Podcasts about il4

Comedian, podcaster, author, and MAYORAL HOPEFUL??!?! Corinne Fisher is in the Mad House this week - and she's officially our first politician on the pod!!! Corinne discusses her decision to run for mayor of NYC, as well as her platform, which has many fresh and insightful ideas, like audition-based artist housing, mandatory mental health checks for the NYPD, tax breaks for volunteers, and idk, maybe keeping dollar pizza a dollar LOLL?!?!??Call the FUPA Hotline: (347) 480-9006Check out Corinne's official NYC Mayoral Campaign site:https://www.corinnefisher.com/Follow Corinne:https://www.instagram.com/philanthropygal/?hl=enhttps://www.instagram.com/corinnefisherformayor/Follow Maddy:https://www.instagram.com/somaddysmith/?hl=enhttps://www.tiktok.com/@somaddysmith?lang=enAll tour dates: https://maddysmithcomedy.com/Want more Mad House?!Go to https://gasdigitalnetwork.com/ to subscribe!Use promo code MAD to save big on your membership :)Get early access to our weekly episodes on Tuesdays, along with EXCLUSIVE episodes every Thursday.UPCOMING STAND UP DATES:3/13-3/15 WASHINGTON, DC3/20-3/23 DENVER, CO3/28 CHICAGO, IL4/4-4/5 AUSTIN, TX4/11-4/12 CARY, NCProducer: Caroline MazzeiSee Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Geoffrey Asmus returns to the Mad House, this time with his fellow comedian and cohost of the You're An Idiot Podcast, Alex Dragicevich! Maddy and the guys discuss female sports announcers, outfits on stage, bullshit college majors, changing up the dating pool, and more! Plus, stay tuned to find out who is in better shape, and for a little history trivia!Call the FUPA Hotline: (347) 480-9006Watch Geoffrey's 'Don't Tell' special 'Cancel Culture Isn't Real':https://www.youtube.com/watch?v=d8PByCD7ANEFollow Geoffrey:https://www.instagram.com/geoffreyatm/?hl=enFollow Alex:https://www.instagram.com/alexdrags/?hl=enFollow Maddy:https://www.instagram.com/somaddysmith/?hl=enhttps://www.tiktok.com/@somaddysmith?lang=enAll tour dates: https://maddysmithcomedy.com/Want more Mad House?!Go to https://gasdigitalnetwork.com/ to subscribe!Use promo code MAD to save big on your membership :)Get early access to our weekly episodes on Tuesdays, along with EXCLUSIVE episodes every Thursday.UPCOMING STAND UP DATES:3/13-3/15 WASHINGTON, DC3/20-3/23 DENVER, CO3/28 CHICAGO, IL4/4-4/5 AUSTIN, TX4/11-4/12 CARY, NCProducer: Caroline MazzeiSee Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

No better way to spend our 1-year anniversary of starting Mad House than with the Blue-Eyed Mexican AKA Shane Torres!!! Maddy and Shane discuss the state of comedy, the books they're reading (Shane is shocked Maddy reads), their time together in Amsterdam, tattoos, and more!Call the FUPA Hotline: (347) 480-9006Watch Shane's Special 'The Blue Eyed Mexican':https://www.youtube.com/watch?v=C9mHurqZh_0Follow Shane:https://www.instagram.com/shanetorres/?hl=enFollow Maddy:https://www.instagram.com/somaddysmith/?hl=enhttps://www.tiktok.com/@somaddysmith?lang=enAll tour dates: https://maddysmithcomedy.com/Want more Mad House?!Go to https://gasdigitalnetwork.com/ to subscribe!Use promo code MAD to save big on your membership :)Get early access to our weekly episodes on Tuesdays, along with EXCLUSIVE episodes every Thursday.UPCOMING STAND UP DATES:2/28-3/2 PHOENIX, AZ3/13-3/15 WASHINGTON, DC3/20-3/23 DENVER, CO3/28 CHICAGO, IL4/4-4/5 AUSTIN, TX4/11-4/12 CARY, NCProducer: Caroline MazzeiSee Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Welcome back to another episode of Rinse & Repeat Radio!Another year full of new music & some of the best guests from around the country is coming to your airwaves.For this week's episode - I will be taking over the whole hour with new music from Jake Shore & Henry Fong, Alesso, & Max StylerMake sure to subscribe for new music every Wednesday on both Apple Podcasts & Mixcloud.Episode 203 - Turn it up!Upcoming dates & more - www.cazesthedj.comInstagram/TikTok/Twitter - @cazesthedj**Tracklisting**1.) Adrian Lux X Faithless X Meduza - Teenage Crime (Cazes 2024 Edit)2.) James Hype - Wild3.) Dimitri Vegas & Like Mike & Tiësto & Dido & W&w - Thank You (Ape Rave Club Remix)4.) Max Styler - Kiki5.) David Penn, Offaiah - Satisfied6.) Jake Shore & Henry Fong - Take Control7.) Zerb & The Chainsmokers Feat. Ink - Addicted8.) Baddies Only, Cavalli, Mathieu Ruz - Dame Mas9.) Alesso - Zig Zag10.) Groove Armada (Feat. Stush & Red Rat) - Get Down (Mark Knight Remix)11.) Ivan Gough & Feenixpawl Feat. Georgi Kay X Waves X Anyma, Chris Avantgarde & Massano - In My Mind (Cazes 2024 Vip Edit)12.) Fatboy Slim - Love Island (Crusy Remix)13.) Deeper Purpose, Jalja, Lazy Joe - One By One14.) Diplo & Riva Starr Feat. Kareen Lomax - Heaven Or NotUpcoming Dates4/12 - Good Night John Boy - Cleveland, OH4/13 - Good Night John Boy - Chicago, IL4/18 - American Social - Fort Lauderdale, FL4/27 - Barstool - Nashville, TN

