people that are 50 who behave more like they're 65. Dr. Jason Roberts: And in that context, biological aging, we wondered whether or not, does biological aging independent of chronological aging potentially impacts the risk of atrial fibrillation. If that was the case, because there are gradually accumulating to suggest that biological aging is potentially modifiable, that could potentially open up the possibility of tackling aging as a respective for atrial fibrillation. So that drove us to ask this question. In terms of what we found in the approach that we used. So we used our biological marker of aging, was something called an epigenetic clock. So it's been found that modifications to DNA, specifically methylation at CpG at dinucleotides, they correlate with aging. This has been appreciated for a few decades. It was initially felt that with aging, methylation levels gradually reduced over time. But with more careful interrogation, it's shown that there's patterns. Some methylation areas increase, other methylation areas there's decreases. Dr. Jason Roberts: And Steve Horvath, who is a scientist at UCLA has found that using mathematical algorithms, you're able to very accurately ascertain chronological age based on the patterns of DNA methylation, he's called these things epigenetic o'clock. That said, even though they very accurately ascertain chronological age, they aren't perfect in each individual in terms of matching up to their chronological age, but that's actually turned out to be a good thing. So when people, their epigenetic age is older than their chronological age, they're said to have positive epigenetic age acceleration. They may be biologically older than their actual chronological age. And then the reverse also holds. So using this concept of epigenetic age acceleration, we ask whether or not do people that are older biologically on the basis of their epigenetic age, do they have an increased risk of atrial fibrillation? And then we tackle that using a few different core works that I'm certainly happy to elaborate on in terms of what we found. Dr. Jason Roberts: So we used three population based cohorts from the United States, the well known Framingham Heart Study, the Cardiovascular Health Study and Eric as well. There were approximately just under 6,000 people from those studies that had undergone genome wide methylation analysis that in the enabled us to calculate their epigenetic ages. The follow period for these people was just under 13 years. And then we look to see whether or not these epigenetic clocks associated with instant atrial fibrillation. In these cohorts, we look at five different clocks. So there's the Horvath Clock and the Hannum clock that were designed to predict chronological aging. The more recent clocks, things like DNAm PhenoAge and DNAm GrimAge are more designed to predict aspects of clinical phenotype and also mortality. We found that in unadjusted analyses, all of these clocks were associated with atrial fibrillation. When we then adjusted for multiple different clinical variables, we found that the DNAm PhenoAge clock and the DNAm GrimAge clock continued to exhibit statistically significant associations with atrial fibrillation. Dr. Jason Roberts: Interestingly, the multi-variable adjustment, one concern is, do these clinical factors, are they confounders where we should be adjusting, or are they potentially mediators. If we adjust for mediators that potentially masks the effect of the clock. But regardless of how we treat them both DNAm PhenoAge and DNAm GrimAge, we're associated with increased risks of incident atrial fibrillation. Alluding to the possibility that biological aging independent of chronological aging is important in terms of determining risk for atrial fibrillation. And it may be that if we're able to modify biological aging, we could potentially reduce the risk of atrial fibrillation. So that's the study in a nutshell. Dr. Mercedes Carnethon: No, that is really exciting. You said something early on about chronological age being immutable. And I would have to say, both Vlad and I are not aging. And in fact, we are going in the opposite direction. If only this were not just an audio podcast, you would see that I steadily gotten younger and younger and I'm suddenly about 25 now. But no, these are really important findings. I really like the innovation of using multiple different strategies to characterize epigenetic age and genetic aging. So tell me Vlad, I want to turn to you. When this came across your desk, what excited you about this particular piece and why did you think that it would be of great interest to our readership? Dr. Vlad Zaha: Good morning Merci and Jason. This is a great question. And as in associate editor at Circulation for the bridging discipline section, it was fascinating to see this topic coming on my desk, thinking about all the genome wide association studies in nature of fibrillation and predisposition to atrial fibrillation, that in that case would not be changed by interventions because of different loci that would be determined. This was coming as a completely new perspective that was opening some new potentials. And it was very interesting to see some of the findings. Dr. Mercedes Carnethon: Certainly. So Jason, I have a question. So what surprised you about the findings of this particular study? Jason Roberts: Yeah, that's a great question. So we had hoped that biological aging would be associated with atrial fibrillation. I think the concept of being able to tackle biological aging is exciting. In terms of what surprised us, I guess we were hoping for these results, I guess. Dr. Mercedes Carnethon: Yeah. Dr. Jason Roberts: But we were…Yeah. So I guess we were pleasantly surprised that our hypothesis was born out. It's important to note that the epigenetic clocks don't tell the full story with chronological aging. So after we insert the clock into the model, chronological age continues to remain associated with instant atrial fibrillation. So this measure biological aging is just part of the story. So I think that's very important. I had wondered whether or not inserting the epigenetic clocks would that potentially eliminate the subsequent association of chronological aging. So that finding suggests it's part of the story. Dr. Jason Roberts: I think that in terms of the overall concept, the idea of this being reversible really excites me. In terms of the approach of how to reverse biological aging. Right now healthy lifestyle seems to be very important. I think it provides more evidence to suggest to patients with atrial fibrillation, living healthy from a diet perspective, from exercise, keeping your weight under control, all of these things that seem to impact epigenetic aging and biological aging can be helpful for preventing atrial fibrillation. So I think that can help reinforce this message to our patients. Dr. Jason Roberts: I think ultimately in terms of where we'll be at in 15 to 20 years, it's possible that new therapies in the future are developed that are able to more powerfully address biological aging. As you alluded to, will it be possible to reverse biological aging as you and Vlad are experiencing that? Dr. Mercedes Carnethon: Most definitely. Yes. Dr. Jason Roberts: I think it may be possible. This is an intense area of investigation that's being pursued and it's still in its relative infancy. But I think that could it be small molecules? Could it be potentially gene editing that can help adjust biological aging and not only increase lifespan, but also health span? I think those concepts are really exciting. Dr. Mercedes Carnethon: I completely agree. There's a lot of richness in this paper and I think our readership is going to really enjoy digging in. Part of the richness is the use of three different cohorts and the use of multiple measures of epigenetic age. And I think you provided a really nice description of the unique information that each of these markers of epigenetic age provide. One thing I note are differences in the strength of association across the different measures of epigenetic age, which I think makes sense, because you said they characterize different aspects of the phenomenon, but I also see what looks like some variability across the cohorts with Framingham in particular seeming to stand out. And that being the only cohort that is 100% one race. It's white. Versus both the cardiovascular health study and the Eric study, which have more diverse study populations. I'm wondering what your hypothesis is about the differential strength of association that it seems Framingham is demonstrating and what you think is possibly the source of those differences. Dr. Jason Roberts: Yeah. I think those are great questions for all of genetics. The question is, does it apply to all races? For example, polygenic risk scores. It seems like when a polygenic risk scores develop for one race, it may not perfectly translate over to other races. So how relevant is that for epigenetic age acceleration. In this study, I think it's difficult to make definitive conclusions about it. We needed the three cohorts to have adequate statistical power in terms of being able to determine a differential effect of race. I think it would really be primarily hypothesis generating. We weren't really powered to look at the different races. So it's difficult for me to comment. Dr. Jason Roberts: I think ultimately and I want to believe anyways, that epigenetic age acceleration is relevant to all races, but in terms of, was it race that drove the differential impacts that we saw to some extent in terms of the magnitude of the hazard ratios, it's difficult to know in terms of tests for interaction and were these actually truly statistically different. We weren't adequately powered to address that hypothesis. So it's difficult for me to comment in a definitive matter I'd say. And sorry to cop out on… Dr. Mercedes Carnethon: No, not at all. I mean, I think there are a lot of things where there is no firm answer and that was just one of my hypotheses when I saw what was going on differently across the cohorts. I think that's a perfectly reasonable answer that sets us on a course for thinking about how we set up future studies. So I wanted to turn to you Vlad for the closing frame around this. As the editor, how do you hope that our readership will use these findings? Dr. Vlad Zaha: That is an excellent question. I was going to follow on this excellent unpacking of the core messages of the manuscript by Jason here to get his perspective as an electrophysiologist into what these type of work may represent for the everyday life of an electrophysiologist in the connecting with the patients and how would this type of approach influence, and maybe now, maybe later when our treatment for atrial fibrillation. Dr. Jason Roberts: Yeah. So that's a great question. I think, as I alluded to some extent before, as far as reinforcing healthy lifestyle, I think this provides more evidence in that respect. So we know that things like excessive alcohol consumption, being excessively obese, poor diets, not engaging in enough exercise, all of those things seem to accelerate your epigenetic age. And those are all things that we think or feel that are important with atrial fibrillation in terms of driving the path of physiology and people progressing. So I think this gives more data to us to reinforce the patients that in addition to the treatments that we're offering in terms of catheter ablation and antiarrhythmic drugs, the concern is that the substrate can continue you to progress. And that's likely driven by to some extent these modifiable risk factors. So keeping all of these under best control as possible, and hence trying to slow your biological aging as much as possible. Dr. Jason Roberts: I think that this will provide us more motivation to push these messages to our patients. A lot of patients can sometimes be like, "Let's just get on with a catheter ablation and I want to get on with my life…" but it really I think, provides more data to suggest that modifying these very important risk factors that can lead to accelerated biological agents, is very important. And in terms of the future as mentioned, so chronological aging, as people get older, people view it as, "Well, there's nothing I can do, and I'm just going to get gradually more and more unhealthy." I think, and this is somewhat futuristic, but to what extent can we slow biological aging? Can we potentially reverse it in the future? There's certainly lots of very compelling and interesting animal work and people are starting to delve into this in a big way. Dr. Jason Roberts: And not only to increase lifespan, will we some day live until we're 200. Who knows? But the concept of prolonging your health span as well. So the number of healthy years that you have before your body starts to gradually give way, I guess to some extent. Hopefully in the future will have therapies that will help keep us healthy. And if we do that increased health span, I think this data suggests that atrial fibrillation will be one thing that benefits from this. So hopefully in the future, maybe in terms of curbing the AFib pandemic, being able to address biological aging will help push things in the right direction. Dr. Mercedes Carnethon: Well, thank you so much Jason. And thank you so much Vlad for your thoughtful questions. I really like that the final bottom line leans towards my area as an epidemiologist, which is maintaining and promoting healthy lifestyles as a way to hopefully help prevent some of the difficulties of atrial fibrillation and its long-term outcomes. Really pleased to have you on this episode of Circulation on the Run, Jason, and thank you again Vlad, and I hope everyone enjoys this episode of the journal and has an opportunity to really dig into this piece. This is Mercedes Carnethon from Northwestern University Feinberg School of Medicine, saying thanks for listening today. Dr. Greg Hundley: This program is copyright of the American Heart Association 2021. 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 visit ahajournals.org.

