Physiology

Identifying Your Body’s Weaknesses in the Saddle: A Clinic with Mary Wanless – Eventing Nation

They say you should never meet your idols and while I have been to a Paul McCartney concert, meeting Mary Wanless was about as amazing as a rock concert. In May I attended a Mary Wanless Clinic. I have had her books on my shelf since before I can remember; in fact, Ride With Your Mind is one of the first horse book that I ever read. The moment I discovered I could audit her clinic literally right up the road, I immediately jumped on the opportunity.

It was an incredibly hot day in May one of those days where the breeze almost felt hotter than the ambient air. I pulled into the other side of Loch Moy Farms (who knew they had an indoor over there) and walked into an arena not knowing my mind was about to be rocked.

I am not going to lie when I say I had high expectations for this clinic. I had read cover-to-cover many books before but none of them had it me as hard as The New Anatomy of Rider Connection. This book came out at a time when I was deeply immersed in anatomy trains and the importance of facia through my yoga teacher training. When I saw that Mary Wanless had applied the anatomy trains not only to the rider but to the horse I was hooked. I have read this book at least three times and every time I pick it up, I am learning something new.

If you are a total nerd for anatomy and physiology like me, this book is for you. However, if you are just looking to ride better, this book is also for you. That was one of the things that amazed me about Marys teaching style: she could meet the rider at the level they are at.

Whether that was a young girl just taking her first canter steps or a professional dressage rider, Marys knowledge of the riders body could talk circles around me, and I consider myself pretty well versed in the body (I have a four year degree in Kinesiology with a concentration in exercise science, have been a personal trainer for close to ten years and spent the last two years working for a physical therapy practice). That said I have dedicated my life to learning about the body, and it excites me when I find somebody who is truly a master of their craft.

AND she signed the book!

I missed the first day of the clinic because I had to work (damn mortgages). If I could go back in time, I would have rearranged to be there all three days, preferably with a horse but that was not meant to be at this time. I walked into the second day thinking I have read this book I can catch on and I did but I would have loved to see the transformation in the riders way of going across all three days.

The biggest take away and what I am bringing back to you is the kneel exercise she taught on the second days lecture portion. This is a great way to determine if you are relying more heavily on your Superficial Back Line or your Superficial Front Line these lines are the fascia trains that make up everyones body.

So what is fascia? According to Google, Fascia is a thin casing of connective tissue that surrounds and holds every organ, blood vessel, bone, nerve fiber and muscle in place. The tissue does more than provide internal structure; fascia has nerves that make it almost as sensitive as skin. It has been said that if you were to take everything else out of the body and only leave the fascia you would still be able to recognize the person in front of you. It was thought for many years in western medicine that fascia was mostly inert. But how could something so pervasive be useless? The simple is answer is: it is not!

If you havent heard of this, read the book! If you have heard of it, good! This should interest you READ THE BOOK. There is a reason its a book and not a blog post. The concepts simply can not be boiled down into a cliff notes version.

This exercise is quite hard on the knees, so I do not recommend this for those that struggle with knee pain. I also do not recommend doing it to muscle failure, but rather use it as a fact-finding mission.

1: Start by kneeling on even ground.

2. Place your hands on your stomach and you back just above your pelvis with your palms flat.

3. Engage through your core keep you tail bone tucked under.4. Lift up by leading with your belt buckle, so that your hips are over top of your knees.

The goal of this exercise is to keep even pressure on your hands and not round your back or arch your back as you go through the range of motion. If you do round or arch your back, this is telling:

If you tend to round your back, you are stronger on your superficialfrontline.

If your tendency is to arch your back to come up, youre more tight in you superficial back line.

If your tendency is to round your back, you are strong on your superficial front line. This means your tendency would be to be to get into more of a crouched position in the saddle.

If your tendency is to arch your back to come up, youre more tight in you superficial back line. This means that you will more likely lean back in the saddle and get into more on a water skiing position. Continue to work on this exercise until you can keep even pressure on your stomach and back.

Want more Rider Physiology? Read Horse Nations review of The New Anatomy of Rider Connection here.

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Identifying Your Body's Weaknesses in the Saddle: A Clinic with Mary Wanless - Eventing Nation

Physiology

Dr Christopher Thompson Discusses Innovative Treatment for Type 2 Diabetes and Obesity – AJMC.com Managed Markets Network

Christopher Thompson, MD, MSc, FASGE, FACG, AGAF, FJGES, director of endoscopy and codirector of the Center for Weight Management and Wellness at Brigham & Womens Hospital, professor of medicine at Harvard Medical School, discusses duodenal jejunal bypass liner treatment and future innovations in gastroenterology.

Christopher Thompson, MD, MSc, FASGE, FACG, AGAF, FJGES, director of endoscopy and codirector of the Center for Weight Management and Wellness at Brigham & Womens Hospital, professor of medicine at Harvard Medical School,discusses findings on treatment with duodenal jejunal bypass liner for patients experiencing type 2 diabetes and obesity. This interview took place during the recent annual meeting, Digestive Disease Week.

In this first part of a 2-part interview, Thompson discusses a study involving duodenal jejunal bypass liner (DJBL). This interview is edited lightly for clarity.

AJMC: When treating patients with type 2 diabetes and obesity who were being treated with insulin, what are some patient experiences you saw firsthand?

