Complexity around childhood obesity

January 6, 2020

Science Daily/University of Notre Dame

In a new study, researchers examined how various psychological characteristics of children struggling with their weight, such as loneliness, anxiety and shyness, combined with similar characteristics of their parents or guardians and family dynamics affect outcomes of nutritional intervention.

The World Health Organization has estimated more than 340 million children and adolescents ages 5-19 are overweight or obese, and the epidemic has been linked to more deaths worldwide than those caused by being underweight.

The Centers for Disease Control recently reported an estimated 1 in 5 children in the United States, ages 12-18, are living with prediabetes -- increasing their risk of developing type 2 diabetes as well as chronic kidney disease, heart disease and stroke.

Efforts to stem the crisis have led clinicians and health professionals to examine both the nutritional and psychological factors of childhood obesity. In a new study led by the University of Notre Dame, researchers examined how various psychological characteristics of children struggling with their weight, such as loneliness, anxiety and shyness, combined with similar characteristics of their parents or guardians and family dynamics affect outcomes of nutritional intervention.

What they found was a "network effect," suggesting a personalized, comprehensive approach to treatment could improve results of nutritional interventions.

"Psychological characteristics clearly have interactional effects," said Nitesh Chawla, the Frank M. Freimann Professor of Computer Science and Engineering at Notre Dame, director of the Center for Network and Data Science and a lead author of the study. "We can no longer simply view them as individualized risk factors to be assessed. We need to account for the specific characteristics for each child, viewing them as a holistic set for which to plan treatment."

The Notre Dame team collaborated with the Centre for Nutritional Recovery and Education (CREN), a not-for-profit, nongovernmental nutritional clinic in São Paulo, Brazil, where patients participate in a two-year interdisciplinary treatment program including family counseling, nutritional workshops and various physical activities. Researchers analyzed the medical records and psychological assessments of 1,541 children who participated in the program.

The study's key takeaway points to the significant impact parents and guardians have on their child's health when it comes to nutrition. Strong family dynamics, such as concern for behavior and treatment and a sense of protectiveness for the child, led to improved outcomes of nutritional interventions. A lack of authority, however, led to minimal changes in results.

"This is quantitative evidence of the success and failure of interactions as they relate to the characteristics and interactions between the child and the parent or guardian," Chawla said.

The study also highlights the need for clinics to expand their views on patient populations. For example, while treatment programs that incorporate development of interpersonal relationship -- familial and otherwise -- may improve outcomes of nutritional interventions, the same treatment plan may not have the same result for children experiencing loneliness coupled with anxiety.

"For the group without anxiety, this makes sense when you consider a treatment plan focused on strengthening a child's social circle and address issues stemming from loneliness, such as poor social network, bullying or self-imposed isolation," said Gisela M.B. Solymos, co-author of the study, former general manager of CREN and former guest scholar at the Kellogg Institute for International Studies at Notre Dame and at the Center for Network and Data Science. "But patients feeling loneliness and anxiety actually showed minimal changes to nutritional interventions, and may be more likely to benefit from additional services at clinics like CREN."

https://www.sciencedaily.com/releases/2020/01/200106161935.htm

Research identifies changes in neural circuits underlying self-control during adolescence

Research identifies changes in neural circuits underlying self-control during adolescence

Study shows developing brain networks support cognition in youth

January 3, 2020

Science Daily/University of Pennsylvania School of Medicine

Researchers applied tools from network science to identify how anatomical connections in the brain develop to support neural activity underlying executive function.

The human brain is organized into circuits that develop from childhood through adulthood to support executive function -- critical behaviors like self-control, decision making, and complex thought. These circuits are anchored by white matter pathways which coordinate the brain activity necessary for cognition. However, little research exists to explain how white matter matures to support activity that allows for improved executive function during adolescence -- a period of rapid brain development.

Researchers from the Lifespan Brain Institute of the Perelman School of Medicine at the University of Pennsylvania and Children's Hospital of Philadelphia applied tools from network science to identify how anatomical connections in the brain develop to support neural activity underlying these key areas. The findings were published in the Proceedings of the National Academy of Sciences.

"By charting brain development across childhood and adolescence, we can better understand how the brain supports executive function and self-control in both healthy kids and those with different mental health experiences," said the study's senior author Theodore Satterthwaite, MD, an assistant professor of Psychiatry at Penn. "Since abnormalities in developing brain connectivity and deficits in executive function are often linked to the emergence of mental illness during youth, our findings may help identify biomarkers of brain development that predict cognitive and clinical outcomes later in life."