Author Interview: Professor Atul Deodhar

Cytokine Signalling Forum

Play Episode Listen Later Dec 6, 2021 24:20

Professor Atul Deodhar, professor of medicine at Oregon Health & Science University. Join Professor Peter Nash as he interviews authors of recent notable papers in rheumatology. In this edition, Professor Atul Deodhar discusses his review on JAK-STAT signalling in spondyloarthritis and what that means for the use of JAK inhibitors for SpA treatment.

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Discussing Rheumatology: Risk of HZ with UPA, and JAKs in SpA

Cytokine Signalling Forum

Play Episode Listen Later Dec 6, 2021 8:25

Prof Iain McInnes reviews two papers this month, and discusses the increased risk of HZ infection with upadacitinib, as well as the role of the JAK-STAT pathway in SpA pathenogenesis. Keep-up to date with the latest in arthritis and cytokine signalling with Prof Iain McInnes. Everything discussed is available in a more detailed slide format in the publications section at cytokinesignalling.com.

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Is Dose-Adjusted EPOCH-R the Optimal Treatment for Children with Primary Mediastinal B-Cell Lymphoma?

Journal of Clinical Oncology (JCO) Podcast

Play Episode Listen Later Oct 20, 2021 8:30

This podcast will discuss data from a phase II trial evaluating the dose-adjusted EOPCH-R chemo-immunotherapy regimen for the treatment of primary mediastinal B-cell lymphoma in children. TRANSCRIPT [MUSIC PLAYING] LISA GIULINO-ROTH: This JCO podcast provides observations and commentary on the JCO article "Dose-Adjusted Rituximab Therapy in Children and Adolescents with Primary Mediastinal B-cell Lymphoma, a Multicenter Phase II Trial" by Burke et al. My name is Lisa Giulino-Roth, and I am a pediatric oncologist at Weill Cornell Medical College in New York. My oncology specialty is lymphoma in children, adolescents, and young adults. I have no relevant disclosures. Primary mediastinal B-cell lymphoma, or PMBCL, is an aggressive non-Hodgkin lymphoma derived from thymic B-cells. While previously classified as a subtype of diffuse large B-cell lymphoma, PMBCL is now recognized as a distinct clinical and pathologic entity. Unlike diffuse large B-cell lymphoma, PMBCL has a peak incidence among adolescents and young adults and is more common in females. PMBCL also shares many molecular characteristics with Hodgkin lymphoma, including alterations in JAK-STAT pathway signaling and amplification of the 9p24.1 locus, leading to upregulation of PD-L1. Adults with PMBCL have historically been treated on regimens designed for diffuse large B-cell lymphoma, which in the US was most commonly R-CHOP and radiation therapy. More recently, adult patients have been treated with a dose-adjusted EPOCH-R regimen, which is composed of dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab. This radiation-free approach is of interest, given this young and predominantly female population who are at risk for significant long-term toxicity from chest radiation. In a single center NCI-led study by Dunleavy and colleagues, dose-adjusted EPOCH-R was administered for six to eight cycles without radiation therapy and resulted in excellent outcomes with a five-year event free survival of 93% and overall survival of 97% among 51 adult patients. Pediatric patients with PMBCL have historically been treated on regimens designed for mature B non-Hodgkin lymphoma, which in pediatrics is most commonly Burkitt lymphoma or diffuse large B-cell lymphoma. These dose intensive multi-agent regimens include doxorubicin, high dose methotrexate, and intrathecal chemotherapy without radiation. Outcomes for children with PMBCL treated on these regimens are inferior to pediatric patients with diffuse large B-cell lymphoma treated on the same protocol. Children with PMBCL have a five-year event-free survival ranging from 65% to 75% in different international series. Given the excellent outcomes observed with dose-adjusted EPOCH-R in the adult NCI trial, an international phase II trial of this approach was conducted by two cooperative groups, The European Intergroup for Childhood Non-Hodgkin Lymphoma and the Children's Oncology Group. This single arm trial enrolled patients age 18 and under with primary mediastinal B-cell lymphoma. All patients were treated with six cycles of dose-adjusted EPOCH-R without radiation. The primary endpoint was event-free survival with events defined as any of the following-- viable cells in any residual mass after six cycles of treatment, relapse, progressive disease, secondary malignancy, or death from any cause. The four-year event-free survival from this trial would be compared with the event-free survival from historic controls, which was estimated at 67%. A total of 46 pediatric patients were enrolled between 2012 and 2016. All patients received six cycles of dose-adjusted EPOCH-R without RT. At a median follow-up of 59 months, there were 14 events, including four patients with viable cells in the residual mass at the completion of therapy, eight progressions or relapses, and two secondary malignancies, including one case of Hodgkin lymphoma and one case of acute promyelocytic leukemia. The event-free survival of the entire cohort at four years was disappointing at 69.6% with a 95% confidence interval of 55.2% to 80.9%. This was not statistically different than historic controls treated on pediatric mature B and HL regimens. Overall survival at four years was 84.8% with a 95% confidence interval of 71.8% to 92.4%. The authors acknowledge several limitations in the current study and challenges when comparing this study to the NCI trial. Not all patients adhered to the dose escalation rules, and 29% should have received a higher dose level in at least one course of treatment. Among the 10 cases of local relapse or primary refractory disease, five were noted to have a failure to dose escalate, including one patient with a clinical complication that precluded dose escalation. Comparing this trial to the NCI trial is challenging due to several important differences. Adults in the NCI trial were treated with six or eight cycles of dose-adjusted EPOCH-R based on the response between cycles 4 and 6. In pediatrics, eight cycles was not deemed appropriate, given the potential for greater than 600 milligrams per meter squared of cumulative doxorubicin exposure and concern for significant long-term cardiac toxicity at this exposure level. In addition, the NCI trial did not consider residual viable cells or secondary malignancy as an event, both of which were defined as events in the current pediatric trial. In a reanalysis of the pediatric data using the NCI event definitions, there was only a modest change in event-free survival with a four-year event-free survival of 73.9%. So where does this leave dose-adjusted EPOCH-R and the management of pediatric patients with PMBCL? In my opinion, there's no single superior regimen to treat pediatric PMBCL. Outcomes are similar across regimens. However, the toxicities are different. Dose-adjusted EPOCH-R offers significantly less short-term toxicity, but the potential for a higher cumulative doxorubicin dose compared to pediatric mature B and HL regimens. Regardless of the chemotherapy backbone, it is clear that for children with PMBCL, outcomes remain suboptimal, and further studies are needed to advance treatment. Given the rare nature of PMBCL and the peak incidence in the AYA population, combined pediatric and adult trials may allow us to evaluate novel agents and advance outcomes. Both children and adults with PMBCL may benefit from the incorporation of novel agents. Retrospective multicenter data from adults treated with dose-adjusted EPOCH-R have also failed to reproduce the excellent outcomes observed in the NCI trial. In two large retrospective series, adults with PMBCL treated with dose-adjusted EPOCH-R had a two- and three-year progression-free survival of 85% and 87% respectively. To advance outcomes in PMBCL across age groups, our team at the Children's Oncology Group in collaboration with Alliance and the National Clinical Trials Network is conducting a randomized phase III trial of the checkpoint inhibitor nivolumab in combination with chemo immunotherapy for adult and pediatric patients with PMBCL. Checkpoint inhibitors, including pembrolizumab and nivolumab, have demonstrated efficacy and PMBCL in the relapsed setting. And pembrolizumab is FDA approved for children and adults with relapsed PMBCL after two or more lines of therapy. However, these agents have not been evaluated in the upfront setting. In this trial, the treating physician will choose between R-CHOP and dose-adjusted EPOCH-R as the chemotherapy backbone. And patients will then be randomized to standard of care with six cycles of chemo immunotherapy alone or six cycles of nivolumab plus chemo immunotherapy. We are optimistic that this will define the role for checkpoint inhibition in the upfront management of PMBCL and work towards improved outcomes for both adult and pediatric patients. This concludes this JCO podcast. Thank you for listening. [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. For more original research, editorials, and review articles, please visit us online at jco.org. This production is copyrighted to the American Society of Clinical Oncology. Thank you for listening.

How Oxysterol LDL associates with macrophage and T lymphocyte infiltration during aging to generate the hyperinflammatory atherosclerotic plaque. DJGPhD. 19.10.21. Authentic Biochemistry.

