POPULARITY
13 episodes with mmps
10 episodes with mmps
3 episodes with mmps
3 episodes with mmps
2 episodes with mmps
2 episodes with mmps
2 episodes with mmps
5 episodes with mmps
2 episodes with mmps
What if reversing joint pain, skin aging, and inflammation wasn't about more supplements, but about better signals?In this episode, we're joined by Dr. Ross Carter, a regenerative medicine expert and founder of the Young For Life protocol, to explore how stem cells, exosomes, peptides, and biologics are shaping the future of aging.We unpack the science of cell signaling, inflammation, and tissue regeneration, and why most people approach regenerative medicine all wrong. We dive into how perinatal stem cells work, the truth about exosomes and MMPs, why enzyme neutralization matters more than collagen creams, and what makes biohacking with biologics effective, or completely useless.Dr. Ross Carter is a regenerative medicine pioneer, speaker, and founder of the Young For Life method. Let's get into it.We Also Discuss:00:01 — Stem Cells: Hype or the Future of Healing?10:29 — Can You Actually Reverse Biological Age?22:16 — Why Your Joints Aren't Healing (and What to Do About It)37:31 — The Wild Future of Regenerative Medicine + AI49:50 — Who You Trust with Your Stem Cells MattersLearn more about:Young GooseUse code PODCAST10 to get 10% off your first purchase, and if you're a returning customer use the code PODCAST5 to get 5% off at https://www.younggoose.com/ Instagram: @young_goose_skincareDr. Ross CarterWebsite: https://youngforlife.org/ Instagram: @drrosscarterllc Instagram: @younglife Youtube: @Youngforlifeprogram
Live from MAU Las Vegas and sponsored by InMobi, this episode features a dynamic conversation about mobile performance marketing. Hosted by Kunal Nagpal, the discussion includes insights from Zach Gryphon (WaveMaker) and Maulana Moore (AppsFlyer). Together, they explore measurement frameworks, attribution challenges, AI in marketing, fraud detection, and the strategic importance of mobile apps as a growth channel and not just a companion tool. They stress the need for collaboration across brands, agencies, and MMPs, especially as privacy regulations, consumer behavior, and tech platforms continue to shift. The theme? It takes a village to win in modern performance marketing. Key Timestamps: 00:00–01:39 – Introductions: Roles at WaveMaker and AppsFlyer, and why performance marketing matters more than ever 02:33 – “Spy skills” icebreaker (time travel via Motown and home DIY skills) 04:55 – The modern measurement landscape: slow, medium, and fast decision frameworks 06:42 – Why internal data silos and misaligned incentives remain a challenge 09:00 – The role of education in promoting smarter attribution models like incrementality 10:22 – Privacy vs. personalization: Navigating a chaotic regulatory environment 13:00 – Cookies, SKAdNetwork, and why Apple's and Google's shifting strategies matter 17:20 – Regional differences in mobile maturity (APAC vs. North America) 20:10 – Why mobile apps are now key growth engines, not just support tools 21:30 – Full-funnel performance thinking and aligning KPIs with LTV 23:13 – The misunderstood role of MMPs in identifying fraud and optimizing outcomes 25:30 – Real-world uses of AI: From predictive analytics to creative optimization 29:13 – A philosophical take: Moving beyond spreadsheets and embracing AI architecture 32:49 – What marketers should expect from their agency, MMP, and DSP partners 36:30 – Why a true “village” mindset beats a collection of siloed experts Learn more about your ad choices. Visit megaphone.fm/adchoices
Scientists have engineered small, targeted proteins that can penetrate brain cancer cells and prevent them from invading healthy tissue, offering a promising new approach to treating glioblastoma multiforme (GBM), one of the deadliest forms of brain cancer. This strategy was developed by researchers at the University of Nevada, Reno, and published recently in Oncotarget. The Challenge of Treating Glioblastoma Multiforme Glioblastoma is an aggressive and fast-growing brain tumor that infiltrates healthy brain tissue, making complete surgical removal nearly impossible. Standard treatments like chemotherapy and radiation can slow its growth but rarely prevent it from returning. One major reason for this invasiveness is a group of enzymes known as matrix metalloproteinases (MMPs), which break down surrounding tissue to allow cancer cells to spread. Among these, MMP-9 plays a particularly important role in driving tumor progression and resisting existing therapies. Attempts to block MMPs using small-molecule drugs have failed in clinical trials due to problems like poor selectivity and harmful side effects. Researchers have been searching for safer, more targeted methods to interfere with these enzymes and limit glioblastoma's spread. The Study: Engineered Proteins to Inhibit Tumor Invasion In the study called “Effect of TIMPs and their minimally engineered variants in blocking invasion and migration of brain cancer cells,” researchers Elham Taheri and Maryam Raeeszadeh-Sarmazdeh investigated tissue inhibitors of metalloproteinases (TIMPs), which are natural blockers of MMPs, and their engineered modified versions made to work better. Specifically, the team studied TIMP-1, TIMP-3, along with two engineered molecules, mTC1 and mTC3, in laboratory cell models of GBM. Full blog - https://www.oncotarget.org/2025/05/21/engineered-proteins-show-promise-in-stopping-glioblastoma-invasion/ Paper DOI - https://doi.org/10.18632/oncotarget.28691 Correspondence to - Maryam Raeeszadeh-Sarmazdeh - maryamr@unr.edu Video short - https://www.youtube.com/watch?v=tdBlkOX50D8 Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28691 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, TIMP minimal variants, glioblastoma multiforme (GBM), brain cancer, MMP inhibitors To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM
Mobile attribution is getting better than ever before. And that's in spite of it becoming more and more complex.There's so many measurement methodologies. Advanced SAN. AEM. Advanced AEM. Unified Measurement. SKAN. AAK. Privacy Sandbox. GAID. IDFA. Probabilistic. Modeled.You name it, there's MORE of everything.But in spite of all that, mobile attribution is getting better. Way better. And maybe, it's actually BECAUSE of all that. And the great news: it's also getting EASIER.Makes sense? Insane?Impossible?Check out this convo in Growth Masterminds between John Koetsier and Singular CTO Eran Friedman
Friction is no fun, and moving our joints freely and without pain requires that it is minimised as much as possible. Cartilage is the cushiony, slippery and translucent tissue that lines the ends of our long bones and acts as a lubricating layer within our joints to make their movements smooth and effortless, or at least that's the theory. For millions of people, ease of joint movement is painfully disrupted by osteoarthritis, a condition that gradually and progressively erodes this protective and functional cartilage layer and leads to pain, stiffness, and reduced mobility. No fun at all. The work of Dr. Marina Danalache of the Department of Orthopedic Surgery at the University Hospital of Tübingen, Germany, and her colleagues sheds new light on how this cartilage breakdown begins and proceeds. Meet matrix metalloproteinase enzymes (or MMPs for short): master regulators of cartilage remodelling, balancing renewal and destruction. In osteoarthritis, this equilibrium shifts - the researchers are decoding their precise roles aiming to unlock targeted interventions and transformative therapies.
BUFFALO, NY - March 3, 2025 – A new #research paper was #published in Oncotarget, Volume 16, on February 28, 2025, titled “Effect of TIMPs and their minimally engineered variants in blocking invasion and migration of brain cancer cells." Elham Taheri and Maryam Raeeszadeh-Sarmazdeh from the University of Nevada, Reno, explored a new approach to slowing the spread of glioblastoma multiforme (GBM), the most aggressive and deadly form of brain cancer. Their study highlights the potential of both natural and engineered molecules to block cancer cell movement, offering a promising strategy to combat this challenging disease. Glioblastoma multiforme is difficult to treat because it quickly spreads into healthy brain tissue, making complete surgical removal nearly impossible. A major driver of this invasive behavior is a group of enzymes called matrix metalloproteinases (MMPs), which break down surrounding tissue and create space for cancer cells to spread. Among them, MMP-9 plays a particularly significant role in GBM progression and resistance to current treatments. To address this challenge, the researchers investigated tissue inhibitors of metalloproteinases (TIMPs), natural MMP blockers, and specially engineered versions designed for better effectiveness. The study used cell line models of GBM to test both TIMP-1 and TIMP-3 and their engineered counterparts (mTC1 and mTC3), specific blockers of MMP-9. “Our study focused on minimal TIMP variants, due to their small molecular size and potential in higher cellular uptake and delivery, to assess their potential in cell-based assays.” The results indicated that the engineered TIMPs were just as effective as, or even better than, the natural ones at reducing cancer cell migration and invasion. These findings are particularly promising because previous attempts to block MMPs with small-molecule drugs faced challenges such as poor selectivity and unwanted side effects. In contrast, these engineered TIMPs offer a more targeted and potentially safer approach. One of the greatest obstacles in treating brain cancer is delivering drugs across the blood-brain barrier, a protective layer that prevents many therapeutic compounds from reaching the brain. To address this, the researchers used cell-penetrating peptides to help the TIMP variants reach and enter cancer cells more effectively. Their results confirmed that the engineered TIMPs successfully reached tumor cells, further increasing their potential as a treatment. Additionally, the study found that these engineered TIMPs did not significantly affect healthy cells at lower doses, suggesting they could be used safely. This makes them strong candidates for further drug development. These findings could lead to new treatment options for GBM, a cancer with very few effective therapies. Future research will focus on testing these TIMP variants in animal models to evaluate their long-term effects and safety. Researchers also plan to investigate whether combining these engineered TIMPs with existing treatments, such as chemotherapy or immunotherapy, could improve outcomes. In summary, given the aggressive nature of GBM and the urgent need for better therapies, this study represents an important step forward. If further research confirms these results, engineered TIMPs could become a valuable tool in the fight against brain cancer, offering new hope for improved treatments and patient survival. DOI - https://doi.org/10.18632/oncotarget.28691 Correspondence to - Maryam Raeeszadeh-Sarmazdeh - maryamr@unr.edu Video short - https://www.youtube.com/watch?v=tdBlkOX50D8 To learn more about Oncotarget, please visit https://www.oncotarget.com. MEDIA@IMPACTJOURNALS.COM
On the podcast, I talk with Ashley about what makes Google App campaigns a powerful growth tool, proven optimization strategies, and how lower CPMs aren't always the win they seem to be.Top Takeaways:
Leading mobile gaming experts break down everything you need to know about Mobile Measurement Partners (MMPs) in 2025. Get insider perspectives from AppsFlyer, Wildcard Games, and industry veterans on when to use MMPs, how much they really cost, and where the industry is heading. Perfect for mobile game developers, UA managers, and studio executives looking to optimize their marketing strategy and understand the evolving role of MMPs in today's privacy-first environment. OUTLINE: 00:00 - Introduction & Overview 03:43 - What is an MMP? Core Functions Explained 05:28 - SDK Integration Benefits 08:02 - Attribution & Performance Tracking 12:24 - Impact of IDFA Deprecation 16:32 - When Do Studios Need an MMP? 24:42 - Cost Breakdown for Studios 27:54 - Self-Attributing Networks (SANs) 32:45 - Working with Multiple Ad Networks 38:59 - Creative Optimization & AI Tools 43:08 - Data Clean Rooms & Privacy 51:09 - Open Source MMP Projects 53:52 - Future Trends in Mobile Marketing 57:47 - Industry Changes & Consolidation 1:01:02 - Final Thoughts & Recommendations SPEAKERS: ✅ Josh Chandley. Co-founder and COO at WildCard Games. ✅ Joseph Kim. CEO at Lila Games. ✅ Brian Murphy. Head of Gaming and New Product Strategy at AppsFlyer. ✅ James O'Claire. Former COO at Bubbleye. Founder Open Attribution. For links and additional info go to Gamemakers.com
Have we finally discovered the key to youthful energy, longevity, and cellular health? In this episode, Dave Asprey sits down with Dr. Anurag Singh, Chief Medical Officer at Timeline Nutrition and a leading expert on mitochondrial health, cellular regeneration, and anti-aging science. With over 20 years of research, 50 clinical trials, and 15 patents under his belt, Dr. Singh unpacks the groundbreaking science behind Urolithin A, a revolutionary postbiotic that boosts mitochondrial function, enhances immune system resilience, and combats chronic inflammation. This episode goes beyond cutting-edge science. Dr. Singh reveals practical, real-world strategies to combat “inflammaging”—the chronic, low-grade inflammation that accelerates aging. Learn how fasting, gut health, and mitochondrial boosters like Urolithin A can rejuvenate your cells, fight fatigue, and supercharge your energy, vitality, and longevity. Here's what you'll learn in this episode: • What Urolithin A is and its role in mitochondrial health and cellular energy production • How to reverse “inflammaging” and reduce inflammation through nutrition, fasting, and biohacking • The connection between mitochondrial dysfunction and immune system aging • Real-life benefits of Urolithin A for energy levels, athletic recovery, skin health, and longevity • Why mitochondrial support is critical for combating aging and improving overall performance Resources: • 2025 Biohacking Conference – https://biohackingconference.com/2025 • Timeline Nutrition - https://www.timeline.com/dave to get 10% off your first order • Timeline Instagram – https://www.instagram.com/timeline_longevity/ • Dave Asprey's Website – https://daveasprey.com • Dave Asprey's Book: Smarter Not Harder – https://daveasprey.com/books • Danger Coffee – https://dangercoffee.com • Danger Coffee Instagram – https://www.instagram.com/dangercoffeeofficial/ • Dave Asprey's Linktree – https://linktr.ee/daveasprey • Upgrade Collective: Join The Human Upgrade Podcast Live – https://www.ourupgradecollective.com • Own an Upgrade Labs – https://ownanupgradelabs.com • Upgrade Labs – https://upgradelabs.com • 40 Years of Zen – Neurofeedback training for advanced cognitive enhancement – https://40yearsofzen.com Timestamps: • 00:00 Introduction to Longevity and Mitochondria • 01:28 The Role of Mitochondria in Immune Health • 03:36 Understanding Inflammaging and Immune Aging • 07:47 Measuring Immune Health and Inflammation • 13:33 Urolithin A: A Mitochondrial Booster • 16:46 Dosage and Effects of Urolithin A • 26:11 Urolithin A and Exercise Performance • 28:31 Urolithin A for Skin Health • 31:34 Collagen and Aging: The Role of MMPs • 33:27 Personal Experience with MMPs and Recovery • 35:04 Measuring MMPs and Their Impact on Longevity • 36:18 Skin Health and Urolithin A • 38:39 Exploring Urolithin A's Broader Benefits • 40:33 Brain Health and Urolithin A • 43:33 Combining Supplements for Optimal Health • 45:54 Omega-3s and Mitochondrial Health • 46:51 Ketones, MCTs, and Urolithin A • 54:30 Final Thoughts on MitoPure and Supplementation See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.