After discussing a few spring news items, Eno and DVR return to their Team Preview series to break down the Twins, Guardians, and Tigers. Will the Twins' position player core take a leap forward with a full season of Royce Lewis at third base? Is the Twins' pitching depth and bullpen good enough to withstand the loss of Sonny Gray from the rotation? How much will the Guardians lean on Kyle Manzardo and Chase DeLauter this season in a bid to improve their run production, and can the Guardians' young starters to take another step forward in 2024? As the Tigers' rebuild continues, are they primed to close the gap and contend for a division title?Rundown0:59 Kodai Senga: Will Begin Season on IL4:46 Mitch Keller: Signs Extension with Pirates7:39 Tim Anderson: Finds New Home in Miami16:11 2024 Minnesota Twins Preview27:33 Can Joe Ryan Find a Quality Secondary Offering?40:35 2024 Cleveland Guardians Preview47:34 Assessing the Draft-Day Value in the Guardians' Top-Four Starters55:28 2024 Detroit Tigers Preview1:06:55 Buying Reese Olson's Improved Changeup?Follow Eno on Twitter: @enosarrisFollow DVR on Twitter: @DerekVanRipere-mail: ratesandbarrels@theathletic.comJoin our Discord: https://discord.gg/r9u5jBvVCheck out our YouTube page: https://www.youtube.com/c/ratesbarrels and join us on Fridays at 1p ET/10a PT for our new livestream episodes w/Trevor May!Subscribe to The Athletic for just $2/month for the first year: theathletic.com/ratesandbarrels Hosted on Acast. See acast.com/privacy for more information.

Bienvenue dans notre série de podcasts Derm'Action, dans laquelle nous allons vous aider à mieux comprendre la dermatite atopique pour mieux la soigner.Dans l'épisode d'aujourd'hui, nous allons nous intéresser au rôle et à la place des interleukines IL4 & IL13 dans la dermatite atopique.Pour aborder ce sujet, le Dr Michel Piot, allergologue dans une unité d'allergologie au centre hospitalier de Pau, s'est entretenu au micro de Juliette de Noiron, rédactrice médicale.Bonne écoute! Hébergé par Acast. Visitez acast.com/privacy pour plus d'informations.

If you listen to the recording, the featured background audio is an original track of my 18-month-old daughter crying. I think you can still hear me just fine. I promise she was okay and was being supervised. No wonder why Elon wants everyone back in the office!Shares of Okta traded up 5% today closing at $98.38. Year-to-date, shares are down 55% and the next twelve-month enterprise value to revenue (NTM EV/R) has dropped from 28 in July 2021 to 7.6 today.That’s a 76% contraction in NTM EV/S multiple.Since Okta’s IPO in April, 2017 the shares have increased from $23.51 to 98.38, a compound annual growth rate (CAGR) of 31% which would have turned a $10,000 investment into $40,000, beating the SPY CAGR of 13% over the same period.Okta is currently trading at a trailing-twelve-month (TTM) EV/R of 10.8, roughly 20% higher than its all-time low of 9.0 in 2017.Revenue per share (which takes into account share dilution due to acquisitions and stock-based compensation) has grown 30% per year since IPO and analysts are expecting revenue per share to grow roughly 32% per year from FY 23 to FY 25. This could either be an incredible buying opportunity or a falling knife.. so lets dive in. Subscribe for free and make sure you are a Smart SaaS InvestorOkta First Quarter Fiscal Year 2023 Financial Results“We delivered solid first-quarter results highlighted by strength in new customer additions, dollar-based net retention rate, and the success we’re having with large customers as they continue their journey to the cloud,” - Todd McKinnon, Chief Executive Officer and co-founder of Okta.First Quarter Fiscal 2023 Financial Highlights:Revenue: Total revenue was $415 million, an increase of 65% year-over-year. This beat analyst expectations by $26 million or roughly 6.7%. Subscription revenue was $398 million, an increase of 66% year-over-year. Organic revenue grew 39%.Remaining Performance Obligations (RPO): RPO, or subscription backlog, was $2.71 billion, an increase of 43% year-over-year. cRPO, which is contracted subscription revenue expected to be recognized over the next 12 months, was $1.41 billion, up 57% compared to the first quarter of fiscal 2022.GAAP Net Loss: GAAP net loss was $243 million, compared to a GAAP net loss of $109 million in the first quarter of fiscal 2022. GAAP net loss per share was $1.56, compared to a GAAP net loss per share of $0.83 in the first quarter of fiscal 2022.Non-GAAP Net Loss: Non-GAAP net loss was $43 million, compared to non-GAAP net loss of $13 million in the first quarter of fiscal 2022. Non-GAAP basic and diluted net loss per share was $0.27, compared to non-GAAP basic and diluted net loss per share of $0.10 in the first quarter of fiscal 2022. This beat analyst expectations by $0.07 or 20%.Cash Flow: Net cash provided by operations was $19 million, or 5% of total revenue, compared to net cash provided by operations of $56 million, or 22% of total revenue, in the first quarter of fiscal 2022. Free cash flow was $11 million, or 3% of total revenue, compared to $53 million, or 21% of total revenue, in the first quarter of fiscal 2022.Cash, cash equivalents, and short-term investments were $2.49 billion at April 30, 2022.Financial Outlook:For the second quarter of fiscal 2023, the Company expects:Total revenue of $428 million to $430 million, representing a growth rate of 36% year-over-year. This beat analyst expectations of $423 million by $6 million or 1.4%.Current RPO of $1.48 billion to $1.49 billion, representing a growth rate of 35% to 36% year-over-year;Non-GAAP operating loss of $44 million to $43 million; andNon-GAAP net loss per share of $0.32 to $0.31, assuming weighted-average shares outstanding of approximately 156 million. This beat analyst expectations by $0.02.For the full-year fiscal 2023, the Company now expects:Total revenue of $1.805 billion to $1.815 billion, representing a growth rate of 39% to 40% year-over-year. This beat analyst expectations by $30 million or 1.7%.Non-GAAP operating loss of $167 million to $162 million; andNon-GAAP net loss per share of $1.14 to $1.11, assuming weighted-average shares outstanding of approximately 157 million. This beat analyst expectations by $0.12 or 9.6%.If you love this research. please share it!Management Commentary: Todd McKinnon, Co-Founder, Chairman & CEO On the Lapsus$ security hack in Q4 While we've done a lot of analysis, it's difficult to attribute any quantifiable impact on our solid Q1 results. When looking at key indicators, our competitive win rates and renewal rates have remained strong. In Q1, RPO grew 43% and current RPO grew 57%. Total revenue grew 65% and Okta standalone revenue grew 39%. New customer additions remain strong at 800, bringing our total customer base to 15,800, representing growth of 48%. We also continue to do well with large customers.Notable customer winA Fortune 500 insurance company was a great Okta SIEM and Workforce win. What's more, this customer was sourced through the AWS Marketplace, which has been doing well for Okta since we became available there in late 2020. The company sought best-of-breed tools to modernize the organization's aging IT infrastructure. Their legacy on-prem tools lack the capacity and stability to meet the needs of the business. Okta will provide a cloud-native identity solution to support their modernization efforts, while also addressing their on-prem infrastructure needs with Okta Access Gateway.Management Commentary: Brett Tighe, CFOOn dollar-based net retention rateOur dollar-based net retention rate for the trailing 12-month period remains strong at 123%. This was driven by the strong upsell motion we are seeing with our existing customers across both Okta and Auth0 as they expand on both products and users.On FY 26 financial goalsOur long-term financial goals anchor on at least $4 billion of revenue in FY '26 with organic growth of at least 35% each year and 20% free cash flow margin in FY '26. To achieve these targets, we will continue to scale the company from a people and processes standpoint, including investing in talent across all areas of the company as well as in systems to prepare us for the next phase of growth.Investor Q & AOn the future of identity and federal/department of defense interestJust yesterday, we had the global CIO of one of the major branches of the DoD in our office with his entire executive team talking to us for the entire day about the future of identity and what it was going to look like. And I mean these are just the kinds of conversations, frankly, that regardless of what happened in Q1 with that security event or not, we were not having these conversations 6 or 12 months ago, and I think it portends very well for the future.The federal government opportunity is a massive one for us.Federal was the biggest deal of our quarter this year -- this quarter in terms of ARR. And that federal division was specifically focused on customer identity and access management. And you really see that the government is thinking about how they can adopt more of these modern solutions for a lot of their forward-thinking initiatives. You -- we've been working for a long time on bolstering up our federal capabilities. And we've got -- we've been FedRAMP Medium, Moderate for some time. We've got FedRAMP High and IL4 that are scheduled for this summer.Austin’s takeawaysThis was a strong quarter considering the macro fears and Okta’s security incident in Q1Management seems confident and excited about both international and federal opportunitiesManagement reiterated FY26 goal of $4 billion in revenue with 35% organic growth and 20% free cash flow margin representing a score of 55 on the rule of 40This is on my watchlist due to its low multiple, important market, and growth expectations but I’m hesitant to start a position because of questions around profitability at scale. I have no position in Okta at the time of this writing.Paying members are always first to find out what I’m buying (before I buy it)Price Multiples, FY 18 - FY 22 Results, & FY 23 - FY 27 analyst expectationsPaying members have access to my live database that has these spreadsheets for all of the companies I follow. Access it at this link This is a public episode. If you’d like to discuss this with other subscribers or get access to bonus episodes, visit austin.substack.com/subscribe