Authentic Biochemistry

Play Episode Listen Later Oct 20, 2021 29:33

That there are senescence-associated decreases in the JAK-STAT signaling transduction cascade has been observed in human lymphocyte lineages. This phenomena, as associated with a decreased JAK- tyrosine phosphorylation of STAT5, is linked to plasma membrane cholesterol content. Therefore, plasma membrane cholesterol content is involved in T cells modulation and proliferation. Acid sphingomyelinase- mediated ceramide lipid raft mobilization and aggregation of membrane receptors plays a crucial role in this pathobiochemical dynamic leading to multiple disease and comorbidity states in the elderly. Classical Papers Examined: Mech Ageing Dev. 2001 Sep 15;122(13):1413-30 Cytometry A. 2006 Mar;69(3):189-91 J Lipid Res. 2007 Jan;48(1):19-29. doi: 10.1194 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

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April W. Armstrong, MD, MPH / Kenneth B. Gordon, MD - Taking Aim at the TYK2 Pathway in Psoriasis: Addressing Unmet Treatment and Patient Needs With an Innovative Therapeutic Approach

PeerView Internal Medicine CME/CNE/CPE Video Podcast

Play Episode Listen Later Sep 30, 2021 58:51

Go online to PeerView.com/TWD860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, experts in psoriatic disease offer learners an in-depth look at the complex pathophysiology of psoriasis, current management paradigms, and challenges in the care of patients with moderate to severe disease. Upon completion of this accredited CE activity, participants should be better able to: Recognize the burden of disease and unmet needs experienced by patients with moderate to severe psoriasis, Discuss the rationale for blocking the JAK-STAT pathway with small molecules as a treatment approach to psoriasis, Compare and contrast novel JAK inhibitors for the treatment of psoriasis in the context of selectivity, efficacy, and safety, Treat psoriasis in accordance with current evidence and guidelines, identifying patients with moderate to severe disease, who would likely derive benefit from novel nonbiologic oral therapeutic options.

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April W. Armstrong, MD, MPH / Kenneth B. Gordon, MD - Taking Aim at the TYK2 Pathway in Psoriasis: Addressing Unmet Treatment and Patient Needs With an Innovative Therapeutic Approach

PeerView Internal Medicine CME/CNE/CPE Audio Podcast

Play Episode Listen Later Sep 30, 2021 58:09

Go online to PeerView.com/TWD860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, experts in psoriatic disease offer learners an in-depth look at the complex pathophysiology of psoriasis, current management paradigms, and challenges in the care of patients with moderate to severe disease. Upon completion of this accredited CE activity, participants should be better able to: Recognize the burden of disease and unmet needs experienced by patients with moderate to severe psoriasis, Discuss the rationale for blocking the JAK-STAT pathway with small molecules as a treatment approach to psoriasis, Compare and contrast novel JAK inhibitors for the treatment of psoriasis in the context of selectivity, efficacy, and safety, Treat psoriasis in accordance with current evidence and guidelines, identifying patients with moderate to severe disease, who would likely derive benefit from novel nonbiologic oral therapeutic options.

patients treat treatments addressing recognize innovative compare pathway armstrong jak therapeutic psoriasis md mph unmet kenneth b jak stat april w armstrong

April W. Armstrong, MD, MPH / Kenneth B. Gordon, MD - Taking Aim at the TYK2 Pathway in Psoriasis: Addressing Unmet Treatment and Patient Needs With an Innovative Therapeutic Approach

PeerView Family Medicine & General Practice CME/CNE/CPE Video Podcast

Play Episode Listen Later Sep 30, 2021 58:51

Go online to PeerView.com/TWD860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, experts in psoriatic disease offer learners an in-depth look at the complex pathophysiology of psoriasis, current management paradigms, and challenges in the care of patients with moderate to severe disease. Upon completion of this accredited CE activity, participants should be better able to: Recognize the burden of disease and unmet needs experienced by patients with moderate to severe psoriasis, Discuss the rationale for blocking the JAK-STAT pathway with small molecules as a treatment approach to psoriasis, Compare and contrast novel JAK inhibitors for the treatment of psoriasis in the context of selectivity, efficacy, and safety, Treat psoriasis in accordance with current evidence and guidelines, identifying patients with moderate to severe disease, who would likely derive benefit from novel nonbiologic oral therapeutic options.

patients treat treatments addressing recognize innovative compare pathway armstrong jak therapeutic psoriasis md mph unmet kenneth b jak stat april w armstrong

April W. Armstrong, MD, MPH / Kenneth B. Gordon, MD - Taking Aim at the TYK2 Pathway in Psoriasis: Addressing Unmet Treatment and Patient Needs With an Innovative Therapeutic Approach

PeerView Family Medicine & General Practice CME/CNE/CPE Audio Podcast

Play Episode Listen Later Sep 30, 2021 58:09

Go online to PeerView.com/TWD860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, experts in psoriatic disease offer learners an in-depth look at the complex pathophysiology of psoriasis, current management paradigms, and challenges in the care of patients with moderate to severe disease. Upon completion of this accredited CE activity, participants should be better able to: Recognize the burden of disease and unmet needs experienced by patients with moderate to severe psoriasis, Discuss the rationale for blocking the JAK-STAT pathway with small molecules as a treatment approach to psoriasis, Compare and contrast novel JAK inhibitors for the treatment of psoriasis in the context of selectivity, efficacy, and safety, Treat psoriasis in accordance with current evidence and guidelines, identifying patients with moderate to severe disease, who would likely derive benefit from novel nonbiologic oral therapeutic options.

patients treat treatments addressing recognize innovative compare pathway armstrong jak therapeutic psoriasis md mph unmet kenneth b jak stat april w armstrong

April W. Armstrong, MD, MPH / Kenneth B. Gordon, MD - Taking Aim at the TYK2 Pathway in Psoriasis: Addressing Unmet Treatment and Patient Needs With an Innovative Therapeutic Approach

PeerView Clinical Pharmacology CME/CNE/CPE Audio Podcast

Play Episode Listen Later Sep 30, 2021 58:51

Go online to PeerView.com/TWD860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, experts in psoriatic disease offer learners an in-depth look at the complex pathophysiology of psoriasis, current management paradigms, and challenges in the care of patients with moderate to severe disease. Upon completion of this accredited CE activity, participants should be better able to: Recognize the burden of disease and unmet needs experienced by patients with moderate to severe psoriasis, Discuss the rationale for blocking the JAK-STAT pathway with small molecules as a treatment approach to psoriasis, Compare and contrast novel JAK inhibitors for the treatment of psoriasis in the context of selectivity, efficacy, and safety, Treat psoriasis in accordance with current evidence and guidelines, identifying patients with moderate to severe disease, who would likely derive benefit from novel nonbiologic oral therapeutic options.

patients treat treatments addressing recognize innovative compare pathway armstrong jak therapeutic psoriasis md mph unmet kenneth b jak stat april w armstrong

April W. Armstrong, MD, MPH / Kenneth B. Gordon, MD - Taking Aim at the TYK2 Pathway in Psoriasis: Addressing Unmet Treatment and Patient Needs With an Innovative Therapeutic Approach

Play Episode Listen Later Sep 30, 2021 58:09

Go online to PeerView.com/TWD860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, experts in psoriatic disease offer learners an in-depth look at the complex pathophysiology of psoriasis, current management paradigms, and challenges in the care of patients with moderate to severe disease. Upon completion of this accredited CE activity, participants should be better able to: Recognize the burden of disease and unmet needs experienced by patients with moderate to severe psoriasis, Discuss the rationale for blocking the JAK-STAT pathway with small molecules as a treatment approach to psoriasis, Compare and contrast novel JAK inhibitors for the treatment of psoriasis in the context of selectivity, efficacy, and safety, Treat psoriasis in accordance with current evidence and guidelines, identifying patients with moderate to severe disease, who would likely derive benefit from novel nonbiologic oral therapeutic options.

patients treat treatments addressing recognize innovative compare pathway armstrong jak therapeutic psoriasis md mph unmet kenneth b jak stat april w armstrong