In this study, the researchers mapped structure-function coupling -- the degree to which a brain region's pattern of anatomical connections supports synchronized neural activity. This could be thought of like a highway, where the anatomical connections are the road and the functional connections are the traffic flowing along those roads. Researchers mapped and analyzed multi-modal neuroimaging data from 727 participants ages 8 to 23 years, and three major findings emerged.

First, the team found that regional variability in structure-function coupling was inversely related to the complexity of the function a given brain area is responsible for. Higher structure-function coupling was found in parts of the brain that are specialized for processing simple sensory information, like the visual system. In contrast, there was lower structure-function coupling in complex parts of the brain that are responsible for executive function and self-control, which require more abstract and flexible processing.

Results showed that structure-function coupling also aligned with known patterns of brain expansion over the course of primate evolution. Previous work comparing human, ape, and monkey brains has showed that sensory areas like the visual system are highly conserved across primate species and have not expanded much during recent evolution. In contrast, association areas of the brain, such as the prefrontal cortex, have expanded dramatically over the course of primate evolution. This expansion may have allowed for the emergence of uniquely complex human cognitive abilities. The team found that the brain areas which expanded rapidly during evolution had lower structure-function coupling, while simple sensory areas that have been conserved in recent evolution had higher structure-function coupling.

Researchers also found that structure-function coupling increased throughout childhood and adolescence in complex frontal brain regions. These are the same regions that tend to have lower baseline structure-function coupling, are expanded compared to monkeys, and are responsible for self-control. The prolonged development of structure-function coupling in these regions may allow for improved executive function and self-control that develops into adulthood. Indeed, the team found that higher structure-function coupling in the lateral prefrontal cortex -- a complex brain area which plays important roles in self-control -- was associated with better executive function.

"These results suggest that executive functions like impulse control -- which can be particularly challenging for children and adolescents -- rely in part on the prolonged development of structure-function coupling in complex brain areas like the prefrontal cortex," explained lead author Graham Baum, PhD, a postdoctoral fellow at Harvard University, who was a Penn neuroscience PhD student during the time of the research. "This has important implications for understanding how brain circuits become specialized during development to support flexible and appropriate goal-oriented behavior."

https://www.sciencedaily.com/releases/2020/01/200103111723.htm

Study finds dopamine, biological clock link to snacking, overeating and obesity

Study finds dopamine, biological clock link to snacking, overeating and obesity

January 3, 2020

Science Daily/University of Virginia

A new study finds that the pleasure center of the brain and the brain's biological clock are linked, and that high-calorie foods -- which bring pleasure -- disrupt normal feeding schedules, resulting in overconsumption.

During the years 1976 through 1980, 15% of U.S. adults were obese. Today, about 40% of adults are obese. Another 33% are overweight.

Coinciding with this increase in weight are ever-rising rates of heart disease, diabetes, cancer and health complications caused by obesity, such as hypertension. Even Alzheimer's disease may be partly attributable to obesity and physical inactivity.

"The diet in the U.S. and other nations has changed dramatically in the last 50 years or so, with highly processed foods readily and cheaply available at any time of the day or night," Ali Güler, a professor of biology at the University of Virginia, said. "Many of these foods are high in sugars, carbohydrates and calories, which makes for an unhealthy diet when consumed regularly over many years."

In a study published Thursday in the journal Current Biology, Güler and his colleagues demonstrate that the pleasure center of the brain that produces the chemical dopamine, and the brain's separate biological clock that regulates daily physiological rhythms, are linked, and that high-calorie foods -- which bring pleasure -- disrupt normal feeding schedules, resulting in overconsumption. Using mice as study models, the researchers mimicked the 24/7 availability of a high-fat diet, and showed that anytime snacking eventually results in obesity and related health problems.

Güler's team found that mice fed a diet comparable to a wild diet in calories and fats maintained normal eating and exercise schedules and proper weight. But mice fed high-calorie diets laden with fats and sugars began "snacking" at all hours and became obese.

Additionally, so-called "knockout" mice that had their dopamine signaling disrupted -- meaning they didn't seek the rewarding pleasure of the high-fat diet -- maintained a normal eating schedule and did not become obese, even when presented with the 24/7 availability of high-calorie feeds.

"We've shown that dopamine signaling in the brain governs circadian biology and leads to consumption of energy-dense foods between meals and during odd hours," Güler said.

Other studies have shown, Güler said, that when mice feed on high-fat foods between meals or during what should be normal resting hours, the excess calories are stored as fat much more readily than the same number of calories consumed only during normal feeding periods. This eventually results in obesity and obesity-related diseases, such as diabetes.

Speaking of the modern human diet, Güler said, "The calories of a full meal may now be packed into a small volume, such as a brownie or a super-size soda. It is very easy for people to over-consume calories and gain excessive weight, often resulting in obesity and a lifetime of related health problems.