ENERGY....there are so many ways to use it trap it,save it conserve it waste it. Our guests today are organizing the 32nd Annual Energy Fair in Crestone Colorodo, the longest running sustainable energy fair in the country. If there was one industry that needs help with its energy footprint it's Cannabis we will talk with the Organizers Nick Nevares Lisa Bodey and advisor Donovan Spitzman and see what trends may help Cannabis and also get a little insight into why Crestone is the hub to all of these like minded people with a focus on self sustainability. Speaking of which we will be getting someone one step closer to self sustainability by giving away a new illuminar IL4 clone lamp to a lucky winner. This will be the first giveaway this month we will be giving away a far red ILOGIC 8 at the end of the month so make sure you send a message why you NEED a Iluminar light in your life and don't forget to include your phone number so we can call ya please send entries to dunndeal@adamdunnshow.com to get a chance to win that lamp. So clean up that bong , charge that E Rig and roll those joints and join us on YouTube.com/adamdunnshow this fri 8/6/21 4:20 - 7:10MT #crestoneenergyfair #sagemastaselect #area420 #iluminargiveaway #seedsherenow #ilumonthar

Keke Fairfax joins Immune to discuss the work from her laboratory on understanding how maternal schistosomiasis impairs IL-4 production and B cell expansion in offspring, and modulation of macrophage immunometabolism by helminths. Hosts: Vincent Racaniello, Stephanie Langel, Cynthia Leifer, and Brianne Barker Guest: Keke Fairfax Subscribe (free): iTunes, Google Podcasts. RSS, email Become a patron of Immune! Links for this episode Maternal schistosomiasis impairs offspring immunity (PloS Path) Helminth modulation of macrophage immunometabolism (Immune) Time stamps by Jolene. Thanks! Music by Steve Neal. Immune logo image by Blausen Medical Send your immunology questions and comments to immune@microbe.tv