The Gary Null Show - 08.13.21

The Gary Null Show

Play Episode Listen Later Aug 13, 2021 58:48

Curcumin: modulator of key molecular signaling pathways in hormone-independent breast cancer Monash University Malaysia, August 10, 2021 According to news reporting originating from Selangor, Malaysia, research stated, “Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among women worldwide.” Our news correspondents obtained a quote from the research from Monash University Malaysia: “Despite the overall successes in breast cancer therapy, hormone-independent HER2 negative breast cancer, also known as triple negative breast cancer (TNBC), lacking estrogens and progesterone receptors and with an excessive expression of human epidermal growth factor receptor 2 (HER2), along with the hormone-independent HER2 positive subtype, still remain major challenges in breast cancer treatment. Due to their poor prognoses, aggressive phenotype, and highly metastasis features, new alternative therapies have become an urgent clinical need. One of the most noteworthy phytochemicals, curcumin, has attracted enormous attention as a promising drug candidate in breast cancer prevention and treatment due to its multi-targeting effect. Curcumin interrupts major stages of tumorigenesis including cell proliferation, survival, angiogenesis, and metastasis in hormone-independent breast cancer through the modulation of multiple signaling pathways. The current review has highlighted the anticancer activity of curcumin in hormone-independent breast cancer via focusing on its impact on key signaling pathways including the PI3K/Akt/mTOR pathway, JAK/STAT pathway, MAPK pathway, NF-qB pathway, p53 pathway, and Wnt/b-catenin, as well as apoptotic and cell cycle pathways.” According to the news reporters, the research concluded: “Besides, its therapeutic implications in clinical trials are here presented.” Ultrasound remotely triggers immune cells to attack tumors in mice without toxic side effects University of California San Diego, August 11, 2021 Bioengineers at the University of California San Diego have developed a cancer immunotherapy that pairs ultrasound with cancer-killing immune cells to destroy malignant tumors while sparing normal tissue. The new experimental therapy significantly slowed down the growth of solid cancerous tumors in mice. The team, led by the labs of UC San Diego bioengineering professor Peter Yingxiao Wang and bioengineering professor emeritus Shu Chien, detailed their work in a paper published Aug. 12 in Nature Biomedical Engineering. The work addresses a longstanding problem in the field of cancer immunotherapy: how to make chimeric antigen receptor (CAR) T-cell therapy safe and effective at treating solid tumors. CAR T-cell therapy is a promising new approach to treat cancer. It involves collecting a patient's T cells and genetically engineering them to express special receptors, called CAR, on their surface that recognize specific antigens on cancer cells. The resulting CAR T cells are then infused back into the patient to find and attack cells that have the cancer antigens on their surface. This therapy has worked well for the treatment of some blood cancers and lymphoma, but not against solid tumors. That's because many of the target antigens on these tumors are also expressed on normal tissues and organs. This can cause toxic side effects that can kills cells—these effects are known as on-target, off-tumor toxicity. “CAR T cells are so potent that they may also attack normal tissues that are expressing the target antigens at low levels,” said first author Yiqian (Shirley) Wu, a project scientist in Wang's lab. “The problem with standard CAR T cells is that they are always on—they are always expressing the CAR protein, so you cannot control their activation,” explained Wu. To combat this issue, the team took standard CAR T cells and re-engineered them so that they only express the CAR protein when ultrasound energy is applied. This allowed the researchers to choose where and when the genes of CAR T cells get switched on. “We use ultrasound to successfully control CAR T cells directly in vivo for cancer immunotherapy,” said Wang, who is a faculty member of the Institute of Engineering in Medicine and the Center for Nano-ImmunoEngineering, both at UC San Diego. What's exciting about the use of ultrasound, noted Wang, is that it can penetrate tens of centimeters beneath the skin, so this type of therapy has the potential to non-invasively treat tumors that are buried deep inside the body. The team's approach involves injecting the re-engineered CAR T cells into tumors in mice and then placing a small ultrasound transducer on an area of the skin that's on top of the tumor to activate the CAR T cells. The transducer uses what's called focused ultrasound beams to focus or concentrate short pulses of ultrasound energy at the tumor. This causes the tumor to heat up moderately—in this case, to a temperature of 43 degrees Celsius (109 degrees Fahrenheit)—without affecting the surrounding tissue. The CAR T cells in this study are equipped with a gene that produces the CAR protein only when exposed to heat. As a result, the CAR T cells only switch on where ultrasound is applied. The researchers put their CAR T cells to the test against standard CAR T cells. In mice that were treated with the new CAR T cells, only the tumors that were exposed to ultrasound were attacked, while other tissues in the body were left alone. But in mice that were treated with the standard CAR T cells, all tumors and tissue expressing the target antigen were attacked. “This shows our CAR T-cell therapy is not only effective, but also safer,” said Wu. “It has minimal on-target, off-tumor side effects.” The work is still in the early stages. The team will be performing more preclinical tests and toxicity studies before it can reach clinical trials. Lycopene ameliorates diabetic osteoporosis via anti-inflammatory, antioxidation Shaanxi University of Technology (China), August 10, 2021 According to news originating from Shaanxi University of Technology research stated, “Diabetic osteoporosis (DOP) is one of the complications of diabetes, with high morbidity, and high disability rate. Here, we established a diabetic rat model and administered lycopene to observe its effect on DOP.” Our news editors obtained a quote from the research from Shaanxi University of Technology: “Our results showed that ten weeks lycopene treatment lowered blood glucose, improved diabetic induced polydipsia, overeating and body weight loss. Lycopene treatment also enhanced bone mineral density, restored bone mechanical and bone Micro-CT parameters of diabetic rats. Subsequently, lycopene decreased serum inflammatory cytokines levels and increased serum anti-oxidant indicators levels. Moreover, lycopene reduced the number of bone marrow adipocytes, and osteoclasts numbers of diabetic rats. The serum bone turnover markers levels were down-regulated after lycopene treatment. Meanwhile, the bone and serum OPG, RUNX 2 expression levels were up-regulated by lycopene in diabetic rats, and the OPG/RANKL ratio was also up-regulated.” According to the news editors, the research concluded: “This study showed that lycopene could ameliorate diabetic induced bone loss via anti-inflammatory, anti-oxidation, and increasing OPG/RANKL ratio in diabetic rats. Lycopene could be used for nutritional intervention in patients with diabetic osteoporosis.” Research shows just 8 weeks of meditation studies can make your brain quicker Birmingham University (UK), August 12, 2021 Researchers at Binghamton University scanned students' brains before and after eight weeks of meditation training. Credit: Binghamton University Millions of people around the world seek mental clarity through meditation, most of them following or inspired by the centuries-old practices of Buddhism. Anecdotally, those who meditate say it helps to calm their minds, recenter their thoughts and cut through the "noise" to show what really matters. Scientifically, though, showing the effects of meditation on the human brainhave proved to be tricky. A new study from Binghamton University's Thomas J. Watson College of Engineering and Applied Science tracked how practicing meditation for just a couple of months changed the brain patterns of 10 students in the University's Scholars Program. The seed for the research came from a casual chat between Assistant Professor Weiying Dai and lecturer George Weinschenk, MA '01, Ph.D. '07, both from the Department of Computer Science. Weinschenk is a longtime meditation practitioner whose wife worked as an administrator at the Namgyal Monastery in Ithaca, which is the North American seat of the Dalai Lama's personal monastery. "I developed very close friendships with several of the monks," he said. "We would hang out together, and I even received instruction from some of the Dalai Lama's teachers. I took classes there, I read a lot and I earned a three-year certificate in Buddhist studies." Dai has studied brain mapping and biomedical image processing, and while earning her Ph.D. at the University of Pittsburgh, she tracked Alzheimer's disease patients using magnetic resonance imaging (MRI) scans. "I'm interested in brain research to see how our brains are really functioning and how all different kinds of disease affect our brain," she said. "I really have zero medical training, but I pick up all this knowledge or background from reading the literature and talking with the experts." The two faculty members had neighboring offices and shared a conversation one day about their backgrounds. Weinschenk mentioned that he had been asked to teach a semester-long class for the Scholars Program on meditation. "I told Weiying, 'Yeah, meditation really can have a transformative effect on the brain,'" Weinschenk said. "She was a little skeptical, especially about whether such a short amount of time spent learning how to meditate, whether that would make any difference. She suggested we might be able to quantify such a thing with modern technology." For the fall 2017 semester, Dai secured grant funding, and their collaboration began. Near the beginning of the semester, she took the participants to Cornell University for MRI scans of their brains. Weinschenk taught students how to meditate, told them to practice five times a week for 10 or 15 minutes, and asked them to keep a journal record of their practice. (The syllabus also included other lessons about the cultural transmissions of meditation and its applications for wellness.) "Binghamton University Scholars are high achievers who want to do the things they are assigned and do well on them, so they didn't require much prompting to maintain a regular meditation routine," he said. "To guarantee objective reporting, they would relate their experiences directly to Weiying about how frequently they practiced." The results, recently published in the journal Scientific Reports, show that meditation training led to faster switching between the brain's two general states of consciousness. One is called the default mode network, which is active when the brain is at wakeful rest and not focused on the outside world, such as during daydreaming and mind-wandering. The other is the dorsal attention network, which engages for attention-demanding tasks. The findings of the study demonstrate that meditation can enhance the brain connection among and within these two brain networks, indicating the effect of meditation on fast switching between the mind wandering and focusing its attention as well as maintaining attention once in the attentive state. "Tibetans have a term for that ease of switching between states—they call it mental pliancy, an ability that allows you to shape and mold your mind," Weinschenk said. "They also consider the goal of concentration one of the fundamental principles of self-growth." Dai and Weinschenk are still parsing through the data taken from the 2017 MRI scans, so they have yet to test other Scholars Program students. Because Alzheimer's disease and autism could be caused by problems with the dorsal attention network, Dai is making plans for future research that could use meditation to mitigate those problems. "I'm thinking about an elderly study, because this population was young students," she said. "I want to get a healthy elderly group, and then another group with early Alzheimer's disease or mild cognitive impairment. I want to see whether the changes in the brain from meditation can enhance cognitive performance. I'm writing the proposal and trying to attract the funds in that direction." Though once skeptical about the subject, "I'm pretty convinced about the scientific basis of meditation after doing this study," she added. "Maybe I'll just go to George's class when he teaches it so that I can benefit, too!" Study shows how food preservatives may disrupt human hormones and promote obesity Cedars-Sinai Medicine Institute, August 9, 2021 Can chemicals that are added to breakfast cereals and other everyday products make you obese? Growing evidence from animal experiments suggests the answer may be "yes." But confirming these findings in humans has faced formidable obstacles - until now. A study published in Nature Communications details how Cedars-Sinai investigators developed a novel platform and protocol for testing the effects of chemicals known as endocrine disruptors on humans. The three chemicals tested in this study are abundant in modern life. Butylhydroxytoluene (BHT) is an antioxidant commonly added to breakfast cereals and other foods to protect nutrients and keep fats from turning rancid; perfluorooctanoic acid (PFOA) is a polymer found in some cookware, carpeting and other products; and tributyltin (TBT) is a compound in paints that can make its way into water and accumulate in seafood. The investigators used hormone-producing tissues grown from human stem cells to demonstrate how chronic exposure to these chemicals can interfere with signals sent from the digestive system to the brain that let people know when they are "full" during meals. When this signaling system breaks down, people often may continue eating, causing them to gain weight. "We discovered that each of these chemicals damaged hormones that communicate between the gut and the brain," said Dhruv Sareen, PhD, assistant professor of Biomedical Sciences and director of the Induced Pluripotent Stem Cell Core Facility at the Cedars-Sinai Board of Governors Regenerative Medicine Institute. "When we tested the three together, the combined stress was more robust." Of the three chemicals tested, BHT produced some of the strongest detrimental effects, Sareen said. While other scientists have shown these compounds can disrupt hormone systems in laboratory animals, the new study is the first to use human pluripotent stem cells and tissues to document how the compounds may disrupt hormones that are critical to gut-to-brain signaling and preventing obesity in people, Sareen said. "This is a landmark study that substantially improves our understanding of how endocrine disruptors may damage human hormonal systems and contribute to the obesity epidemic in the U.S.," said Clive Svendsen, PhD, director of the institute and the Kerry and Simone Vickar Family Foundation Distinguished Chair in Regenerative Medicine. More than one-third of U.S. adults are considered to be obese, according to federal statistics. The new testing system developed for the study has the potential to provide a much-needed, safe and cost-effective method that can be used to evaluate the health effects of thousands of existing and new chemicals in the environment, the investigators say. For their experiments, Sareen and his team first obtained blood samples from adults, and then, by introducing reprogramming genes, converted the cells into induced pluripotent stem cells. Then, using these stem cells, the investigators grew human epithelium tissue, which lines the gut, and neuronal tissues of the brain's hypothalamus region, which regulates appetite and metabolism. The investigators then exposed the tissues to BHT, PFOA and TBT, one by one and also in combination, and observed what happened inside the cells. They found that the chemicals disrupted networks that prepare signaling hormones to maintain their structure and be transported out of the cells, thus making them ineffective. The chemicals also damaged mitochondria - cellular structures that convert food and oxygen into energy and drive the body's metabolism. Because the chemical damage occurred in early-stage "young" cells, the findings suggest that a defective hormone system potentially could impact a pregnant mother as well as her fetus in the womb, Sareen said. While other scientists have found, in animal studies, that effects of endocrine disruptors can be passed down to future generations, this process has not been proved to occur in humans, he explained. More than 80,000 chemicals are registered for use in the U.S. in everyday items such as foods, personal care products, household cleaners and lawn-care products, according to the National Toxicology Program of the U.S. Department of Health and Human Services. While the program states on its website that relatively few chemicals are thought to pose a significant risk to human health, it also states: "We do not know the effects of many of these chemicals on our health." Cost and ethical issues, including the health risk of exposing human subjects to possibly harmful substances, are among the barriers to testing the safety of many chemicals. As a result, numerous widely used compounds remain unevaluated in humans for their health effects, especially to the hormone system. "By testing these chemicals on actual human tissues in the lab, we potentially could make these evaluations easier to conduct and more cost-effective," Sareen said. Social activities help dementia patients stay sharp, avoid depression University of Sheffield (UK), August 12, 2021 Approximately 6 million people in the U.S. are suffering from dementia, as well 50 million people worldwide. There is currently no cure for the degenerative condition and medical treatments often have side effects such as vomiting, loss of appetite, and muscle pains. Now, researchers say patients can greatly benefit from a type of treatment that doesn't come with such downsides and helps their brain avoid additional decline. A new study suggests that mixing with other people helps dementia patients stay sharp and fend off depression. Scientists say the type of treatment known as “cognitive stimulation” could make living with dementia easier for hundreds of thousands of people. “Dementia is one of the biggest global challenges that we face,” says senior author Dr. Claudia von Bastian, of the University of Sheffield, in a statement. “Our research highlights that cognitive stimulation can be a safe, relatively cheap, and accessible treatment to help reduce some of the core symptoms of dementia and may even alleviate symptoms of depression.” The researchers analyzed the use of cognitive stimulation as an effective treatment for people with dementia. They found that getting patients involved in social and group activities helped combat depression and boost global cognition. Global cognition refers to five types of brain function: attention, memory, verbal fluency, language, and awareness. “It's great that governments now recognize the importance for people to live well with dementia. We've seen far more energy and resources put into developing initiatives to support this, such as cognitive stimulation, which is now used widely across the world,” notes co-author Dr. Ben Hicks, of Brighton and Sussex Medical School. “We still need to learn more about the key ingredients of cognitive stimulation which lead to these benefits and how they influence the progression of dementia. However, the absence of negative side-effects and the low costs of this treatment means the benefits are clear,” adds Dr. von Bastian. More research is needed to determine whether cognitive stimulation and other non-pharmaceutical treatments could help the growing number of people who suffer fromdementia. “Our research is the first to comprehensively interrogate the evidence base for its effectiveness, using the most up-to-date statistical techniques. While early signs are positive, there's an urgent need to improve the rigor of evaluative research and better assess the long-term benefits of cognitive stimulation. People with dementia need effective treatments, and, as a research community, this is what we must deliver,” added Dr. Hicks. Resveratrol supplementation improves arterial stiffness in type 2 diabetics Toho University (Japan), August 18 2021 A randomized, double-blind study reported on in the International Heart journal found improvements in arterial stiffness and oxidative stress among type 2 diabetics who were supplemented with resveratrol. The trial included 50 diabetic men and women who received 100 milligrams resveratrol or a placebo daily for 12 weeks. Cardio-ankle vascular index (CAVI, a novel diagnostic measure of arterial stiffness that is a marker of atherosclerosis) and blood pressure were assessed at the beginning and end of the study, in addition to blood assessments of oxidative stress and other factors. At the end of the study, subjects who received resveratrol had significantly lower blood pressure, less oxidative stress and decreased arterial stiffness in comparison with values obtained at the beginning of the study. Participants who received a placebo experienced no significant changes in these areas. “The primary finding in the present study was that oral supplementation of resveratrol for 12 weeks decreased CAVI in patients with type 2 diabetes mellitus,” authors Haruki Imamura, MD, and colleagues at Toho University Sakura Medical Center in Japan write. “Many previous studies have demonstrated increased CAVI in atherosclerotic diseases such as acute coronary syndrome and stroke, and these reports indicate that CAVI reflects organic atherosclerosis.” They suggest that a reduction in oxidative stress may be one mechanism involved in the improvement in arterial stiffness observed in this study among participants who received resveratrol. Improved endothelial function via increased nitric oxide production may be another mechanism.