Appointed: A Canadian Senator Bringing Margins to the Centre
On this episode of Appointed, Senator Pate speaks with The Honourable Marion Buller, Chancellor of the University of Victoria and former Chief Commissioner of the National Inquiry into Missing and Murdered Indigenous Women and Girls, and the first Indigenous woman appointed as a judge in British Columbia.The two discuss the connections between poverty, violence against Indigenous women and girls, the mass incarceration and institutionalization of Indigenous women, and the overarching violence of colonialism. Chancellor Buller's years of experience on the bench and as chief commissioner provide invaluable perspective vis-a-vis how to address miscarriages of justice experienced by Indigenous women, including via the Calls for Justice of the MMIWG, the proposed Miscarriage of Justice Reviews Act (Bill C-40), the Senator's report on the Miscarriages of Justices Experienced by 12 Indigenous Women, and Bills C-223 & S-233, both aimed at introducing a framework for a Guaranteed Livable Basic Income in Canada.MMIWG Call for Justice 4.5 directs the government to implement a Guaranteed Livable Basic Income, and 5.14 requires the federal and provincial governments to collaborate on a thorough evaluation of the impact that mandatory minimum sentences have on the over-incarceration of Indigenous women, girls and 2SLGBTQQIA+ People. Given the manner in which MMPs have contributed to the mass incarceration of racialized people, especially Indigenous women, like the TRC, the MMIWG expected the government to follow through on its commitment to repeal mandatory minimum penalties. Chancellor Buller and Senator Pate speak to the intersections of their work and respective struggles to achieve equality and justice.Content Warning: this episode mentions violence against women, rape, and murder.Episode Citations:Reclaiming Power and Place: The Final Report of the National Inquiry into Missing and Murdered Indigenous Women and Girls can be read online hereInjustices and Miscarriages of Justice Experienced by 12 Indigenous Women report can be read online hereBill C-40: An Act to amend the Criminal Code, to make consequential amendments to other Acts and to repeal a regulation (miscarriage of justice reviews) can be found hereBill S-233, An Act to develop a national framework for a guaranteed livable basic income can be found hereBill C-223, An Act to develop a national framework for a guaranteed livable basic income can be found here
In this episode, we delve into the complexities of how Borrelia burgdorferi, the bacterium responsible for Lyme disease, impacts the brain, leading to neuroinflammation and a spectrum of neurological symptoms. We'll explore the pathophysiology of Borrelia's interaction with the brain's blood-brain barrier, its evasion of the immune system, and the direct effects on neural cells. Additionally, we'll discuss specific neurological symptoms and manifestations. Topics: 1. Introduction - Overview of Lyme disease and its causative agent, Borrelia burgdorferi. - Explanation of Borrelia's invasive nature and its ability to cross biological barriers like the blood-brain barrier (BBB). 2. Understanding the Blood-Brain Barrier (BBB) - Endothelial Cells: Primary cellular component of the BBB, unique to the brain for their tightly joined structure. - Astrocytes: - Role in regulating blood flow through neurovascular coupling. - Interaction with neurons and release of vasoactive substances. - Contribution to BBB integrity by influencing tight junction formation. - Pericytes: - Contribution to BBB permeability and regulation through contractile capabilities. 3. Sponsor Break: Daily Nouri 4. Pathophysiology of Borrelia in the Brain - Invasion Mechanisms: - Borrelia's ability to adhere to and invade endothelial cells. - Role of surface proteins and induction of matrix metalloproteinases (MMPs). - Immune Evasion and CNS Invasion: - Antigenic variation to avoid immune detection. - Triggering of immune responses within the CNS, involving microglia and peripheral immune cells. - Cytokine production and its consequences on neuronal health. 5. Direct Impact on Brain Cells - Neurons: Effects of Borrelia invasion on cellular functions, mitochondrial dysfunction, and apoptosis. - Astrocytes: Transition to reactive astrocytes in the presence of Borrelia and their role in neuroinflammation. - Oligodendrocytes: Impact on myelin production and implications for cognitive and motor functions. 6. Sponsor Break: AX3 Life 7. Neurological Symptoms and Manifestations - Symptoms Overview: Headaches, facial palsy, cognitive impairments, nerve root inflammation, POTS. - Psychiatric Manifestations: Potential psychological symptoms like depression and anxiety due to neuroinflammation. 8. Conclusion - Importance of addressing neurological symptoms of Lyme through a bioindividual and root-cause approach. - Recap of key points and reference to previous relevant episodes for further listening. Thank you to our episode sponsors: Check out Daily Nouri and use code CHLOE20 for 20% off your order. Check out AX3 Astaxanthin and use discount code CHLOE20 for 20% off your first order. Thanks for tuning in! Get Chloe's Book Today! "75 Gut-Healing Strategies & Biohacks" Follow Chloe on Instagram @synthesisofwellness Follow Chloe on TikTok @chloe_c_porter Visit synthesisofwellness.com to purchase products, subscribe to our mailing list, and more! --- Support this podcast: https://podcasters.spotify.com/pod/show/chloe-porter6/support
My guest on this episode of the Mobile Dev Memo podcast is David Philippson, the founder and CEO of Dataseat, a privacy-first mobile DSP. As David notes in our conversation, this is the fourth episode of the MDM podcast on which David has appeared, which likely makes him the most recurring guest. David is a wealth of insight into the mobile advertising ecosystem, having founded one of the first MMPs, Ad-X, which was acquired by Criteo in 2013. In this episode, David and I discuss AdAttributionKit, the advertising attribution framework that Apple introduced at WWDC this year and which is mostly -- currently, anyway -- a re-brand of SKAdNetwork. Among other things, we cover: The changes to mobile attribution introduced with AdAttributionKit; The extent to which AdAttributionKit is an attempt to unify attribution across platforms, and what would that conceivably might look like in a few years' time; Whether Meta or Google are any more likely to adopt AdAttributionKit than they were SKAdNetwork; Why Apple made the change that only allows one view-through impression to be open at a time; Apple's long-term vision for attribution; Whether Private Cloud Compute will have a measurement use case at some point; Updated thoughts on the likelihood of Apple deploying its "nuclear option" of IP obfuscation. Thanks to the sponsors of this week's episode of the Mobile Dev Memo podcast: Rockerbox. Get the clarity your marketing needs and navigate your way to success with Rockerbox. Visit rockerbox.com/maze today to see what it's all about. INCRMNTAL. True attribution measures incrementality, always on.
This week, Dan Neumann and Justin Thatil are joined by Erik Lindgren to discuss the concepts of MVP (Minimum Viable Product) and MMP (Minimum Marketable Product) and the differences between them. In this episode, they explore an example of a successful brand that started the simplest way possible and became a multimillion-dollar success a decade later! Key Takeaways Erik shares the story of Honest Tea, which grew into a multimillion-dollar company. They started with the MVP (making tea at Eric's home to sell later), and ten years later, Coca-Cola bought forty percent for forty-three million dollars. What is the simplest way to get to the market fast? Start with the minimum to get on the market and test your idea. It is crucial to shift from an existing platform to a new one with the minimum risk possible. What is the difference between MVP and MMP? MVP: We are unsure if there is a market for this product, who will buy it, and how they will respond to it; for that, you put together a business hypothesis. MMP: What is something that the market will really adopt broadly? There is a considerable risk in taking the Big Bang approach to a project. An integrative and incremental approach seems more effective than redoing the entire ERP system before going live. Grow a system organically instead of trying to do it all at once. A team must ensure they know whom they are solving a problem for to focus£ on what matters most. Mentioned in this Episode: Watch Flamin'Hot Documentary Scrum@Scale Framework Want to Learn More or Get in Touch? Visit the website and catch up with all the episodes on AgileThought.com! Email your thoughts or suggestions to Podcast@AgileThought.com or Tweet @AgileThought using #AgileThoughtPodcast!
Following an action-packed weekend at the NHRA Finals in Pomona, the World Street Nationals in Orlando, and the No Prep Kings in Dallas, The Wes Buck Show crew is all set to delve into the biggest happenings and storylines. Join us as we break down Doug Kalitta's standout performance at the NHRA Finals, debate the greatest in Pro Stock history, and share our take on all the major moments from the weekend's races. This week on The Wes Buck Show, the Drag Illustrated team, Wes Buck, JT "Murder T" Hudson, and special guest Kayla Zadel, bring their unique insights and analysis to the most electrifying moments and storylines from a packed weekend of drag racing. Don't miss out on the action and conversation - hit SUBSCRIBE for the latest in drag racing: / @dragillustrated Grab your MERCH here: https://dragillustrated.store Stay connected with The Wes Buck Show: @thewesbuckshow @dragillustrated RACERSCLUB MERCH: http://www.racers.club Want to sponsor the show? Contact us: wes@dragillustrated.com #dragracing #wesbuck #dragillustrated #NHRA #PDRA #NoPrep #Streetoutlaws #NoPrepKings #Promod #MWDRS #topfuel #funnycar #prostock #radialracing #NPK #WDRA #dragrace #DI #WBS #WesBuckShow #WSOPM #WorldSeriesOfProMod #Brandenton #MMPS #FloRacing #FloDragRacing #Stroud #RedLineOil #RacersClub #racers.club #BracketBonanza #Hitmanproductions #sgmp Episode 325 --- Support this podcast: https://podcasters.spotify.com/pod/show/thewesbuckshow/support
Following a huge weekend at the season-ending PDRA World Finals, Pro Nitrous world champion Tommy Franklin joins Wes Buck and the boys to discuss the series' 10th anniversary season, his turnaround year, streaming technology, event promotion and much more in this wild and wide-ranging conversation. Each week on the Wes Buck Show the Drag Illustrated staff, Wes Buck, JT "Murder T" Hudson, and Mike Carpenter, talk all things drag racing and more. Join THE drag racing conversation by hitting that SUBSCRIBE button: https://www.youtube.com/@dragillustrated MERCH: https://dragillustrated.store Explore more of The Wes Buck Show: @thewesbuckshow @dragillustrated RACERSCLUB MERCH: http://www.racers.club SPONSOR THE SHOW: wes@dragillustrated.com #dragracing #wesbuck #dragillustrated #NHRA #PDRA #NoPrep #Streetoutlaws #NoPrepKings #Promod #MWDRS #topfuel #funnycar #prostock #radialracing #NPK #WDRA #dragrace #DI #WBS #WesBuckShow #WSOPM #WorldSeriesOfProMod #Brandenton #MMPS #FloRacing #FloDragRacing #Stroud #RedLineOil #RacersClub #racers.club Episode 322 --- Support this podcast: https://podcasters.spotify.com/pod/show/thewesbuckshow/support
The Wes Buck Show, featuring this weeks in-depth interview with Cody Krohn who debuted in NHRA Top Fuel at St. Louis. Travel down the the road with Cody as he dishes on all thats led him to this point. Drag Racing's No. 1 talk show returns to break down all the latest news and hottest topics in the sport of drag racing. Each week on the Wes Buck Show the Drag Illustrated staff, Wes Buck, JT "Murder T" Hudson, and Mike Carpenter, talk all things drag racing and more. Drop in and join the conversation. #dragracing #wesbuck #dragillustrated #NHRA #PDRA #NoPrep #Streetoutlaws #NoPrepKings #Promod #MWDRS #topfuel #funnycar #prostock #radialracing #NPK #WDRA #dragrace #DI #WBS #WesBuckShow #WSOPM #WorldSeriesOfProMod #Brandenton #MMPS #FloRacing #FloDragRacing #Stroud #RedLineOil #RacersClub #SPR Episode 320 --- Support this podcast: https://podcasters.spotify.com/pod/show/thewesbuckshow/support
Matt Hartford Talks Parking Lot Test Session, Pro Stock Win at Maple Grove & Much More! Drag Racing's No. 1 talk show returns to break down all the latest news and hottest topics in the sport of drag racing. Each week on the Wes Buck Show the Drag Illustrated staff, Wes Buck, JT "Murder T" Hudson, and Mike Carpenter, talk all things drag racing and more. Drop in and join the conversation. #dragracing #wesbuck #dragillustrated #NHRA #PDRA #NoPrep #Streetoutlaws #NoPrepKings #Promod #MWDRS #topfuel #funnycar #prostock #radialracing #NPK #WDRA #dragrace #DI #WBS #WesBuckShow #WSOPM #WorldSeriesOfProMod #Brandenton #MMPS #FloRacing #FloDragRacing #Stroud #RedLineOil #RacersClub #SPR Episode 317 --- Support this podcast: https://podcasters.spotify.com/pod/show/thewesbuckshow/support
Special guests, Scott Palmer, Ida Zetterström, Elon Werner, and Kebin Kinsley. Pro Stock News, Drag Week Talk, Arm Drop, NHRA Countdown Kick Off & More!! Drag Racing's No. 1 talk show returns to break down all the latest news and hottest topics in the sport of drag racing. Each week on the Wes Buck Show the Drag Illustrated staff, Wes Buck, JT "Murder T" Hudson, and Mike Carpenter, talk all things drag racing and more. Drop in and join the conversation. #dragracing #wesbuck #dragillustrated #NHRA #PDRA #NoPrep #Streetoutlaws #NoPrepKings #Promod #MWDRS #topfuel #funnycar #prostock #radialracing #NPK #WDRA #dragrace #DI #WBS #WesBuckShow #WSOPM #WorldSeriesOfProMod #Brandenton #MMPS #FloRacing #FloDragRacing #Stroud #RedLineOil #RacersClub #SPR Episode 316 --- Support this podcast: https://podcasters.spotify.com/pod/show/thewesbuckshow/support
CAN WE THROW THE BIGGEST DRAG RACE OF ALL TIME? Drag Racing's No. 1 talk show returns to break down all the latest news and hottest topics in the sport of drag racing. Each week on the Wes Buck Show the Drag Illustrated staff, Wes Buck, JT "Murder T" Hudson, and Mike Carpenter, talk all things drag racing and more. Drop in and join the conversation. #dragracing #wesbuck #dragillustrated #NHRA #PDRA #NoPrep #Streetoutlaws #NoPrepKings #Promod #MWDRS #topfuel #funnycar #prostock #radialracing #NPK #WDRA #dragrace #DI #WBS #WesBuckShow #WSOPM #WorldSeriesOfProMod #Brandenton #MMPS #FloRacing #FloDragRacing #Stroud #RedLineOil #RacersClub #SPR Episode 313 --- Support this podcast: https://podcasters.spotify.com/pod/show/thewesbuckshow/support
Lizzy Musi joins The Wes Buck Show. Catching up with the DI team after a big win at Tulsa NPK's in the 1st outing of Bonnie 2.0. Drag Racing's No. 1 talk show returns to break down all the latest news and hottest topics in the sport of drag racing. Each week on the Wes Buck Show the Drag Illustrated staff, Wes Buck, JT "Murder T" Hudson, and Mike Carpenter, talk all things drag racing and more. Drop in and join the conversation. #dragracing #wesbuck #dragillustrated #NHRA #PDRA #NoPrep #Streetoutlaws #NoPrepKings #Promod #MWDRS #topfuel #funnycar #prostock #radialracing #NPK #WDRA #dragrace #DI #WBS #WesBuckShow #WSOPM #WorldSeriesOfProMod #Brandenton #MMPS #FloRacing #FloDragRacing #Stroud #RedLineOil #RacersClub #SPR Episode 312See less --- Support this podcast: https://podcasters.spotify.com/pod/show/thewesbuckshow/support
A week removed from the announcement of the PRO Superstar Shootout - a star-studded $1.3M drag race coming in February of 2024 - Wes Buck, Mike Carpenter and Bradenton Motorsports Park's own Victor Alvarez answer the hottest questions surrounding the sport's newest marquee event. Drag Racing's No. 1 talk show returns to break down all the latest news and hottest topics in the sport of drag racing. Each week on the Wes Buck Show the Drag Illustrated staff, Wes Buck, JT "Murder T" Hudson, and Mike Carpenter, talk all things drag racing and more. Drop in and join the conversation. #dragracing #wesbuck #dragillustrated #NHRA #PDRA #NoPrep #Streetoutlaws #NoPrepKings #Promod #MWDRS #topfuel #funnycar #prostock #radialracing #NPK #WDRA #dragrace #DI #WBS #WesBuckShow #WSOPM #WorldSeriesOfProMod #Brandenton #MMPS #FloRacing #FloDragRacing #Stroud #RedLineOil #RacersClub #SPR Episode 311 --- Support this podcast: https://podcasters.spotify.com/pod/show/thewesbuckshow/support
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.31.551329v1?rss=1 Authors: Imaz-Iruretagoyena, J., Blanco-Urrejola, M., de la Cruz-Gambra, A., Marquez, M., Sierra, A., Baleriola, J. Abstract: Polarized cells in the brain, such as neurons and glia, rely on the asymmetric distribution of their proteins compartmentalizing the function of dendrites, axons, glial projections and endfeet. Subcellular proteomes can be assembled either by the transport of proteins synthesized in the cell soma or by the delivery of mRNAs to target compartments where they are locally translated into protein. This latter mechanism is known as local protein synthesis or local translation, and it has been best studied in neurons. Increasing evidence suggest it is also required to maintain local protein homeostasis in glial cells, however, in microglia, local translation remains largely unexplored. Given the scant evidence, we aimed at exploring the existence of local translation in microglial peripheral processes (MPPs) and unravel its functional significance. We report that local translation indeed happens in MPPs and it is enhanced by triggering a microglial inflammatory response with bacterial lipopolysaccharides (LPS) suggesting a functional relevance of this molecular mechanism in response to inflammation. We found that Actb and Par3 mRNAs polarize to MMPs and are locally translated upon LPS exposure. Interestingly, downregulation of the Actb binding protein IMP1/ZBP1 impaired Actb mRNA polarization and its localized translation, leading to defects in filopodia distribution, lamellar directed migration and phagocytosis in microglia. Thus, our work contributes to recent findings that localized translation occurs in microglia and gives a mechanistic insight into the relevance of this molecular mechanism in fundamental microglial functions in response to LPS-induced inflammation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
On the podcast: Setting sensible goals for paid marketing, how to measure and learn from the results, and why a single ad creative can completely change the trajectory of a company.Top Takeaways
Enjoy a special episode with reigning Top Fuel champ Brittany Force who is nominated for ESPYS Best Driver Award category. Drag Racing's No. 1 talk show returns to break down all the latest news and hottest topics in the sport of drag racing. Each week on the Wes Buck Show the Drag Illustrated staff, Wes Buck, JT "Murder T" Hudson, and Mike Carpenter, talk all things drag racing and more. Drop in and join the conversation. #dragracing #wesbuck #dragillustrated #NHRA #PDRA #NoPrep #Streetoutlaws #NoPrepKings #Promod #MWDRS #topfuel #funnycar #prostock #radialracing #NPK #WDRA #dragrace #DI #WBS #WesBuckShow #WSOPM #WorldSeriesOfProMod #Brandenton #MMPS #FloRacing #FloDragRacing #Stroud #RedLineOil #RacersClub #SPR #jfr Episode 307.5 --- Support this podcast: https://podcasters.spotify.com/pod/show/thewesbuckshow/support
The gang discusses the patience required to be successful in racing, the last NHRA Mile-High Nationals in Denver and much, much more with the winningest Top Fuel driver in history - Tony Schumacher. Drag Racing's No. 1 talk show returns to break down all the latest news and hottest topics in the sport of drag racing. Each week on the Wes Buck Show the Drag Illustrated staff, Wes Buck, JT "Murder T" Hudson, and Mike Carpenter, talk all things drag racing and more. Drop in and join the conversation. #dragracing #wesbuck #dragillustrated #NHRA #PDRA #NoPrep #Streetoutlaws #NoPrepKings #Promod #MWDRS #topfuel #funnycar #prostock #radialracing #NPK #WDRA #dragrace #DI #WBS #WesBuckShow #WSOPM #WorldSeriesOfProMod #Brandenton #MMPS #FloRacing #FloDragRacing #Stroud #RedLineOil #RacersClub #SPR Episode 308 --- Support this podcast: https://podcasters.spotify.com/pod/show/thewesbuckshow/support
The Wes Buck Show with "The People's Champ" himself, Scott Palmer! Palmer dishes on his Top Fuel Pro Mod Studebaker and his quest to go 300 mph in it, the difficulties of racing a nitro car and much, much more. Drag Racing's No. 1 talk show returns to break down all the latest news and hottest topics in the sport of drag racing. Each week on the Wes Buck Show the Drag Illustrated staff, Wes Buck, JT "Murder T" Hudson, and Mike Carpenter, talk all things drag racing and more. Drop in and join the conversation. #dragracing #wesbuck #dragillustrated #NHRA #PDRA #NoPrep #Streetoutlaws #NoPrepKings #Promod #MWDRS #topfuel #funnycar #prostock #radialracing #NPK #WDRA #dragrace #DI #WBS #WesBuckShow #WSOPM #WorldSeriesOfProMod #Brandenton #MMPS #FloRacing #FloDragRacing #Stroud #RedLineOil #RacersClub #SPR #ScottPalmer Episode 305 --- Support this podcast: https://podcasters.spotify.com/pod/show/thewesbuckshow/support
NHRA Tech Official & No Prep promoter Matt Plotkin joins the gang to talk parity in Pro Mod, debate the most competitive eliminators in drag racing, riff on the potential of the new Factory X category, discuss No Prep Kings performance parity and much, much more. Drag Racing's No. 1 talk show returns to break down all the latest news and hottest topics in the sport of drag racing. Each week on the Wes Buck Show the Drag Illustrated staff, Wes Buck, JT "Murder T" Hudson, and Mike Carpenter, talk all things drag racing and more. Drop in and join the conversation. #dragracing #wesbuck #dragillustrated #NHRA #PDRA #NoPrep #Streetoutlaws #NoPrepKings #Promod #MWDRS #topfuel #funnycar #prostock #radialracing #NPK #WDRA #dragrace #DI #WBS #WesBuckShow #WSOPM #WorldSeriesOfProMod #Brandenton #MMPS #FloRacing #FloDragRacing #Stroud #RedLineOil #RacersClub #SPR #FactoryX Episode 306 --- Support this podcast: https://podcasters.spotify.com/pod/show/thewesbuckshow/support
With FloRacing's own Courtney Enders Co-Hosting and trying to keep the guys in-line but she's probably NO HELP! Drag Racing's No. 1 talk show returns to break down all the latest news and hottest topics in the sport of drag racing. Each week on the Wes Buck Show the Drag Illustrated staff, Wes Buck, JT "Murder T" Hudson, and Mike Carpenter, talk all things drag racing and more. Drop in and join the conversation. #dragracing #wesbuck #dragillustrated #NHRA #PDRA #NoPrep #Streetoutlaws #NoPrepKings #Promod #MWDRS #topfuel #funnycar #prostock #radialracing #NPK #WDRA #dragrace #DI #WBS #WesBuckShow #WSOPM #WorldSeriesOfProMod #Brandenton #MMPS #FloRacing #FloDragRacing #Stroud #RedLineOil #RacersClub #TypeAMotorsports Episode 301 --- Support this podcast: https://podcasters.spotify.com/pod/show/thewesbuckshow/support