Investigating the anti-hypertensive effects of pumpkin seed oil Marymount University and University of Guilan (Iran), September 29, 2021 In a study, researchers from Iran and the U.S. found that pumpkin seed oil can potentially treat hypertension in postmenopausal women. Their report was published in Complementary Therapies in Clinical Practice. Postmenopausal women are more likely to develop hypertension than men of the same age. In vivo studies reveal that pumpkin seed oil has anti-hypertensive activity. The team investigated the effects of pumpkin seed oil supplementation on vascular function and heart rate variability in postmenopausal women with elevated blood pressure. Participants were assigned to take either a pumpkin seed oil supplement or a placebo for the six-week study. Those in the experimental group took 3 grams of pumpkin seed oil every day. Brachial and central blood pressure, wave reflection (augmentation index, AIx), arterial stiffness (SI) and various HRV parameters were measured at baseline and at the end of the study. Those who took pumpkin seed oil had significantly lower AIx, brachial and systolic blood pressure after treatment. SI and HRV parameters remained unchanged for the treatment group and the placebo group at the end of the study. In sum, taking pumpkin seed oil may improve arterial hemodynamics in postmenopausal women.     Health benefits of evening classes revealed   Oxford University, September 20, 2021    Those with a taste for adult education classes have long known it, but now Oxford University scientists have confirmed that taking part in the weekly sessions can boost wellbeing – regardless of the subject studied.   In partnership with the Workers' Educational Association (WEA), the largest voluntary sector provider of adult education in England and Scotland, a team from Oxford's department of experimental psychology studied attendees at seven separate day-time adult education classes. Their findings are published in a series of papers.   Each class took place over seven months and included a break in the middle. Attendees completed questionnaires before and after their class three times over the seven months: at the beginning of their courses, after 3 months, and at the end of the seven months. Participants were involved in one of three activities: singing, crafts or creative writing.   Overall, attendees at all seven classes had improved mental and physical health and reported more satisfaction with their lives at the end of their courses.   Dr Eiluned Pearce led the research. She said: 'The students reported benefits including increased self-confidence, a greater feeling of control over their lives and more willingness to take on new challenges. Some said the classes made them more motivated to be more active, despite the classes not specifically involving physical activity.   'Participants also said that the classes broadened their networks of friends and gave them an increased sense of belonging. We also found that the more someone felt part of their group, the more their health and wellbeing improved.' An intriguing finding was in the singing and creative writing classes. Building on the results of an earlier paper from the same study, which found that people in singing classes felt closer to their group more quickly than those in the other classes, the team looked at how relationships formed between individuals in the classes.   Each person was asked to name those other people in the class whose name they could remember, whether or not they felt connected to each person they named, and whether they had talked to that person during class.   Dr Pearce said: 'The results showed that those in the singing and creative writing groups built up relationships with other individuals more quickly than the crafters, and singers felt more connected to the class as a whole more quickly than both the other groups. 'While this confirms our earlier finding that singing has an 'ice-breaker effect' compared to other activities, it shows that other activities may enable people to increase their social networks just as much, even if it takes them longer to feel connected to their group as a whole.'   Co-author Dr Jacques Launay adds: 'While much of our previous work has demonstrated the importance of music, it is likely that the most socially bonding activities are always those that are personally chosen and enjoyed. This research adds to growing support for the relevance of creative activities in creating happy communities and improving health and well-being, with consequent benefits for public services and society.'   Dr Pádraig Mac Carron, Dr Anna Machin and Professor Robin Dunbar were also involved in the research.   Howard Croft, WEA Regional Education Manager, said: 'The findings reiterate the feedback that we have had from our students over the years: learning is a fantastic way to boost your self-esteem and confidence. Also of note, is its therapeutic effect. For many students, creative courses are a means of finding a new outlet for expressing their feelings. This can be of immense help during times of personal difficulty or emotional upheaval, such as divorce or bereavement. Simply going to a course can offer much-needed respite.   'For others, learning can be an opportunity to reignite a former passion. This could be anything from a subject which you enjoyed at school to an area which you are interested in. Whatever your reason, there are so many benefits to be gained by signing up to a course.'       Want to live forever? Theoretically, you could, study says Swiss Federal Institute of Technology, September 29, 2021 Humans can probably live to at least 130, and possibly well beyond, though the chances of reaching such super old age remain vanishingly small, according to new research. The outer limit of the human lifespan has long been hotly debated, with recent studies making the case we could live up to 150 years, or arguing that there is no maximum theoretical age for humans. The new research, published Wednesday in the Royal Society Open Science journal, wades into the debate by analyzing new data on supercentenarians—people aged 110 or more—and semi-supercentenarians, aged 105 or more. While the risk of death generally increases throughout our lifetime, the researchers' analysis shows that risk eventually plateaus and remains constant at approximately 50-50. "Beyond age 110 one can think of living another year as being almost like flipping a fair coin," said Anthony Davison, a professor of statistics at the Swiss Federal Institute of Technology in Lausanne (EPFL), who led the research. "If it comes up heads, then you live to your next birthday, and if not, then you will die at some point within the next year," he told AFP. Based on the data available so far, it seems likely that humans can live until at least 130, but extrapolating from the findings "would imply that there is no limit to the human lifespan," the research concludes. The conclusions match similar statistical analyses done on datasets of the very elderly. "But this study strengthens those conclusions and makes them more precise because more data are now available," Davison said. The first dataset the team studied is newly released material from the International Database on Longevity, which covers more than 1,100 supercentenarians from 13 countries. The second is from Italy on every person who was at least 105 between January 2009 and December 2015. 'One in a million' The work involves extrapolating from existing data, but Davison said that was a logical approach. "Any study of extreme old age, whether statistical or biological, will involve extrapolation," he said. "We were able to show that if a limit below 130 years exists, we should have been able to detect it by now using the data now available," he added. Still, just because humans can theoretically reach 130 or beyond, doesn't mean we're likely to see it anytime soon. For a start, the analysis is based on people who have already achieved the relatively rare feat of making it to well over 100. And even at age 110, your chances of making it to 130 are "about one in a million... not impossible but very unlikely," said Davison. He thinks we could see people reaching 130 within the century, as more people make it to supercentenarian status, increasing the chances of one becoming that one in a million. "But in the absence of major medical and social advances, ages much over this are highly unlikely ever to be observed," he added. For now, the oldest person on record is Frenchwoman Jeanne Calment, who died in 1997 at the confirmed age of 122. Her true age was the subject of some controversy, with claims of a possible fraud, but in 2019 several experts said a review of the evidence confirmed her age. Other pretenders to the throne of oldest person ever have a long way to go. The oldest verified living person in the world is Japan's Kane Tanaka, a comparatively youthful 118.     Psychological treatment shown to yield strong, lasting pain relief, alter brain networks University of Colorado, September 29, 2021 Rethinking what causes pain and how great of a threat it is can provide chronic pain patients with lasting relief and alter brain networks associated with pain processing, according to new University of Colorado Boulder-led research. The study, published Sept. 29 in JAMA Psychiatry, found that two-thirds of chronic back pain patients who underwent a four-week psychological treatment called Pain Reprocessing Therapy (PRT) were pain-free or nearly pain-free post-treatment. And most maintained relief for one year. The findings provide some of the strongest evidence yet that a psychological treatmentcan provide potent and durable relief for chronic pain, which afflicts one in five Americans. "For a long time we have thought that chronic pain is due primarily to problems in the body, and most treatments to date have targeted that," said lead author Yoni Ashar, who conducted the study while earning his Ph.D. in the Department of Psychology and Neuroscience at CU Boulder. "This treatment is based on the premise that the brain can generate pain in the absence of injury or after an injury has healed, and that people can unlearn that pain. Our study shows it works." Misfiring neural pathways Approximately 85% of people with chronic back pain have what is known as "primary pain," meaning tests are unable to identify a clear bodily source, such as tissue damage. Misfiring neural pathways are at least partially to blame: Different brain regions—including those associated with reward and fear—activate more during episodes of chronic pain than acute pain, studies show. And among chronic pain patients, certain neural networks are sensitized to overreact to even mild stimuli. If pain is a warning signal that something is wrong with the body, primary chronic pain, Ashar said, is "like a false alarm stuck in the 'on' position." PRT seeks to turn off the alarm. "The idea is that by thinking about the pain as safe rather than threatening, patients can alter the brain networks reinforcing the pain, and neutralize it," said Ashar, now a postdoctoral researcher at Weill Cornell Medicine.or the randomized controlled trial, Ashar and senior author Tor Wager, now the Diana L. Taylor Distinguished Professor in Neuroscience at Dartmouth College, recruited 151 men and women who had back pain for at least six months at an intensity of at least four on a scale of zero to 10. Those in the treatment group completed an assessment followed by eight one-hour sessions of PRT, a technique developed by Los Angeles-based pain psychologist Alan Gordon. The goal: To educate the patient about the role of the brain in generating chronic pain; to help them reappraise their pain as they engage in movements they'd been afraid to do; and to help them address emotions that may exacerbate their pain.  