In Conversation provides a glimpse into the life of an outlier an exceptional person going above and beyond to improve outcomes in their field. In 2019, Professor Kathryn North AC won the prestigious Peter Wills Medal Research Australias flagship award in recognition of her outstanding leadership in genomic medicine, which has helped drive Australias international reputation in this field.

As Director of the Murdoch Childrens Research Institute, Professor North plays a key role in integrating genomic testing and diagnosis into standard health care, with the aim to shorten diagnosis times and increase diagnostic rates to enable early intervention as well as provide access to treatment for people with genetic disorders and cancer. Through her own research, she has worked to identify new disease genes and improve diagnosis, setting the benchmark for ongoing research efforts.

This award, which Im incredibly thrilled to receive, really recognises a range of roles Ive played not just as an individual researcher but as part of the efforts of hundreds of researchers in Australia and around the world working together to bring advanced genomics into standard health care.

After training as a child neurologist, I became increasingly fascinated by genetics and its potential to predict, diagnose and help treat disease. The lure of research drew me back to the lab, with a major focus on inherited muscle diseases like muscular dystrophy, which can lead to lifelong disability in affected children and adults. My work in this area led me to discover the effects of the gene ACTN3, which influences muscle power and recovery from damage and was subsequently dubbed the gene for speed.

We studied elite athletes and demonstrated that ACTN3 is a major determinant of skeletal muscle performance, but my team has also recently shown that variations in ACTN3 influence disease severity and progression in Duchenne muscular dystrophy. We are now studying how it influences muscle-wasting associated with ageing, steroid use and cancer.

My research is just one example of how genomic medicine can make a tremendous difference. This led me to help establish Australian Genomics, a national network of clinical and laboratory genetics services, hospitals, universities, research institutions and patient advocacy groups working together to establish procedures to enable all Australians access to genomic health care. The Murdoch Childrens Research Institute is now at the forefront of the genomics revolution, translating the latest discoveries into clinical practice.

An accurate diagnosis is hugely important because it gives answers to both the patient and the clinician. In my work as a paediatrician, Ive seen parents desperately seeking an answer to the cause of their kids intellectual or physical disability, wanting to know about their childs future and whether they would have other affected children.

Previously, we just couldnt answer these questions. Advances in genetic technology mean all genes can now be sequenced quickly and cheaply, and the information used to predict, diagnose and treat rare diseases as well as many forms of cancer.

Medical genetics and genomics has changed dramatically since the mid 90s. In the past we were able to give families with affected children a clinical description, but couldnt accurately put a label on what exactly was wrong.

The Human Genome Project and the development and rollout of advanced next-generation, ultrarapid gene sequencing have been an absolute game changer. I couldnt have imagined that wed be using genome technologies in the clinic within two years of using it in a research setting, increasing the diagnostic rate fivefold, and having geneticists working side by side with intensive care physicians to provide that diagnosis within three days.

We can now provide a genetic diagnosis for 50 to 90% of our families and answer these difficult questions.

Genomics is absolutely going to transform healthcare delivery. Using global data gathered and shared responsibly from millions of people, we can be much more accurate in making a prediction about the individual. We will be able to move to a healthcare model of prediction, prevention, early intervention and targeted treatment, and eventually improve and maintain the wellness of the population rather than focusing solely on illness.

This will no doubt come with significant challenges. To overcome these we need to approach genomics at the local and national level, and partner globally to be able to apply our insights to individuals accurately and with meaning.

Its incredibly important we engage at a public level so the community can understand our work. We need to bring the public along on this journey and explain the applications and great benefits of applying big data and genomic technologies to benefit individual patients. Its up to us as doctors and researchers to convey those messages accurately, strongly and with a united voice.

Research Australias Health and Medical Research Awards are important because they increase the visibility of science in general and medical research in particular within the community. They bring recognition to the researchers behind some of Australias most exciting medical and health discoveries, and kickstart conversations we need to be having to harness the possibilities of science for community benefit.

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In Conversation with Professor Kathryn North - Australian Hospital + Healthcare Bulletin

By Jennifer Couzin-FrankelApr. 9, 2020 , 11:35 AM

In college in the 1990s, Alix Timko wondered why she and her friends didnt have eating disorders. We were all in our late teens, early 20s, all vaguely dissatisfied with how we looked, says Timko, now a psychologist at Childrens Hospital of Philadelphia. Her crowd of friends matched the profile she had seen in TV dramasoverachievers who exercised regularly and whose eating was erratic, hours of fasting followed by a huge pizza.

My friends and I should have had eating disorders, she says. And we didnt.