Thompson: I'm a gastroenterologist and an endoscopist, so I spend most of my time doing procedures. I do remember taking care of patients with diabetes when I was a resident. I know that once they get on insulin, they start to have a decline in their health; insulin causes weight gain and causes all sorts of other problemsit's not well tolerated. So, I guess I would say this is kind of a unique niche for gastroenterologists to care for obesity. There's a growing number of us but since I've really started caring for obesity, I started to see these diabetic patients again, and nothing seemed to have improved. I mean, it was so many years ago, 20 years ago, when I was a residentactually more than that probablytaking care of patients with diabetes and it seemed like it was very similar. There's more oral antidiabetic medications available now, but still, once they go on insulin, they don't seem to do very well. So, it's definitely time for a change, and whatever technology we can have to help these patients I think would be very welcomed.

AJMC: Can you first explain how the duodenal jejunal bypass liner (DJBL) works, and what makes it different from other treatments for patients with T2D and obesity trying to achieve similar results (such as bariatric surgery)? Why is this new method needed?

Thompson: The DJBL is quite unique in that it uses the body's physiology and an understanding of the physiology to treat type 2 diabetes. What it's doing is sheltering the duodenum from seeing any food, and it's also preventing the mixing of food with bile or pancreatic juices. Well, I could start by saying the DJBL is a 60-centimeter-long sheath, like a sleeve, is anchored in the duodenal bulb and extends all the way to just about the jejunum. What it does is it shelters the duodenal from contact with food or chyme, and it prevents the mixing of that food or chyme with bile and/or pancreatic juices. So, it is getting this undigested food and bile to the distal small bowel in a state where it has a pretty dramatic effect on incretin-producing cellswe thinksuch as L-cells, so that we're exploiting the cells production of GLP-1 and probably other substances that then have some beneficial effects on type 2 diabetes. They're known to increase insulin production and decrease glucagon, and cross the blood-brain barrier as a neurotransmitter and signal that the patient may be full, also slows gastric emptying. These substances, these gut hormones, have several beneficial effects.

AJMC: Can you summarize your research and findings into the utilization of the DJBL for this patient group?

Thompson: This was an FDA [approved] clinical trial, and they had some predefined end points. It was a randomized, sham-controlled trial with 2-to-1 randomization, so patients would be randomized. For every 2 patients, they got the procedure, 1 would get a sham procedure. The patients were blinded, as were the investigators that were following them. The predefined end points were both related to safety as well as efficacy. The efficacy end point involved hemoglobin A1C (A1C), and they wanted to see a changean improvementin A1C of at least .4% above the sham. Then, the safety end point was that they wanted the rate of serious adverse event-related device removal to be less than 15%.

So, the study did meet both of those end points, those primary end points. the treatment group was 1.1% drop in A1C. The sham was .3%. Clearly, it was well above that .4% margin, as an efficacy end point. The safety end point, I think it was just above 9% removals due to SAEs [serious adverse event-related device removal] and that's well below the 15%. So, it did meet both of those end points. However, what did also occur in this study was that the hepatic abscess rate was unexpectedly higher than they thought. This was not something they anticipated. All the patients did well, all hepatic abscesses resolved with antibiotics and some cases some percutaneous drainage. But that was just something that caught them off guard, so the company stopped the trial due to that.1

AJMC: Is there another study taking place as a result of these findings?

Thompson: Theres another registry trial run by a Dr Bob Ryder out of England. He's an endocrinologist. He has over 1000 patients in that and the hepatic abscess rate is only 1.1%, I believe. That's a lower rate than we were seeing in our study, but it has much more patients. It turns out that in our protocol, the PPI [proton pump inhibitor], we had maximum-dose PPIs; we were using very high-dose PPIs, and the rest of these patients the registry, they weren't. It makes sense that PPIs are certainlytheyre an independent risk factor for hepatic acid formation, and very high doses in diabetic population certainly could be the cause.

We started another trial. Now, we do not have the patients on PPIs. Were using H2-receptor antagonists, and they're doing really quite well.2 We've not seen any recurrence of hepatic abscesses so far. We've also instituted some measures to make sure that we would catch anything early as well. The patients have Wifi-enabled thermometers, and they take their temperatures every day, and they get monthly ultrasounds to look at the liver. We've not seen any further hepatic abscesses since we stopped PPIs, so we're cautiously optimistic

AJMC: How did this study ensure a diverse population? How do the findings reflect the needs of patients in various demographics?

Thompson: It is an FDA [approved] clinical trial, so they have in therekind of baked into itthey make sure you have a certain amount of diversity. What you try to do is find centers that are in different locations that would make sure to pull in a nice, wide, diverse population. We did, I think, have quite good diversity. Over 50% were womenof the patientsand we had a good breakdown from underrepresented minority status as well.

AJMC: What are the long-term implications of DJBLs? This study had a 12-month follow-up; are there any implications for a longer follow-up?

Thompson: Some other folks have looked at this. Oursyou knowthe analysis was done at 12 months because the sham patients were then offered an open-label placement of the device. That's really all you could do as far as the analysis goes, but other studies have looked at it more longitudinally. It seems like the results you see during the treatment period persist well after device removal, and it's not clear exactly why that's happening. It might be due to some kind of remodeling of the duodenal mucosa. There are other companies are looking at just ablating the mucosa, and they're getting good anti-diabetic effects as well. So, it might be that the duodenum itself changes over time, and that's what leads to the durability of the results.

AJMC: What other lifestyle changes do patients with DJBLs need to make?