Pain is not 'all in your head' "This isn't suggesting that your pain is not real or that it's 'all in your head'," stressed Wager, noting that changes to neural pathways in the brain can linger long after an injury is gone, reinforced by such associations. "What it means is that if the causes are in the brain, the solutions may be there, too." Before and after treatment, participants also underwent functional magnetic resonance imaging (fMRI) scans to measure how their brains reacted to a mild pain stimulus. After treatment, 66% of patients in the treatment group were pain-free or nearly pain-free compared to 20% of the placebo group and 10% of the no-treatment group. "The magnitude and durability of pain reductions we saw are very rarely observed in chronic pain treatment trials," Ashar said, noting that opioids have yielded only moderate and short-term relief in many trials. And when people in the PRT group were exposed to pain in the scanner post-treatment, brain regions associated with pain processing—including the anterior insula and anterior midcingulate —had quieted significantly. The authors stress that the treatment is not intended for "secondary pain"—that rooted in acute injury or disease. The study focused specifically on PRT for chronic back pain, so future, larger studies are needed to determine if it would yeild similar results for other types of chronic pain.  Meanwhile, other similar brain-centered techniques are already ememrging among physical therapists and other clinicians who treat pain. "This study suggests a fundamentally new way to think about both the causes of chronic back pain for many people and the tools that are available to treat that pain," said co-author Sona Dimidjian, professor of psychology and neuroscience and director of the Renee Crown Wellness Institute at CU Boulder. " It provides a potentially powerful option for people who want to live free or nearly free of pain."     Citicoline (CDP-choline) and Memory Function in Healthy Older Adults: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial  Kyowa Hakko Bio (Japan), September 2021 Supplementation of citicoline (CDP-choline), a naturally occurring mononucleotide, has shown beneficial effects on memory function and behavior in populations with a wide range of impairments. However, few studies have investigated its effect in healthy older populations. Objective The objective of this study was to investigate the effects of citicoline, on memory in healthy elderly populations with age-associated memory impairment (AAMI). Methods A total of 100 healthy men and women aged between 50 and 85 y with AAMI participated in this randomized, double-blind, placebo-controlled trial. Participants were randomized to receive placebo (n = 51) or citicoline (n = 49; 500 mg/d) for 12 wk. Memory function was assessed at baseline and end of the intervention (12 wk) using computerized tests (Cambridge Brain Sciences, Ontario, Canada). Safety measurements included adverse events query, body weight, blood pressure, and hematology and metabolic panel. Intent-to-treat analysis was conducted using ANCOVA for the primary and secondary outcome variables with Bonferroni correction for multiple comparisons. Results A total of 99 out of 100 participants completed the study in its entirety. After the 12-wk intervention, participants supplemented with citicoline showed significantly greater improvements in secondary outcomes of episodic memory (assessed by the Paired Associate test), compared with those on placebo (mean: 0.15 vs. 0.06, respectively, P = 0.0025). Composite memory (secondary outcome), calculated using the scores of 4 memory tests, also significantly improved to a greater extent following citicoline supplementation (mean: 3.78) compared with placebo (mean: 0.72, P = 0.0052). Conclusions Dietary supplementation of citicoline for 12 wk improved overall memory performance, especially episodic memory, in healthy older males and females with AAMI. The findings suggest that regular consumption of citicoline may be safe and potentially beneficial against memory loss due to aging.      Sleep may strengthen long-term memories in the immune system   University of Tuebingen (Germany) September 29, 2021   More than a century ago, scientists demonstrated that sleep supports the retention of memories of facts and events. Later studies have shown that slow-wave sleep, often referred to as deep sleep, is important for transforming fragile, recently formed memories into stable, long-term memories. Now, in an Opinion article published  in Trends in Neurosciences, part of a special issue on Neuroimmunology, researchers propose that deep sleep may also strengthen immunological memories of previously encountered pathogens.   "While it has been known for a long time that sleep supports long-term memoryformation in the psychological domain, the idea that long-term memory formation is a function of sleep effective in all organismic systems is in our view entirely new," says senior author Jan Born of the University of Tuebingen. "We consider our approach toward a unifying concept of biological long-term memory formation, in which sleep plays a critical role, a new development in sleep research and memory research."   The immune system "remembers" an encounter with a bacteria or virus by collecting fragments from the bug to create memory T cells, which last for months or years and help the body recognize a previous infection and quickly respond. These memory T cells appear to abstract "gist information" about the pathogens, as only T cells that store information about the tiniest fragments ever elicit a response. The selection of gist information allows memory T cells to detect new pathogens that are similar, but not identical, to previously encountered bacteria or viruses.   Studies in humans have shown that long-term increases in memory T cells are associated with deep slow-wave sleep on the nights after vaccination. Taken together, the findings support the view that slow-wave sleep contributes to the formation of long-term memories of abstract, generalized information, which leads to adaptive behavioral and immunological responses. The obvious implication is that sleep deprivation could put your body at risk.   "If we didn't sleep, then the immune system might focus on the wrong parts of the pathogen," Born says. "For example, many viruses can easily mutate some parts of their proteins to escape from immune responses. If too few antigen-recognizing cells [the cells that present the fragments to T cells] are available, then they might all be needed to fight off the pathogen. In addition to this, there is evidence that the hormones released during sleep benefit the crosstalk between antigen-presenting and antigen-recognizing cells, and some of these important hormones could be lacking without sleep."   Born says that future research should examine what information is selected during sleep for storage in long-term memory, and how this selection is achieved. In the end, this research could have important clinical implications.   "In order to design effective vaccines against HIV, malaria, and tuberculosis, which are based on immunological memory, the correct memory model must be available," Born says. "It is our hope that by comparing the concepts of neuronal and immunological memory, a model of immunological memory can be developed which integrates the available experimental data and serves as a helpful basis for vaccine development."         Standardized astragalus extract for attenuation of the immunosuppression induced by strenuous physical exercise: randomized controlled trial University of Physical Sciences (Poland), September 3, 2021 This paper aimed to verify how a supplementation of rower's diet with Astragalus Membranaceus Root (AMR) modulated their immune system response to maximal physical exertion. Methods The double-blind study included 18 members of the Polish Rowing Team assigned to the supplemented group (n = 10), and the placebo group (n = 8). The participants performed a 2000 m test on a rowing ergometer at the beginning and at the end of the six-week of intensive training camp during which the supplemented group received 500 mg of AMR. Blood samples were obtained prior to, 1 min after completing, and 24 h after the exertion test. The levels of interleukin 2 (IL2), interleukin 4 (IL4), interleukin 10 (IL10), interferon ɤ (IFN-ɣ), and lactic acid were determined. Subpopulations of T regulatory lymphocytes [CD4+/CD25+/CD127−] (Treg), cytotoxic lymphocytes [CD8+/TCRαβ+] (CTL), natural killer cells [CD3−/CD16+/CD56+] (NK), and TCRδγ-positive cells (Tδγ) were determined with flow cytometry. Results After the camp, the initial NK and Treg levels sustained at the baseline, while Tδγ counts increased relative to the levels in the placebo group. In the supplemented subgroup, a decrease in IL2 level in reaction to maximal exertion clearly deepened while the change in IL-2/IL-10 level induced by the recovery after this exertion clearly increased, relative to the changes in the placebo group. Conclusions AMR restored the immunological balance in strenuously trained athletes through a stabilization of NK and Treg cells with a positive trend in Tδγ towards Th1 response during restitution by cytokine IL2 modulation.