"Half of the diseases that affect humans are worsened by obesity. And this results in the need for more medical care and higher health care costs for individuals, and society."

Güler said the human body, through thousands of years of evolution, is hard-wired to consume as much food as possible as long as it's available. He said this comes from a long earlier history when people hunted or gathered food and had brief periods of plenty, such as after a kill, and then potentially lengthy periods of famine. Humans also were potential prey to large animals and so actively sought food during the day, and sheltered and rested at night.

"We evolved under pressures we no longer have," Güler said. "It is natural for our bodies as organisms to want to consume as much as possible, to store fat, because the body doesn't know when the next meal is coming.

"But, of course, food is now abundant, and our next meal is as close as the kitchen, or the nearest fast-food drive-through, or right here on our desk. Often, these foods are high in fats, sugars, and therefore calories, and that's why they taste good. It's easy to overconsume, and, over time, this takes a toll on our health."

Additionally, Güler said, prior to the advent of our electricity-powered society, people started the day at dawn, worked all day, often doing manual labor, and then went to sleep with the setting of the sun. Human activity, therefore, was synchronized to day and night. Today, we are working, playing, staying connected -- and eating -- day and night. This, Guler said, affects our body clocks, which were evolved to operate on a sleep-wake cycle timed to daytime activity, moderate eating and nighttime rest.

"This lights-on-all-the-time, eat-at-any-time lifestyle recasts eating patterns and affects how the body utilizes energy," he said. "It alters metabolism -- as our study shows -- and leads to obesity, which causes disease. We're learning that when we eat is just as important as how much we eat. A calorie is not just a calorie. Calories consumed between meals or at odd hours become stored as fat, and that is the recipe for poor health."

The National Institute of General Medical Sciences and University of Virginia Brain Institute funded the research.

https://www.sciencedaily.com/releases/2020/01/200103111717.htm

Researchers discover brain circuit linked to food impulsivity

This creates the possibility scientists can someday develop therapeutics to address overeating

December 11, 2019

Science Daily/University of Georgia

A team of researchers has now identified a specific circuit in the brain that alters food impulsivity.

You're on a diet, but the aroma of popcorn in the movie theater lobby triggers a seemingly irresistible craving.

Within seconds, you've ordered a tub of the stuff and have eaten several handfuls.

Impulsivity, or responding without thinking about the consequences of an action, has been linked to excessive food intake, binge eating, weight gain and obesity, along with several psychiatric disorders including drug addiction and excessive gambling.

A team of researchers that includes a faculty member at the University of Georgia has now identified a specific circuit in the brain that alters food impulsivity, creating the possibility scientists can someday develop therapeutics to address overeating.

The team's findings were published recently in the journal Nature Communications.

"There's underlying physiology in your brain that is regulating your capacity to say no to (impulsive eating)," said Emily Noble, an assistant professor in the UGA College of Family and Consumer Sciences who served as lead author on the paper. "In experimental models, you can activate that circuitry and get a specific behavioral response."

Using a rat model, researchers focused on a subset of brain cells that produce a type of transmitter in the hypothalamus called melanin concentrating hormone (MCH).

While previous research has shown that elevating MCH levels in the brain can increase food intake, this study is the first to show that MCH also plays a role in impulsive behavior, Noble said.

"We found that when we activate the cells in the brain that produce MCH, animals become more impulsive in their behavior around food," Noble said.

To test impulsivity, researchers trained rats to press a lever to receive a "delicious, high-fat, high-sugar" pellet, Noble said. However, the rat had to wait 20 seconds between lever presses. If the rat pressed the lever too soon, it had to wait an additional 20 seconds.

Researchers then used advanced techniques to activate a specific MCH neural pathway from the hypothalamus to the hippocampus, a part of the brain involved with learning and memory function.

Results indicated MCH doesn't affect how much the animals liked the food or how hard they were willing to work for the food. Rather, the circuit acted on the animals' inhibitory control, or their ability to stop themselves from trying to get the food. "Activating this specific pathway of MCH neurons increased impulsive behavior without affecting normal eating for caloric need or motivation to consume delicious food," Noble said. "Understanding that this circuit, which selectively affects food impulsivity, exists opens the door to the possibility that one day we might be able to develop therapeutics for overeating that help people stick to a diet without reducing normal appetite or making delicious foods less delicious."

https://www.sciencedaily.com/releases/2019/12/191211145630.htm

Oh my aching back: Do yoga, tai chi or qigong help?

February 6, 2020

Science Daily/Florida Atlantic University

About 80 percent of Americans will experience low back pain at some point. Patients are often advised to manage their back pain with exercise and mind-body interventions. But, do they really help? Researchers compared and contrasted yoga, tai chi and qigong, and found them to be effective for treatment of low back pain, reporting positive outcomes such as reduction in pain or psychological distress such as depression and anxiety, reduction in pain-related disability, and improved functional ability.