EHA 2021: key trial updates in myelofibrosis

trial myelofibrosis eha jak stat mpns

Play Episode Listen Later Jul 20, 2021 7:06

The breakthrough discovery of upregulation of the JAK-STAT signaling pathway as the driving force behind myeloproliferative neoplasms (MPNs) has led... The post EHA 2021: key trial updates in myelofibrosis appeared first on VJHemOnc.

EHA 2021: key trial updates in myelofibrosis

trial myelofibrosis eha jak stat mpns

Play Episode Listen Later Jul 20, 2021 7:06

The breakthrough discovery of upregulation of the JAK-STAT signaling pathway as the driving force behind myeloproliferative neoplasms (MPNs) has led... The post EHA 2021: key trial updates in myelofibrosis appeared first on VJHemOnc.

Andrew Blauvelt, MD, MBA - Addressing the Unmet Needs of Patients With Moderate to Severe Psoriasis: A Visual Exploration of Disease Pathogenesis and the Clinical Potential of Targeting the TYK2 Pathway as a Novel Nonbiologic Oral Therapeutic Option

PeerView Internal Medicine CME/CNE/CPE Video Podcast

Play Episode Listen Later Jun 25, 2021 37:46

Go online to PeerView.com/NJS860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, an expert in dermatology discusses unmet needs of patients with moderate to severe psoriasis and the clinical potential of targeting the TYK2 pathway as a novel nonbiologic oral therapeutic option. Upon completion of this accredited CE activity, participants should be better able to: Explain the role of the JAK-STAT signaling pathway in the pathophysiology of psoriasis, Summarize efficacy and safety data related to current and emerging kinase inhibitors for the treatment of psoriasis, Treat moderate to severe psoriasis in accordance with current evidence and guidelines, recognizing the role of nonbiologic therapies in addressing the burden of disease and comorbidities in individual patients.

Andrew Blauvelt, MD, MBA - Addressing the Unmet Needs of Patients With Moderate to Severe Psoriasis: A Visual Exploration of Disease Pathogenesis and the Clinical Potential of Targeting the TYK2 Pathway as a Novel Nonbiologic Oral Therapeutic Option

PeerView Clinical Pharmacology CME/CNE/CPE Audio Podcast

Play Episode Listen Later Jun 25, 2021 37:41

Go online to PeerView.com/NJS860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, an expert in dermatology discusses unmet needs of patients with moderate to severe psoriasis and the clinical potential of targeting the TYK2 pathway as a novel nonbiologic oral therapeutic option. Upon completion of this accredited CE activity, participants should be better able to: Explain the role of the JAK-STAT signaling pathway in the pathophysiology of psoriasis, Summarize efficacy and safety data related to current and emerging kinase inhibitors for the treatment of psoriasis, Treat moderate to severe psoriasis in accordance with current evidence and guidelines, recognizing the role of nonbiologic therapies in addressing the burden of disease and comorbidities in individual patients.