It was an early clue that her understanding of eating disorders was off the mark, especially for the direst diagnosis of all: anorexia nervosa. Anorexia is estimated to affect just under 1% of the U.S. population, with many more who may go undiagnosed. The illness manifests as self-starvation and weight loss so extreme that it can send the body into a state resembling hibernation. Although the disorder also affects boys and men, those who have it are most often female, and about 10% of those affected die. Thats the highest mortality rate of any psychiatric condition after substance abuse, on par with that of childhood leukemia. With current treatments, about half of adolescents recover, and another 20% to 30% are helped.

As a young adult, Timko shared the prevailing view of the disease: that it develops when girls, motivated by a culture that worships thinness, exert extreme willpower to stop themselves from eating. Often, the idea went, the behavior arises in reaction to parents who are unloving, controlling, or worse. But when Timko began to treat teens with anorexia and their families, that narrative crumbledand so did her certainties about who is at risk. Many of those young people dont have body dissatisfaction, they werent on a diet, its not about control, she found. Their mom and dad are fabulous and would move heaven and Earth to get them better.

Timko wasnt alone. Other researchers were also questioning psychological theories of anorexia that had reigned for generations. Hunger is a basic drive, says Cynthia Bulik, a clinical psychologist who runs eating disorder centers at the University of North Carolina, Chapel Hill, and at the Karolinska Institute. The idea that patients use willpower to override hunger never rang true, she says. My patients have said for years that when they starve, they feel better. She began to consider another possibility: What if their biology is driving them to eschew food?

Bulik and Timko are now part of a small band of researchers working to untangle the biology of anorexia. The more they look, the more they find to suggest the diseases biological roots run deep. For instance, genetic studies indicate its about as heritable as obesity or depression. The circuitry of the brains reward system behaves differently in unaffected volunteers than in people with anorexia and those who have recovered. And new treatments drawing on biology are being tested, including deep-brain stimulation and psychedelic drugs. Those experiments aim not only to improve the outlook for patients, but also to explore how closely the disease aligns with others across psychiatry, including obsessive-compulsive disorder (OCD) and addiction.

Scientists pursuing those new ideas face a challenge, in part because of money: For fiscal year 2019, anorexia got $11 million in funding from the National Institutes of Health (NIH), a figure that hasnt changed notably in many years and that researchers decry as shockingly low given the diseases burdens. By contrast, schizophreniawhich has a similar prevalence and also surges during adolescencegarnered $263 million. The dearth of funder interest, many say, springs from the view that anorexias roots are cultural, along with shame and stigma still clouding the disease. But evidence is mounting that biology is at its core.

Many researchers lament that eating disorders, including anorexia nervosa, are underfunded given their prevalence. These numbers are drawn from 2017 data for the United States; the number of individuals affected is an estimate.

(GRAPHIC) X. LIU/SCIENCE; (DATA) BRYN AUSTIN/BOSTON CHILDRENS HOSPITAL; NATIONAL INSTITUTES OF HEALTH

Lori Zeltser pivotedto anorexia from studying obesity. A developmental neuroscientist at Columbia University, she studied the brains of developing mice, trying to identify feeding circuits that increase susceptibility to obesity in adulthood. Then about 10 years ago, Zeltser saw a notice for funding from the Klarman Family Foundation, formed by hedge fund manager Seth Klarman and his wife, Beth, now the foundations president. The foundation wanted to stimulate basic research into eating disorders, and because of Zeltsers research on appetite, she submitted a proposal.

To get up to speed on anorexia, Zeltser turned to the literature. Researchers in Sweden and Minnesota had compared anorexia rates in identical and fraternal twins, a common approach to tease out heritability of complex traits and diseases. Those reports showed that 50% to 60% of the risk of developing anorexia was due to genes, implying DNA is a powerful driver. By contrast, family studies suggest the heritability of breast cancer is about 30%, and that of depression is roughly 40%. I was shocked, Zeltser says.

Layered on the genetics work was a data point that caught Zeltsers attention. An antipsychotic drug, olanzapine, which causes profound weight gain as a side effect, had little to no effect on weight when tested in people with anorexia. Something in peoples biology prevented olanzapine from causing weight gain, Zeltser believes. That is not just [mental] control.

But a deep schism remains, with many practitioners concerned that biology is getting more attention than it deserves. If I had to choose nature versus nurture in the development of anorexia and other eating disorders, I would choose nurture, says Margo Maine, a psychologist who has treated eating disorders for years. Eating disorders are primarily female, she says, in part because gender is a cultural experience.

Psychotherapist Carolyn Costin, who recovered from anorexia in the late 1970s and established a network of private treatment centers around the United States, says biology plays a role but that cultural messages and psychological stressors are also important factors. She worries especially that the way biology research is described could discourage patients about their prospects for recovery. About 8 years ago, she says, Clients started coming in, saying, Its genetic, why bother trying to get well?