It was late March 2018, a pretty unassuming day. Except this is when Apple launched its SKAdNetwork. I bet back then many people weren't sure what letters in this acronym should and shouldn't be capitalized, let alone what impact this ad network API from Apple will have on the app industry. Five years forward - it is one of the most discussed topics among mobile app marketers, app publishers, ad networks, and Mobile Measurement Partners or just MMPs. In this episode, Eran will tell about what SKAdNetwork 4.0 has brought to the table, how big of a deal it is, and more. Today's Topics Include: What is SKAdNetwork SKAdNetwork 4.0 updates: Crowd Anonymity and Source Identifier Multiple Postbacks Postbacks Delays and Locking Conversion Web-to-app support Conversion Value Decrease How well this recent update addressed advertisers' dreams and hopes What Eran would like to change about the mobile app industry Android or iOS? Eran's first mobile phone Leaving his smartphone at home, what features would Eran miss most? What features Eran would like to see added to his smartphone? Links and Resources: Eran Friedman on LinkedIn Singular Business Of Apps - connecting the app industry Quotes from Eran Friedman: “The challenge was though [with the Crowd Anonymity predecessor], and it leads us to the Crowd Anonymity, it was a very simplified threshold. It was practically impossible to optimize for SKAdNetwork" “There is always room for improvement, generally speaking, SKAdNetwork. 4.0 is still new for us. It's very different from what marketers used to know from IDFA." “I think of changes [for the app industry] that encourage more innovation, interesting opportunities. Like a potential new app ecosystem [from Microsoft] that may be launched soon." Follow the Business Of Apps podcast Linkedin | Twitter | Facebook | YouTube
It was late March 2018, a pretty unassuming day. Except this is when Apple launched its SKAdNetwork. I bet back then many people weren't sure what letters in this acronym should and shouldn't be capitalized, let alone what impact this ad network API from Apple will have on the app industry. Five years forward - it is one of the most discussed topics among mobile app marketers, app publishers, ad networks, and Mobile Measurement Partners or just MMPs. In this episode, Eran will tell about what SKAdNetwork 4.0 has brought to the table, how big of a deal it is, and more. Today's Topics Include: What is SKAdNetwork SKAdNetwork 4.0 updates: Crowd Anonymity and Source Identifier Multiple Postbacks Postbacks Delays and Locking Conversion Web-to-app support Conversion Value Decrease How well this recent update addressed advertisers' dreams and hopes What Eran would like to change about the mobile app industry Android or iOS? Eran's first mobile phone Leaving his smartphone at home, what features would Eran miss most? What features Eran would like to see added to his smartphone? Links and Resources: Eran Friedman on LinkedIn Singular Business Of Apps - connecting the app industry Quotes from Eran Friedman: “The challenge was though [with the Crowd Anonymity predecessor], and it leads us to the Crowd Anonymity, it was a very simplified threshold. It was practically impossible to optimize for SKAdNetwork" “There is always room for improvement, generally speaking, SKAdNetwork. 4.0 is still new for us. It's very different from what marketers used to know from IDFA." “I think of changes [for the app industry] that encourage more innovation, interesting opportunities. Like a potential new app ecosystem [from Microsoft] that may be launched soon." Follow the Business Of Apps podcast Linkedin | Twitter | Facebook | YouTube
How do you pick the right MMP? Are there major differences between MMPs? Do you even need a mobile measurement partner in the age of SKAN and (soon) Privacy Sandbox on Android? In this episode of Growth Masterminds, we chat with UA expert and consultant Matej Lancaric about the evolving role of MMPs and things to look for when you need one. (And yes, we also chat about when you need to get an MMP.)
In this conversation Dr Doron and Dr Max discuss weight loss, preventing surgery with low carb eating, insulin, the hormonal model of obesity, risks of bariatric surgery, ethical sourcing of meat, eating the animal nose-to-tail, and much more.Dr. Doron Sher is an Orthopaedic Surgeon from Sydney, Australia. He was an early pioneer in using low carbohydrate and ketogenic diets in patients with osteoarthritis needing knee replacement surgery. He currently practices in Sydney at Randwick and Concord.TIMESTAMPS00:00:18 Dr Sher's journey to surgery00:01:03 The process of knee replacement00:03:01 Obesity and overweight greatly exacerbates knee osteoarthritis and surgical risk00:05:20 Diabetics have increased peri-operative risk00:05:54 Traditional (ineffective) approaches to weight loss prior to surgery00:07:52 Dr Sher's encounters with low carb diets00:09:18 Low carb benefits the Sher family00:11:07 Patients are being let down by incorrect dietary advice00:13:30 MMPs and AGEs exacerbate arthritis in insulin resistant patients irrespective of weight00:15:03 On the harms of fruit and fructose consumption00:17:39 Using continuous glucose monitoring to see which foods spike blood glucose00:19:15 On the benefits fasting and time restricted eating00:21:56 Diverting patients from knee replacement surgery with diet00:24:19 Dr Sher's recommended approach to low carb00:25:19 Keep insulin low and eat more protein00:29:20 On omega-6 polyunsaturated seed oils00:32:44 The challenges of feeding patients a high protein, low carb diet in hospital00:36:05 Thoughts on the benefits and harms of bariatric surgery00:39:44 On ethically sourcing meat and animal foods00:42:21 The challenges of low carb as vegetarian00:44:04 On the purported links between red meat and cancer00:45:00 Changing the healthcare system towards lifestyle-first care00:47:48 Empowering patients with knowledge00:48:15 Closing thoughtsDR DORONDr. Doron Sher - 'Carbs, Insulin and Fat' - https://www.youtube.com/watch?v=E16hfXmPGcADr Sher's personal website – https://www.doron.com.auDR MAXhttps://www.twitter.com/maxgulhaneMDLINKS Dr Paul Mason – https://www.youtube.com/c/DrPaulMason/videos
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.23.517709v1?rss=1 Authors: Ivaldo, C., Passalacqua, M., Furfaro, A. L., d'Abramo, C., Ruiz, S., Chatterjee, P. K., Metz, C. N., Nitti, M., Marambaud, P. Abstract: Classical cadherins, including vascular endothelial (VE)-cadherin, are targeted by matrix metalloproteinases (MMPs) and {gamma}-secretase during adherens junction (AJ) disassembly, a mechanism that might have relevance for endothelial cell (EC) integrity and vascular homeostasis. Here, we show that oxidative stress triggered by H2O2 exposure induced efficient VE-cadherin proteolysis by MMPs and {gamma}-secretase in human umbilical endothelial cells (HUVECs). The cytoplasmic domain of VE-cadherin produced by {gamma}-secretase, VE-Cad/CTF2 - a fragment that has eluded identification so far - could readily be detected after H2O2 treatment. VE-Cad/CTF2, released into the cytosol, was tightly regulated by proteasomal degradation and was sequentially produced from an ADAM10/17-generated C-terminal fragment, VE-Cad/CTF1. Interestingly, BMP9 and BMP10, two circulating ligands critically involved in vascular maintenance, significantly reduced VE-Cad/CTF2 levels during H2O2 challenge, as well as mitigated H2O2- mediated actin cytoskeleton disassembly during VE-cadherin processing. Notably, BMP9/10 pretreatments efficiently reduced apoptosis induced by H2O2, favoring endothelial cell recovery. Thus, oxidative stress is a trigger of MMP- and {gamma}-secretase-mediated endoproteolysis of VE-cadherin and AJ disassembly from the cytoskeleton in ECs, a mechanism that is negatively controlled by the EC quiescence factors, BMP9 and BMP10. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Videos: Heather Mac Donald On How The Delusion of Diversity Destroys Our Common Humanity(11:02) This intense AI anger is exactly what experts warned of, w Elon Musk. (15:50) The FTX corruption is even worse than we thought | Redacted with Clayton Morris (13:00) Almonds can help you cut calories University of South Australia, November 20, 2022 Weight loss is never an easy nut to crack, but a handful of almonds could keep extra kilos at bay according to new research from the University of South Australia. Examining how almonds can affect appetite, researchers found that a snack of 30-50 grams of almonds could help people cut back on the number of kilojoules they consume each day. Published in the European Journal of Nutrition, the study found that people who consumed almonds – as opposed to an energy-equivalent carbohydrate snack – lowered their energy intake by 300 kilojoules (most of which came from junk food) at the subsequent meal. “Our research examined the hormones that regulate appetite, and how nuts – specifically almonds – might contribute to appetite control. We found that people who ate almonds experienced changes in their appetite-regulating hormones, and that these may have contributed to reduced food intake (by 300kJ).” The study found that people who ate almonds had 47 per cent lower C-peptide responses (which can improve insulin sensitivity and reduce the risk of developing diabetes and cardiovascular disease); and higher levels of glucose-dependent insulinotropic polypeptide (18 per cent higher), glucagon (39 per cent higher), and pancreatic polypeptide responses (44 per cent higher). Glucagon sends satiety signals to the brain, while pancreatic polypeptide slows digestion which may reduce food intake, both encouraging weight loss. “Almonds are high in protein, fibre, and unsaturated fatty acids, which may contribute to their satiating properties and help explain why fewer kilojoules were consumed.” The findings of this study show that eating almonds produce small changes to people's energy intake, Dr Carter says this may have clinical effects in the long term. Probiotics help maintain a healthy microbiome when taken with antibiotics Texas Christian University, November 18 2022. A systematic review published in the Journal of Medical Microbiology helps answer the question concerning whether probiotics should be taken along with antibiotics to support gut health. Although probiotics decrease the adverse gastrointestinal effects caused by antibiotics, their ability to preserve intestinal microbial composition that is negatively impacted by antibiotic therapy is not well understood. “Like in a human community, we need people that have different professions because we don't all know how to do every single job,” she explained. “And so, the same happens with bacteria. We need lots of different gut bacteria that know how to do different things.” While it is well known that antibiotics destroy some beneficial intestinal microorganisms, some healthcare professionals have expressed a concern that administering probiotics to antibiotic-treated patients could further alter the established gut microbe balance. The review included 29 studies published during a 7-year period. The authors concluded that consuming probiotics with antibiotics can prevent or reduce some changes caused by antibiotics to the microbiome. “When participants take antibiotics, we see several consistent changes in some bacterial species,” Dr Marroquin observed. “But when treatment was combined with probiotics, the majority of those changes were less pronounced and some changes were completely prevented.” New study shows repeated stress accelerates aging of the eye University of California, Irvine, November 21, 2022 New research from the University of California, Irvine, suggests aging is an important component of retinal ganglion cell death in glaucoma, and that novel pathways can be targeted when designing new treatments for glaucoma patients. The study was published today in Aging Cell. Along with her colleagues, Dorota Skowronska‐Krawczyk, Ph.D., at the UCI School of Medicine, describes the transcriptional and epigenetic changes happening in aging retina. The team shows how stress, such as intraocular pressure (IOP) elevation in the eye, causes retinal tissue to undergo epigenetic and transcriptional changes similar to natural aging. And, how in young retinal tissue, repetitive stress induces features of accelerated aging including the accelerated epigenetic age. Aging is a universal process that affects all cells in an organism. In the eye, it is a major risk factor for a group of neuropathies called glaucoma. Because of the increase in aging populations worldwide, current estimates show that the number of people with glaucoma (aged 40-80) will increase to over 110 million in 2040. In humans, IOP has a circadian rhythm. In healthy individuals, it oscillates typically in the 12-21 mmHg range and tends to be highest in approximately two thirds of individuals during the nocturnal period. Due to IOP fluctuations, a single IOP measurement is often insufficient to characterize the real pathology and risk of disease progression in glaucoma patients. Long-term IOP fluctuation has been reported to be a strong predictor for glaucoma progression. This new study suggests that the cumulative impact of the fluctuations of IOP is directly responsible for the aging of the tissue. Researchers now have a new tool to estimate the impact of stress and treatment on the aging status of retinal tissue, which has made these new discoveries possible. In collaboration with the Clock Foundation and Steve Horvath, Ph.D., from Altos Labs, who pioneered the development of epigenetic clocks that can measure age based on methylation changes in the DNA of tissues, it was possible for researchers to show that repetitive, mild IOP elevation can accelerate epigenetic age of the tissues. What do people experience at the border between life and death? University of London & New York University, November 20, 2022 A new study on near-death experiences featured 567 men and women whose hearts stopped while hospitalized in the United States and the United Kingdom. Out of 28 survivors of cardiac arrest interviewed as part of the study, 11 recalled memories suggesting consciousness while undergoing CPR. Additional cardiac arrest survivors provided self-reports about what they experienced while their hearts stopped. Reports included perceiving separating from their bodies and meaningful examinations of their lives. Researchers discovered spikes of brain activity up to an hour into CPR. Dr. Parnia, who served as lead investigator of the study, explained that he and the other researchers undertook this research in an attempt to scientifically explore something that health professionals have discussed anecdotally for decades: The similar stories people revived by cardiopulmonary resuscitation (CPR) often tell about the time when their hearts stopped. “For decades now, millions of people who've gone through this have reported having lucid heightened consciousness, even though from the perspective of their doctors they were not conscious and they were in death,” Dr. Parnia told MNT. The study centered around 567 men and women who received CPR after their hearts stopped beating while at one of 25 participating hospitals in the United States and the United Kingdom. When health practitioners began CPR on a patient whose heart stopped, researchers rushed to the scene, bringing along a portable electroencephalogram, or EEG, to monitor electrical activity in different parts of the brain, and near-infrared spectroscopy (NIRS) to measure oxygen saturation of superficial brain cortex regions. Taking care not to get in the way of health practitioners performing CPR, researchers also clamped a tablet computer above the patient's head. The tablet was connected to Bluetooth headphones which were placed on the patient's ears. Of 567 subjects, 213 or about 38% experienced sustained return of spontaneous circulation, meaning their pulse was restored for 20 minutes or longer. Only 53, or fewer than 10% of the participants, lived to be discharged from the hospital. Of those 53, 25 were unable to be interviewed by researchers due to poor health. The remaining 28 participants were interviewed 2 to 4 weeks after cardiac arrest depending on their recovery. Of the 28 participants interviewed, 11 — or 39% — reported having memories during cardiac arrest. Two of the 28 participants could hear the medical staff working while receiving CPR. One participant recalled seeing the medical staff working and could feel someone rubbing his chest. Using the near-death scale, six participants had transcendent experiences. Three participants reported dream-like experiences, which included a singing fisherman. Six of the 28 participants interviewed remembered the experience of dying. These recollections included one person who heard a deceased grandmother telling her to return to her body. “We characterize the testimonies that people had and were able to identify that there is a unique recalled experience of death that is different to other experiences that people may have in the hospital or elsewhere,” Dr. Parnia said, “and that these are not hallucinations, they are not illusions, they are not delusions, they are real experiences that emerge when you die.” Fifty-three participants had interpretable EEG data. Researchers discovered spikes of brain activity, including so-called gamma, delta, theta, alpha, and beta waves emerging up to 60 minutes into CPR. Some of these brain waves normally occur when people are conscious and performing functions like memory retrieval and thinking. According to the researchers, this is the first time such biomarkers of consciousness have been identified during CPR for cardiac arrest. “We found the brain electrical markers of heightened […] lucid consciousness, the same markers as you get in people who are having memory retrievals who are having […] high order cognitive processes, except that this was occurring when the brain had shut down. Research suggests agmatine can boost brain health and uplift your mood naturally Yonsei University College of Medicine (S Korea), October 28, 2022. Athletes and bodybuilders are always eager to learn more about new products that can help enhance their workouts by promoting strength and stamina. Agmatine, a natural compound, is often used by health enthusiasts as a pre-workout supplement. According to research, agmatine can also potentially be used to boost brain health and improve mood. In one scientific review, researchers suggest that the compound can help prevent neurodegenerative diseases and assist in the recovery of brain injury patients. Agmatine or 4-aminobutyl-guanidine is produced in your body from arginine, an amino acid found in foods like chickpeas, lentils, pork and poultry. When used as a pre-workout supplement, experts recommend not taking it with protein since dietary protein can slow the absorption of agmatine. This then diminishes its benefits. Agmatine is often listed on supplement labels as agmatine sulfate. Dosages range between 250 mg to 1,000 mg per scoop, with intake recommendations between one to two grams per day. Agmatine has antioxidant and anti-inflammatory effects and can scavenge harmful free radicals that cause oxidative damage to your organs and tissues. Some people believe agmatine can help enhance workouts by increasing levels of beneficial nitric oxide. This then dilates blood vessels and promotes healthy circulation. Data also suggests that agmatine may help activate the release of pain-killing, mood-lifting endorphins, which can boost motivation and mood. This suggests taking agmatine can help make you feel more inclined to exercise. The compound may also help block aged glycation end products. Your body produces these potentially carcinogenic compounds after you eat charcoal-broiled or well-done meats. Agmatine may also help down-regulate matrix metalloproteinases (MMPs), which are tissue-degrading enzymes that can facilitate the spread of malignant tumors. Studies show that agmatine works against the glutamate receptors that affect pain perception. Data from preliminary studies have supported agmatine's ability to reduce pain and strengthen the pain-killing effects of prescription opioids. Experts hope that agmatine can be used to help reduce the amount of medications needed and decrease the possibility of addiction to opioids. Supplementation with agmatine may help activate serotonin, the “feel good” chemical in your body while also decreasing levels of cortisol, the “stress” hormone that builds up when you are under duress. In a review published in the European Journal of Neuropsychopharmacology, scientists suggest that agmatine has antidepressant effects. According to a 2018 study published in the journal Human and Experimental Toxicology, agmatine can help protect brain cells from oxidative stress and inflammation caused by laboratory-induced Parkinson's. Prenatal phthalate exposure can significantly impact infant behavior and cognition, says study University of Illinois Urbana-Champaign, November 16, 2022 Prenatal exposure to phthalates, a set of chemicals commonly found in plastics and personal care products, has been shown to significantly impact aspects of behavior and cognition in infants, according to a team of researchers at the University of Illinois Urbana-Champaign. “Phthalates are widespread, and several well-known studies have reported that 100% of pregnant individuals had detectable levels of phthalates in their bodies,” said developmental neurotoxicologist Jenna Sprowles, a former postdoctoral research associate at the Beckman Institute for Advanced Science and Technology. Children's toys, cosmetics, and constructional materials are all potential sources of phthalate exposure, as are other materials made from polyvinyl chloride. When individuals who are pregnant are exposed to phthalates, the chemical compound crosses the placental barrier to interact directly with the fetus. Phthalates can also be transferred to a newborn through breast milk. Their study, reported in the journal Neurotoxicology and Teratology, investigated the neurobehavioral impacts of prenatal phthalate exposure in infants aged 4.5 and 7.5 months. Since many existing studies focus on individuals in early and middle childhood, providing attention to this age group is especially important. “Phthalates are endocrine-disrupting chemicals, meaning they interact with and alter how hormones typically act in the body. Hormones play crucial roles in brain development, so when the activities of hormones are altered by chemicals like phthalates, adverse functional effects are possible,” Sprowles said. “While we do know that different phthalates can affect different hormone systems, we don't yet know exactly how particular phthalates exert their specific effects.” The researchers found that the impact of prenatal phthalate exposure was specific to each phthalate's particular properties. For example, higher prenatal concentrations of a phthalate called MEP, which is commonly found in personal care products, were associated with lower ASQ scores (indicating below-average development) in certain domains. Their results align with existing studies, some of which have been carried out in animal models, which indicate that both prenatal and neonatal exposure to phthalates alters neural structure and function, resulting in impaired cognition and altered behavior.