TWiP solves the case of the Long Island Man with Unilateral Eye Pain, followed by a discussion of how enteric helminth coinfection enhances host susceptibility to West Nile virus by a tuft cell-IL-4 receptor signaling axis. Hosts: Vincent Racaniello, Dickson Despommier, and Daniel Griffin Guest: Christina Naula Subscribe (free): iTunes, Google Podcasts, RSS, email Links for this episode PWB on Facebook, Instagram, Twitter Helminth infection enhances West Nile viruses pathogenesis (Cell) Hero: Franz Von Lichtenberg Letters read on TWiP 194 Become a patron of TWiP Case Study for TWiP 194 Woman in 40s, on return from Puerto Rico where she often went. Went to local beaches, brought their dogs. Noticed problem on foot, raised red serpiginous lines, slowly moving all over the foot. Bloodwork showed elevated eosinophils.  Send your case diagnosis, questions and comments to twip@microbe.tv Music by Ronald Jenkees

2019 is a wrap. Guardrail had ourselves a pretty neat year. So we sat down at Ken's apartment, used some brand new mics, drank a bunch of wine and White Claws, and talked about it. We do a little Snuzfest recap, talk about our favorite shit from 2019, our recording process for the new EP, and naturally a lot of other nonsense. Happy 2020! Upcoming Guardrail shows:2/15 - Bos Meadery - Madison, WI2/19 - TBA - Chicago, IL3/6 - The 105 - Naperville, IL3/12 - Burlington - Chicago, IL4/24 - TBA - Chicago, IL SOL Best of 2019 Spotify Playlist:https://open.spotify.com/user/122646372/playlist/0yoPBAan4aqcDpj9FZnjqc?si=hHJKY_F5RIKMlOOUCePSHA Sponsor:DicksByMail.com Music:I played a lot in the background, but listen to Til Morning, The Magnifiers, Glory Days, Late Nights, Bad Planning, Zombie Schoolboy, Baggage, Zebrahead, Rival Sons, Miss Vincent, Tightwire, Calling All Captains, Kayak Jones, The Copyrights, Kepi Ghoulie, Bayside, PUP, blink-182, Bilmuri, Stray From The Path, and of course Guardrail. Theme: “Throw Me To The Lions” by Alkaline TrioClosing theme: “I Got Another Girl Pregnant” by Guardrail www.facebook.com/SOLpodcast666www.facebook.com/GuardrailChicago