Such comments agitate researchers like Bulik. The patients she treats, she says, are reassured, not distressed, to learn that the disorder is rooted in biology and that biology doesnt translate into destiny. Although she, Zeltser, and others agree that anorexia has environmental drivers, as most chronic conditions do, they object to the idea that environment leads the way. Exposure to this ideal [of thinness] is ubiquitous, but everybody doesnt get anorexia nervosa, Bulik says. None of the sociocultural literature has ever been able to explain why. She adds, A lot of patients will say, It was never about being thin for me, ever.

If you look at psychiatric syndromes over 200 years, anorexia hasnt changed at all, whereas our culture has, says James Lock, a child psychiatrist who heads the child and adolescent eating disorders program at Stanford University School of Medicine.

To begin digging into the biology of anorexia, Zeltser used a 2010 grant from the Klarman foundation to build a mouse model of the disease. Because feeding is easy to measure, she reasoned that anorexias restrained feeding behavior is well-suited for animal modeling. Her goal was to study the eating and starvation patterns of the mice and explore how genetics and the environment interact to trigger the disorder.

In a 2016 issue ofTranslational Psychiatry,Zeltser described micewith a variant in a gene that in people is linked to anorexia. On its own, the variant didnt noticeably affect mouse feeding behavior. To mimic the pullback from eating that often precedes a diagnosis, the researchers restricted the animals caloric intake by 20% to 30%. Then they induced stress, another factor linked to anorexia, by housing the normally social animals alone. The result: The mice stop eating, Zeltser says.

Lori Zeltser, a developmental neuroscientist at Columbia University, has developed a mouse model of anorexia nervosa.

Zeltser is talking with clinical colleagues about comparing her rodents behavior with videos of patients in a feeding lab, where researchers observe how much people eat, which nutrients they choose, and which they avoid. If the behaviors seem parallel, the mice could help point the way to new treatments or even different environments that could better support eating.

But publishing her animal work has proved difficult. Zeltser is often asked, How do you know if what youre finding is relevant to humans? Thats a common question of anyone doing mouse work, but Zeltser says the challenge here runs deeper. This is not taken seriously as a disease that has a biological basis, she says. Instead, its dismissed as extreme girl behavior and oh my God, theyre crazy, pushback she finds immensely frustrating.

Accumulating genetic data could change that by making anorexias biological roots harder to ignore. Some of the strongest evidence emerged last summer, when Bulik and others published inNature Geneticsthe largest genetics study on the disease, with roughly $9 million in funding from the Klarman foundation and additional funds from NIH. By analyzing the genomes of nearly 17,000 people with anorexia and more than 55,000 people without, the researchers identified eight statistically significant genomic regions, along with other patterns of genetic associations that yielded important clues. Some of those associations tracked with results of studies of other psychiatric illnesses, including OCD and depression, which didnt surprise Bulik. What did were overlapping associations with DNA controlling body mass index (BMI), lipids, and other metabolic traits.

We said, This doesnt look like any other psychiatric disorder, Bulik says. It might be the inverse of obesitythese people might be genetically predisposed to low BMI. In the February 2019 issue of theJournal of the American Academy of Child & Adolescent Psychiatry, she and her teamsifted through BMI recordsfor young people later diagnosed with anorexia and other eating disorders. The BMIs of 243 people diagnosed with anorexia began to diverge from those of a control group before they started kindergarten.

Bulik is now launchingthe Eating Disorders Genetics Initiative, with more than $7 million from NIH, additional funding from Sweden and the United Kingdom, and potential infusions from other countries and individual donors. The initiative aims to include 100,000 people with anorexia nervosa, bulimia nervosa, and binge eating disorder. Although genetics is unlikely to offer quick solutions, Bulik hopes it can shine the light in the direction you need to go for effective therapies, including medications.

The genetic findingsmight one day intersect with another line of research: studies of brain structures and signaling that are revealing tantalizing differences between people with and without anorexia. At Columbia, psychiatrist Joanna Steinglass wanted to understand how the brains of people with anorexia guide their food choices. In two studies, she and her colleagues recruited inpatients with eating disorders along with a control group. In people with anorexia, both during and after hospitalization, MRI scans showed the region of the brain associated with selecting foods was the dorsal striatum, which is key to forming habits. In people without an eating disorder, a different brain region guides choices. The work first appearedin 2015 inNature Neuroscience, and the team presented more findings at a conference last year.

Theyre using different circuits when they make decisions, Steinglass says. This jibes with her idea that as people repeatedly restrict eating, the behavior moves to a different brain region and becomes less amenable to change. That could help explain why many recovered patients relapse.