It's a pain. About 80 percent of adults in the United States will experience lower back pain at some point. Treating back pain typically involves medication, including opioids, surgery, therapy and self-care options. Efforts to reduce opioid use and increase physically based therapies to reduce pain and increase physical function and safety are crucial.

Patients are often advised to use non-pharmacological treatments to manage lower back pain such as exercise and mind-body interventions. But, do they really help? In a review published in the journal Holistic Nursing Practice, researchers from Florida Atlantic University's College for Design and Social Inquiry and Christine E. Lynn College of Nursing evaluated the evidence of effects of three movement-based mind-body interventions on chronic low back pain. They examined yoga, tai chi, which combines gentle physical exercise and stretching with mindfulness, and qigong, a traditional Chinese meditative movement therapy focused on body awareness and attention during slow, relaxed, and fluid repetitive body movements. Little is known about the effects of movement-based mind-body intervention, in particular qigong and tai chi.

Researchers compared and contrasted yoga, tai chi and qigong by examining frequency and duration of these interventions; primary and secondary outcomes; attrition rates and possible adverse events; and results. Findings from their review provide empirical evidence regarding the benefits of yoga, tai chi, and qigong, which have been recommended by health care providers for patients with lower back pain.

"Back pain is a major public health issue often contributing to emotional distress such as depression and anxiety, as well as sleep issues and even social isolation," said Juyoung Park, Ph.D., corresponding author and an associate professor in the Phyllis and Harvey Sandler School of Social Work within FAU's College for Design and Social Inquiry. "We reviewed data to determine the effects of movement-based mind-body interventions on chronic back pain, psychological factors, coping strategies, and quality of life in people suffering with back pain. Our goal was to provide a comprehensive assessment of the effects of these interventions to be able to offer information across disciplines to implement evidence-based interventions to reduce such pain."

Of the 625 peer-reviewed articles the researchers identified, 32 met inclusion criteria and were included in the review. Results found that the majority of these articles showed movement-based mind-body interventions to be effective for treatment of low back pain, reporting positive outcomes such as reduction in pain or psychological distress such as depression and anxiety, reduction in pain-related disability, and improved functional ability. Among the key findings, researchers discovered that longer duration and high-dose yoga intervention showed reductions in back pain while tai chi reduced acute lower back pain in males in their 20s. Tai chi also was more effective than stretching for lower back pain in young males. In the general community, tai chi showed greater reductions in pain intensity, bothersomeness of pain symptoms, and pain-related disability than the control intervention. Because there are only three qigong studies to date, it was unclear to the researchers whether this intervention is useful in treating chronic lower back pain. Existing research suggests positive benefits of yoga, however, tai chi and qigong for lower back pain are still under-investigated.

"Two of the studies we examined in our review were focused on the effects of movement modality, specifically yoga, in veterans. Many military veterans and active duty military personnel experience chronic low back pain and are affected by this pain more than the general population," said Cheryl Krause-Parello, Ph.D., co-author, a professor and director of Canines Providing Assistance to Wounded Warriors (C-P.A.W.W.) within FAU's Christine E. Lynn College of Nursing, and a faculty fellow of FAU's Institute for Human Health and Disease Intervention (I-HEALTH). "Our review provides emerging evidence that movement-based mind-body interventions could benefit veterans and others experiencing chronic low back pain."

The review included both randomized and nonrandomized studies with a total of 3,484 subjects ages 33 to 73 years old. Study sample sizes ranged from 25 to 320 subjects. The majority of articles reported on yoga (25), followed by tai chi (four), and qigong (three). Most of the yoga studies were conducted in India, followed by the U.S., while other studies were conducted in Australia (tai chi) and Germany (qigong).

People with chronic low back pain are at increased risk of functional limitations, job-related disability, and potential long-term disability. Moreover, the economic burden of chronic low back pain is high due to the cost of medications such as opioids, procedures, hospitalization, surgical treatment, and absence from work.

"Yoga, tai chi and qigong could be used as effective treatment alternatives to pain medications, surgery, or injection-based treatments such as nerve blocks, which are associated with high incidence of adverse effects in treating lower back pain," said Park. "We need more clinical trials and empirical evidence so that clinicians can prescribe these types of interventions with more confidence for managing lower back pain in their patients."

https://www.sciencedaily.com/releases/2020/02/200206102727.htm

Motivational aspects of mindfulness: Quality differs by situation

January 29, 2020

Science Daily/Virginia Commonwealth University

What makes people more or less mindful from one situation to the next? Researchers have found that mindfulness is not entirely something an individual brings to a situation and rather is partly shaped by the situations they encounter.