Thompson: I think lifestyle is hugely important in achievement of obesity and diabetes, and keep in mind this population was a population of patients with obesity and diabetes, so it wasn't thin type 2 diabetics, which is a different population. No one had type 1 diabetes. Additionally, no one in this study was on insulin. Thats probably another important point to make, that these were people that you were trying to prevent them from going on insulin, right? It's not to say that it might not help get people off insulin, but I think that just the focus of the trial was to have a uniform population in a sense, and give it enough power and be able to understand the results. We had limited to people that were kind of poorly controlled diabetics, so their A1C had to be above 7.5% to 10%, somewhere in that range, and kind of maximal therapy, if you would, just short of insulin. We were trying to kind of look at that population specifically.

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Dr Christopher Thompson Discusses Innovative Treatment for Type 2 Diabetes and Obesity - AJMC.com Managed Markets Network

Physiology

Cameron Smith: If you want to understand politics, train to be a foster parent – AL.com

This is an opinion column.

Foster parent training has helped me understand more about American politics than years of experience in the halls of Congress ever could. The psychology and physiology of a traumatized child puts the interconnected web of politics, policy, and power in a whole new light. In truth, many foster children arent that different from modern American partisans.

Trauma and stress attend almost any situation where the state intervenes in a relationship between parent and child. As a result, foster parents train to address those factors which deeply influence both behavior and development. Thankfully, my wife and I trained with Dr. Daniel Siegels hand model of the brain to help us understand some complex neurological interactions.

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Look at your hand. The wrist represents the spinal cord, the palm is the brainstem (basic body functions), and the thumb is the amygdala (danger detection). Place the thumb into the palm to form the limbic system. The other four fingers fold over the thumb to represent the cerebral cortex, and the tips of those fingers are the prefrontal cortex (emotional governor).

If theres a simpler model of brain anatomy, I certainly havent found it.

The limbic system is the instinctual survival part of our brain which also handles memories and emotions. The cortex is responsible for imagination, creativity, problem-solving, and our higher level thinking in general.

If a grizzly bear is chasing me through the woods, Im quite grateful for my limbic system which triggers a rush of cortisol, a stress hormone, increasing my heart rate and giving me a burst of energy to flee. If I stopped and reasoned through my options before moving to escape, Id become bear food.

On the other hand, I cant effectively consider the best policies to reduce gun violence while chased by said bear, because the limbic system is in the drivers seat. If I need to think and process, the cortex must retake control. That happens when I feel safe from the bear and calm down.

The prefrontal cortex is especially important because it allows us to evaluate a signal from the amygdala and control our emotions before they get to the point where our fight or flight response takes over. For example, it helps us keep our cool even after someone says something particularly offensive.

Our foster trainers explained that our prefrontal cortex isnt fully developed until were almost 30 years old. As such, children have less of an ability to control their emotions. When they flip their lids, its often up to parents to help them calm down before their thought centers can effectively engage and address a situation.

Sounds good for parenting. What about politics?

For the longest time, I couldnt understand why politicians I respected ran negative, fear-based ads I absolutely despised. Brain physiology explains so much.

Thinking, rational people challenge politicians. They ask all kinds of questions, discuss issues in detail, and expect politicians to demonstrate statesmanship.

Rather than rise to the challenge, many politicians create grizzly bears barreling towards us. Democrats want to take our constitutional rights. Republicans are white supremacists. Liberals want to force you to clap for drag queens performing at your church. Conservatives will commandeer your uterus. If the other party wins, your future and family are at risk.

In response, our lids flip and too often stay that way. The limbic system drives our actions. We look to our leaders to tell us what to do to address the immediate threats. We become reactionary and aggressive. As far as our brains are concerned, stress is stress. Our belief in the threats around us is every bit as relevant as reality. My brain doesnt care whether the grizzly is actually chasing me. Im running until I believe Im safe.

Cable news makes for a toxic political partner. If were angry or afraid, were glued to the screen awaiting the next grizzly coming over the horizon. As long as were focused on a string of partisan monsters, we dont hold our own elected officials accountable or stop watching. We become strung out, inconsistent, and unquestionably compliant.

If our political leaders and media companies were foster parents, theyd calm us down. Theyd help us sort through our emotions in productive ways. Theyd help us prioritize what really impacts our families and communities.

But then we might not vote for them. We might realize that so many of them are directionally loud and otherwise incompetent. We might turn off the televisions and play with our children and grandchildren in a creek somewhere. Above all, wed operate in reality and not useful political fiction.

Our only path to a better future is understanding whats happening to us and ending the cycle. Whether its cable news, social media, or even casual conversation, were all worse off participating in a political battle royale. When we sense anger and rage developing because of something we watch, read, or hear, we should put our lids back on. Change the subject, step back for a bit, or do something unexpectedly kind. Keep the thoughtful parts of our brains in control and realize we cant effectively communicate when theyre not.

Better yet, train to be a foster parent. Many children need a calming adult influence, and many of us could use a little help learning to be just that.

Smith is a recovering political attorney with three boys, two dogs, and an extremely patient wife. He engages media, business, and policy through the Triptych Foundation and Triptych Media. Please direct outrage or agreement to csmith@al.com or @DCameronSmith on Twitter.

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Cameron Smith: If you want to understand politics, train to be a foster parent - AL.com

Physiology

Could reptiles and amphibians hold the key to the fountain of youth? – Popular Science

When it comes to longevity, scientists have long suspected that scaly and slimy vertebrates have an edge. Galpagos tortoises, eastern box turtles, cave-dwelling salamanders known as olms, and a number of other reptiles and amphibians can live more than a century. And the oldest known land animal, a Seychelles giant tortoise named Jonathan, recently celebrated his 190th birthday.