Another clue to how the brain might throw eating off trackwas reported last month inThe American Journal of Psychiatry. Walter Kaye, a psychiatrist who directs the eating disorders program at the University of California (UC), San Diego, led a study looking at how the brains of people with anorexia behave when their bodies are hungry. Kaye, whose program treats about 70 patients per day, ran a study that included 48 women, 26 of whom had anorexia. Each was studied twice with brain imaging, once immediately after a meal and, on a separate visit, after fasting for 16 hours.

Kaye knew hunger activates brain circuits that in turn motivate eating, making food desirable. That relationship was clear during brain imaging of the control group volunteers: When they were offered sugar water after 16 hours of fasting, their reward and motivation circuits lit up. But in people with anorexia, those circuits were much less active after fasting. They could identify being hungry, Kaye says, but their brains couldnt convert that into a desire to eat. The patients also experienced heightened anxiety and inhibition, along with diminished reward signaling in their brains. That effect may further impair their drive to eat. Kaye suggests people with anorexia miscode food as risky rather than rewarding.

A lot of patients will say, It was never about being thin for me, ever.

Psychiatrist Rebecca Park at the University of Oxford also suspects the disease hijacks the brains reward system. Some of her patients experience this sense of aberrant reward, almost a high from starvation, she says. Parks neuroscience research indicates aberrant brain responses to reward cues.

Are those brain differences a cause or a result of starvation? Studying people in remission eliminates the effects of malnutrition on the brain but cant definitively answer the question. Its likely that starvation in adolescence is going to damage your brain, Park says. One way to begin to disentangle whether the brain differences predate the disease is to study people very early in its course. Steinglass is in the third year of a brain scanning study of reward circuitry, which now includes 55 recently diagnosed teenagers and a control group of 25 others. The coronavirus pandemic has halted enrollment for now, but Steinglass hopes to have results in 2 to 3 years. Other researchers are working to understand how, and to what degree, the brain recovers once eating resumes.

Theres an overall sensethat were joining the rest of the world by finally applying scientific methods to anorexia nervosa, Steinglass says. The ultimate goal is new treatments, which are sorely needed.

The most studied and most effective strategy to date is called family-based treatment (FBT), which originated at the Maudsley Hospital in London. It was later refined by Lock and psychologist Daniel Le Grange, of UC San Francisco, who trained at Maudsley.

FBT asks parents to set aside many of their familys day-to-day activitiesscaling back school, work, hobbiesto sit with their children, requiring them to eat. Faced with food as a form of medicine, and with their world having contracted, many young people do start to eat again despite the fear and anxiety it causes them. Researchers are working to understand how FBT is intertwined with the biology of the illness, but for about half who try FBT in adolescenceand perhaps 70% who try it early in the diseasethe treatment is effective.

But many families arent told about that therapeutic strategy, even though decades have passed since it first showed success in a randomized trial, in 1987. Practitioners may not be familiar with FBT, Timko says, they may believe the family played a role in anorexias onset, or they may feel that adolescents must want to get better before starting FBTa view she disputes.

Laura Collins Lyster-Mensh experienced the regimen up close after her daughter Olympia, then 14, stopped eating one day in 2002. Lyster-Mensh says a succession of therapists urged her and her husband to stand back and let Olympia eat when she was ready. Meanwhile, her weight continued to spiral downward. We had been told she wouldnt recover, families were really at fault, to back off and let her do this on her own, Lyster-Mensh says. Then she learned about FBT from a newspaper article and raced to try it.

The first agonizing meals took hours, while Olympia mashed her food into a pulp or cried and raged at her parents. I know families whose kids have jumped out of moving cars to avoid a sandwich, says Lyster-Mensh, echoing comments of many clinicians who describe patients crushing fear of food. Olympia ultimately recovered, although not without challenges that included a relapse during college.

The young patients treated with FBT who do start to eat again do well on the one measure that predicts longer-term prognosis: early weight gain. In 2019, a study in theEuropean Eating Disorders Reviewled by Le Grange confirmed earlier research showing thatgaining about 2.3 kilograms in the first month of treatment is a predictor of health1 year later. Girls with anorexia who boosted their calorie intake and gained weight experienced increases in estrogen levels (which plummet in starvation), reduced stress, and improved ability to navigate different situations, a psychological trait called flexibility.

Researchers are exploring ways to build on and improve FBTor find new strategies to help patients in whom it has failed. Some clinical trials are testing whether certain talk therapies, such as cognitive behavioural therapy to help patients reframe their thinking, can helpfor example, by reducing anxiety or other impediments to eating.