Before the whole mess of ATT, the one genre that bore the brunt of “no-tracking” privacy regulations were kids apps. That also meant that they had the opportunity to learn how to overcome the challenges of IDFA way before most other apps.In today's episode, we're in conversation with Todd Kane, VP of Growth at Homer Learning. We dive into how Todd and his team unlocked web-based flows to stay way ahead of the curve. We dive into the specifics of their flows, how they first tested these - and how they optimized and improved these to unlock massive scale.Check out the show notes here:https://mobileuseracquisitionshow.com/episode/web-flows-kids-app-todd-kane-homer-learning/KEY HIGHLIGHTS
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.28.514236v1?rss=1 Authors: Lewandowski, S. I., Hodebourg, R., Wood, S. K., Carter, J. S., Nelson, K., Kalivas, P. W., Reichel, C. M. Abstract: Relapse to drug seeking involves transient synaptic remodeling that occurs in response to drug associated cues. This remodeling includes activation of matrix metalloproteinases (MMPs) to initiate catalytic signaling in the extracellular matrix (ECM) in the nucleus accumbens core (NAcore). We hypothesized that MMP activity would be increased in the NAcore during cue-induced methamphetamine (meth) seeking in a rat model of meth use and relapse. Male and female rats had indwelling jugular catheters and bilateral intracranial cannula targeting the NAcore surgically implanted. Following recovery, rats underwent meth or saline self-administration (6hr/day for 15 days) in which active lever responding was paired with a light+tone stimulus complex, followed by home cage abstinence. Testing occurred after 7 or 30 days of abstinence. On test day, rats were microinjected with a FITC-quenched gelatin substrate that fluoresces following cleavage by MMPs, allowing for the quantification of gelatinase activity by MMP-2 and -9 during cued relapse testing. MMP-2,9 activity was significantly increased in the NAcore by meth cues presentation after 7 and 30 days of abstinence, indicating that remodeling by MMPs occurs during presentation of meth associated cues. Surprisingly, while cue-induced seeking increased between days 7 and 30, suggesting behavioral incubation, MMP-2,9 activity did not increase. These findings indicate that while MMP activation is elicited during meth cue-induced seeking, MMP activation did not parallel the behavioral incubation that occurs during extended drug abstinence. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
On the podcast we talk with Adam about when and why to use an MMP, which subscription events to track in your analytics, and why A/B testing doesn't always work the way you think it works.Top Takeaways
Un Podcast sobre marketing de aplicaciones móviles en español. En los distintos episodios vamos a hablar sobre Growth, comportamientos del usuario, adquisición, retención, MMPs, producto y todo lo que quieres saber sobre esta industria de la mano de Matias Fernandez Battolla, VP of Strategy de Rocket Lab y host del podcast…
Privacy Sandbox on Android is out and it looks good. But there's still a lot of questions about how advertisers, ad networks, and MMPs will work together. If the industry can't find a way to innovate in tandem, we risk having confusing data and unclear insights from marketing campaigns that won't enable proper measurement or optimization. In this episode of the Growth Masterminds podcast, we chat with Singular product manager Jonathan Chen, who's working on ways of solving Privacy Sandbox on Android for the industry, including how we can ensure that we don't get siloed attribution (where multiple ad networks claim credit for a conversion and advertisers don't know whether they should credit one, or both, or neither) and coordinating aggregation keys so that advertisers, ad networks, and measurement partners can make sense of the aggregated privacy-safe data Google will be releasing. We chat solutions, integrations, results ... and what still needs to be figured out.
It was hard to imagine how mobile measurement platforms (MMPs) could survive Apple's ATT changes. But the MMPs aren't dying, they're thriving, says Branch's Alex Bauer, on the heels of raising $300 million.
This week Andrew, Gavin, and Pierre are on the panel. The topic is guns, lots of guns. A bill is introduced to reduce mandatory minimums for gun crimes, Montreal gangs use CERB to buy illegal pistols, parliament forms a committee to study gun trafficking, no new details have emerged 2 months after the police shooting of gun smith Rodger Kotanko. Intro Hello to all you patriots out there in podcast land and welcome to Episode 327 of Canadian Patriot Podcast. The number one book and rifle podcast in Canada. Recorded Dec 13, 2021. Andrew Gavin Pierre We'd love to hear your feedback about the show. Please visit canadianpatriotpodcast.com/feedback/ or email us at feedback@canadianpatriotpodcast.com A version of the show is Available on Stitcher at and iTunes http://www.stitcher.com/s?fid=77508&refid=stpr and iTunes at https://itunes.apple.com/ca/podcast/canadian-patriot-podcast/id1067964521?mt=2 We need your help! To support Canadian Patriot Podcast visit patreon.com/cpp and become a Patreon. You can get a better quality version of the show for just $1 per episode. Show you're not a communist, buy a CPP T-Shirt, for just $24.99 + shipping and theft. Visit canadianpatriotpodcast.com home page and follow the link on the right. What are we drinking Andrew - Highlander Smoked Porter Gavin - Crown Royal Northern Harvest Rye & Diet Pepsi Pierre - forty creek Patriot Challenge We're asking patriots to do 5 things everyday; Exercise for at least 45 minutes Practice a skill for at least 10 minutes Read a book for at least 15 minutes Drink at least 2 liters of water Complete 1 task that will improve your life Grab the template from our website and post it in your social media Section 74 Challenges GoFundMe link… https://www.gofundme.com/f/s74-appeals?utm_source=customer&utm_medium=email&utm_campaign=p_cp+share-sheet To get involved emails74process@gmail.c News Liberals table bill that would repeal mandatory minimums for some drug, gun crimes https://www.cp24.com/news/liberals-table-bill-that-would-repeal-mandatory-minimums-for-some-drug-gun-crimes-1.5697398 https://www.canada.ca/en/department-justice/news/2021/12/mandatory-minimum-penalties-to-be-repealed.html Bill C-5 based on previous Bill C-22 1 day after 32 anniversary of the Ecole Polytechnique massacre This is all to address systemic racism MMPs would be repealed for 14 offences in the Criminal Code. 13 are weapons or firearms LILLEY: Gangsters, guns and CERB a real headache for Trudeau Liberals https://ottawasun.com/opinion/columnists/lilley-gangsters-guns-and-cerb-a-real-headache-for-trudeau-liberals/wcm/e0789bf6-18a7-4a11-a375-43f0b761a444 House unanimously passes Quebec MP motion to set up parliamentary committee to study gun trafficking https://montreal.ctvnews.ca/house-unanimously-passes-quebec-mp-motion-to-set-up-parliamentary-committee-to-study-gun-trafficking-1.5697901 Toronto police officer who shot renowned gunsmith won't talk to SIU https://www.cbc.ca/news/canada/hamilton/rodger-kotanko-gunsmith-siu-update-1.6269099 Gunsmith's family appeals to mysterious 'customer' who witnessed shooting https://lfpress.com/news/local-news/gunsmiths-family-appeals-to-mysterious-customer-who-witnessed-fatal-shooting Book Club December Small-Unit Leaders' Guide to Counterinsurgency: The Official U.S. Marine Corps Manual USMC January The True North Tradecraft Disaster Preparedness Guide: A Primer on Urban and Suburban Disaster Preparedness Boris Milinkovich Outro We're on discord now https://discord.gg/rwA4yeeaC8 Pierre - Off The Wall Customizing on facebook and instagram and email offthewallcustomizing@gmail.com Andrew - https://ragnaroktactical.ca/ Visit us at www.canadianpatriotpodcast.com We value your opinions so please visit www.canadianpatriotpodcast.com/feedback/ or email us at feedback@canadianpatriotpodcast.com and let us know what you think. Apologies to Rod Giltaca Remember “You are the True North Strong and Free”
iOS 14.5. If you aren't in the app marketing industry, this version number of the Apple's mobile operating system won't tell about the whole drama associated with it. It is just what the Settings app on your iPhone suggested you to update your smartphone with. That's it. But if your job is to promote mobile apps, I bet you've been following the fallout of its release by Apple this spring real close. In this episode Guido sheds light on what's going on with App Retargeting, iOS versus Android ad campaigns shift, IDFA and more. Today's Topics Include: ✔️Guido started his career as a Search Engine Optimization specialist in a small but vibrant and dynamic Argentinian tech community ✔️ Jampp, part of the Affle company, is a programmatic advertising platform used by the most ambitious companies to accelerate their mobile businesses. ✔️ The update on what's going with app retargeting, after Apple's introduction of its ATT (App Tracking Transparency) framework early on this year. ✔️ Reality check on the current status of IDFA - are people really rejecting app tracking in messes as many people afraid they will a few months ago? ✔️ With all recent updates what's coming up next for the mobile app industry? ✔️On which side of the Android & iOS duopoly Guido is? iOS on his iPhone 12 Pro ✔️ What apps would Guido miss the most if he leaves the smartphone home. Google Maps ✔️ What hardware / software features Guido is waiting for? Augmented Reality tech Links and Resources: Guido Crego Linkedin profile. Jampp website. Jampp iOS 14 resources section. Quotes from Guido Crego: "Argentina is actually a pretty interesting place for tech, although the internal market is small, a lot of successful companies in Latin Americas are started from Argentina. The reality is when it comes to the split per operating system, it changes a lot depending on the region mostly because, as you may know, different markets and different countries in the world will have different penetration of operating systems. In places like Latin America they are really big on Android and iOS is not that big. The reality is we are all learning, advertisers are learning how to do it, DSPs are learning how to do it and MMPs are learning how to do it (work with SKADnetwork efficiently)" Follow the Business Of Apps podcast Linkedin | Twitter | Facebook | YouTube
Last week, we talked about what's up with Facebook - and this week we're taking a look at what's happening with Google post iOS 14.5/ATT. What is changing, what is working with creatives, reporting and day to day ops - and what is a big hot mess right now? It's been just over a month since Apple pulled the trigger on iOS 14.5 - and in this episode we wanted to highlight the key changes that we are seeing with Google Ads/UAC.**By the way, we go into this in much much more detail in our workshop series Mobile Growth Lab - where we share case studies, examples and data around what is happening. Recorded sessions from the Mobile Growth Lab are available right now. See more details here: https://www.notion.so/Mobile-Growth-Lab-2021-Recorded-Sessions-7132fcdf1d8b4d98a4a91c624423b94f (You can also just join the waitlist for the next edition here: http://MobileGrowthLab.com ).**KEY HIGHLIGHTS
Esta aplicación web se conecta con tu Strava y te da datos y estadísticas de tus carreras y MMPs en las distintas distancias a lo largo del tiempo. La web Strafforts https://pdrun.es/strafforts . Pedro en Instagram: https://www.instagram.com/palabraderunner/ - Todo el material que recomiendo: https://www.amazon.es/shop/palabraderunner - Grupo en Telegram: https://t.me/grupopalabraderunner - Lista de música colaborativa en Spotify: https://open.spotify.com/playlist/3HKZ7jyeix7lgyXuOmaZU9?si=LxewE053T96-KesQA7Ze7g Instagram: https://instagram.com/palabraderunner/ Web: https://www.palabraderunner.com Grupo en Telegram: https://t.me/grupopalabraderunner Mi Strava: https://www.strava.com/athletes/1169830 Facebook: https://facebook.com/palabraderunner/ Twitter: https://twitter.com/palabraderunner/ Club Palabra de Runner en Strava: https://www.strava.com/clubs/palabraderunner
En este episodio de “Hablemos de Mobile Marketing” invitamos a Juanjo Monge, Head of Sales de Adjust, para hablar sobre automatización y MMPs. ¿Cómo hago para escalar mi base de usuarios? ¿Cómo automatizo mis campañas? y mucho más…
Our guest today is Adam Lovallo, CEO and founder of Thesis, host of the MAU [Talk] podcast, and founder of grow.co. Adam was our first guest on How Things Grow, and his episode on the rise and fall of daily deals was a very interesting behind-the-scenes peek into a roller-coaster of time that he lived through. Today, we are excited to talk to him about a subject that he feels strongly about: incrementality. We start with talking about what incrementality testing is, how to identify signs of underlying issues in campaigns, and why Facebook and Google reported numbers can be problematic. Adam then goes on to describe prescriptions on how UA teams can solve incrementality issues, discussing the efficacy and potential outcomes of each. Finally, we talk about the role of MMPs, how iOS 14 plays into the picture, the critical importance of channel mix in budgeting and performance decisions, and the importance of seemingly old-school ways to measure performance like blended CPAs or marketing-as-percentage-of-sales. This is a masterclass in understanding the true impact of your marketing, and an unmissable episode for anyone who has questions about how to diagnose issues and implement fixes in their strategy. Enjoy! KEY HIGHLIGHTS
From rewarded video to gaming, slots to asian vegetables, Jonathan Lau has a fascinating background in performance marketing and growth strategies. This week we discuss how eCommerce differs from gaming in team dynamics, LTV modeling, channel mix and more. We also discuss the breaking news of how Apple is beginning it's crack down on its ATT privacy initiative! We also discuss the breaking news of how Apple is punishing MMPs for fingerprinting! Learn more about how to grow your mobile app at upptic.com Guest: Jonathan Lau References: Arizona's App Store bill is quietly killed Nexon makes large investment in entrenched gaming brands Strikes smacks down Adjust for fingerprint Weee! is where you can buy Asian and Hispanic groceries eCommerce Growth Strategies with Jonathan Lau
What happens under the hood of SKAdNetwork? Sure, there is the timer and there are the conversion values - but what is changing under the hood, and what does it mean to you as a marketer or publisher?In today's interview, David Phillipson takes us through the process of attribution on SKAdNetwork, and how it differs from our existing paradigm(and where it remains the same). He talks through the lifecycle of a bid in an SKAdNetwork paradigm, how publishers can become SKAdNetwork compatible, and how the bidding logic is set to be dramatically different going forward. This is a fantastic episode for insights into SKAdNetwork, and much more besides. Absolutely unmissable!KEY HIGHLIGHTS
We are down to the short strokes now: Apple’s iOS 14.5 will roar in next week or soon after, changing mobile marketing on iPhone and iPad forever. But is the mobile advertising ecosystem ready? Is there SKAdNetwork-ready ad supply from mobile publishers? And how will MMPs, mobile web customer journeys, and deep links work? In short: there are still a lot of questions. I spent some time with Jonathan Chen, who leads Singular’s attribution product and manages integration with top partners, to answer these questions.