Until now, though, most of the evidence highlighting the long lifespans of these animals have come from anecdotal reports from zoos, says Beth Reinke, a biologist at Northeastern Illinois University in Chicago. She and a team of more than 100 researchers from around the globe have compared rates of aging in 77 species of reptiles and amphibians in the wild. The study initially grew out of the long-running notion that turtles can live for a long time. We wanted to know how widespread that is, Reinke says.

The researchers found that although aging and lifespan varied greatly from one species to the next, turtles, crocodilians, and salamanders generally aged very slowly and had disproportionately long lifespans for their size. Meanwhile, another group of researchers in Denmark reached similar conclusions after comparing 52 species of turtles and tortoises living in zoos and aquariums: roughly 75 percent of the reptiles showed slow or negligible senescence, and 80 percent aged more slowly than modern humans.

Both teams reported their results on June 23 in Science. The new findings arent particularly surprising but do challenge the idea that senescencea gradual decline in bodily functions that increases the mortality risk after an organism reaches sexual maturityis universal, says Rob Salguero-Gmez, an ecologist at the University of Oxford who wasnt involved in the research.

Theyre both excellent pieces of research, he says. They add a new layerupon our understanding of senescence across the tree of life.

For their analysis, Reinke and her collaborators drew from long-running studies on a wide variety of animals that included turtles, frogs, salamanders, crocodilians, snakes, lizards, and the lizard-like tuatara. These studies tracked reptile and amphibian populations over an average period of 17 years and encompassed more than 190,000 individual animals.

To determine how quickly a species aged, Reinke and her team calculated the rate at which its individual members died over time after hitting sexual maturity. The team estimated lifespan from the number of years it took for 95 percent of these adult animals to die.

One caveat to these estimates, Reinke notes, is that the researchers didnt distinguish between different causes of death. When people hear aging, they tend to think of just physiology, she says. Our measure of aging includes not just physiology, but all things that could cause death in the wild.

[Related: These jellyfish seem to cheat death. Whats their secret?]

The team also compared their estimates with previously published data on aging in mammals and birds. These groups of vertebrates are warm-blooded or endothermic, meaning they are capable of regulating their own body temperature. Reinke and her team expected to find that the cold-blooded, or ectothermic, reptiles and amphibians would age more slowly on the whole than birds and mammals because their slower metabolisms put less physiological wear and tear on their bodies. But the results revealed a mixed bag. While some reptiles and amphibians did age more slowly than most birds and mammals, others aged faster. Longevity in reptiles and amphibians varied from 1 to 137 yearsa much wider range than the 4 to 84 years seen in primates.

However, species with negligible aging appeared across the reptile and amphibian family tree, and turtles as a group were uniquely slow agers, she says.

Species equipped with protective shells, scaly armor, or venom aged more slowly and lived longer. In both reptiles and amphibians, species that began reproducing later in life ended up living longer. The team also observed that reptiles that lived in warm temperatures aged more quickly, while amphibians in similar conditions aged more slowly.

More research is needed to tease out how these and other variables drive differences in aging and longevity. There are a lot of really interesting patterns that we brought to light that need to be explored further, Reinke says. I think that ectotherms could have the answers to a lot of what we want to know about aging for human health.

In the quest to extend human life, salamanders may be a particularly promising group to focus on. A lot of them can live for 10 years or more, which for their size is a lot, Reinke says. These amphibians are famous for their ability to regrow lost limbs and tails, leading some scientists to believe that there may be a connection between these regenerative capabilities and the salamanders impressive longevity.

For the second new paper, the team out of Denmark focused on aging in captive reptiles.

All these theories of senescence state thatthe risk of mortality would increase with age after sexuality maturity, when we stop putting so much energy into repairing cell damage and tissues and put more energy into reproduction, says Rita da Silva, a biologist at the University of Southern Denmark in Odense and coauthor of the findings.

The best candidates for a species that might escape the damaging effects of getting old are those that continue growing their entire lives, such as turtles and tortoises.

What we were mainly interested in is if their risk of mortality increases with age as it does in humans for instance, and in other mammals and in birds, da Silva says. She and her colleagues analyzed records of captive turtles and tortoises, with data for each species ranging from 58 to several thousand individuals.

In most species, mortality either remained constant with age or actually decreased. On average, male turtles and tortoises lived longer than femalesthe opposite of whats seen in mammals. For three of the species, the team also examined data on wild populations, and found that captive animals enjoyed lower rates of aging.

In some way these populations found a way to lower their aging rates when the conditions are favorable, da Silva says. In captivity, reptiles dont need to pour energy into finding food or shelter. But its not clear why only some reptiles seem to respond to this bounty by minimizing or avoiding senescence. For some other species either the conditions are not ideal or they are not really able to switch off the senescence, da Silva speculates.

[Related: Has the fountain of youth been in our blood all along?]

While the majority of turtle and tortoise species studied aged more slowly than humans, its too soon to say what implications the findings could have for efforts to understand human health and aging.

We need to be careful when making these comparisons, da Silva says. We cannot draw a clear connection between this and humans, [but] I can say that we are one step closer to understanding the mechanisms of aging.

The two new papers show how much remains to be discovered about aging and how it differs among humans and other animals, plants, and more distantly related organisms, Salguero-Gmez says.

Theres true value in this type of research beyond the potential translations into biomedical research, just for a higher appreciation for our place in the tree of life and also for the realization that not everything follows a human way of living, he says.