Andrew Blauvelt, MD, MBA - Addressing the Unmet Needs of Patients With Moderate to Severe Psoriasis: A Visual Exploration of Disease Pathogenesis and the Clinical Potential of Targeting the TYK2 Pathway as a Novel Nonbiologic Oral Therapeutic Option

PeerView Immunology & Transplantation CME/CNE/CPE Video Podcast

Play Episode Listen Later Jun 25, 2021 37:46

Go online to PeerView.com/NJS860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, an expert in dermatology discusses unmet needs of patients with moderate to severe psoriasis and the clinical potential of targeting the TYK2 pathway as a novel nonbiologic oral therapeutic option. Upon completion of this accredited CE activity, participants should be better able to: Explain the role of the JAK-STAT signaling pathway in the pathophysiology of psoriasis, Summarize efficacy and safety data related to current and emerging kinase inhibitors for the treatment of psoriasis, Treat moderate to severe psoriasis in accordance with current evidence and guidelines, recognizing the role of nonbiologic therapies in addressing the burden of disease and comorbidities in individual patients.

Andrew Blauvelt, MD, MBA - Addressing the Unmet Needs of Patients With Moderate to Severe Psoriasis: A Visual Exploration of Disease Pathogenesis and the Clinical Potential of Targeting the TYK2 Pathway as a Novel Nonbiologic Oral Therapeutic Option

PeerView Family Medicine & General Practice CME/CNE/CPE Audio Podcast

Play Episode Listen Later Jun 25, 2021 37:41

Go online to PeerView.com/NJS860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, an expert in dermatology discusses unmet needs of patients with moderate to severe psoriasis and the clinical potential of targeting the TYK2 pathway as a novel nonbiologic oral therapeutic option. Upon completion of this accredited CE activity, participants should be better able to: Explain the role of the JAK-STAT signaling pathway in the pathophysiology of psoriasis, Summarize efficacy and safety data related to current and emerging kinase inhibitors for the treatment of psoriasis, Treat moderate to severe psoriasis in accordance with current evidence and guidelines, recognizing the role of nonbiologic therapies in addressing the burden of disease and comorbidities in individual patients.

Andrew Blauvelt, MD, MBA - Addressing the Unmet Needs of Patients With Moderate to Severe Psoriasis: A Visual Exploration of Disease Pathogenesis and the Clinical Potential of Targeting the TYK2 Pathway as a Novel Nonbiologic Oral Therapeutic Option

PeerView Family Medicine & General Practice CME/CNE/CPE Video Podcast

Play Episode Listen Later Jun 25, 2021 37:46

Go online to PeerView.com/NJS860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, an expert in dermatology discusses unmet needs of patients with moderate to severe psoriasis and the clinical potential of targeting the TYK2 pathway as a novel nonbiologic oral therapeutic option. Upon completion of this accredited CE activity, participants should be better able to: Explain the role of the JAK-STAT signaling pathway in the pathophysiology of psoriasis, Summarize efficacy and safety data related to current and emerging kinase inhibitors for the treatment of psoriasis, Treat moderate to severe psoriasis in accordance with current evidence and guidelines, recognizing the role of nonbiologic therapies in addressing the burden of disease and comorbidities in individual patients.

Andrew Blauvelt, MD, MBA - Addressing the Unmet Needs of Patients With Moderate to Severe Psoriasis: A Visual Exploration of Disease Pathogenesis and the Clinical Potential of Targeting the TYK2 Pathway as a Novel Nonbiologic Oral Therapeutic Option

PeerView Immunology & Transplantation CME/CNE/CPE Audio Podcast

Play Episode Listen Later Jun 25, 2021 37:41

Go online to PeerView.com/NJS860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, an expert in dermatology discusses unmet needs of patients with moderate to severe psoriasis and the clinical potential of targeting the TYK2 pathway as a novel nonbiologic oral therapeutic option. Upon completion of this accredited CE activity, participants should be better able to: Explain the role of the JAK-STAT signaling pathway in the pathophysiology of psoriasis, Summarize efficacy and safety data related to current and emerging kinase inhibitors for the treatment of psoriasis, Treat moderate to severe psoriasis in accordance with current evidence and guidelines, recognizing the role of nonbiologic therapies in addressing the burden of disease and comorbidities in individual patients.

Andrew Blauvelt, MD, MBA - Addressing the Unmet Needs of Patients With Moderate to Severe Psoriasis: A Visual Exploration of Disease Pathogenesis and the Clinical Potential of Targeting the TYK2 Pathway as a Novel Nonbiologic Oral Therapeutic Option

PeerView Internal Medicine CME/CNE/CPE Audio Podcast

Play Episode Listen Later Jun 25, 2021 37:41

Go online to PeerView.com/NJS860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, an expert in dermatology discusses unmet needs of patients with moderate to severe psoriasis and the clinical potential of targeting the TYK2 pathway as a novel nonbiologic oral therapeutic option. Upon completion of this accredited CE activity, participants should be better able to: Explain the role of the JAK-STAT signaling pathway in the pathophysiology of psoriasis, Summarize efficacy and safety data related to current and emerging kinase inhibitors for the treatment of psoriasis, Treat moderate to severe psoriasis in accordance with current evidence and guidelines, recognizing the role of nonbiologic therapies in addressing the burden of disease and comorbidities in individual patients.

Andrew Blauvelt, MD, MBA - Addressing the Unmet Needs of Patients With Moderate to Severe Psoriasis: A Visual Exploration of Disease Pathogenesis and the Clinical Potential of Targeting the TYK2 Pathway as a Novel Nonbiologic Oral Therapeutic Option

PeerView Internal Medicine CME/CNE/CPE Audio Podcast

Play Episode Listen Later Jun 25, 2021 37:46

Go online to PeerView.com/NJS860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, an expert in dermatology discusses unmet needs of patients with moderate to severe psoriasis and the clinical potential of targeting the TYK2 pathway as a novel nonbiologic oral therapeutic option. Upon completion of this accredited CE activity, participants should be better able to: Explain the role of the JAK-STAT signaling pathway in the pathophysiology of psoriasis, Summarize efficacy and safety data related to current and emerging kinase inhibitors for the treatment of psoriasis, Treat moderate to severe psoriasis in accordance with current evidence and guidelines, recognizing the role of nonbiologic therapies in addressing the burden of disease and comorbidities in individual patients.

Jonathan I. Silverberg, MD, PhD, MPH / Eric Simpson, MD, MCR - Advancing Care for People Living With Moderate to Severe Atopic Dermatitis: The Future Looks Clear

Play Episode Listen Later Jun 24, 2021 65:25

Go online to PeerView.com/KCX860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Over the past decade, the understanding of atopic dermatitis (AD) pathogenesis has evolved, giving way to numerous potential therapeutic targets. During this time, Janus kinase (JAK) inhibitors—a new class of medications—have also emerged. While the JAK-signal transducer and activator of transcription (JAK-STAT) pathway did not seem to be an obvious target early on, JAK inhibitors are likely to be the next generation of agents FDA approved for the treatment of moderate to severe AD. Indeed, JAK inhibitors are demonstrating benefit across multiple dermatologic diseases and constitute a promising frontier for dermatologic therapy overall. In this activity, based on a recent live web broadcast, our expert faculty examine the complex pathogenesis that underlies AD, focusing on the rationale for development of novel therapeutic approaches. In addition, key information (eg, mechanism of action, side-effect profiles, and dosing) for these new and emerging agents for moderate to severe AD will be provided, as well as the most up-to-date efficacy and safety data and practical considerations for clinical use. Upon completion of this accredited CE activity, participants should be better able to: Recognize recent insights into the pathogenesis of atopic dermatitis (AD) that have led to the development of new molecules targeting key cytokine signaling pathways, Evaluate recent safety and efficacy data related to emerging treatment options for moderate to severe AD, identifying potential implications for patient care, Develop strategies to identify candidates for newer therapeutic options and overcome barriers to achieving treatment goals in patients with moderate to severe AD.

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Jonathan I. Silverberg, MD, PhD, MPH / Eric Simpson, MD, MCR - Advancing Care for People Living With Moderate to Severe Atopic Dermatitis: The Future Looks Clear

PeerView Clinical Pharmacology CME/CNE/CPE Audio Podcast

Play Episode Listen Later Jun 24, 2021 65:25

Go online to PeerView.com/KCX860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Over the past decade, the understanding of atopic dermatitis (AD) pathogenesis has evolved, giving way to numerous potential therapeutic targets. During this time, Janus kinase (JAK) inhibitors—a new class of medications—have also emerged. While the JAK-signal transducer and activator of transcription (JAK-STAT) pathway did not seem to be an obvious target early on, JAK inhibitors are likely to be the next generation of agents FDA approved for the treatment of moderate to severe AD. Indeed, JAK inhibitors are demonstrating benefit across multiple dermatologic diseases and constitute a promising frontier for dermatologic therapy overall. In this activity, based on a recent live web broadcast, our expert faculty examine the complex pathogenesis that underlies AD, focusing on the rationale for development of novel therapeutic approaches. In addition, key information (eg, mechanism of action, side-effect profiles, and dosing) for these new and emerging agents for moderate to severe AD will be provided, as well as the most up-to-date efficacy and safety data and practical considerations for clinical use. Upon completion of this accredited CE activity, participants should be better able to: Recognize recent insights into the pathogenesis of atopic dermatitis (AD) that have led to the development of new molecules targeting key cytokine signaling pathways, Evaluate recent safety and efficacy data related to emerging treatment options for moderate to severe AD, identifying potential implications for patient care, Develop strategies to identify candidates for newer therapeutic options and overcome barriers to achieving treatment goals in patients with moderate to severe AD.

care clear develop fda recognize advancing evaluate jak severe moderate janus md phd people living silverberg atopic dermatitis jak stat eric simpson jonathan i silverberg

Jonathan I. Silverberg, MD, PhD, MPH / Eric Simpson, MD, MCR - Advancing Care for People Living With Moderate to Severe Atopic Dermatitis: The Future Looks Clear