New biological models of anorexia hint at other kinds of interventions. An 18-person study at Johns Hopkins University is offering the psychedelic drug psilocybin to patients. Early data suggest it holds promise in helping smokers quit and combating alcoholismand many researchers believe that in certain ways, anorexia shares some features with addiction. Park is leading a seven-person study of deep-brain stimulation in people with severe enduring anorexia, some of whom also have OCD.

Theres a certain neural network thats well characterized in OCD, she says, and disrupting the signaling in that network with deep-brain stimulation can help those patients. Because OCD and anorexia have shared features and some genetic links, shes interested in whether disrupting the same neural network might also help people with the eating disorder.

Still, studies remain sparse, Lock says. With limited funding, theres little chance of attracting new scientists to a small field. As researchers, you dont want to go to the pot thats empty, he says. Why arent we investing more? Its especially frustrating because, Lock points out, many patients with anorexia successfully heal and enjoy a bright future. What [other] illness in psychiatry can you say you cure? he asks.

For families, regardless of whether a patient recovers, the shame can persistand with it hesitation to speak up and lobby for funding. Lyster-Mensh is an exception. After her familys experience, she began to voice support for evidence-based treatmentfirst in a memoir,Eating with Your Anorexic, which she wrote under the name Laura Collins, and then throughFEAST, a message board turned advocacy group.

Its still a pretty small group, Lyster-Mensh says, of those willing to speak openly. Most families are so burned out, crushed, guilty, that they dont want to come forward, she says. There are still these myths out therethat these are chosen illnesses and parents somehow failed to prevent, or caused, or exacerbated the problem. Still, she hopes that as researchers doggedly track the diseases biological roots in genes and the brain, those enduring myths will fade.

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Rethinking anorexia: Biology may be more important than culture, new studies reveal - Science Magazine

Newswise MORGANTOWN, W.Va. Engineers in the Benjamin M. Statler College of Engineering and Mineral Resources at West Virginia University are using their expertise and equipment in a campus-wide effort to create personal protective equipment to keep up with the needs of health care providers in the fight against the COVID-19 pandemic.

Josh Bintrim and Kelsey Crawford, both Statler College graduates and Innovation Hub shop managers, have worked in collaboration with Hub Director Gene Cilento, Assistant Director Kolin Brownand health care professionals at WVU Health Sciences Center to design surgical mask extenders, face shields and intubation boxes for use in medical facilities.

Since initial production began two weeks ago, the Innovation Hub, a new prototyping center in development in the Statler College, has gone through multiple design iterations of products with input from physicians on the front lines of the pandemic.

The team has distributed more than 3,000 surgical mask extenders to local medical facilities, with calls coming in from California to Massachusetts, and even Ireland, requesting supplies and templates to create the mask extenders.

Now that medical professionals are required to wear surgical masks throughout their entire shift, there have been numerous reports of the masks causing irritation to the skin behind the ears. The mask extenders created in the Innovation Hub reduce the pressure behind the ears, affording the user an increased measure of comfort.

As long as supplies last, Bintrim and Crawford can use a laser cutter to create 300 extenders every hour.

Sourcing materials has been a big challenge, Crawford said. The response from the maker community has been great, but it has led to a shortage on clear, thin plastics. We have reached out to various companies and are adjusting previous designs to fit the materials that are available.

To maintain production of the face shields, the team is in need of 4 feet by 8 feet sheets of 0.03, 0.04 and .125 inch polycarbonate and 0.5 inch spools of elastic fabric, at least 6 inches long.

The team hopes to have an additional 3,000 surgical mask extenders, approximately 2,000 face shields and 40 intubation boxes completed and distributed to WVU Health Sciences Center and J.W. Ruby Memorial Hospital by the end of the week.

Parsing through all of the ideas and narrowing our focus on what we could do the fastest was a big challenge, Bintrim said. We went from 3D printing a face shield visor in five hours to completely redesigning the entire system to make an entire face shield in three minutes.

The Innovation Hub has made the directions for creating the face shields publicly available. The downloadable(231KB .zip) fileincludesface shield, visor and visor insert templates. See assembly video and materials required at bottom of article.

While the facility is not a manufacturing center, the team hopes that the templates will be used by companies who have the capacity to undergo mass distribution.

Obviously we wish that we could do everything, but we only have limited equipment and man hours, Bintrim said. I have always said that we are the college of engineering and that we should be the engineers for WVU. We now have a major collaboration between ourselves, HSC, Davis College and Eberly College and it allows us to do and be just that.

Now that the mask extenders and face shields have been in use for several days, Bintrim and Crawford explained that the feedback from health care workers has been very positive.