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Could reptiles and amphibians hold the key to the fountain of youth? - Popular Science

Immunology

Locum Consultant in Paediatric Immunology job with Cambridge University Hospitals NHS Foundation Trust | 156644 – The BMJ

Applications are invited for the post of Locum Consultant in Paediatric Clinical Immunology at Cambridge University Hospitals NHS Foundation Trust to commence from 27 June 2022 until 25 June 2023 to cover sabbatical leave.

The Paediatric Immunology Service provides a regional service focused on diagnosis and management of immune deficiency in children presenting with severe, frequent, or atypical infection and autoimmune or autoinflammatory diseases. Additional to providing a consult service within the hospital, the post holder will run regular outpatient immunology clinics taking referrals from across region, and support multidisciplinary clinics for 22q11 deletion syndrome, respiratory complications of immune deficiency, complex haematological syndromes and rheumatic diseases.

The post holder will work closely with Great Ormond Street Clinical Immunologist, providing shared care as clinically indicated.

Main duties of the job

You will be fully registered with the GMC and have CCT in Paediatrics with a specialist interest in Paediatric Immunology and Infectious Diseases or be within six months of award of CCT at the time of interview. Applications are welcomed from those unable to work full time for personal reasons or those wishing to job-share.

Working for our organisation

The applicant must have demonstrable skills in listening, reading, writing and speaking in English that enable effective communication about medical topics with patients and colleagues, as set out in the GMCs Good Medical Practice (2013). Non-UK applicants must possess the IELTS/OET exam before obtaining a GMC licence to practice.

Applications from job seekers who require skilled worker sponsorship to work in the UK are welcome and will be considered alongside all other applications. For further information please visit the UK Visas and Immigration website.

It is a requirement for skilled worker applicants, applying for entry clearance into the UK, to present a criminal record certificate from each country they have resided continuously or cumulatively for 12 months or more in the past 10 years. Adult dependants (over 18 years old) will also be subject to this requirement.

Cambridge University Hospitals NHS Foundation Trust is an Equal Opportunities Employer.

Job description and main responsibilities

Please refer to the Job description and Person specification attached for further details on the main responsibilities and duties for this post.

Additional contact information

Visiting the Department should be arranged through Ms Tracey White, PA/Paediatric Medical Secretary via email attracey.white@addenbrookes.nhs.ukor by telephone on 01223 256291.

Informal enquiries about this post should be addressed to Dr Donna McShane, Consultant in Paediatric Respiratory Medicine via email atdonna.mcshane@addenbrookes.nhs.uk

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Locum Consultant in Paediatric Immunology job with Cambridge University Hospitals NHS Foundation Trust | 156644 - The BMJ

Immunology

New textbook addresses the timely topic of molecular immunology – EurekAlert

The recent experience of the COVID-19 pandemic and the ensuing vaccine development have drawn our attention to the system that keeps us alive: immunity. However, our immune system does more than fight against microbes. The new textbook Molecular Immunology: How Science Works by Professor Carsten Carlberg and Dr Eunike Velleuer provides an essential background in molecular immunology. This includes the basic principles and underlying processes of immunity against bacteria and viruses, immune responses to cell and organ transplants, the overboarding immune activation in allergies and autoimmune reactions, as well as the way how a properly functioning immune system protects us against cancer.

Understanding these mechanisms will highlight that a fight against viruses uses the same mechanisms as the battle against thousands of transformed cancer cells arising every day in each of us, the authors remark.

Our immune system is composed of biological structures like the lymphatic system and bone marrow, as well as cellular immunity mediated by cell types such as leukocytes and humoral immunity mediated by proteins such as antibodies and complement proteins. The perfect balance of these components protects us against infectious diseases and cancer. Molecular immunology aims to understand the collective and coordinated response of these cells and proteins to substances that are foreign to our body. The main purpose of this immune response is the fight against microbes, such as viruses, bacteria, fungi and parasites. However, the example of allergic reactions, which nowadays are getting continuously more common, demonstrates that also non-microbial molecules can induce a strong reaction of our immune system. Moreover, incorrect reactions of the immune system can lead to autoimmune diseases, such as type I diabetes and multiple sclerosis. Immune responses can cause tissue injuries that are more harmful than the effects of pathogenic microbes. These collateral damages may be even fatal, such as in the case of bacterial sepsis or strong responses to SARS-CoV-2 infections.

The different chapters of the book explain the cellular basis of immunology, the key molecules mediating the effector functions of B and T cells, and how molecular immunology is associated with infections caused by bacteria and viruses, organ transplantation, allergy and autoimmunity as well as different types of cancers.

We hope that readers will enjoy this rather visual book and get as enthusiastic as the authors about life and its protection reflected in the fine-tuned molecular immunology.

Molecular Immunology: How Science Works is the fifth textbook in the series How Science Works co-authored by Professor Carlberg. The earlier books in the undergraduate book series are Cancer Biology: How Science Works, Mechanisms of Gene Regulation: How Science Works, Human Epigenetics: How Science Works and Nutrigenomics: How Science Works. They are linked to the lecture courses in Molecular Immunology, Molecular Medicine and Genetics, Cancer Biology and Nutrigenomics given by Professor Carlberg at the University of Eastern Finland in Kuopio. The book series now covers each lecture course.

Carsten Carlberg graduated in 1989 with a PhD in biochemistry at the Free University Berlin. After positions as postdoc at Roche in Basel, group leader at the University of Geneva and docent at the University of Dsseldorf, he is since 2000 full professor of biochemistry at the University of Eastern Finland in Kuopio. His work focuses on the mechanisms of gene regulation by nuclear hormones, in particular on vitamin D. At present, Professor Carlbergs projects focus on the epigenome-wide effects of vitamin D on the human immune system in the context of cancer.