Paul Bowen, the GM at AlgoLift, has 20 years of experience in digital advertising and among the folks we look to for his expertise on SKAdNetwork.In our conversation today, Paul breaks down the various ways in which developers need to think about measurement for SKAdNetwork. He touches upon the complexities and limitations of the conversion value framework - and how it might be used along with IDFV based data to infer probabilistically the value or LTVs of users or campaigns. This is an episode with quite a few technical details and nuances, and we strongly recommend listening to it carefully to absorb all the wisdom Paul has shared. Enjoy!KEY HIGHLIGHTS
Today’s guest is Susan Kuo, the COO and Co-Founder of Singular, a key mobile measurement partner. Susan got her start in the industry at Electronic Arts, and from there continued to work in senior mobile marketing and analytics roles at companies throughout Silicon Valley until starting up Singular.Questions Susan Answered in this Episode:What changes is Apple making to IDFA with iOS14?Why do you think Apple is doing this?Apple delayed these changes. When do you think they’ll happen?Do you think the industry will be ready by early spring 2021?What are the attribution solutions that will be available? And the pros and cons?How does Singular improve or mitigate the experience of working with an SKAdNetwork?Timestamp:4:19 Susan’s experience starting up Singular over the last 6 years5:47 What sets Singular apart from other MMPs8:51 What’s been happening since Apple announced what it’s changing with IDFA with iOS1411:36 Primary reason for Apple’s IDFA changes14:35 Pulse on how ready the industry is17:15 IDFA-based attribution won’t be dead22:21 Fingerprinting24:50 SKAd Network: privacy-first attribution network29:30 The MMPs’ role with SKAd NetworkQuotes (129 characters):(11:36-11:52) “There’s definitely a primary reason, which is very much focused around user privacy. It’s been such a real core focus, not only across Apple, but all the largest media partners are getting tackled with this question in the last couple years.”(15:38-15:48) “Right now, in talking to the top 25 media partners, I get a good sense that most of them are going to be ready.”Mentioned in this Episode:Susan KuoSingular
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.28.272104v1?rss=1 Authors: Manka, S. W., Brew, K. Abstract: Local unwinding of the collagen triple helix is a necessary step for initiating the collagen degradation cascade in extracellular matrices. A few matrix metalloproteinases (MMPs) are known to support this key process, but its energetic aspects remain unknown. Here, we captured the thermodynamics of the triple helix unwinding by monitoring interactions between a collagen peptide and MMP-1(E200A) - an active-site mutant of an archetypal vertebrate collagenase - at increasing temperatures, using isothermal titration calorimetry (ITC). Coupled binding and unwinding manifests as a curved relationship between the total enthalpy change and temperature of the reaction, producing increasingly negative heat capacity change ({Delta}{Delta}Cp {approx} -36.3 kcal/molK2). A specially designed solid-phase binding and cleavage assay (SPBCA) reported strain in the catalytically relevant unwound state, suggesting that this state is distinct from the horizon of sampled conformations of the collagenase-susceptible site. MMP-1 appears to blend selected fit with induced fit mechanisms to catalyse collagen unwinding prior to cleavage of individual collagen chains. Copy rights belong to original authors. Visit the link for more info
Meet Daniel Lopez, Director of Mobile Growth at Electronic Arts (EA), the second-largest gaming company in the Americas and Europe by revenue. Daniel got his start in mobile marketing at Machine Zone and has since worked at DraftKings and GSN Games. Questions Daniel Answered in this Episode:During your time at Machine Zone, what do you think made you effective?What are mobile marketers overlooking? Oversaturation of consumers: Are you more concerned about it from a cost perspective or user experience? Is there value in saturating a market to develop the brand and be top-of-mind to consumers? Have we overvalued Facebook and Google as sources to drive growth? Why do you think MMPs haven’t built a way for marketers to track impressions and clicks across multiple vendors? What are you looking forward to or unsure of in regards to the future of mobile marketing?Timestamp:3:10 What made Machine Zone team very effective.4:15 From customer support role to marketing.10:18 What mobile marketers are overlooking.12:09 Why managing towards a unique, incremental device universe matters.16:02 When mass marketing and saturating the market is useful.19:11 Open exchanges.20:00 What is Facebook good for? 21:35 Incrementality measurement.24:30 IDFA as an opportunity to develop more robust measurements.27:05 EA Future and open Positions.Quotes:(10:18-11:07) “I honestly think there’s not enough attention being paid to drivers of unique traffic and managing towards a unique, incremental device universe as opposed to just managing sources, channels, AT apps, and things of that nature. Because the nature of our business is that we need to identify an audience and then we need to figure out how to get to that audience. And then once we actually figure that out, then we try to scale. And then once we start scaling, we start dealing with this thing called saturation. And we start dealing with losses of incrementality, losses of effectiveness, and whatnot. And I think there’s not enough being done within the industry to challenge the lack of transparency on, let’s just single out, impressions counts.”(25:32-15:58) “The thing that I am most concerned about is--it also goes back to the death of the idea phase--is that that just pushes power more and more into the hands of the big companies, to where it’s going to be like, “Hey, they have all the data. Let’s allow them to do everything.” And then that just kills the spirit of the problem-solving attitude because then everyone can just blame the algo[rithm]. And that’s something that maddens me to no end.”Mentioned in this Episode:Daniel Lopez’s LinkedInElectronic Arts
Our guest today is Gadi Elisahiv, co-founder and CEO at Singular. Gadi is among the folks who has been deeply involved in conversations about IDFA deprecation - and what the world can look like post iOS 14. Today we talk about what might happen to MMPs - and how we might work with SKAdNetwork in a post-IDFA world.Key Highlights:
Our guest today is David Philippson, CEO of DataSeat, which offers in-house programmatic capabilities and a custom bidding algorithm to app advertisers. David earlier founded one of the first MMPs, Ad-X Tracking, which they sold to Criteo in 2013. We're excited to host David because he's seen the evolution of tracking on mobile from the very early days. He's had a ringside view into the forces that have driven change over the years that have ultimately led us to the impending IDFA deprecation. Today we explore this history - and look at what lies ahead for mobile marketers.Key Highlights:1️⃣When was the first time there was a need for having some accountability for mobile marketing dollars?
The dust has settled on the apocalypse. It's clear that the post-IDFA world is here to stay. Marketing isn't going away, mobile apps aren't going away - however we need a new way to operate in the new post-IDFA paradigm. This session offers a playbook - and outlines some of our key recommendations for adapting your mobile marketing strategy. We offer concrete examples, outline exactly how things will be different - and describe what you need to do to adapt.Key Highlights: ⚙️How does SKAdNetwork work?⚖️How is conversion tracking different with SKAdNetwork vs. MMPs?
Low back pain (LBP) from a herniated disk often leads to surgical intervention. However, there are patients with this painful malady who can successfully “ride it out” and repeat MRI imaging six to twelve months later often fails to show little, if any, evidence of the original herniated disk that was initially very obvious. How is this possible? The proposed theory is that there must be some unique interplay between molecular signals that might explain why some herniated disks heal themselves while others do not. Researchers at Vanderbilt University Medical Center are investigating this and published a report on their progress in the January 2016 issue of the Journal of Clinical Investigation. LBP affects 60-80% of Americans during their lifetime, and there are upwards of 300,000 surgeries for herniated disks annually in the United States alone. A disk can herniate when its outer fibers tear or give way, allowing the semi-fluid center to leak out. If the herniated disk material hits the nerve root exiting the spine, the classic sciatica, or pain down the leg, can result. Dr. Dan Spengler states that about 50% of patients with disk herniation will improve within six weeks, and the actual herniated material may completely resorb over time. What troubles Dr. Spengler and other researchers is why this doesn't occur with everyone. Looking specifically at the molecules that are frequently present when disks herniate, researchers have identified a group of proteins called matrix metalloproteinases (MMPs). Certain MMPs have the ability to act like “Pac-Man” and literally chew through other proteins making it highly suspect that MMPs may be at the forefront of why some disks resorb while others do not! Additionally, when a disk herniates, bleeding occurs and white blood cells—specifically macrophages, which are immune system cells in our blood that ingest foreign materials and bacteria—also flood into the area. What most surprised the authors was the interplay between the macrophages and the MMPs. They found that when the blood/macrophages and one of two specific MMPs interacted in a very specific manner, disk resorption occurred and they were even able to replicate this process in a lab. They concluded the following, “These enzymes are more complicated and interesting than we originally thought. Rather than being big bulldozers, they're a fine pair of scissors that cut certain things.” The TAKE-HOME MESSAGE here is unless you are having progressive neurological loss (meaning muscle weakness or sensory pain that is progressing, and/or especially bowel or bladder weakness), there is NO RUSH to run and have surgery! Doctors of chiropractic can offer natural, non-invasive treatments to manage pain while you let your body manage the herniation! www.PainReliefChiroOnline.com
On this episode of the Mobile User Acquisition Show, we wanted to share some updates based on Apple's announcements from WWDC that have the potential of having a significant impact on the mobile app ecosystem. The IDFA, which has formed the backbone of much of mobile ad tech infrastructure, will be rendered basically useless effective September 2020. We will dive into mobile marketers' most pressing questions surrounding this monumental change. Key Highlights:
Welcome to the first episode of the Mobile Dev Memo Academy preview series.Our guest today is Thomas Petit. Thomas is an independent mobile growth consultant working primarily with non-gaming B2C apps. He is an external consultant for large apps (inc. 2 unicorns), a collaborator assisting several app agencies and an advisor for very early-stage startups. He's run campaigns since the first day, spending 7 digits on the platform directly and also run audits on many other accounts, is certified by Apple, SearchAdsHQ & ASOdesk - and is a regular public speaker on the topic.In today's episode, we dive into a crucial but underappreciated aspect of user acquisition on Apple Search(and also elsewhere) - LAT - or Limit Ad Tracking. Limit Ad Tracking essentially means you cant track your users because their IDFAs show up as zero. In this masterclass, Thomas shows us ways to think about and make estimations to understand and capitalize on LAT, which can have a significant impact on user acquisition strategy. Also: Thomas is teaching the course ‘Apple Search Ads: Beyond The Basics' for Mobile Dev Memo Academy. If you are interested in going much deeper into LAT and all things Apple Search related, you should definitely check out his course on the Mobile Dev Memo Academy at http://mdm.academy.Key Highlights:
In this podcast, members from the Ridgeview Medical Center Wound Care Center, address the team approach of wound management, issues seen with chronic wounds, and treatment modalities. Objectives: Upon completion of this podcast, participants should be able to: Describe the etiology, management and prevention of diabetic foot ulcers. Express that wound clinics and providers use evidence-based, outcome-driven measurements to heal wounds. Recognize which wounds may need referral to a wound clinic. Identify advanced wound care modalities. Recognize wound clinics are a multidisciplinary specialty. CME credit is only offered to Ridgeview Providers for this podcast activity. Complete and submit the online evaluation form, after viewing the activity. Upon successful completion of the evaluation, you will be e-mailed a certificate of completion within 2 weeks. You may contact the accredited provider with questions regarding this program at rmccredentialing@ridgeviewmedical.org. Click on the following link for your CME credit: CME Evaluation: "Advances in Wound Care" (**If you are listening to the podcasts through iTunes on your laptop or desktop, it is not possible to link directly with the CME Evaluation for unclear reasons. We are trying to remedy this. You can, however, link to the survey through the Podcasts app on your Apple and other smart devices, as well as through Spotify, Stitcher and other podcast directory apps and on your computer browser at these websites. We apologize for the inconvenience.) The information provided through this and all Ridgeview podcasts as well as any and all accompanying files, images, videos and documents is/are for CME/CE and other institutional learning and communication purposes only and is/are not meant to substitute for the independent medical judgment of a physician, healthcare provider or other healthcare personnel relative to diagnostic and treatment options of a specific patient's medical condition.” FACULTY DISCLOSURE ANNOUNCEMENT It is our intent that any potential conflict should be identified openly so that the listeners may form their own judgments about the presentation with the full disclosure of the facts. It is not assumed any potential conflicts will have an adverse impact on these presentations. It remains for the audience to determine whether the speaker’s outside interest may reflect a possible bias, either the exposition or the conclusions presented. Planning committee members and presenter(s) have disclosed they have no significant financial relationship with a pharmaceutical company and have disclosed that no conflict of interest exists with the presentation/educational event. SHOW NOTES: Today, we’re talking about wounds. Not acute wounds, but chronic wounds. We’re joined by several members of the Ridgeview Wound Care Center team. It’s their mission to heal the chronic wounds suffered by many in our patient population. According to the American Professional Wound Care association, in 2017, it was estimated that 8.2 million medicare beneficiaries have chronic non-healing wounds, and the cost for chronic wound care stretches into the 20-30 billion dollar range. Joining us are Deb Netsch, nurse practitioner and highly experienced wound care specialist. Dr. Scott Standa, podiatrist and medical director of the Wound Care Center at Ridgeview. Also, Dr. David Arens, podiatrist with Lakeview Clinic and member of the wound care team. Finally, Laurie Grotzinger, physician assistant specializing in Infectious disease medicine and also part of the wound care team at Ridgeview. CHAPTER 1 SUMMARY: Once upon a time, there was no uniform approach to wound management. It ended up being the person or people who took on the work. Nowadays, there is a wound care center team approach which involves multiple spokes on the hub that is chronic wound management. Nurses, physical therapy, physician assistants, nurse practitioners, podiatrists, and other physicians, to name a few. There has been definite improvement in overall patient care and outcomes, at least in the experience of Ridgeview Wound Care Center (WCC) team members. The medical literature would also support this, not to mention patient satisfaction over time. As Dr. Standa and Laurie Grotzinger discuss regarding the merits of a wound care team and it’s many pronged approach, there is a concerted effort and we are able to uncover the less likely but real alternative diagnoses, like pyoderma gangrenosum. A lot of patients are referred to the WCC by primary care, EDs and other front line providers. If a wound is not vastly changing in two weeks time, then a wound care referral is likely necessary. As Dr. Davis and Deb mention, those little, non-healing toe ulcers can harbor serious prognoses and complexity. They both advocate for prompt wound care team evaluation, along with close follow-up, on a weekly basis at least. Sometimes it’s hard to follow-up with primary care due to heavy patient loads in the primary care clinic and patient non-compliance. Primary care has been managing chronic wounds in a progressively improved way over the years, but let’s face it, these patients can require heavy resources and multiple closely spaced visits, which is why Dr. Standa makes the point about the need for a WCC team. Acute versus chronic wounds. How do we differentiate? Normally a wound heals in 4 stages with: 1. Hemostasis 2. Inflammatory-think WBC infiltration of the wound, platelet derived growth factor, etc. 3. Proliferation, which involves angiogenesis and epithelialization 4. Remodeling, or scarring essentially of the wound. This can take up to a year, and that new tissue is only about 80% as strong as the original tissue. MMP or matrix metalloproteinases, are actually important for normal wound healing, but must be at the right time, and in the right amount. They remove damaged proteins in wounds. Chronic wounds basically hang out in stage 2. More or less a pro-inflammatory phase; ongoing injury and wound ischemia with continued biofilm. There are high cytokines, MMPs/proteases and low inhibitors. Overall a decrease in cell mitosis. Basically a vicious cycle of wound impaired healing. CHAPTER 2 SUMMARY: Assessing a chronic wound. What’s entailed? Deb tells us that past medical history and past surgical history are key to the story of a wound. Smoking, obesity and diabetes are the holy trinity of wound care risk factors for chronic wounds, as stated by Dr. Standa. Let’s not forget other immunocompromised states. In addition, is the patient off-loading from a wound properly? Is he or she incontinent or lacking in proper hygiene? So how does the wound look, feel and smell? Is the wound pale/gray in color versus having pink, healthy granulation tissue. Smell is key, and pseudomonas does have sweet pungent aroma along with a green, fluorescent drainage, for instance. Polymicrobial infections tend to have a more foul odor. Hyperkeratotic tissue or dense callous around a wound is a sign that there is too much pressure surrounding a wound. Dr. Arens reminds us that an orthotist is an essential member of the wound care team. Deb mentions she can tell if a wound is not being tended to, such as improper offloading, thick callous, darker hemosiderin staining, as well as a ruddy looking wound bed. There are different types of wounds and location matters. Pressure injuries are typically in the ischial and sacral regions as well as the heels and other bony prominences. Wounds associated with hemosiderin staining and lipodermatosclerosis are classically due to venous stasis. Diabetic ulcers tend to have overlap of ischemic, neuropathic and venous insufficiency components. Laurie talks through wound assessment, and a particular protocol is followed for this. A detailed history and physical assessment. Measuring and photodocumenting the wound, assessing ankobrachial indices (ABIs). A poor ABI will be promptly referred to a vascular surgeon. Is there hair growth? Can a pulse be detected by doppler? Is their nutrition up to snuff? Twice the amount of normal protein is needed for proper healing. How is their blood sugar control? A prealbumin and albumin can be helpful to assess nutrition status. Inflammatory markers or a “wound care bundle” includes a CMP, CBC with diff, sed. rate and CRP. Cultures are important, as long as they are reliable, preferably deeper tissue and/or drainage samples. Per Dr. Standa, intraoperative tissue biopsies for gross exam, as well as aerobic/anaerobic cx and bone samples as well. If it’s an amputation, Dr. Arens removes a wafer of proximal bone as well. Patient follow-up is paramount in terms of deciding when a wound is infected. How has the wound changed? Pain and tenderness is key, but redness peripherally and increased drainage are also important. Labs and inflammatory markers can be helpful. Hemosiderin can mimic inflammatory, cellulitic skin changes. Dr. Arens tends to take patients to the OR predominantly on clinical grounds as opposed to specific lab or xray findings. And as