"As mindfulness has become prevalent within organizational practice and scholarly research on organizations, there is a growing need to situate mindfulness more fully within organizational contexts," said Christopher S. Reina, Ph.D., assistant professor in the Virginia Commonwealth University Department of Management and Entrepreneurship in the School of Business.

In "Wherever you go, there you become: How mindfulness arises in everyday situations," published in the journal Organizational Behavior and Human Decision Processes, Reina and co-author Ravi S. Kudesia, Ph.D., assistant professor at the Temple University Fox School of Business, introduce a theoretical framework that explains how mindfulness arises based on an individual's capacity for self-regulation as well as three motivational forces: their metacognitive beliefs, their mental fatigue and how they appraise the situations they experience.

While metacognitive beliefs aid individuals in higher levels of self-regulation, mental fatigue draws resources away from self-regulation. Meanwhile, how individuals appraise a situation influence how much self-regulation is needed to maintain mindfulness.

"These motivational aspects of mindfulness have received little attention to date," Reina said. "Despite the increasing prevalence of mindfulness in organizational research, we have yet to seriously consider its antecedents: how and why people become more or less mindful from one situation to the next." In other words, while researchers have previously explored what mindfulness predicts, little to no research has studied what predicts mindfulness, which represents the core contribution of Reina's study.

The research comprises over 558 participants and 9,390 responses from across three separate studies.

If mindfulness indeed produces positive outcomes, it seems important to identify what situational features can increase or decrease mindfulness. Understanding this can help managers better design organizational situations that enhance mindfulness, Reina said.

"Mindfulness is often assumed to be something that people bring with them into situations, some stable psychological property that is inherent to them," the study concludes. "The present research helps nuance this assumption. If we instead see mindfulness as arising from the coming together of people and their situations, we can better conceptualize mindfulness and design organizational situations that enhance it."

https://www.sciencedaily.com/releases/2020/01/200129125550.htm

Mindfulness makes it easier to forget your fears

January 6, 2020

Science Daily/University of Southern Denmark Faculty of Health Sciences

Mindfulness has previously been shown to help people handle negative emotions and is used as a treatment for anxiety related psychological disorders, but the underlying biological mechanisms are not fully understood. In a new study, researchers show that brief daily mindfulness training delivered through the HEADSPACE mindfulness app makes it easier to achieve lasting extinction of fear reactions.

Mindfulness has been shown to reduce negative emotions in both healthy individuals as well as patients with psychological problems. Studies have also shown that mindfulness is effective for treating clinical emotional problems like anxiety, depression, stress and trauma related disorders. The biological mechanisms that underlie these positive effects on emotional functioning are not sufficiently understood but brain imaging studies have shown that mindfulness training is associated with changes in regions of the brain previously known to be involved in extinction learning, making extinction a likely candidate. However, an actual effect of mindfulness training on extinction learning has never been demonstrated.

In a new study, researchers at University of Southern Denmark, Uppsala University, Lund University, Peking University and Icahn School of Medicine at Mount Sinai, can now show that mindfulness training facilitates extinction of conditioned fear reactions, producing lasting reductions in threat related arousal responses.

In this study, healthy subjects were randomly assigned to receive either 4 weeks of daily mindfulness training delivered through the Headspace mindfulness app, or were assigned to a wait list control condition. Subsequently, the participants underwent psychological experiments on two consecutive days in which conditioned fear reactions were established on day 1 and then immediately extinguished.

On day 2, the subjects returned and the lasting effects of extinction were evaluated.

Conditioned fear reactions were established by showing the participants neutral images on a computer screen and then some of the images were directly followed by an uncomfortable electric shock to the hand.

After a number of such pairings, the subjects showed elevated autonomic arousal responses just when viewing the pictures, demonstrating that conditioned fear reactions had been learnt.

Fear reactions were measured using skin conductance, an index for how much the subject is sweating, which is a corollary for the fight-or-flight response in humans.

Then, the researchers extinguished these reactions by repeatedly showing the images again but this time omitting the shocks.

In this way, the participants learnt that the images that previously signaled an upcoming uncomfortable shock no longer did so, and consequently subjects showed a substantial decrease in autonomic arousal when viewing the images.

After 24 hours, in order to test the retention of extinction learning, the participants returned to the lab, were hooked up to the shock apparatus and again shown the images they had viewed on the previous day, although no shocks were delivered.

This was the critical test of the study since extinction learning is normally unstable, and fear reactions typically return after a delay even when the subject has gone through successful extinction. In line with the researchers' hypotheses, the group that had been doing mindfulness training now showed lower fear reactions compared to the control group.