Eunike Velleuer graduated in 2006 as MD at the University of Dsseldorf and specialized in 2016 in pediatric hemato-oncology. At present, she serves as senior physician at the Helios Childrens Clinic Krefeld as well as a research associate at the University of Dsseldorf. Her special clinical focus is the cancer predisposition syndrome Fanconi anemia. Herein, her research interest is early detection and prevention of oral squamous cell carcinoma and identifying patients with Fanconi anemia at risk. Furthermore, Dr. Velleuer is interested in increasing patients resilience and finding alternative ways for long-lasting empowerment.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Immunology

KalVista Pharmaceuticals to Present Data at the 2022 Meeting of the European Academy of Allergy and Clinical Immunology (EAACI) – Business Wire

CAMBRIDGE, Mass. & SALISBURY, England--(BUSINESS WIRE)--KalVista Pharmaceuticals, Inc. (NASDAQ: KALV), a clinical stage pharmaceutical company focused on the discovery, development, and commercialization of oral, small molecule protease inhibitors, today announced the acceptance of multiple abstracts at the 2022 European Academy of Allergy and Clinical Immunology (EAACI) Congress, taking place in Prague, Czech Republic and virtually, from July 1-3, 2022. The presentations are:

About KalVista Pharmaceuticals, Inc.

KalVista Pharmaceuticals, Inc. is a pharmaceutical company focused on the discovery, development, and commercialization of oral, small molecule protease inhibitors for diseases with significant unmet need. KalVista has developed a proprietary portfolio of novel, small molecule plasma kallikrein inhibitors initially targeting hereditary angioedema (HAE) and diabetic macular edema (DME). KalVista is developing sebetralstat as an oral on-demand therapy for acute HAE attacks and is enrolling the Phase 3 KONFIDENT clinical trial. KVD824 is in development for prophylactic treatment of HAE, with the Phase 2 KOMPLETE clinical trial underway. In addition, KalVistas oral Factor XIIa inhibitor program represents a new generation of therapies that may further improve the treatment of HAE for patients. In DME, an intravitreally administered plasma kallikrein inhibitor, called KVD001, has completed a Phase 2 clinical trial.

For more information about KalVista, please visit http://www.kalvista.com.

For more information on the sebetralstat HAE on-demand Phase 3 KONFIDENT study, please visit http://www.konfidentstudy.com.

For more information on the KVD824 HAE prophylaxis Phase 2 KOMPLETE study, please visit http://www.kompletestudy.com.

Forward-Looking Statements

This press release contains "forward-looking" statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such as: "anticipate," "intend," "plan," "goal," "seek," "believe," "project," "estimate," "expect," "strategy," "future," "likely," "may," "should," "will" and similar references to future periods. These statements are subject to numerous risks and uncertainties, including the potential impact of COVID-19, that could cause actual results to differ materially from what we expect. Examples of forward-looking statements include, among others, timing or outcomes of communications with the FDA, our expectations about safety and efficacy of our product candidates and timing of clinical trials and its results, our ability to commence clinical studies or complete ongoing clinical studies, including our Phase 3 KONFIDENT and Phase 2 KOMPLETE clinical trials, and to obtain regulatory approvals for sebetralstat, KVD824 and other candidates in development, the ability of sebetralstat, KVD824 and other candidates in development to treat HAE or DME, and the future progress and potential success of our oral Factor XIIa program. Further information on potential risk factors that could affect our business and financial results are detailed in our filings with the Securities and Exchange Commission, including in our annual report on Form 10-K for the year ended April 30, 2021, our quarterly reports on Form 10-Q, and our other reports that we may make from time to time with the Securities and Exchange Commission. We undertake no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.

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KalVista Pharmaceuticals to Present Data at the 2022 Meeting of the European Academy of Allergy and Clinical Immunology (EAACI) - Business Wire

Immunology

Beyond the spike: New antibody analysis predicts severe COVID-19 outcomes – EurekAlert

image:Jishnu Das, Ph.D., assistant professor of immunology and of computational and systems biology in the University of Pittsburgh School of Medicine view more

Credit: University of Pittsburgh

PITTSBURGH, June 27, 2022 Most research on immunity to the SARS-CoV-2 virus and COVID-19 vaccine development has focused on antibody responses to the spike protein and other viral surface proteins. But antibodies that recognize the viruss internal proteins could also be important for immunity and disease outcomes, according to a new study led by University of Pittsburgh, Georgia Institute of Technology and Emory University researchers.

In the study, online now in Cell Reports, the team performed the most comprehensive analysis to date of COVID-19 antibodies in a small set of patients with severe disease. They found that antibody profiles of internal viral proteins, including those conserved across coronaviruses, predicted which patients survived or died just as well as corresponding profiles for surface proteins, suggesting that targeting other parts of the virus beyond the spike protein could be important for enhancing COVID-19 vaccines and therapies.

The novel aspect of this study is that we conducted very deep profiling of SARS-CoV-2 antibodies and looked at many different aspects of these antibodies, said co-senior author Jishnu Das, Ph.D., assistant professor of immunology and of computational and systems biology in Pitts School of Medicine. The whole world has been focused on the spike protein and the receptor binding domain, but this study is the first concrete evidence that specific antibodies against internal proteins are also positively associated with survival in severe COVID-19.