Dr. Standa states, the findings on surgical exploration don’t always jive with imaging, and vice versa. Deb circles back on hyperkeratotic findings, basically significant callous formation. It needs to be recognized in the front line, primary care settings, because these patients are setups for significant wounds. Compression as well of lower extremity edema is also imperative. Dr. Arens stresses again the need to assess the wounds in follow-up, even after they’re healed. Ensure proper offloading, especially with significant valgus or varus foot deformities, does the patient need a brace and an orthotic of sorts? CHAPTER 3 SUMMARY: Treatment of the wound is straightforward, but complex at the same time. Are the edges of the wound rolled (demonstrating epibili)? Debriding the dead tissue from the wound, especially wounds above the knee, tends to happen right out of the chute. Below the knee, if the eschar or scab is healthy appearing, the first step is to assess vascular status. If it’s decent, then debridement should proceed. The plan is to help the body recognize that the wound is not healing and to stimulate this. Dressings exist that actually bind the proteases in the wound, and essentially promote growth factor presence. Basically waking up the wound into the acute phase again. Addressing blood sugars and shooting for better control is so very important. A dry, thick scab is what we’re aiming for ultimately. Wound healing tends to be a proxy for degree of diabetic control. Can the patient work toward quitting tobacco? Wound dressings have become more complex and technical. In addition, maggot therapy has a place in wound care, although not performed currently at Ridgeview. The goal is to keep the wound somewhat moist—not too dry, not too wet. Silicone foam dressings, such as mepilex or leave in life dressings are some examples. There must be high exudate levels for these dressings to get reimbursed. Wet to dry dressings have gone by the wayside. It is expensive to actually employ someone to do these dressing changes. Full thickness wounds actually go through the entireity of the skin and into the subcutaneous tissue. While she has no special interest in the product, Deb recommends Mepilex or similar dressings for most of these kinds of wounds. Dressings tend to be partially occlusive. We don’t want to create an anerobic environment. Therefore she avoids tegaderm type dressings. Dressings for partial thickness wounds should be nonadherent and there are many kinds here. Telfa, adaptic, and overlaying gauze, in addition to silicone foam. Also, one should use the skin tear itself as an autologous graft dressing. Silicone foam over this can then also be applied. Antibiotic therapy is geared toward the type and location of the wound. Usually antistaph and strep antibiotics are appropriate. The more pus, think of staph. Polymicrobial infections, such as on the lower leg and foot, require broader spectrum antibiotics, like amoxicillin/clavulanate. Strep tends to have the brighter red appearance. If it looks pseudomonal, since the foot spends a lot of time in an anaerobic environment, the fluoroquinolones are appropriate, but there are many adverse effects with this class of antibiotic. More serious infection, namely osteomyelitis, will require IV antibiotics in most cases. The wounds associated with osteo will tend to open and close chronically, until the infection is fully treated. Surgical treatment of the wound is best done in the OR. The main goals, per Dr. Arens, are infection control and tissue salvage. Sharp debridement as well as blunt removal of infectious, friable tissue and bone is essential. Irrigation debridement is also employed. Most studies don’t really support antibiotic solution over saline. Pulsevac, or pressure lavage is not a favorite due to the high PSI. The second goal is to save as much tissue as possible to allow the patient to be mobile and to be fit with a prosthesis. Grafting of wounds in the distal extremities is not used often. Skin substitutes such as PriMatrix, along with NPWT (wound vacuum) is used by Dr. Arens. Many patients opt for amputations of infected, non-healing foot wounds, for instance. Grafts will really only work if there is decent vascular status. We will go further into Hyperbaric, negative pressure, as well as other treatments and interesting new do-dads in the field of chronic wound care in the 4th and final part of this discussion with Ridgeview’s wound care team. CHAPTER 4 SUMMARY: NPWT (Negative Pressure Wound therapy) is indicated in some cases. If there is good blood flow and treated osteomyelitis, for instance. Structures must be closed and active bleeding from a vessel is a contraindication. The wound is actually pulled inward and together, as well as pulling out infected fluid and helping angiogenesis. Micro and macro-deformation of the wound is happening here. Usually the pressure applied is 125mmHg. Intermittent is more effective, but it’s more painful than continous negative pressure. Pressure is reduced if there are hematomas or cyanotic areas. HBOT (Hyperbaric Oxygen Therapy): While there is skepticism over the use of hyperbaric therapy, since there is not broad scale RCT data on it, there is significant observational data that demonstrates improved healing. Hyperbaric O2 allows for supersaturation of oxygen in the plasma. The theory is that some bacteria doesn’t like high levels of O2, and ischemic wounds tend to do well with this, too. Wounds associated with radiation tend to improve moreso with HBOT. Dr. Standa states that some wounds really don’t warrant HBOT, such as the little toe wound that won’t heal. HBOT is not a panacea. The other important factors (DM, smoking cessation, off-loading, etc.) need to be addressed as well. Also, it’s important to know that all HB treatment centers follow the same guidelines, and multiple sessions are needed, 30 to 50 and the dive time is about 2 hours. There needs to be caution with COPD patients. Does the COPD patient have a bleb that is going to pop under pressure? ECG and echo sometimes are also performed on heart patients before diving. ENT complications must be prevented, and sometimes ear tubes are necessary for this. Newer innovations in wound management include the following: Skin substitutions such as matrices that promote wound healing, including stem cells and growth factors. These come from various animals such as sheep, cow and pork. Be sure your patient doesn’t have religious beliefs that would contraindicate use of animal products. Deb mentioned as well that vast amounts of tissue can be produced from placenta and neonatal foreskin, for instance. In general, when the wound hasn’t healed by 80% in 4 weeks, HBOT, and some of these various skin substitutes can be utilized. According to Deb as well, we will at some point be able to test the wounds specifically for various types and amounts of proteases, in order to tailor the wound dressing choice more accurately. PCR testing of the wound is in development and not quite ready for prime time. Dr. Arens also discusses a device now used in the OR that asseses vascular sufficiency in the flaps that are created in an amputation procedure. It uses fluorescence to visualize the vascularization of the flap. Topical analgesia such as lidoderm 1% patches are used, but topical ibuprofen is also used presently in Canada, although not yet here in the U.S. Venous and arterial pumps can be utilized in the nearly 30% of patients who are potentially in need of amputation, but the limb is still salvageable. Observationally, their pain is significantly improved with these devices.
The NDP MPPs in Hamilton issued a letter to City Council yesterday requesting a judicial inquiry into the Red Hill Valley Parkway. Guest: Sam Merulla, City Councillor, Ward 4.
Well, the beltway is in full flight now, dramatically interviewing their typewriters, seeing two plus two and coming up with five.Last night Tova O’Brien was breathlessly reporting a power battle between Winston Peters and Jacinda Ardern. A slug em out battle of the Titans with the future of the coalition hanging in the balance.This came after two of the country’s biggest unions, FIRST Union and the Council of Trade Unions (CTU), came out and said they fear the Government's employment law reforms could be hijacked by Winston Peters.The unionists went on to say they are a bit worried about the dominance on a number of issues that is coming from New Zealand First. Yes said the pundits, look at how Winston scuppered the reform of the three strikes rule. We now have co-leaders of the coalition and Jacinda has lost controlNow you could say that but it’s a bit over-excitable, over-egged and overhyped. We won’t really know the influence of NZ First until the legislation is tabled. That’s why Winston says it’s a work in progress. Until then it’s only speculation and conjecture and beltway babbling.It strikes me that despite it being our electoral system for 22 years, so many people, including commentators don’t seem to get MMP. They seem to believe that if a Prime Minister and his or her party can’t steam roller their policies into legislation then we have a power vacuum and stand on a precipice of disaster and chaos.The truth is that since 1996 no ruling party of New Zealand has ever had total control of legislation because they’ve never had the numbers to get stuff through. They’ve had to mitigate and compromise. It’s why National never reformed the RMA or got rid of Working For Families. It’s why they did bring in policies they weren’t fond of like the Maori party’s Whanau Ora.Now, this gets under the haters of MMPs skin. Under First Past the Post this wasn’t a problem they say. But Government’s got a blank cheque to do what they wanted. Not really a good thing. It was a kind of totalitarian where extremists and ideologues could do what they want. Labour and Rogernomics and National with Ruth Richardson’s Mother of All Budgets. Now I have no problem with MMP. It’s because we have only one house of representatives. In the UK, Australia and America there are up to three houses or branches of government providing checks and balances and ironing out the worst excesses. Here though, get a straight majority, do what you want. I laugh when people say MMP is undemocratic because it’s far more indicative of people as a whole rather than a ruling elite.So the unions should calm down. You’re not going to get everything you want and that’s good because not everyone wants everything you want.What I will say about leadership is that Jacinda Ardern needs more of her colleagues to start pulling their weight. At their best National was a two headed beast with Key, English and Joyce. NZ First is very much the Winston and Shane show. But Jacinda seems to be facing all these challenges alone.
Maggie makes sure Annie's birthday isn't forgotten.
The O'Gorman's meet up wit a Cheyenne hunting party.
Out of the fire and into the night. Ready or not Maggie's baby is about to make its entrance into the world.
Kate is a Pediatric Speech Language Pathologist with experience in early childhood education and has created the “toolkit for postpartum healing” with her sister. Has an interest in early intervention and went into business with her sister and husband who is a mental health counsellor. Her passion is inspired by the fact that there isn't a lot of education or preparation around motherhood. She often asked herself “why didn't anyone tell me this?” in the early days of being a mom. Not much talk of how to take care of yourself and your family and your baby. Sunit agrees that there is so much energy put into the “fun” parts about becoming a mom that there isn't a lot of proper preparation for the things that really matter. The overwhelm from being caught off guard and being unprepared can lead to PPD. Sunit asks Kate what effect PPD can have on the baby and why it's important to prepare better before baby comes. Kate shares how the unexpected early arrival of her preemie son (while she was still in school) caused her overwhelm in the early days. The combination of still being in school, a preemie baby and the psychosomatic thoughts affected her greatly in the early days, but postpartum can present itself even over a year after having a baby-often caused by something that happens early on. Because she is a SLP-she knew that when a mom has PPD-it puts the child at risk for social and cognitive delays all the way into early childhood. There is research that shows this and it gave her anxiety as a new mom knowing that her mental state was affecting her baby. The focus is always on the baby being healthy-ie the pediatrician always checks over the baby to make sure baby is healthy and growing well but never checks in to see how mom is doing. But the mom's mental health affects the baby. Sunit asks Kate to share tips of things to do and keep in mind if early childhood education isn't your forte. Kate says that preparing by having some nursery rhymes and songs in your toolkit is a great thing to do. You tube is a great resource. Kate says that hand gestures along with music and singing are a great way to engage babies. Sunit asks about baby sign language and Kate says it is a controversial topic but a safe bet is to pair the verbal word with the gesture if you want to do baby signing with your kids. Hand motions and pointing to objects help babies learn attention skills. DOs-get your arsenal of songs/games ready before baby comes and become aware and intentional of your hand gestures and pointing in early stages. Talk to them and acknowledge what they are doing (I see you! I see you are sitting up in your chair! Wow, you must have a strong belly!). It grows their vocabulary, gives them reassurance and reinforcement. DONTs – Don't NOT interact with your baby. They're never too young to interact with them. Also, don't cater to their every whimper. Resist the urge to “save” them all the time. It's ok for them to be left to their own devices for a few minutes. Use the “talk and acknowledge” from a distance. If your baby is truly distressed you'll know. Sunit refers to the sleep expert she interviewed who also said that you need to teach babies to self soothe while still tending to their needs. Sunit asks if babies can hear you in the womb and Kate says there is research to show that they can and that they can identify you. They are able to pair up and build neural connections to decipher around what they heard in the womb (which was muffled) and what they hear now. Get dads in on the fun of talking to baby in utero because they will recognize dads tone when they are born. Sunit says her biggest takeaway is to recognize that your own mental health does affect babies in the early days and that's why it's so important to prepare well and get your support system set up BEFORE baby comes. She asks Kate for tips for an overwhelmed new mom who may be doing more of the “donts” right now. Kate says that she recommends setting very small goals for yourself-like-5 minutes to get outside every day. Kate says you can even just start with 1. Just do what you can handle and work your way up. She reiterates adopting the “village” mentality and building your support system so that you don't feel alone. If you feel like you don't have a village, check out the resources available to you in your community and online. There are many resources and support groups that are free. When people offer to come see the baby, tell them to come over and tell them what you need! Take the baby so you can have a nap, clean your house, do your dishes, etc. Ask for the time you need to interact with your child. Sunit asks Kate for one piece of advice for the mom who doesn't have a baby yet-how can she prepare? Kate says that right now you have the opportunity to set yourself up for success-organize PP aspects BEFORE the baby is born. Figure out your support, figure out your systems and do dry runs before hand to ensure you are ready. Make it easy for yourself, station the things you will need often in every area of your house where you spend the most time. Ask for multiples of things that you may use a lot of (ie-more than one “baby seat” for more than one room of the house). Get your finances in order-who will pay the bills if you are the one that pays them right now? Get your logistics in order. Think past the birth experience at all the other practical things you need to be thinking about. Sunit says that's why she started MMPS-to inspire moms to think about this stuff ahead of time. She asks Kate about her Self and how she holds on to what she loves to do. Kate says she loves to write and her blog was inspired by that love. After her son was born, starting her blog was a place for her to express herself without rules and do something for her SELF. Her blog is at www.bayridgebirdroom.com www.toolkitforpostpartumhealing.com to access the toolkit
Jennifer Blossom is the host of the Blossom to be Fit show and is interviewing Sunit to introduce her to Modern Mommy Prepschool listeners. Jenny asks Sunit to tell listeners about the show format-Sunit says that the first episode is meant to share her vision for the podcast but moving forward it will be Sunit interviewing experts who can help moms to be prepare better for motherhood. Jennifer says that when Sunit was a guest on her show, that episode is still their most downloaded episode. Sunit says that right now they are launching in seasons but it will be once a week on Tuesdays and listeners can expect about 30-45 minutes. Jenny asks Sunit what is MMPS and why did she start this. Sunit says it started with her passion for coaching and inspiring women to prepare a little better for motherhood. Sunit is a planner and was having twins and by default ended up thinking about things maybe others do not think about and had a good experience in motherhood. She realized there are core things that you can address before being a mom that will help you navigate motherhood better. She wanted to expand her reach so started creating an online course and then had the idea for disseminating this info over a podcast also. Podcasts allow you to multitask. The whole idea behind the brand is to inspire women to prepare better for motherhood. Jenny says that as a medical professional, she really sees a need for this. Women are drowning in overwhelm and are going to be benefit from being better prepared. Sunit says she is trying to create a movement for this next generation of moms-she is tired of the negativity around motherhood. there is no doubt parenthood is the hardest job in the world but you can truly have it all. She wants women to come listen to this podcast and walk away feeling inspired to have a good experience. She wants it to be a mindset shift. Sunit says she is here to serve anyone for whom motherhood is in the near future. Or if you're a new mom who might be starting to feel overwhelmed. Dads too. Sunit says she coaches women to include the partner in everything and this includes this podcast. this podcast is for anyone for whom PARENTHOOD is int he near furtuere. Every week Sunit will interview guests who are experts in their field-Sunit coaches to pillars of motherhood-the self, the partner, the past the present and the future-and she will have guests on who address various facets of these pillars. Sunit says women get caught up in the same things when they get pregnant-baby names, nurseries etc. And they forget to address the stuff that REALLY matters. Jenny says that the way this is being done is sure to “produce” amazing mothers. She is very excited for this! Jenny asks how listeners can support Sunit. Sunit says “sharing is caring”-if you listen to the episode and you think someone will benefit, just share and listen. Subscribe. Download. Jenny says never underestimate the power you have as a listener to share with someone who may not know about it but could really use it. Sunit says this is even more than a movement-she wants to stop the cycle of overwhelm and you never know how you might be helping someone. Maybe even a new mom who is struggling. Jenny says yes “never rob somebody of the blessing of experiencing this”. Sunit says she is going to have a guest on who lost her best friend to PPD and this is bigger than anything-it affects women on many different levels and can affect lives and families. Sunit wants her listeners to know that she is an open book-she has twin 4 year old boys and an amazing and supportive husband who is encouraging her to pursue MMPS the brand and she is excited for the future of this brand and future collaboration with Blossom to be Fit. Sunit encourages listeners to reach out and tell her what they like and don't like and she adds that she loves fashion and makeup and all things pretty and that people can keep up with her at www.moderntwinmom.com and the podcast and course are over at www.modernmommyprepschool.com Sunit is on all social media handles as Modern Twin Mom and has a private fb group “Modern Mommy Prepschool” that she invites listeners to come to for more discussion and a direct line to some of her guests. Jenny says she might stalk Sunit on Social Media. Sunit closes off by saying she's very excited for this and asks people to share, download and subscribe and tells listeners to stay tuned for all the exciting things her and Jenny have planned. Tune in next week for the next episode!