PeerView Family Medicine & General Practice CME/CNE/CPE Video Podcast

Play Episode Listen Later Jun 24, 2021 65:35

Go online to PeerView.com/KCX860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Over the past decade, the understanding of atopic dermatitis (AD) pathogenesis has evolved, giving way to numerous potential therapeutic targets. During this time, Janus kinase (JAK) inhibitors—a new class of medications—have also emerged. While the JAK-signal transducer and activator of transcription (JAK-STAT) pathway did not seem to be an obvious target early on, JAK inhibitors are likely to be the next generation of agents FDA approved for the treatment of moderate to severe AD. Indeed, JAK inhibitors are demonstrating benefit across multiple dermatologic diseases and constitute a promising frontier for dermatologic therapy overall. In this activity, based on a recent live web broadcast, our expert faculty examine the complex pathogenesis that underlies AD, focusing on the rationale for development of novel therapeutic approaches. In addition, key information (eg, mechanism of action, side-effect profiles, and dosing) for these new and emerging agents for moderate to severe AD will be provided, as well as the most up-to-date efficacy and safety data and practical considerations for clinical use. Upon completion of this accredited CE activity, participants should be better able to: Recognize recent insights into the pathogenesis of atopic dermatitis (AD) that have led to the development of new molecules targeting key cytokine signaling pathways, Evaluate recent safety and efficacy data related to emerging treatment options for moderate to severe AD, identifying potential implications for patient care, Develop strategies to identify candidates for newer therapeutic options and overcome barriers to achieving treatment goals in patients with moderate to severe AD.

care clear develop fda recognize advancing evaluate jak severe moderate janus md phd people living silverberg atopic dermatitis jak stat eric simpson jonathan i silverberg

Jonathan I. Silverberg, MD, PhD, MPH / Eric Simpson, MD, MCR - Advancing Care for People Living With Moderate to Severe Atopic Dermatitis: The Future Looks Clear

PeerView Family Medicine & General Practice CME/CNE/CPE Audio Podcast

Play Episode Listen Later Jun 24, 2021 65:25

Go online to PeerView.com/KCX860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Over the past decade, the understanding of atopic dermatitis (AD) pathogenesis has evolved, giving way to numerous potential therapeutic targets. During this time, Janus kinase (JAK) inhibitors—a new class of medications—have also emerged. While the JAK-signal transducer and activator of transcription (JAK-STAT) pathway did not seem to be an obvious target early on, JAK inhibitors are likely to be the next generation of agents FDA approved for the treatment of moderate to severe AD. Indeed, JAK inhibitors are demonstrating benefit across multiple dermatologic diseases and constitute a promising frontier for dermatologic therapy overall. In this activity, based on a recent live web broadcast, our expert faculty examine the complex pathogenesis that underlies AD, focusing on the rationale for development of novel therapeutic approaches. In addition, key information (eg, mechanism of action, side-effect profiles, and dosing) for these new and emerging agents for moderate to severe AD will be provided, as well as the most up-to-date efficacy and safety data and practical considerations for clinical use. Upon completion of this accredited CE activity, participants should be better able to: Recognize recent insights into the pathogenesis of atopic dermatitis (AD) that have led to the development of new molecules targeting key cytokine signaling pathways, Evaluate recent safety and efficacy data related to emerging treatment options for moderate to severe AD, identifying potential implications for patient care, Develop strategies to identify candidates for newer therapeutic options and overcome barriers to achieving treatment goals in patients with moderate to severe AD.

care clear develop fda recognize advancing evaluate jak severe moderate janus md phd people living silverberg atopic dermatitis jak stat eric simpson jonathan i silverberg

Jonathan I. Silverberg, MD, PhD, MPH / Eric Simpson, MD, MCR - Advancing Care for People Living With Moderate to Severe Atopic Dermatitis: The Future Looks Clear

PeerView Internal Medicine CME/CNE/CPE Video Podcast

Play Episode Listen Later Jun 24, 2021 65:35

Go online to PeerView.com/KCX860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Over the past decade, the understanding of atopic dermatitis (AD) pathogenesis has evolved, giving way to numerous potential therapeutic targets. During this time, Janus kinase (JAK) inhibitors—a new class of medications—have also emerged. While the JAK-signal transducer and activator of transcription (JAK-STAT) pathway did not seem to be an obvious target early on, JAK inhibitors are likely to be the next generation of agents FDA approved for the treatment of moderate to severe AD. Indeed, JAK inhibitors are demonstrating benefit across multiple dermatologic diseases and constitute a promising frontier for dermatologic therapy overall. In this activity, based on a recent live web broadcast, our expert faculty examine the complex pathogenesis that underlies AD, focusing on the rationale for development of novel therapeutic approaches. In addition, key information (eg, mechanism of action, side-effect profiles, and dosing) for these new and emerging agents for moderate to severe AD will be provided, as well as the most up-to-date efficacy and safety data and practical considerations for clinical use. Upon completion of this accredited CE activity, participants should be better able to: Recognize recent insights into the pathogenesis of atopic dermatitis (AD) that have led to the development of new molecules targeting key cytokine signaling pathways, Evaluate recent safety and efficacy data related to emerging treatment options for moderate to severe AD, identifying potential implications for patient care, Develop strategies to identify candidates for newer therapeutic options and overcome barriers to achieving treatment goals in patients with moderate to severe AD.

care clear develop fda recognize advancing evaluate jak severe moderate janus md phd people living silverberg atopic dermatitis jak stat eric simpson jonathan i silverberg

Jonathan I. Silverberg, MD, PhD, MPH / Eric Simpson, MD, MCR - Advancing Care for People Living With Moderate to Severe Atopic Dermatitis: The Future Looks Clear

Beast Fitness Radio's Podcast

Play Episode Listen Later Jun 24, 2021 65:35

Go online to PeerView.com/KCX860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Over the past decade, the understanding of atopic dermatitis (AD) pathogenesis has evolved, giving way to numerous potential therapeutic targets. During this time, Janus kinase (JAK) inhibitors—a new class of medications—have also emerged. While the JAK-signal transducer and activator of transcription (JAK-STAT) pathway did not seem to be an obvious target early on, JAK inhibitors are likely to be the next generation of agents FDA approved for the treatment of moderate to severe AD. Indeed, JAK inhibitors are demonstrating benefit across multiple dermatologic diseases and constitute a promising frontier for dermatologic therapy overall. In this activity, based on a recent live web broadcast, our expert faculty examine the complex pathogenesis that underlies AD, focusing on the rationale for development of novel therapeutic approaches. In addition, key information (eg, mechanism of action, side-effect profiles, and dosing) for these new and emerging agents for moderate to severe AD will be provided, as well as the most up-to-date efficacy and safety data and practical considerations for clinical use. Upon completion of this accredited CE activity, participants should be better able to: Recognize recent insights into the pathogenesis of atopic dermatitis (AD) that have led to the development of new molecules targeting key cytokine signaling pathways, Evaluate recent safety and efficacy data related to emerging treatment options for moderate to severe AD, identifying potential implications for patient care, Develop strategies to identify candidates for newer therapeutic options and overcome barriers to achieving treatment goals in patients with moderate to severe AD.

care clear develop fda recognize advancing evaluate jak severe moderate janus md phd people living silverberg atopic dermatitis jak stat eric simpson jonathan i silverberg

What T -cell Acute Lymphoblastic Leukaemia and Senescing microglial CNS disease have in common relate to Notch and Glucocorticoid signaling. DJGPhD 07 December 2020

Authentic Biochemistry

Play Episode Listen Later Dec 8, 2020 29:46

Aging and chronic stress can obtain activation of CNS-resident microglia and astrocytes, that produce type 1 interferons (T1 IFNs) which signal through the heterodimeric IFN-α/β receptor (IFNAR) where receptor binding of T1 IFNs activates the JAK/STAT thus inducing IFN-stimulated genes (ISGs) which mediate both pro- and anti-inflammatory functions depending upon the cellular micro-environment. Now consider how aging is linked to elevated & activated leukocyte counts and it becomes clear that this is a patho-biochemical phenocopy to T cell acute lymphoblastc leukaemia (T-ALL) where signaling through Notch, Jak/Stat, PI3K/Akt/mTOR, and MAPK are shared. IL7-induced glucocorticoid resistance is diagnostic of certain subtypes of T-ALL and this is also associated with the senescence associated secretory phenotype of aging-linked morbidity and mortality. Finally, consider that chronic CNS stress leads to increased glucocorticoid production leading to a suppression of cell adhesion protein thus corrupting synaptic plasticity, memory re-formation, and cognitive acuity while promoting sarcopenia by stimulating proteasomal removal of contractile proteins and inhibiting the PI3-kinase/Akt pathway. Glucocorticoids also prevent IL-2 synthesis and secretion thus causing immune suppression by blocking T cell activation. J Neuroinflammation. 2019; 16: 236. Cytokine & Growth Factor Reviews, 22 Apr 2017, 35:85-96 --- Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

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Complete Growth Hormone Guide Part 1