Everyone has been extremely grateful for the efforts that everyone is doing at WVU, Crawford said. We have had nurses and doctors almost in tears as they thank us.

The responses have been overwhelmingly positive, and people are incredibly thankful, Bintrim said. The hardest part is trying to tell everyone that we are the ones that are thankful for what they do and the risks they take every day by just going to work. We are just trying our best to support them in the fight.

To make donations of materials, questions regarding templates or distribution, contact Gene Cilento atGene.Cilento@mail.wvu.edu or by phone at 304-293-4088.

Downloadable templates, required materials and assembly video:

-WVU-

om/04/09/20

Call 1-855-WVU-NEWS for the latest West Virginia University news and information from WVUToday.

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West Virginia University partnerships help WVU Medicine community and beyond amidst personal protective equipment shortage - Newswise

Dr. Emeran Mayer is a gastroenterologist who specialises in the communication between the brain, the gut and our environment. He is widely recognised as a pioneer of medical research into the brain, gut and microbe interactions and author of The Mind-Gut Connection: How the Hidden Conversation Within Our Bodies Impacts our Mood, Our Choices and Our Overall Health. (Our conversation has been condensed and edited for clarity.)

You discuss in your book, The Mind-Gut Connection, the journey you took at medical school to study the link between the brain and body in disease. What was the prevailing thought at the time and how were you going against it?

When I got into medical school, I was interested in studying the biological underpinnings of psychological constructs. When looking for a thesis advisor, I went from one professor to the next and they all said that mind gut connections cant be studied even though they knew it was important. After doing a rotation in gastroenterology at the Mass General Hospital at Harvard I was convinced that I wanted to study how the brain interacts with the digestive system. It was surprising to me how big the disconnect was between psychological and holistic concepts and traditional medicine at the time. Coventional Medicine selected people who were interested in mechanical, linear concepts of disease rather than an interest in health as a complex whole.

What is this mechanical, linear view of traditional medicine and why is it not sufficient in treating disease?

The linear viewpoint of the world around us represents the whole paradigm of the Western World. We go from point A to point B and dont look at the holistic context in which this interaction is happening. This model has been very successful in surgery in treating infectious diseases, where you identify a pathogen and develop an antibiotic to kill it. In reality, chronic diseases are not linear phenomena. Chronic diseases are dysregulations of a whole network, in which every organ in the body is interconnected, including the brain. For instance, if you are suffering from obesity, you also have a high risk of metabolic syndrome, of cardiovascular, liver and brain disease and cancer. This is no longer a linear phenomenon. You are looking at a paradigm of interconnectedness of every organ in the body. Chronic disease is a rearrangement in this global network that links every cell in our bodies together. Western medicine has not recognised that and as a result, nearly half of the US population are on chronic medicines. We are clearly not healing the disease. We are treating the systems and suppressing the issue.

How would you describe your approach to disease?

My view is as a systems biology approach. I look at the connections between every part of the body, down to every cell. For instance, if you look at genes, initially we thought that a single gene determines how old you are going to get. Now we know that it is a whole network of genes. Its the same with microbes. We have a hundred trillion microbes in our gut. We have to apply a systems approach of interconnectedness to understand and model it. In chronic disease, the systems go way beyond our bodies. The microbes in your gut live off the food systems from which you get your food, for instance the plants in the soil. And if you pursue this consistently, you all of a sudden see that we are all part of this gigantic interconnected system. I think what is happening with these viral epidemics is in some ways a systems phenomenon. We are attacking the normal system by cutting down the forests, encroaching on ecological niches of wild animals, and overcrowding in cities. And the way these diseases spread is not linear either. The whole world and system is affected.

Why did you decide to focus your research specifically on the connection between the brain and the gut?

From an evolutionary standpoint, our nervous system and our gut were always very closely connected, more so than any other organ. The first primitive organisms were simply a floating digestive tube with a nerve net around them. This basic architecture persisted through millions of years, and we still have a similar design in our gut. I think if you had to choose two organs that are the core of our being I would say it is the gut and the brain. The gut itself is not just a digestive tube, it is also the immune system, the nervous system, and the endocrine system. Contrary to popular belief, 95% of our bodys serotonin is stored in our gut. We interact with the world more through our gut than we do with our skin.

Why are there so many hormones such as serotonin stored in our gut?

We still dont know the full answer to this question. On the one side, the serotonin that is released in the gut communicates with the brain by stimulating the vagus nerve. Serotonin is only one molecule; tryptophan is broken down by the microbes and cells in the gut into many molecules, one of which is serotonin. The ratio of serotonin to some of the other tryptophan metabolites is influenced by microbial activities. The microbes can talk to some of the cells lining our gut and tell them to make more serotonin and release it onto the vagus nerve, which carries the signal to the brain. It also is released back into the gut and influences the behaviour of the microbes, so its going full circle. The molecule that allows microbes to take up the serotonin is the same molecule that acts when you take an antidepressant. We are still at the beginning of understanding the mechanisms of this. What we do know for now is that there is a major link between what we eat, what the microbes do with our food and how it affects brain function.