The fear reactions in the mindfulness group remained at the same low level they had been by the end of extinction the previous day indicating an improved ability to form and retain extinction memories, whereas the control group showed a substantial increase in fear reactions compared to extinction the previous day.

When comparing the groups reactions during conditioning and extinction on day 1, no differences could be observed, showing that the two groups learned and extinguished the conditioned fear reactions to a similar extent, and the authors conclude that mindfulness appears to have a specific effect on extinction retention.

According to the study's first author Johannes Björkstrand, the findings are interesting for a number of reasons.

"We can show that mindfulness does not only have an effect on subjective experiences of negative emotions, as has been shown previously, but that you can actual see clear effects on autonomic arousal responses, even with a limited amount of training. It is also interesting that the intervention appears to have a specific effect on extinction retention, which is in line with previous brain imaging studies on mindfulness, and also has some implications for how these types of interventions could be used to treat anxiety related problems in a clinical context.

"Anxiety and trauma related disorders are often treated using exposure therapy, a psychological treatment that is based on extinction learning, but not everyone responds to these treatments. One possible explanation is that individuals with these disorders have been shown to have difficulties in forming lasting extinction memories when compared to healthy individuals, which could represent an underlying vulnerability that increases the risk of developing these types of problems to begin with and constitutes an impediment to successful treatment.

"Our results suggest, that if you combine mindfulness training with exposure therapy, maybe you can achieve larger and longer lasting treatment effects. In this way you could get at an underlying vulnerability factor and more people would respond to these treatments, but studies in clinical populations and actual treatment studies are needed before we can draw any firm conclusions in this matter," says Johannes Björkstrand.

The researchers now want to move forward and investigate the underlying neurobiological mechanisms that are involved.

"We are currently repeating the experiment with twice the number of participants, and the whole thing is carried out inside an fMRI-scanner equipped with an extra strong electromagnetic field so that we can measure their brain activity to a high degree of precision throughout all parts of the experiment. We hope to show that the effect is robust and that we can replicate the current findings, and also say what processes in the brain are involved in producing these effects. We just finished data-collection but we still have a rather large amount of analysis work to do before we arrive at any results," says senior author, associate professor Ulrich Kirk.

https://www.sciencedaily.com/releases/2020/01/200106123431.htm

Risk of coronavirus importation in Africa

February 20, 2020

Science Daily/INSERM (Institut national de la santé et de la recherche médicale)

Egypt, Algeria and Republic of South Africa are the African countries most at risk for coronavirus COVID-19 importation in the continent, due to high air traffic with the contaminated Chinese provinces. But these countries are also among the best equipped on the continent to quickly detect and deal with new cases. In other African countries, the risk of importation is lower, but health organization deficiencies raise concerns about rapid spread.

The COVID-19 coronavirus continues to spread in China and cases have been reported in more than 25 countries. The African continent was spared for a long time until a first case was recently reported in Egypt. Vittoria Colizza, research director at Inserm (French Institute for Health and Medical Research), and her team from Unit 1136 Pierre Louis Institute of Epidemiology and Public Health (Inserm / Sorbonne University), in collaboration with the Université libre de Bruxelles, the Oxford Martin Programme on Pandemic Genomics and the University of California Los Angeles, assessed the risk of importing the virus into Africa, country by country, and the capacities of each of them to detect and deal with it.

The researchers evaluated the risk of the virus importation according to the number of cases declared by each chinese province and according to air traffic between the three main airports of each of these provinces (except Hubei due to flights suspension) and each African country. Moreover, they analyzed the potential of each country to face the risk of the spread of a contagious disease using WHO data and official data.

Each country makes a mandatory annual declaration to the WHO of its resources to deal with an epidemic (State Parties self-assessment Annual Reporting SPAR). It includes twenty-four items weighted into an overall score between 0 and 100, 100 showing a strong preparedness to face an epidemic.

These indicators are legislation, adherence to WHO standards, laboratory skills, medical staff, emergency organization, food safety, level of equipment in healthcare centers and public communication.

The researchers also took into account the IDVI score (for Infectious Disease Vulnerability Index), also noted out of 100, 0 corresponding to an extreme vulnerability and 100 to the lowest vulnerability. The IDVI takes into account factors not directly linked to the health system but which can influence the response to an epidemic: the size of the population, the socio-economic level or even political stability. Thus, high IDVI and SPAR scores are predictive to an efficient response in case of virus importation.

The results show that Egypt, Algeria and Republic of South Africa are the countries most at risk of importing the virus to Africa due to high trade exchanges with China. On the other hand, their SPAR and IDVI scores are among the best on the continent, letting expect effective detection and containment of the virus. Other countries as Nigeria, Ethiopia, Sudan, Angola, Tanzania, Ghana and Kenya, are at lower risk of virus importation but their SPAR and IDVI scores are lower, raising fears of the nondetection of possible imported cases and of local or even national spread.