When the immune system encounters a virus, it produces antibodies that help neutralize and clear the infection. Each antibody specifically recognizes just one antigen, often a viral protein. Most COVID-19 immunity research has focused on the spike and other surface proteins, which form the viruss outer coat, but beyond these so-called canonical antigens, SARS-CoV-2 has about 25 other internal proteins.

To see whether immune responses to these non-canonical antigens could predict survival outcomes in patients with severe COVID-19, Das teamed up with co-senior authors Aniruddh Sarkar, Ph.D., assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, and Harinder Singh, Ph.D., professor of immunology and the director of the Center for Systems Immunology at Pitt.

The researchers analyzed blood samples that had been collected from 21 patients who were hospitalized with severe COVID-19 in 2020 prior to the approval of vaccines. Seven of these patients died from the disease, and the other 14 survived. Using a microscale antibody profiling platform developed by Sarkar, the team comprehensively analyzed antibodies to three canonical and four non-canonical antigens.

According to Sarkar, the platform analyzes three key features of antibodies. One is antigen specificity, or what the antibody is binding to. The second is effector function, which relates to the antibodys role in immune response. The third feature is glycosylation, or the addition of carbohydrate molecules to the antibody, which dramatically impacts antibody function.

By simultaneously profiling these three features, we can get a far deeper understanding of a given antibody than just looking at antibody titers, explained Sarkar.

The researchers found that no single antibody feature could differentiate between patient survival outcomes. But when they analyzed overall antibody profiles either canonical or non-canonical they noticed clear differences between survivors and non-survivors.

We were surprised to find such compelling evidence that antibodies directed at canonical and non-canonical antigens were equally predictive of survival outcomes, said Singh. Our findings suggest that non-canonical antibodies may play a role in recovery from severe disease, although more research is needed to prove causation and pinpoint the mechanisms.

Most COVID-19 vaccines and monoclonal antibodies artificial antibodies used to treat COVID-19 have become less effective with the emergence of delta and omicron variants because mutations in the spike help the virus avoid detection. According to Singh, far fewer mutations have accumulated in the viruss internal proteins, suggesting that augmenting vaccines or therapies to target these non-canonical antigens could elicit more robust immunity against emerging variants of concern.

When the team restricted their analysis to antibodies against non-canonical antigens conserved across coronaviruses including those that cause the common cold and other respiratory infections in COVID-19 patients, they could still distinguish survivors and non-survivors. These antibodies were also found in nine pre-pandemic, healthy control subjects, suggesting that exposure to coronaviruses besides SARS-CoV-2 could induce antibody responses linked with favorable outcomes in severe COVID-19.

According to Das, these findings could inform development of pan-coronavirus vaccines.

In ongoing work, the team is using their platform to look at antibodies in vaccinated people with breakthrough infections compared with unvaccinated individuals. Theyre also interested in understanding whether different antibodies play different roles in protection against COVID-19 over time.

They also plan to extend the platform to understanding antibodies in other contexts, including rejection of organ transplants and other infectious diseases.

Other authors who contributed to this study were co-first authors Sai Preetham Peddireddy, of the Georgia Institute of Technology, and Syed A. Rahman, Ph.D., of Pitt, as well as Anthony R. Cillo, Ph.D., Godhev Manakkat Vijay, Ph.D., Ashwin Somasundaram, M.D., Creg J. Workman, Ph.D., William Bain, M.D., Bryan J. McVerry, M.D., Barbara Methe, Ph.D., Janet S. Lee, M.D., Prabir Ray, Ph.D., Anuradha Ray, Ph.D., Tullia C. Bruno, Ph.D., Dario A.A. Vignali, Ph.D., Georgios D. Kitsios, M.D., Ph.D., and Alison Morris, M.D., all of Pitt.

This research was supported by the National Institutes of Health (DP2AI164325 and U01AI141990) and the UPMC Immune Transplant and Therapy Center.

Observational study

Human tissue samples

Antibodies targeting conserved non-canonical antigens and endemic coronaviruses associate with favorable outcomes in severe COVID-19

12-Jun-2022

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Beyond the spike: New antibody analysis predicts severe COVID-19 outcomes - EurekAlert

Immunology

argenx Receives Positive CHMP Opinion for Efgartigimod for the Treatment of Adult Patients with Generalized Myasthenia Gravis in Europe – BioSpace

Breda, the NetherlandsJune 24, 2022argenx (Euronext & Nasdaq: ARGX), a global immunology company committed to improving the lives of people suffering from severe autoimmune diseases, today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended European Commission (EC) approval of efgartigimod as an add-on to standard therapy for the treatment of adult patients with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody positive.

The positive CHMP opinion is a scientific recommendation for marketing authorization, serving as a basis for the ECs final decision on argenxs application for efgartigimod. The EC is expected to make a decision within approximately 60 days following CHMP recommendation, which will be applicable to all 27 European Union Member States, in addition to Iceland, Norway and Liechtenstein.

The current treatment of generalized MG in Europe leaves many patients with insufficiently controlled symptoms that markedly decrease quality of life. Caregivers and medical teams are well aware of the need for new treatment options that are safe, effective and targeted to the disease biology said Anthony Bhin, MD neuromuscular physician at Institut de Myologie, La Piti Salptrire, Paris. As a practicing neurologist regularly seeing people who live with this debilitating chronic disease, the CHMPs positive opinion of efgartigimod represents an exciting advancement toward bringing a new treatment option to these patients in Europe.