As well as the link between what we eat, our gut and brain function, you also discuss the effects of negative emotions such as stress on our body. What effect does this have in our gut?

Everybody now talks about the healthy diet and what it does to your gut and microbiome. Very few people talk about the fact that negative emotions in the brain can do almost the same damage as unhealthy food. Chronic stress decreases the diversity of your microbes, and changes the behaviour and leakiness of your gut. Your gut is a mirror image of your emotions. We dont listen and sense the effects of negative emotions or food on our gut on a daily basis. We tend to only notice the effects when we are in a lot of pain. People talk about the negative effects of the Western diet and obesity on cancer. You can imagine the combination of negative emotions and stress, plus the Western diet, will have twice the effect on increasing your risk of chronic disease. Typically in Western medicine, we dont pay too much attention to the mind but it is really key to realise this importance.

You also discuss how those with a positive attitude to life tend to heal faster from disease. What is the explanation behind this?

This comes back to the concept of our body as an interconnected network. How this network is constructed in our lives, determines how resilient it is to disease. This is shaped early in life, in the first two years of our lives for the microbiome and the first 18 years for the brain. The way this is programmed determines your resilience later in life. If framed in a positive way, such as with grit, enthusiasm, passion, compassion, and with the right diet, you are likely to be more resilient later in life. It offers an explanation for chronic diseases and longevity, determining how long we live and how healthy we are. As humans, we have this amazing ability to learn, our prefrontal cortex is incredibly plastic, providing our body with the opportunity to adapt and change to varying situations. I think our health ultimately all comes down to attitude and diet.

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What You Should Know About the Mind Gut Connection - Thrive Global

Scientists at the Icahn School of Medicine at Mount Sinai have discovered a new role for the brain chemical dopamine that is independent of classic neurotransmission. The new role appears to be critical to changes in gene expression related to chronic exposure to, or abuse of, cocaine, according to a study published Friday, April 10, in the journal Science.

Our study provides the first evidence of how dopamine can directly impact drug-induced gene expression abnormalities and subsequent relapse behavior, says Ian Maze, Ph.D., Associate Professor of Neuroscience, and Pharmacological Sciences, at the Icahn School of Medicine at Mount Sinai, and lead author of the study. Beyond transmission of signals between neurons in the brain, we have found that dopamine can be chemically attached to histone proteins, which causes cells to switch different genes on and off, affecting regions of the brain that are involved in motivation and reward behavior. This biochemical process significantly affects cocaine vulnerability and relapse when perturbed by drugs of abuse.

The study revolves around DNA and how it works to form each persons individual biological map. Each cell in the body contains two meters of DNA, the blueprint for all functions of all cells in the body. This DNA is wound around spools of histone proteins (proteins that package DNA in the nucleus of cells, and are heavily prone to chemical modifications that aid in the regulation of gene expression) into structures referred to as nucleosomes. When DNA encoding a specific gene is wound tightly within the spool, that gene is less likely to be expressed. When the gene is not wound as tightly, it is more likely to be expressed. This can affect many functions of a given cell.

Dopamine, known as the feel-good neurotransmitter, is a chemical that ferries information between neurons. The brain releases it when we eat food that we crave or while we have sex, contributing to feelings of pleasure and satisfaction as part of the natural reward system. This important neurochemical boosts mood, motivation, and attention, and helps regulate movement, learning, and emotional responses. Dopamine also enables us not only to see rewards but to take action to move toward them.

Vulnerability to relapse during periods of cocaine withdrawal is believed to result from functional rewiring of the brains reward circuitry, particularly within mid-brain regions, such as the ventral tegmental area (VTA). The research team discovered that a protein called transglutaminase 2 can directly attach dopamine molecules to histone proteins (a process called histone dopaminylation or H3Q5dop) which, in turn, affects the histone-DNA spool to enable environmentally regulated alterations in gene expression. They found that histone dopaminylation plays a critical role in fueling heightened vulnerability to relapse over a prolonged period of time. Specifically, accumulation of H3Q5dop in the VTA can, in effect, hijack the reward circuitry, making it difficult to distinguish between good and maladaptive behavior. The study found, however, that reducing H3Q5dop in rats programmed to undergo withdrawal from cocaine significantly reversed cocaine-mediated gene expression changes and reduced cocaine-seeking behavior.