Finally, the researchers clustered the African countries at risk into three groups according to the influence of the Chinese provinces in these countries. Thus, a first group including 18 countries will be more vulnerable in the event of a major epidemic in the province of Beijing, a second comprising 7 countries will be more exposed in the event of a strong growth of the epidemic in the province of Guangdong and a third group of two countries is risking virus importation only from Fujian province.

"This work will allow the international community to make projections and plans according to the evolution in China. It also alerts the countries most exposed to the need of being prepared for the possible introduction of the virus. We can see how hard it is to quickly detect imported cases, as even well prepared developed countries missed some of them. For several poorly equipped African countries, the risks are significant of not having sufficient organization and infrastructure for detection, containment and urgent care, raising fears of a risk of epidemic on the continent," concludes Vittoria Colizza.

https://www.sciencedaily.com/releases/2020/02/200220104049.htm

Breakthrough in coronavirus research results in new map to support vaccine design

February 19, 2020

Science Daily/University of Texas at Austin

Researchers have made a critical breakthrough toward developing a vaccine for the 2019 novel coronavirus by creating the first 3D atomic scale map of the part of the virus that attaches to and infects human cells. Mapping this part, called the spike protein, is an essential step so researchers around the world can develop vaccines and antiviral drugs to combat the virus.

Mapping this part, called the spike protein, is an essential step so researchers around the world can develop vaccines and antiviral drugs to combat the virus. The paper is publishing Wednesday, Feb. 19 in the journal Science.

The scientific team is also working on a related viable vaccine candidate stemming from the research.

Jason McLellan, associate professor at UT Austin who led the research, and his colleagues have spent many years studying other coronaviruses, including SARS-CoV and MERS-CoV. They had already developed methods for locking coronavirus spike proteins into a shape that made them easier to analyze and could effectively turn them into candidates for vaccines. This experience gave them an advantage over other research teams studying the novel virus.

"As soon as we knew this was a coronavirus, we felt we had to jump at it," McLellan said, "because we could be one of the first ones to get this structure. We knew exactly what mutations to put into this, because we've already shown these mutations work for a bunch of other coronaviruses."

The bulk of the research was carried out by the study's co-first authors, Ph.D. student Daniel Wrapp and research associate Nianshuang Wang, both at UT Austin.

Just two weeks after receiving the genome sequence of the virus from Chinese researchers, the team had designed and produced samples of their stabilized spike protein. It took about 12 more days to reconstruct the 3D atomic scale map, called a molecular structure, of the spike protein and submit a manuscript to Science, which expedited its peer review process. The many steps involved in this process would typically take months to accomplish.

Critical to the success was state-of-the-art technology known as cryogenic electron microscopy (cryo-EM) in UT Austin's new Sauer Laboratory for Structural Biology. Cryo-EM allows researchers to make atomic-scale 3D models of cellular structures, molecules and viruses.

"We ended up being the first ones in part due to the infrastructure at the Sauer Lab," McLellan said. "It highlights the importance of funding basic research facilities."

The molecule the team produced, and for which they obtained a structure, represents only the extracellular portion of the spike protein, but it is enough to elicit an immune response in people, and thus serve as a vaccine.

Next, McLellan's team plans to use their molecule to pursue another line of attack against the virus that causes COVID-19, using the molecule as a "probe" to isolate naturally produced antibodies from patients who have been infected with the novel coronavirus and successfully recovered. In large enough quantities, these antibodies could help treat a coronavirus infection soon after exposure. For example, the antibodies could protect soldiers or health care workers sent into an area with high infection rates on too short notice for the immunity from a vaccine to take effect.

https://www.sciencedaily.com/releases/2020/02/200219152850.htm

New 'universal' target for antiviral treatment

New 'universal' target for antiviral treatment

February 11, 2020

Science Daily/Massachusetts General Hospital

Researchers have uncovered a novel potential antiviral drug target that could lead to treatments protecting against a host of infectious diseases

As the coronavirus outbreak shows, viruses are a constant threat to humanity. Vaccines are regularly developed and deployed against specific viruses, but that process takes a lot of time, doesn't help everyone who needs protection, and still leaves people exposed to new outbreaks and new viruses.

Now, researchers at Massachusetts General Hospital (MGH) have uncovered a novel potential antiviral drug target that could lead to treatments protecting against a host of infectious diseases -- creating a pan, or universal, treatment. Their work suggests that the protein Argonaute 4 (AGO4) is an "Achilles heel" for viruses.