Hosts: Vincent Racaniello, Dickson Despommier, and Daniel Griffin The TWiPyzoites solve the case of the Uncommon Parasite, and discuss the role of eosinophils in promoting the growth of Trichinella in skeletal muscle.   Links for this episode: Eosinophils and IL-4 support nematode growth (PLoS Path) Balantidiasis (CDC) Letters read on TWiP 102  Case study for TWiP 102 This week's case involves a 24 yo housewife, from a village outside of Calcutta. Comes into a tertiary care hosp, 6 months coughing up blood, fever, no weight loss. Drinks rainwater, milks her cow. Dogs everywhere, no livestock except cows. Eats meat, well cooked. No extramarital encounters. Husband well. 4 children. Cistern for drinking water is covered.  No health issues. Reports salty, clear mucus. No blood in stool, no changes in stool. Exam: looks healthy, lungs clear. Lab tests: White count of 9000, 12% eosinophils (elevated). So she has eosinophilia. Chest X-ray and CT: lesion on left side in xray. CT: shows 4 cm cavity, with air pocket on left side, mid-lung. HIV negative. Dusty soil, birds. Send your diagnosis to twip@microbe.tv Send your questions and comments to twip@microbe.tv

Vincent and Dickson discuss how infection of mice with helminths induces cytokines that reactivate a latent gamma-herpesvirus. Hosts: Vincent Racaniello and Dickson Despommier Links for this episode: Helminths reactivate herpesvirus (Science) How helminths go viral (Science) Herpesvirus latency protects from bacterial infection (Nature) Image credit Letters read on TWiP 76 Contact Send your questions and comments (email or mp3 file) to twip@twiv.tv Subscribe Subscribe to TWiP (free) in iTunes, by the RSS feed or by email

The first genome wide association study (GWAS) for childhood asthma identified a novel major susceptibility locus on chromosome 17q21 harboring the ORMDL3 gene, but the role of previous asthma candidate genes was not specifically analyzed in this GWAS. We systematically identified 89 SNPs in 14 candidate genes previously associated with asthma in >3 independent study populations. We re-genotyped 39 SNPs in these genes not covered by GWAS performed in 703 asthmatics and 658 reference children. Genotyping data were compared to imputation data derived from Illumina HumanHap300 chip genotyping. Results were combined to analyze 566 SNPs covering all 14 candidate gene loci. Genotyped polymorphisms in ADAM33, GSTP1 and VDR showed effects with p-values

Background: The interleukin (IL) 4/IL13 pathway is involved in the regulation of IgE production associated with atopic diseases. Numerous polymorphisms have been identified in the coding region of the IL4 receptor alpha chain (IL4Ra) and previous association studies have shown conflicting results. Based on their putative functional role, polymorphisms A148G, T1432C and A1652G, located in the coding region of IL4Ra, were selected for association and haplotype studies in a large German population sample (n = 1,120). Methods: Genotyping was performed using allele-specific PCR and restriction-enzyme-based assays. Haplotypes were estimated, and population-derived IgE percentiles (50% IgE >60 IU/ml, 66% IgE >115 IU/ml and 90% IgE >457 IU/ml) were calculated as outcome variables in a haplotype trend regression analysis. Results: In our population, only polymorphism T1432C showed a trend for a protective effect against atopic rhinitis ( odds ratio, OR: 0.52, 95% confidence interval, CI: 0.26 - 1.02, p = 0.05). When haplotypes were calculated, one haplotype was significantly associated with elevated serum IgE levels at the 50th percentile ( OR 1.60, 95% CI 1.08 - 2.37, p = 0.02). Conclusions: These data indicate that IL4Ra polymorphisms, although suggested to be functionally relevant by in vitro studies, have only a minor influence on IgE regulation in our large population sample. Copyright (C) 2004 S. Karger AG, Basel.