Play Episode Listen Later Nov 3, 2020 32:45

Episode 347 is an updated guide to somatropic hormone and GOD did I go crazy on this one! I honestly want to know more about growth hormone than anyone alive and thus, begins this string of GH based guides! I DID finally discuss the MoA for how GH causes localized fat loss which really had me excited since no one in our industry has EVER talked about this so that definitely was an interesting avenue to go down! Below I am going to reference a lot of the literature for this hormone that I was read through over the past few years on this topic so please DO NOT TAKE MY WORD FOR THIS - READ THESE YOURSELF! Keep in mind this is a brief snippet of every bit of literature on the topic however. REFERENCES Daughaday WH, Rotwein P. Insulin-like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations. Endocr Rev. 1989;10:68–91. [PubMed] [Google Scholar] Jones JI, Clemmons DR. 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(1992) Molecular cloning and expression of the rat β3‐adrenergic receptor. Mol Pharmacol 40: 895– 899. Web of Science®Google Scholar Hollenga, C. H., Zaagsma, J. (1989) Direct evidence for the atypical nature of functional β‐adrenoceptors in rat adipocytes. Br J Pharmacol 98: 1420– 1424. Wiley Online Library CAS PubMed Web of Science®Google Scholar Lacasa, D., Agli, B., Giudicelli, Y. (1985) Direct assessment of β‐adrenergic receptors in intact rat adipocytes by binding of [3H]CGP 12177. Eur J Biochem 146: 339– 346. Wiley Online Library CAS PubMed Web of Science®Google Scholar Umekawa, T., Yoshida, T., Sakane, N., Kondo, M. (1996) Effect of CL316, 243, a highly specific β3‐adrenoceptor agonit, on lipolysis of human and rat adipocytes. Horm Metab Res 28: 394– 396. Crossref CAS PubMed Web of Science®Google Scholar Bojanic, D., Nahorski, SR. (1983) Identification and subclassification of rat adipocyte β‐adrenoceptors using (±)‐[125I]cyanopindolol. Eur J Pharmacol 93: 235– 243. Crossref CAS PubMed Web of Science®Google Scholar Langin, D., Portillo, M., Saulnier‐Blache, J. S., Lafontan, M. (1991) Coexistence of three beta‐adrenergic receptor subtypes in white fat cells of various mammalian species. Eur J Pharmacol 199: 291– 301. Crossref CAS PubMed Web of Science®Google Scholar •••WANT YOUR QUESTION ANSWERED?••• Create a free account at www.theprepcoachforum.com and post up your question in the Mike Arnold PED Q&A open threat! •••SUPPORT OUR PEPTIDE/RESEARCH CHEMS SPONSORS••• (RESEARCH CHEMS) www.maresearchchems.net___use discount code “alex15” to save off your order! (SPECIALTY SUPPS) www.masupps.com___use discount code “alex20” to save off your order! 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Late-Breaking Data in Moderate-to-Severe Atopic Dermatitis

data statement severe allergy asthma moderate dermatology cme rmd atopic dermatitis reachmd cme/ce jak stat allergy and clinical immunology

Play Episode Listen Later Oct 1, 2020

CME credits: 0.25 Valid until: 01-10-2021 Claim your CME credit at https://reachmd.com/programs/cme/late-breaking-data-in-moderate-to-severe-atopic-dermatitis/11797/ Statement of NeedRecent investigations into the underlying mechanisms of atopic dermatitis have revealed the importance of the JAK/STAT pathway and downstream cytokines in driving inflammatory response and AD pathogenesis and have informed the recent development of novel targeted agents. The recent and rapid emergence of new data on novel targeted treatments for moderate-to-severe AD creates a knowledge gap for dermatologists and allergists. These clinicians need to be familiar with the characteristics and latest data associated with targeted agents in clinical development for the treatment of moderate-to-severe AD so that they are prepared to rapidly integrate the agents into clinical practice as they become available.

Moderate-to-Severe Atopic Dermatitis: Expert Insights on Late-Breaking Data in Systemic Treatment

data treatments severe systemic allergy asthma moderate dermatology cme expert insights rmd atopic dermatitis reachmd cme/ce jak stat allergy and clinical immunology

Play Episode Listen Later Oct 1, 2020

CME credits: 0.25 Valid until: 01-10-2021 Claim your CME credit at https://reachmd.com/programs/cme/moderate-to-severe-atopic-dermatitis-expert-insights-on-late-breaking-data-in-systemic-treatment/11796/ Statment of NeedRecent investigations into the underlying mechanisms of atopic dermatitis have revealed the importance of the JAK/STAT pathway and downstream cytokines in driving inflammatory response and AD pathogenesis and have informed the recent development of novel targeted agents. The recent and rapid emergence of new data on novel targeted treatments for moderate-to-severe AD creates a knowledge gap for dermatologists and allergists. As emerging targeted therapies have the potential to become available relatively quickly, dermatologists and allergists must be familiar with the practical considerations associated with using these agents so that they are prepared to integrate these agents into the management of patients with moderate-to-severe AD in a safe and appropriate manner. This activity will bridge the knowledge gap by providing expert perspective on the translation of these data into clinical practice to optimize patient outcomes.

Moderate-to-Severe Atopic Dermatitis: Expert Insights on Late-Breaking Data in Systemic Treatment

data treatments severe systemic allergy asthma moderate dermatology cme expert insights rmd atopic dermatitis reachmd cme/ce jak stat allergy and clinical immunology

Play Episode Listen Later Oct 1, 2020

CME credits: 0.25 Valid until: 01-10-2021 Claim your CME credit at https://reachmd.com/programs/cme/moderate-to-severe-atopic-dermatitis-expert-insights-on-late-breaking-data-in-systemic-treatment/11796/ Statment of NeedRecent investigations into the underlying mechanisms of atopic dermatitis have revealed the importance of the JAK/STAT pathway and downstream cytokines in driving inflammatory response and AD pathogenesis and have informed the recent development of novel targeted agents. The recent and rapid emergence of new data on novel targeted treatments for moderate-to-severe AD creates a knowledge gap for dermatologists and allergists. As emerging targeted therapies have the potential to become available relatively quickly, dermatologists and allergists must be familiar with the practical considerations associated with using these agents so that they are prepared to integrate these agents into the management of patients with moderate-to-severe AD in a safe and appropriate manner. This activity will bridge the knowledge gap by providing expert perspective on the translation of these data into clinical practice to optimize patient outcomes.

Late-Breaking Data in Moderate-to-Severe Atopic Dermatitis

data statement severe allergy asthma moderate dermatology cme rmd atopic dermatitis reachmd cme/ce jak stat allergy and clinical immunology

Play Episode Listen Later Oct 1, 2020

CME credits: 0.25 Valid until: 01-10-2021 Claim your CME credit at https://reachmd.com/programs/cme/late-breaking-data-in-moderate-to-severe-atopic-dermatitis/11797/ Statement of NeedRecent investigations into the underlying mechanisms of atopic dermatitis have revealed the importance of the JAK/STAT pathway and downstream cytokines in driving inflammatory response and AD pathogenesis and have informed the recent development of novel targeted agents. The recent and rapid emergence of new data on novel targeted treatments for moderate-to-severe AD creates a knowledge gap for dermatologists and allergists. These clinicians need to be familiar with the characteristics and latest data associated with targeted agents in clinical development for the treatment of moderate-to-severe AD so that they are prepared to rapidly integrate the agents into clinical practice as they become available.

Leonard H. Calabrese, DO - Mapping the Path to Better Patient Outcomes in Rheumatoid Arthritis and Psoriatic Arthritis: Need-to-Know Information and Practical Guidance About JAK Inhibitors for Advanced Practice Providers

PeerView Internal Medicine CME/CNE/CPE Audio Podcast

Play Episode Listen Later Sep 28, 2020 24:44

Go online to PeerView.com/ZHN860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, an expert in rheumatic diseases discusses strategies to select and optimize treatment for individual patients with RA and PsA, focusing on the appropriate clinical utilization of newer treatment options (ie, JAK inhibitors). Upon completion of this activity, participants will be able to: Outline advances that have improved the quality of care in rheumatic diseases, Explain the role of the JAK/STAT signaling pathway in the pathophysiology of RA and PsA, Summarize efficacy and safety data related to current JAK inhibitors for the treatment of RA and PsA, Treat RA and PsA in accordance with current evidence and guidelines, recognizing the role of non-anti-TNF therapies in patients with active disease, Incorporate JAK inhibitors into treatment plans for individual patients with RA or PsA, recognizing the importance of achieving therapeutic targets and a patient-centered approach to care.

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Leonard H. Calabrese, DO - Mapping the Path to Better Patient Outcomes in Rheumatoid Arthritis and Psoriatic Arthritis: Need-to-Know Information and Practical Guidance About JAK Inhibitors for Advanced Practice Providers

PeerView Clinical Pharmacology CME/CNE/CPE Audio Podcast

Play Episode Listen Later Sep 28, 2020 24:44

Go online to PeerView.com/ZHN860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, an expert in rheumatic diseases discusses strategies to select and optimize treatment for individual patients with RA and PsA, focusing on the appropriate clinical utilization of newer treatment options (ie, JAK inhibitors). Upon completion of this activity, participants will be able to: Outline advances that have improved the quality of care in rheumatic diseases, Explain the role of the JAK/STAT signaling pathway in the pathophysiology of RA and PsA, Summarize efficacy and safety data related to current JAK inhibitors for the treatment of RA and PsA, Treat RA and PsA in accordance with current evidence and guidelines, recognizing the role of non-anti-TNF therapies in patients with active disease, Incorporate JAK inhibitors into treatment plans for individual patients with RA or PsA, recognizing the importance of achieving therapeutic targets and a patient-centered approach to care.

ra explain psa mapping thursday night football jak outline rheumatoid arthritis inhibitors summarize calabrese patient outcomes psoriatic arthritis practical guidance advanced practice providers jak stat leonard h calabrese

Leonard H. Calabrese, DO - Mapping the Path to Better Patient Outcomes in Rheumatoid Arthritis and Psoriatic Arthritis: Need-to-Know Information and Practical Guidance About JAK Inhibitors for Advanced Practice Providers