In episode 25, Insulin Resistance Isn't All About Carbs and Insulin, I explained why an individual cell would "decide" to stop taking up energy. Here in episode 26, I explain tissue-level energy overload, focusing on adipose tissue and liver. At adipose tissue, the problem with fatness isn't the amount of fat. It's that we've reached the point where we can't get any fatter. Well, we can, but we can no longer do so while maintaining a healthy organizational structure within adipose tissue that allows blood, oxygen, and nutrients to get to where they need to go. Surprisingly, some of the things that enable proper expansion, and thus protect our metabolic health, are things that we usually think of as "bad," such as inflammation. In fact, the pro-inflammatory changes in the gut microbiome in response to an obesogenic diet provide information to adipose tissue that it needs to prepare for healthy expansion. And adipose expansion is most protective at the site of the "bad" body fat: visceral fat in the abdomen. At liver, the problem is fat gets trapped in the liver, flattening out everything in the cell and hogging the space needed for glycogen storage, and this can happen even in a lean person. I conclude with some practical recommendations about body composition and nutrient density. In this episode, you will find all of the following and more: How adipose tissue expands (triglyceride and lipid droplet formation, extracellular matrix reorganization, capillary bed growth and reorganization); consequences of poor adipose tissue expansion (liver spillover into ectopic deposition in tissues like liver, skeletal muscle, and pancreas, internal oxidative and endoplasmic reticulum stress, hypoxia); providing more glycerol for greater triglyceride formation (via genetic manipulation of PEPCK to allow greater glyceroneogenesis) protects against metabolic dysfunction (which may indicate a protective role of carbohydrate, which provides the glycerol on a mixed diet); deletion of genes involved in lipid droplet formation exacerbates metabolic dysfunction; allowing matrix metallopproteinases (MMPs) to reorganize the collagen-based extracellular matrix known as septa protects against metabolic dysfunction; expression of hypoxia-inducible factor 1-alph (HIF1alpha) contributes to metabolic dysfunction; inflammation (tumor necrosis factor alpha or TNF-alpha, interleukins or ILs, toll-like receptors or TLRs) is necessary to allow proper extracellular matrix (ECM) reorganization and capillary bed reorganization; visceral abdominal fat expansion is most protective because visceral fat drains directly into the liver via the portal vein, and releases more fat into the liver when it cannot expand further; ectopic fat deposition at the liver is central because the liver is the metabolic hub of fat and carbohydrate metabolism; fat accumulation in liver likely directly compromises glycogen storage; sources of liver fat: include adipose and dietary fat; de novo lipogenesis (DNL) from carbohydrate is a minor source of liver fat; oxidative stress and poor choline status are major factors governing triglyceride export; the choline requirement is increased more by fat than other macronutrients and more by long-chain saturated fats than other fats; practical strategies: body composition is king, but it might not be the right time to lose fat; a well rounded, nutrient-dense diet is low-hanging fruit at any time; additional strategies require nutritional analysis with help of health care professional and data generation and interpretation.
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 06/06
Organisms respond to changes in their environment affecting their physiological or ecological optimum by reactions called stress responses. These stress responses may enable the organism to survive by counteracting the consequences of the environ- mental change, the stressor, and usually consist of plastic alterations of traits related to physiology, behaviour, or morphology. In the ecological model species Daphnia, the waterflea, stressors like predators or parasites are known to have an important role in adaptive evolution and have been therefore studied in great detail. However, although various aspects of stress responses in Daphnia have been analysed, molecu- lar mechanisms underlying these traits are not well understood so far. For studying unknown molecular mechanisms, untargeted ‘omics’ approaches are especially suit- able, as they may identify undescribed key players and processes. Recently, ‘omics’ approaches became available for Daphnia. Daphnia is a cosmo- politan distributed fresh water crustacean and has been in research focus for a long time because of its central role in the limnic food web. Furthermore, the responses of this organism to a variety of stressors have been intensively studied e.g. to hypoxic conditions, temperature changes, ecotoxicological relevant substances, parasites or predation. Of these environmental factors, especially predation and interactions with parasites have gained much attention, as both are known to have great influence on the structure of Daphnia populations. In the work presented in this thesis, I characterised the stress responses of Daphnia using proteomic approaches. Proteomics is particularly well suited to analyse bio- logical systems, as proteins are the main effector of nearly all biological processes. However, performing Daphnia proteomics is a challenging task due to high proteolytic activity in the samples, which most probably originate from proteases located in the gut of Daphnia, and are not inhibited by proteomics standard sample pre- paration protocols. Therefore, before performing successful proteomic approaches, I had to optimise the sample preparation step to inhibit proteolytic activity in Daph- nia samples. After succeeding with this task, I was able to analyse stress responses of Daphnia to well-studied stressors like predation and parasites. Furthermore, I stud- ied their response to microgravity exposure, a stressor not well analysed in Daphnia so far. My work on proteins involved in predator-induced phenotypic plasticity is de- scribed in chapter 2 and 3. Daphnia is a textbook example for this phenomenon and is known to show a multitude of inducible defences. For my analysis, I used the system of Daphnia magna and its predator Triops cancriformis. D. magna is known to change its morphology and to increase the stability of its carapace when exposed to the pred- ator, which has been shown to serve as an efficient protection against T. cancriformis predation. In chapter 2, I used a proteomic approach to study predator-induced traits in late-stage D. magna embryos. D. magna neonates are known to be defended against Triops immediately after the release from the brood pouch, if mothers were exposed to the predator. Therefore, the formation of the defensive traits most probably oc- curs during embryonic development. Furthermore, embryos should have reduced protease abundances, as they do not feed inside the brood pouch until release. To study proteins differing in abundance between D. magna exposed to the predator and a control group, I applied a proteomic 2D-DIGE approach, which is a gel based method and therefore enables visual monitoring of protein sample quality. I found differences in traits directly associated with known defences like cuticle proteins and chitin-modifying enzymes most probably involved in carapace stability. In addition, enzymes of the energy metabolism and the yolk protein vitellogenin indicated alterations in energy demand. In chapter 3, I present a subsequent study supporting these results. Here, I analysed responses of adult D. magna to Triops predation at the proteome level using an optimised sample preparation procedure, which was able to generate adult protein samples thereby inhibiting proteolysis. Furthermore, I established a different proteomic approach using a mass-spectrometry based label- free quantification, in which I integrated additional genotypes of D. magna to create a more comprehensive analysis. With this approach, I was able to confirm the results of the embryo study, as similar biological processes indicated by cuticle proteins and vi- tellogenins were involved. Furthermore, additional calcium-binding cuticle proteins and chitin-modifying enzymes and proteins involved in other processes, e.g. protein biosynthesis, could be assigned. Interestingly, I also found evidence for proteins in- volved in a general or a genotype dependent response, with one genotype, which is known to share its habitat with Triops, showing the most distinct responses. Genotype dependent changes in the proteome were also detectable in the study which I present in chapter 4. Here, I analysed molecular mechanisms underlying host-parasite interactions using the well characterised system of D. magna and the bacterial endoparasite Pasteuria ramosa. P. ramosa is known to castrate and kill their host and the infection success is known to depend strongly on the host’s and the para- site’s genotype. I applied a similar proteomic approach as in chapter 3 using label- free quantification, but contrastingly, I did not use whole animal samples but only the freshly shed cuticle. It has been shown, that the genotypic specificity of P. ramosa infection is related to the parasite’s successful attachment to the cuticle of the host and is therefore most probably caused by differences in cuticle composition. Hence, I analysed exuvia proteomes of two different genotypes known to be either suscept- ible to P. ramosa or not. Furthermore, I compared exuvia proteomes of susceptible Daphnia exposed to P. ramosa to a control group for finding proteins involved in the infection process and in the stress response of the host. The proteomes of the different genotypes showed indeed very interesting abundance alterations, connected either to cuticle proteins or matrix metalloproteinases (MMPs). Additionally, the cuticle pro- teins more abundant in the susceptible genotype showed a remarkable increase in predicted glycosylation sites, supporting the hypothesis that P. ramosa attaches to the host’s cuticle by using surface collagen-like proteins to bind to glycosylated cuticle proteins. Most interestingly, in all replicates of the susceptible genotype exposed to P. ramosa, such a collagen-like protein was found in high abundances. Another group of proteins found in higher abundance in the non-susceptible genotype, the MMPs, are also connected to this topic, as they may have collagenolytic characteristics and therefore could interfere with parasite infection. Furthermore, the data indicate that parasite infection may lead to retarded moulting in Daphnia, as moulting is known to reduce the infection success. Contrastingly to the work presented so far, the study described in chapter 5 invest- igated the protein response of Daphnia to a stressor not well studied on other levels, namely microgravity. As gravity is the only environmental parameter which has not changed since life on earth began, organisms usually do not encounter alterations of gravity on earth and cannot adapt to this kind of change. Daphnia has been part of one mission to space, however, responses of the animals to microgravity are not well described so far. In addition, as Daphnia are an interesting candidate organisms for aquatic modules of biological life support systems (BLSS), more information on their response to microgravity is necessary. For this reason, proteomics is an interesting ap- proach, as biological processes not detectable at the morphological or physiological level may become apparent. Therefore, a ground-based method, a 2D-clinostat, was used to simulate microgravity, as studies under real microgravity conditions in space need high technical complexity and financial investment. Subsequently, a proteomic 2D-DIGE approach was applied to compare adult Daphnia exposed to microgravity to a control group. Daphnia showed a strong response to microgravity with abundance alterations in proteins related to the cytoskeleton, protein folding and energy meta- bolism. Most interestingly, this response is very similar to the reactions of a broad range of other organisms to microgravity exposure, indicating that the response to altered gravity conditions in Daphnia follows a general concept. Altogether, the work of my thesis showed a variety of examples of how a proteomic approach may increase the knowledge on stress responses in an organisms not well- established in proteomics. I described both, the analysis of molecular mechanisms underlying well-known traits and the detection of proteins involved in a response not well characterised. Furthermore, I gave examples for highly genotype dependent and also more general stress responses. Therefore, this thesis improves our understanding of the interactions between genotype, phenotype and environment and, moreover, offers interesting starting points for studying the molecular mechanisms underlying stress responses of Daphnia in more detail.
Background Tendons are dense connective tissues subjected periodically to mechanical stress upon which complex responsive mechanisms are activated. These mechanisms affect not only the development of these tissues but also their healing. Despite of the acknowledged importance of the mechanical stress for tendon function and repair, the mechanotransduction mechanisms in tendon cells are still unclear and the elucidation of these mechanisms is a key goal in tendon research. Tendon stem/progenitor cells (TSPC) possess common adult stem cell characteristics, and are suggested to actively participate in tendon development, tissue homeostasis as well as repair. This makes them an important cell population for tendon repair, and also an interesting research target for various open questions in tendon cell biology. Therefore, in our study we focused on TSPC, subjected them to five different mechanical protocols, and investigated the gene expression changes by using semi-quantitative, quantitative PCR and western blotting technologies. Results Among the 25 different genes analyzed, we can convincingly report that the tendon-related genes - fibromodulin, lumican and versican, the collagen I-binding integrins - α1, α2 and α11, the matrix metalloproteinases - MMP9, 13 and 14 were strongly upregulated in TSPC after 3 days of mechanical stimulation with 8% amplitude. Molecular signaling analyses of five key integrin downstream kinases suggested that mechanical stimuli are mediated through ERK1/2 and p38, which were significantly activated in 8% biaxial-loaded TSPC. Conclusions Our results demonstrate the positive effect of 8% mechanical loading on the gene expression of matrix proteins, integrins and matrix metalloproteinases, and activation of integrin downstream kinases p38 and ERK1/2 in TSPC. Taken together, our study contributes to better understanding of mechanotransduction mechanisms in TPSC, which in long term, after further translational research between tendon cell biology and orthopedics, can be beneficial to the management of tendon repair.
Background: Approximately 7% of survivors from meningococcal meningitis (MM) suffer from neurological sequelae due to brain damage in the course of meningitis. The present study focuses on the role of matrix metalloproteinases (MMPs) in a novel mouse model of MM-induced brain damage. Methods: The model is based on intracisternal infection of BALB/c mice with a serogroup C Neisseria meningitidis strain. Mice were infected with meningococci and randomised for treatment with the MMP inhibitor batimastat (BB-94) or vehicle. Animal survival, brain injury and host-response biomarkers were assessed 48 h after meningococcal challenge. Results: Mice that received BB-94 presented significantly diminished MMP-9 levels (p < 0.01), intracerebral bleeding (p < 0.01), and blood brain barrier (BBB) breakdown (p < 0.05) in comparison with untreated animals. In mice suffering from MM, the amount of MMP- 9 measured by zymography significantly correlated with both intracerebral haemorrhage (p < 0.01) and BBB disruption (p < 0.05). Conclusions: MMPs significantly contribute to brain damage associated with experimental MM. Inhibition of MMPs reduces intracranial complications in mice suffering from MM, representing a potential adjuvant strategy in MM post-infection sequelae.
The aim of this study was to characterize the anti-inflammatory mode of action of botanical extracts from rosehip (Rosa canina), willow bark (Salix alba), and nettle leaf (Urtica dioica) in an in vitro model of primary canine articular chondrocytes. Methods. The biological effects of the botanical extracts were studied in chondrocytes treated with IL-1 beta for up to 72h. Expression of collagen type II, cartilage-specific proteoglycan (CSPG), beta 1-integrin, SOX-9, COX-2, and MMP-9 and MMP-13 was examined by western blotting. Results. The botanical extracts suppressed IL-1 beta-induced NF-kappa B activation by inhibition of I kappa B alpha phosphorylation, I kappa B alpha degradation, p65 phosphorylation, and p65 nuclear translocation. These events correlated with downregulation of NF-kappa B targets including COX-2 and MMPs. The extracts also reversed the IL-1 beta-induced downregulation of collagen type II, CSPG, beta 1-integrin, and cartilage-specific transcription factor SOX-9 protein expression. In high-density cultures botanical extracts stimulated new cartilage formation even in the presence of IL-1 beta. Conclusions. Botanical extracts exerted anti-inflammatory and anabolic effects on chondrocytes. The observed reduction of IL-1 beta-induced NF-kappa B activation suggests that further studies are warranted to demonstrate the effectiveness of plant extracts in the treatment of OA and other conditions in which NF-kappa B plays pathophysiological roles.