The question that has always challenged neuroscientists is, what are the underlying molecular phenomena that drive increased vulnerability to drug relapse in people, says Ashley Lepack, Ph.D., a researcher in the Department of Neuroscience, The Friedman Brain Institute, in Dr. Mazes lab at Mount Sinai, and first author of the study. Our research is shedding valuable light on this area by identifying histone dopaminylation as a new, neurotransmission-independent role for dopamine that hasnt been implicated before in brain pathology.

We believe these findings represent a paradigm shift in how we think of dopamine, not just in the context of drug abuse, but also potentially in other reward-related behaviors and disorders, as well as in neurodegenerative diseases like Parkinsons, where dopamine neurons are dying, says Dr. Maze. In this case, the question becomes, could this neuronal death be due, in part, to aberrant dopaminylation of histone proteins?

In a study published last year, Dr. Maze and his team found that another neurotransmitter, serotonin, a chemical involved in the regulation of mood, acts in a similar way as dopamine on gene expression inside brain cells.

When we observed this unique signaling mechanism with serotonin, we decided to look at other neurotransmitters, particularly dopamine, and found that it could also undergo this type of chemical modification on the same histone protein, explains Dr. Maze.

Early-stage work with human post-mortem tissues has demonstrated to Dr. Maze that strong parallels may well exist, but that basic questions around biochemical function still remain before human trials can begin. From a therapeutic standpoint, weve started to identify from rodent models the mechanisms that can actually reverse aberrant and addictive behaviors, says Dr. Maze, and that knowledge could be vital to moving this novel research into the clinic.

Provided byThe Mount Sinai Hospital

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Researchers discover a novel role for dopamine that impacts gene expression related to cocaine abuse. - Brinkwire

Indians have some genetic advantage, but these are still early days to come to any conclusion

The fewer-than-expected cases positive to the novel coronavirus (SARS-CoV-2) in Indiahave spawned severaltheories, one of them being,Indians being immune to the virus.

It is theoretically possible as Indians are constantly exposed to microbes that keep the immune system primed, destroying pathogens attempting to attack. This is why children in very clean environments fall sick at the slightest exposure to a pathogen a concept known as the hygiene hypothesis.

Indians have some genetic advantage as well: Theyhave evolved to gain more genes that protect against viral infections, according to Rajalingam Raja, director of Immunogenetics and Transplantation Laboratory at the University of California in San Francisco, US. He said:

These genes enable natural killer (NK) cells, a type of white blood cells in our body that provide a first line of defense against viral infections

Two families of genes KIR genes and HLA genes playa part in this protective function. Indians have more KIR genes than the Chinese and caucasians. This could makeIndians more immune to the virus, according to Raja.

A similar mechanismprotectsbats from viruses like Ebola and SARS. Bats are immune since they have expanded gene families that enhance NK cell function, said Raja, who first wrote about NK cells in 2008 in journal Genes and Immunity.

This alone is, however, not enough to guide Indias strategy to fight the disease or even suggest that strict measures are not needed. A team of researchers from India and the US studied umbilical cord blood of children in the two countries and found differences. The findings were published in journal PLoS One in 2018.

We interpreted our study to suggest that Indian babies could be more susceptible to early-life infections if they had lower frequencies of certain immune cells, said Holden Maecker, director of the Human Immune Monitoring Center at Stanford University School of Medicine.

Persistent pathogen assault especially early in life is almost certainly detrimental. Thisisseen in the phenomenon of environmental enteropathy, where kids with poor sanitation and high enteric pathogen loadsdevelop malnutrition and stunting, Maecker said. But he agreed exposure to pathogens could equip the immune system better to fight new assaults like Zika or coronavirus, to an extent.

This was similar to the protective effect provided by latent tuberculosis. It was certainly possible that there was increasing resistance if not specific immunity to COVID-19 in certain genetic groups. It is difficult, however, to extrapolate this to all Indians who are a diverse collection of ethnic groups.

It is a balance and my guess is that its too soon to say where Indians as a whole will fall on this balance in terms of their sensitivity to COVID-19, hesaid.

Arguments about the Indian immune systemsare mostly speculative, according to Satyajit Rath of the National Institute of Immunology. He co-authored the 2018 study with Maecker.

I am yet to see any indication that COVID-19 will, in fact, turn out to be less prevalent and/or milder in India, since the epidemic is still in its early stages in the subcontinent, he said.

There are no publications, as of now, on the differential prevalence or outcome of COVID-19 among Indians and those of other ancestries worldwide.

Good nutrition, exercise and sleep can improve the immune system.

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COVID-19: Do Indians have higher immunity to novel coronavirus - Down To Earth Magazine