Die vorliegende Arbeit beschäftigt sich mit neuen Ansätzen zur Immuntherapie von B-Zell-Lymphomen. Als Mausmodell wurden das Lymphom A20 und der eher leukämisch wachsende BCL1-Tumor verwendet. Alle Zellen eines B-Zell-Lymphoms produzieren einen identischen Antikörper, den sogenannten Idiotyp, der als tumorspezifisches Antigen benutzt werden kann: Die antigenbindenden variablen Regionen von schwerer und leichter Kette sind für die Tumorzellen jedes Patienten spezifisch. Die variablen Regionen lassen sich mit einem flexiblen Linker-Peptid zu single-chain Fragmenten (scFv) fusionieren. Die Antigenbindung und die Struktur als Tumorantigen bleiben dabei erhalten. Die BCL1-Sequenz war bereits bekannt, sie ließ sich mit Hilfe familienspezischer Primer mit PCR amplifizieren und klonieren. Bei der stark hypermutierten Sequenz des A20-Idiotyps versagte das Standardverfahren der Konsensus-Primer, erst eine 5'-RACE-PCR war erfolgreich. Der optimale Effektormechanismus (humoral, CD4 oder CD8 vermittelt) zur Immuntherapie von Lymphomen ist nicht bekannt. Bei DNA-Vakzinen lässt sich die Immunantwort besonders effektiv modulieren. Hier wurde ein System entwickelt, um rasch die Wirksamkeit verschiedener Kombinationen in vivo untersuchen zu können: Der scFv-Idiotyp wurde mit einem Zytokin (IL1beta, IL4, IL12, GM-CSF oder Flt3 ligand) und/oder einem Adjuvans (Tetanus Toxin Fragment C oder HBsAg) gekoppelt. In vitro wurde die Expression, die Faltung des scFv und die biologische Aktivität bestätigt. Neben der spezifischen Zytokinwirkung stabilisieren die Fusionspartner die scFv-Proteine deutlich. Zunächst wurde mit dem Modellantigen HBsAg die Immunisierungstechnik optimiert: Intradermale Plasmid-Injektion in die Ohr Pinna ergab konsistent hohe Antikörper-Titer. Bereits ohne in vitro-Restimulation konnte eine starke zelluläre Antwort nachgewiesen werden. Weiterhin wurde für die beiden Tumormodelle A20 und BCL1 die Wachstumskinetik invivo bestimmt und ein Pilotversuch (32 Tiere) mit drei ausgewählten Konstrukten durchgeführt: Von sechs splenektomierten Mäusen zeigte nur eine nach zwei Immunisierungen eine spezifische zelluläre Antwort gegen A20. In keiner Versuchsgruppe zeigte sich eine signifikante Lebensverlängerung nach Lymphomchallenge. Zusammenfassend ist erstmalig ein System entwickelt worden, das es auf einfache Weise ermöglicht, die Wirksamkeit von verschiedenen Zytokinen und Adjuvantien zur Idiotyp-Vakzinierung zu untersuchen. Dieses System bietet viel Raum für Optimierungen.

Im Rahmen der hier vorliegenden Arbeit über die Organisation und Regulation der Faktor HGenfamilie wurden folgende drei Themenkomplexe bearbeitet: Zur Aufklärung der genomischen Organisation der HF-Genfamilie wurden humane Mega YACund BAC-Klone mittels Restriktionsanalyse, Southernblothybridisierung, PCR und Sequenzierung analysiert. Alle Gene der Faktor H-Familie HF1- 5 konnten auf diesen Klonen lokalisiert werden, d.h. diese Genfamilie liegt zusammen auf einem DNS-Abschnitt von ca. 400 kb auf Chromosom 1q32. Weitere HF1-verwandte Genabschnitte wurde identifiziert, die in die Nähe von HF3, HF5 und F13B lokalisiert wurden. Flankierend zur Faktor H-Genfamilie wurden die Gene für F13B und PCP-2 kartiert. Die Gene können wie folgt von telomer nach zentromer angeordnet werden: PCP-2, HF1, HF4, HF2, HF5 gefolgt von HF3/HF6/F13B, deren Orientierung nicht eindeutig festgelegt werden konnte. Die Häufung der HF-Gene auf einem DNS-Abschnitt und deren Anordnung in Tandem- Orientierung läßt vermuten, daß diese Genfamilie ihren Ursprung in Genduplikation hat. In dieser chromosomalen Region werden Rekombinations-Hotspots vermutet, die eine erhöhte Rekombinationsfrequenz verursachen infolge derer Duplikationen entstehen können. Durch Fehler bei der Rekombination kann es jedoch auch zum Verlust von genetischem Material kommen. Vermutlich kann man die Deletion im Bereich des HF2- und HF4-Gens, die bei 4-5% der untersuchten Probanden gefunden werden kann, durch einen solchen Mechanismus erklären. Diese Deletion, ein genetischer Marker in dieser Region, kann nun mit einem einfachen PCR-basierenden Test, festgestellt werden. Die Isolierung und Kartierung des Faktor H-Genkomplexes erleichtert die Suche nach Kandidatengenen für das hämolytisch urämische Syndrom (HUS), da die Region als Kandidatenregion für dieses Syndrom identifiziert wurde. Es ist möglich, daß Faktor H oder die Faktor H-verwandten Proteine eine Rolle bei der Entstehung dieser Krankheit spielen. Ob die oben erwähnten HF2-Deletion eine Rolle bei der Pathogenese von entzündlichen Erkrankungen insbesondere rheumatischer Arthritis, spielt, wurde an einem großen Patientenkollektiv untersucht. Es wurde jedoch keine Korrelation zwischen Deletion und Erkrankung gefunden. Zur weiteren Untersuchung der Funktion der Faktor H-verwandten Proteine, wurde deren Expression auf Protein und mRNS-Ebene untersucht. Faktor H und die Faktor H verwandten Proteine 1 und 2 wurden im Liquor cerebralis entdeckt. Der Hauptsyntheseort im Gehirn für Faktor H scheint des Endothel des Plexus chorioideus und die Gliazellen zu sein. Die HFverwandten Transkripte sind nur auf geringem Niveau nachweisbar. Die Transkription von HF1 ist in den allen getesteten Gliomazellinien mit IFNg stimulierbar. Faktor H verhält sich also im Gehirn, ebenso wie in der Leber, als Akute-Phase-Protein und verhindert eine ungewünschte Komplementaktivierung im Zuge von Infektionen, Verletzungen und Erkrankungen des Gehirns. Durch die inflammatorischen Cytokine IL4 und IL6 wird die Transkription von HF1 nicht beeinflußt. Die HF1-verwandten Gene HF1- 5 sind in den Gliomazellinien nicht mit IFNg stimulierbar und auch IL4 und IL6 zeigen keinen Einfluß auf die Expression dieser Gene. Im Gegensatz zu Faktor H sind diese Proteine wahrscheinlich nicht an der Akute-Phase-Antwort des Gehirns beteiligt. Welche Aufgabe ihnen zufällt ist offen.