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 04/06
Die vorliegende Dissertation befasst sich mit den durch S-Lost-verursachten Symptomen in der Haut, die zunächst durch starke Blasenbildung und später durch eine verzögerte Wund-heilung charakterisiert sind. Bei S-Lost handelt es sich um einen chemischen Kampfstoff, der erstmals im ersten Weltkrieg zum Einsatz kam und bis heute in vielen internationalen Kon-flikten großen Schaden anrichtete, obwohl der Gebrauch schon 1925 durch die Genfer Konvention verboten wurde. Aktuell stellt S-Lost zudem eine Bedrohung durch terroristische Aktivitäten dar. Da für S-Lost-induzierte Verletzungen bislang keine spezifisch wirksamen Behandlungs-methoden verfügbar sind, besteht großes Interesse an der Aufklärung der dem Krankheitsbild zugrunde liegenden molekularen Pathomechanismen, um daraus Rückschlüsse auf besser ge-eignete therapeutische Maßnahmen ziehen zu können. In unseren ersten Experimenten wurden als mögliche Auslöser der Blasenbildung die Expression und Sekretion ausgewählter Matrix-Metalloproteinasen (MMPs) und deren endogenen Inhibitoren, den tissue inhibitors of matrix metalloproteinases (TIMPs) in einem 3D-Haut-modell und in verschiedenen Zelltypen der Haut (Keratinozyten, Fibroblasten, mikrovaskuläre Endothelzellen, mesenchymale Stammzellen, monozytäre Zellen, PMN-Granulozyten) sowohl in Mono- als auch in Mischkultur untersucht. Unter Verwendung von molekularbiologischen und proteinbiochemischen Methoden wie qRT-PCR, Zymographie und Western Blot gelang der Nachweis, dass MMPs - insbesondere MMP-9 - nach Exposition der Zellen (v.a. Fibroblasten und monozytäre Zellen) mit S-Lost deutlich hochreguliert wurden. Zu Erhärtung der Annahme, dass MMP-9 durch Degradation der Basalmembran zwischen Epidermis und Dermis zur Blasenbildung beiträgt, konnte als Pathomechanismus nun erstmals eine parakrine Stimulation von Fibroblasten durch S-Lost-behandelte Keratinozyten identifiziert werden, als deren Folge eine vermehrte MMP-9-Sekretion resultierte. Darüber hinaus zeigte sich in weiteren Versuchen unter Verwendung des sog. Scratch-Assays und eines Transwell-basierten Invasionsassays, dass das Migrations- und Invasionsverhalten der Fibroblasten in Gegenwart des konditionierten Mediums der S-Lost-behandelten Keratinozyten positiv beeinflusst wurde. Aus klinischer Sicht sprechen diese Erkenntnisse für neue therapeutische Ansätze, die darauf beruhen sollten, die S-Lost-induzierte, auf proteolytischer Aktivität basierende Blasenbildung der Haut durch Applikation spezifischer MMP-Inhibitoren zu behandeln. In einem weiteren Projekt wurde die verzögerte Wundheilung als spätes Symptom der S-Lost-Vergiftung auf zellulärer Ebene untersucht, bei der eine eingeschränkte Re-Epithelialisierung der betroffenen Hautstellen beobachtet wird. Sowohl für den Prozess der Wundheilung als auch für die stetige Erneuerung der Haut werden epidermale Stammzellen benötigt, die für die Bildung von Keratinozyten verantwortlich sind. Diese unipotenten Progenitorzellen befinden sich in der basalen Schicht der Epidermis und sind in der Lage zu proliferieren und anschließend terminal zu differenzieren. Um eine Beeinflussung dieser Prozesse durch S-Lost zu untersuchen, wurden primäre unreife Keratinozyten (NHEK) verwendet und hinsichtlich ihres Differenzierungspotenzials untersucht. Dabei erwies sich S-Lost als potenter Induktor der Differenzierung von NHEK, was durch Bestimmung der Expression typischer Markerproteine wie Keratin-1, Involucrin und Loricrin gezeigt wurde. Die Induktion des Reifungsprozesses war sowohl von einem Rückgang der Proliferation als auch von einer verminderten Migrationsrate der Zellen begleitet. Die eingehende Analyse von mitogen-activated protein kinase (MAPK)-Signaltransduktionswegen führte zu der Erkenntnis, dass die Aktivitäten von p38 und ERK1/2 gegenteilige Rollen im Differenzierungsprozess einnehmen. Studien mit spezifischen Inhibitoren der MAPK be¬legten, dass p38 für den Reifungsvorgang in NHEK essentiell ist, während ERK1/2 diesem entgegen wirkt. So konnte durch Blockade von p38 die von S-Lost ausgelöste Differenzierung der Zellen verhindert werden. Ebenso war es durch diese Behandlung möglich, die von S-Lost stark beeinträchtige Migrationsfähigkeit der Keratinozyten wiederherzustellen, welche mit einer erhöhten MMP-1-Expression einherging. Davon abgeleitet erscheint es therapeutisch sinnvoll, selektive p38-Inhibitoren für die Behandlung von Wundheilungsstörungen nach Exposition der Haut mit S-Lost einzusetzen. Zusammenfassend erbrachten unsere Studien also den Nachweis, dass der S-Lost-induzierten Blasenbildung (als frühes Symptom) die spezifische Induktion der MMP-9 zugrunde liegt. Darüber hinaus konnte erstmals eine verfrühte Differenzierung in unreifen Keratinozyten der Haut (als mögliche Ursache für die verzögerte Wundheilung) nachgewiesen werden, wobei die MAPK p38 bei der Initiierung des Prozesses von entscheidender Bedeutung ist. Aufgrund dieser Resultate empfiehlt sich eine kombinierte Applikation von Inhibitoren der Aktivitäten von MMP-9 und p38, wobei der Einsatz jedoch zeitlich abgestimmt erfolgen sollte, um pathologische Effekte (Blasenbildung bzw. Differenzierungsinduktion in Keratinozyten) zu blockieren, ohne die positiven Auswirkungen von MMP-9 und p38 auf die Heilung (Migration von Immunzellen und Keratinozyten bzw. Reepithelialisierung) zu hemmen.
Tierärztliche Fakultät - Digitale Hochschulschriften der LMU - Teil 05/07
Evaluierung von Metamizol und Carprofen als postoperative Analgetika nach Hüftgelenksersatz bei Hunden. Das Ziel dieser Studie war es, die analgetische Wirkung der von den jeweiligen Arzneimittelfirmen für den Hund empfohlenen Dosierungen von Metamizol im Vergleich zu Carprofen nach Hüftgelenkersatz zu bewerten. Es ist bekannt, dass Metamizol ein potentes Analgetikum beim Menschen ist. Bis heute gibt es keine Studien zur postoperativen Wirksamkeit von Metamizol beim Hund. Subjektive (Melbourne Schmerzskala (mMPS) und visuelle Analogskala (VAS)) und objektive (Ganganalyse, in welcher die vertikale Spitzenkraft (PVF) und der vertikale Impuls gemessen wurden) Bewertungsverfahren wurden in dieser Studie für die Evaluierung der Schmerzen herangezogen. 39 klinisch gesunde Hunde mit einem Körpergewicht zwischen 5,5 und 60,5 kg (keine Rassespezifität) wurden in diese Studie eingeschlossen. Die Hunde wurden nach Randomisierung in zwei Gruppen verteilt: Tiere der Gruppe M (n = 19) erhielten 50 mg•kg-1 IV Metamizol TID. Tiere der Gruppe C (n = 20) erhielten 4 mg•kg-1 Carprofen IV SID. Die Patienten wurden 3, 6, 9, 12, 20, 24, 28, 32, 36, 44, 48 and 56 Stunden nach Operationsende subjektiv beurteilt. Wurden bei der Evaluierung mittels mMPS bzw. VAS Punktwerte von 12 bzw. 50 Punkten überschritten, so wurde dies als Anzeichen von Schmerzen betrachtet, welche mit einer intravenösen Gabe von Buprenorphin, 10 μg•kg-1, behandelt wurden (rescue analgesia). Eine Ganganalyse wurde einmal präoperativ (preOP) und dann am ersten (OP1) und zweiten (OP2) postoperativen Tag durchgeführt. Drei Patienten in der Gruppe C benötigten in den ersten 3 bis 6 postoperativen Stunden rescue analgesia. Keines der Tiere in Gruppe M benötigte die Gabe zusätzlicher Schmerzmittel. Sowohl bei der mMPS als auch bei der VAS zeigten Tiere der Gruppe M im Vergleich zu Gruppe C über den gesamten Zeitraum niedrigere Schmerz-Werte. Je nach verwendeter Schmerzskala waren diese Unterschiede nach 6 h (mMPS) bzw. nach 24 h (VAS) als signifikant zu betrachten (p < 0.05). Die postoperativen Ganganalysen zeigten bei Hunden der Gruppe M eine bessere Belastung der operierten Gliedmaße (p < 0.05). Diese Ergebnisse zeigen, dass die alleinige Verwendung von Metamizol als Analgetikum eine potente und zufriedenstellende Analgesie nach orthopädischen Eingriffen bei Hunden gewährleistet. Des Weiteren wurde gezeigt, dass die alleinige Verwendung von Carprofen in der vom Hersteller empfohlenen Dosierung nach Hüftgelenksersatz bei Hunden nicht immer eine zufriedenstellende Analgesie hervorruft.
Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that plays a key role in the pathogenesis of osteoarthritis (OA). Growth factors (GFs) capable of antagonizing the catabolic actions of cytokines may have therapeutic potential in the treatment of OA. Herein, we investigated the potential synergistic effects of insulin-like growth factor (IGF-1) and platelet-derived growth factor (PDGF-bb) on different mechanisms participating in IL-1β-induced activation of nuclear transcription factor-κB (NF-κB) and apoptosis in chondrocytes. Primary chondrocytes were treated with IL-1β to induce dedifferentiation and co-treated with either IGF-1 or/and PDGF-bb and evaluated by immunoblotting and electron microscopy. Pretreatment of chondrocytes with IGF-1 or/and PDGF-bb suppressed IL-1β-induced NF-κB activation via inhibition of IκB-α kinase. Inhibition of IκB-α kinase by GFs led to the suppression of IκB-α phosphorylation and degradation, p65 nuclear translocation and NF-κB-regulated gene products involved in inflammation and cartilage degradation (COX-2, MMPs) and apoptosis (caspase-3). GFs or BMS-345541 (specific inhibitor of the IKK) reversed the IL-1β-induced down-regulation of collagen type II, cartilage specific proteoglycans, β1-integrin, Shc, activated MAPKinase, Sox-9 and up-regulation of active caspase-3. Furthermore, the inhibitory effects of IGF-1 or/and PDGF-bb on IL-1β-induced NF-κB activation were sensitive to inhibitors of Src (PP1), PI-3K (wortmannin) and Akt (SH-5), suggesting that the pathway consisting of non-receptor tyrosine kinase (Src), phosphatidylinositol 3-kinase and protein kinase B must be involved in IL-1β signaling. The results presented suggest that IGF-1 and PDGF-bb are potent inhibitors of IL-1β-mediated activation of NF-κB and apoptosis in chondrocytes, may be mediated in part through suppression of Src/PI-3K/AKT pathway, which may contribute to their anti-inflammatory effects.
Purpose: Ileal carcinoids are gut epithelial tumors originating from serotonin-containing enterochromaffin (EC) cells. Therapeutic options for effectively inhibiting the growth and spread of metastatic carcinoids are still limited. We aimed to identify the role of matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) during tumor development and metastasis. Patients and Methods: Tissue samples were obtained from surgically treated patients. Expression of the EC-cell marker, vesicular monoamine transporter-1 (VMAT-1), was used to verify ileal carcinoids. We investigated the differential expression of MMP-2, 7, 9, 11, and 13 and their endogenous inhibitors (TIMP-1, 2, and 3) by quantitative real-time RT-PCR in 25 primary tumors, their corresponding lymph node metastases and/or liver metastases and matched normal mucosa. Results: Significantly increased expression of VMAT-1, MMP-2, MMP-11, TIMP-1 and TIMP-3 was determined by quantitative RT-PCR in EC-cell carcinoids compared to normal intestinal mucosa (p < 0.05). In contrast, MMP-2 and MMP-9 as well as TIMP-1, TIMP-2, and TIMP-3 expression in primary tumors of patients with liver metastases (M1) was significantly lower than in patients lacking liver metastases (M0). EC-cell tumors were significantly larger in the M1 group of tumors, while VMAT-1 expression was significantly decreased. We found an inverse correlation between tumor size and prognosis. Univariate analysis further revealed that decreased expression of VMAT-1, MMP-2 and TIMP-3 in primary tumors was significantly associated with a reduced survival time of the patients. Conclusion: Our data reveal that MMP-2 and TIMP-3 expression together with VMAT-1 expression are of potential prognostic and clinical value in ileal carcinoids. Copyright (C) 2008 S. Karger AG, Basel
Background: Myocardial infarction results as a consequence of atherosclerotic plaque rupture, with plaque stability largely depending on the lesion forming extracellular matrix components. Lipid enriched non-calcified lesions are considered more instable and rupture prone than calcified lesions. Matrix metalloproteinases (MMPs) are extracellular matrix degrading enzymes with plaque destabilisating characteristics which have been implicated in atherogenesis. We therefore hypothesised MMP-1 and MMP-9 serum levels to be associated with non-calcified lesions as determined by CT-angiography in patients with coronary artery disease. Methods: 260 patients with typical or atypical chest pain underwent dual-source multi-slice CT-angiography (0.6-mm collimation, 330-ms gantry rotation time) to exclude coronary artery stenosis. Atherosclerotic plaques were classified as calcified, mixed or non-calcified. Results: In multivariable regession analysis, MMP-1 serum levels were associated with total plaque burden (OR: 1.37 (CI: 1.02-1.85); p < 0.05) in a model adjusted for age, sex, BMI, classical cardiovascular risk factors, hsCRP, adiponectin, pericardial fat volume and medication. Specification of plaque morphology revealed significant association of MMP-1 serum levels with non-calcified plaques (OR: 1.16 (CI: 1.0-1.34); p = 0.05) and calcified plaques (OR: 1.22 (CI: 1,03-1.45); p < 0.05) while association with mixed plaques was lost in the fully adjusted model. No associations were found between MMP-9 serum levels and total plaque burden or plaque morphology. Conclusion: MMP-1 serum levels are associated with total plaque burden but do not allow a specification of plaque morphology.
Dissemination of metastatic cells probably occurs long before diagnosis of the primary tumor. Metastasis during early phases of carcinogenesis in high risk patients is therefore a potential prevention target. The plant polyphenol Curcumin has been proposed for dietary prevention of cancer. We therefore examined its effects on the human breast cancer cell line MDA-MB-231 in vitro and in a mouse metastasis model. Curcumin strongly induces apoptosis in MDA- MB- 231 cells in correlation with reduced activation of the survival pathway NF kappa B, as a consequence of diminished I kappa B and p65 phosphorylation. Curcumin also reduces the expression of major matrix metalloproteinases (MMPs) due to reduced NF kappa B activity and transcriptional downregulation of AP-1. NF kappa B/p65 silencing is sufficient to downregulate c-jun and MMP expression. Reduced NF kappa B/AP-1 activity and MMP expression lead to diminished invasion through a reconstituted basement membrane and to a significantly lower number of lung metastases in immunodeficient mice after intercardiac injection of 231 cells (p=0.0035). 68% of Curcumin treated but only 17% of untreated animals showed no or very few lung metastases, most likely as a consequence of down-regulation of NF kappa B/AP-1 dependent MMP expression and direct apoptotic effects on circulating tumor cells but not on established metastases. Dietary chemoprevention of metastases appears therefore feasible. Copyright (c) 2007 S. Karger AG, Basel.
Tierärztliche Fakultät - Digitale Hochschulschriften der LMU - Teil 02/07
The study is subdivided into two different parts: the first part deals with the development of a method to gain uterus milk in vivo during the preimplantation periode in cattle for the investigation of regulatory factors. The second part investigates different proteases in bovine follicles 20 hours after GnRH (Gonadotropin releasing hormone) injection (shortly bevor ovulation) for comparable as well as in the corpus luteum (CL) during oestrous cycle and induced luteolysis. In addition apoptotic as well as anti-apoptotic factors were evaluated in the CL during oestrous cycle and induced luteolysis. For the development of a method for gaining uterus milk in vivo during the first 24 days of gravidity in cattle, nine heifers were cycle synchronised using the Ovsynch method and artificially inseminated. Before flushing an epiduralanaesthesia was given and both uterus horns were flushed with 13ml 0.9% NaCl using a balloon embryo transfer catheter at day 5, 7, 12, 17 and 24 of gravidity. The catheter was placed 1cm cranial to the bifurcatio uteri in both horns. It was possible to retrive between 3ml and 13ml of the used flushing fluid. The uterus milk from the ipsilateral horn was inspected for an embryo and an EDTA-stabilisator was given to the uterus milk of both horns. An infection of the uterus occured in three heifers after the second and in five heifers after the third flushing. In one heifer no infection was found. Between day 17 and day 24 all heifers showed clear signs of oestrus. It was possible to detect progesterone, oestradiol-17-beta, PGF2alpha and VEGF via enzyme immunoassay (EIA) and radio immunoassay (RIA), respectively. Because of the occurred infection no statistic analysis was made. But it could be seen that the level of progesterone ranged between
We monitored serum levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) before and during intravenously applied immunoglobulin (IVIG) therapy in 33 patients with chronic immune-mediated neuropathies and myopathies and 15 controls. Baseline MMP-2 and TIMP-2 serum levels were lower and MMP-9 and TIMP-1 serum levels higher in all patients compared to age-matched controls. Eight days after IVIG treatment, MMP-2, TIMP-2, and TIMP-1 serum levels increased, while MMP-9 serum levels decreased, indicating tissue repair. After 60 days, MMP-9 levels increased, MMP-2 approached normal levels, while TIMP-1 and TIMP-2 serum levels were below day 8 levels, indicating relapsing tissue damage. Comparing the MMP/TIMP results with the clinical courses, IVIG treatment tended to change MMP/TIMP levels in a way that paralleled clinical improvement and relapse. In sum, during a distinct time period, IVIG therapy seems to be able to modulate VIMP-mediated tissue repair. Copyright (c) 2006 S. Karger AG, Basel.
© 2020-2025 Ivy Podcast Discovery LLC