The MAA included results from the pivotal Phase 3 ADAPT trial, which were published in the July 2021 issue of The Lancet Neurology. The ADAPT trial met its primary endpoint, demonstrating that significantly more anti-acetylcholine receptor (AChR) antibody positive gMG patients were responders on the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale following treatment with efgartigimod compared with placebo (68% vs. 30%; p<0.0001). Responders were defined as having at least a two-point reduction on the MG-ADL scale sustained for four or more consecutive weeks during the first treatment cycle.

There were additionally significantly more responders on the Quantitative Myasthenia Gravis (QMG) scale following treatment with efgartigimod compared with placebo (63% vs. 14%; p<0.0001). Responders were defined as having at least a three-point reduction on the QMG scale sustained for four or more consecutive weeks during the first treatment cycle.

Efgartigimod had a demonstrated safety profile in the ADAPT clinical trial. The most frequently reported adverse reactions were upper respiratory tract infections (10.7% following treatment with efgartigimod vs. 4.8% of placebo) and urinary tract infections (9.5% vs. 4.8%).

We are thrilled by the CHMPs recommendation in favor of efgartigimod, which brings us one step closer to delivering this therapy to people living with gMG in Europe and around the world, said Anant Murthy, Ph.D., General Manager, EU, argenx. We are confident in the European team we have built, and pending marketing authorization, look forward to close collaboration with regulatory bodies and government authorities across the region to ensure this treatment option will be available for as many patients as possible.

Efgartigimod is the first-and-only approved FcRn blocker in the U.S. as VYVGART (efgartigimod alfa-fcab) for the treatment of adult gMG patients who are anti-AChR antibody positive and in Japan for those who do not have sufficient response to steroids or non-steroidal immunosuppressive therapies (ISTs). argenx also plans to launch efgartigimod in Canada, China through its collaboration with Zai Lab, and select additional regions.

About Phase 3 ADAPT Trial

The Phase 3 ADAPT trial was a 26-week randomized, double-blind, placebo-controlled, multi-center, global trial evaluating the safety and efficacy of efgartigimod in adult patients with gMG. A total of 167 adult patients with gMG in North America, Europe and Japan enrolled in the trial. Patients were randomized in a 1:1 ratio to receive efgartigimod or placebo, in addition to stable doses of their current gMG treatment. ADAPT was designed to enable an individualized treatment approach with an initial treatment cycle followed by subsequent treatment cycles based on clinical evaluation. The primary endpoint was the comparison of percentage of MG-ADL responders in the first treatment cycle between efgartigimod and placebo treatment groups in the anti-AChR antibody positive population.

About Efgartigimod

Efgartigimod is an antibody fragment designed to reduce pathogenic immunoglobulin G (IgG) antibodies by binding to the neonatal Fc receptor and blocking the IgG recycling process. Efgartigimod is being investigated in several autoimmune diseases known to be mediated by disease-causing IgG antibodies, including neuromuscular disorders, blood disorders, and skin blistering diseases. It is currently approved in the United States for the treatment of adult patients with gMG who are anti-acetylcholine receptor antibody positive, and Japan for adult patients with gMG who do not have sufficient response to steroids or non-steroidal immunosuppressive therapies.

About Generalized Myasthenia Gravis

Generalized myasthenia gravis (gMG) is a rare and chronic autoimmune disease where IgG autoantibodies disrupt communication between nerves and muscles, causing debilitating and potentially life-threatening muscle weakness. Approximately 85% of people with MG progress to gMG within 24 months1, where muscles throughout the body may be affected. Patients with confirmed AChR antibodies account for approximately 85% of the total gMG population1.

About argenx

argenx is a global immunology company committed to improving the lives of people suffering from severe autoimmune diseases. Partnering with leading academic researchers through its Immunology Innovation Program (IIP), argenx aims to translate immunology breakthroughs into a world-class portfolio of novel antibody-based medicines. argenx developed and is commercializing the first-and-only approved neonatal Fc receptor (FcRn) blocker in the U.S. and Japan.

For further information, please contact:

Media:Kelsey Kirkkkirk@argenx.com

Investors:Beth DelGiaccobdelgiacco@argenx.com

Michelle Greenblattmgreenblatt@argenx.com

Forward-looking Statements The contents of this announcement include statements that are, or may be deemed to be, forward-looking statements. These forward-looking statements can be identified by the use of forward-looking terminology, including the terms believes, hope, estimates, anticipates, expects, intends, may, will, or should and include statements argenx makes concerning the timing of any approval or marketing authorization by the ECof efgartigimod as an add-on to standard therapy for the treatment of adult patients with gMG who are AChR antibody positive. By their nature, forward-looking statements involve risks and uncertainties and readers are cautioned that any such forward-looking statements are not guarantees of future performance. argenxs actual results may differ materially from those predicted by the forward-looking statements as a result of various important factors. A further list and description of these risks, uncertainties and other risks can be found in argenxs U.S. Securities and Exchange Commission (SEC) filings and reports, including in argenxs most recent annual report on Form 20-F filed with the SEC as well as subsequent filings and reports filed by argenx with the SEC. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements. These forward-looking statements speak only as of the date of publication of this document. argenx undertakes no obligation publicly update or revise the information in this press release, including any forward-looking statements, except as may be required by law.

1 Behin et al. New Pathways and Therapeutics Targets in Autoimmune Myasthenia Gravis. J Neuromusc Dis 5. 2018. 265-277

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argenx Receives Positive CHMP Opinion for Efgartigimod for the Treatment of Adult Patients with Generalized Myasthenia Gravis in Europe - BioSpace