AGO4 is one of a family of AGO proteins. Until now, there has been little evidence of why they are important. The researchers, led by Kate L. Jeffrey, PhD, and her collaborators found that AGO4 plays a key role protecting cells against viral infections.

Specifically, this protein is uniquely antiviral in mammalian immune cells. The group studied the anti-viral effects of several Argonaute proteins, and found that only cells that were deficient in AGO4 were "hyper-susceptible" to viral infection. In other words, low levels of AGO4 make mammalian cells more likely to become infected.

This study was published today by Cell Reports.

The MGH researchers suggest that boosting levels of AGO4 could shore up the immune system to protect against multiple viruses. "The goal is to understand how our immune system works so we can create treatments that work against a range of viruses, rather than just vaccines against a particular one," says Jeffrey.

Mammals have four Argonaute proteins (1-4), which act by silencing genes and which are remarkably conserved throughout multiple living things, including plants. These are RNAi and microRNA effector proteins and RNAi is the major antiviral defense strategy in plants and invertebrates. Studies of influenza infected mice have shown that AGO4-deficient animals have significantly higher levels of the virus.

The next steps are to "determine how broad spectrum this is to any virus type," says Jeffrey. "Then we need to discover how to boost AGO4 to ramp up protection against viral infections."

https://www.sciencedaily.com/releases/2020/02/200211170106.htm

Coronavirus outbreak raises question: Why are bat viruses so deadly?

Bats' fierce immune systems drive viruses to higher virulence, making them deadlier in humans

February 10, 2020

Science Daily/University of California - Berkeley

A study of cultured bat cells shows that their strong immune responses, constantly primed to respond to viruses, can drive viruses to greater virulence. Modelling bat immune systems on a computer, the researchers showed that when bat cells quickly release interferon upon infection, other cells quickly wall themselves off. This drives viruses to faster reproduction. The increased virulence and infectivity wreak havoc when these viruses infect animals with tamer immune systems, like humans.

It's no coincidence that some of the worst viral disease outbreaks in recent years -- SARS, MERS, Ebola, Marburg and likely the newly arrived 2019-nCoV virus -- originated in bats.

A new University of California, Berkeley, study finds that bats' fierce immune response to viruses could drive viruses to replicate faster, so that when they jump to mammals with average immune systems, such as humans, the viruses wreak deadly havoc.

Some bats -- including those known to be the original source of human infections -- have been shown to host immune systems that are perpetually primed to mount defenses against viruses. Viral infection in these bats leads to a swift response that walls the virus out of cells. While this may protect the bats from getting infected with high viral loads, it encourages these viruses to reproduce more quickly within a host before a defense can be mounted.

This makes bats a unique reservoir of rapidly reproducing and highly transmissible viruses. While the bats can tolerate viruses like these, when these bat viruses then move into animals that lack a fast-response immune system, the viruses quickly overwhelm their new hosts, leading to high fatality rates.

"Some bats are able to mount this robust antiviral response, but also balance it with an anti-inflammation response," said Cara Brook, a postdoctoral Miller Fellow at UC Berkeley and the first author of the study. "Our immune system would generate widespread inflammation if attempting this same antiviral strategy. But bats appear uniquely suited to avoiding the threat of immunopathology."

The researchers note that disrupting bat habitat appears to stress the animals and makes them shed even more virus in their saliva, urine and feces that can infect other animals.

"Heightened environmental threats to bats may add to the threat of zoonosis," said Brook, who works with a bat monitoring program funded by DARPA (the U.S. Defense Advanced Research Projects Agency) that is currently underway in Madagascar, Bangladesh, Ghana and Australia. The project, Bat One Health, explores the link between loss of bat habitat and the spillover of bat viruses into other animals and humans.

"The bottom line is that bats are potentially special when it comes to hosting viruses," said Mike Boots, a disease ecologist and UC Berkeley professor of integrative biology. "It is not random that a lot of these viruses are coming from bats. Bats are not even that closely related to us, so we would not expect them to host many human viruses. But this work demonstrates how bat immune systems could drive the virulence that overcomes this."

The new study by Brook, Boots and their colleagues was published this month in the journal eLife.

Boots and UC Berkeley colleague Wayne Getz are among 23 Chinese and American co-authors of a paper published last week in the journal EcoHealth that argues for better collaboration between U.S. and Chinese scientists who are focused on disease ecology and emerging infections.

Vigorous flight leads to longer lifespan -- and perhaps viral tolerance

As the only flying mammal, bats elevate their metabolic rates in flight to a level that doubles that achieved by similarly sized rodents when running.

Generally, vigorous physical activity and high metabolic rates lead to higher tissue damage due to an accumulation of reactive molecules, primarily free radicals. But to enable flight, bats seem to have developed physiological mechanisms to efficiently mop up these destructive molecules.

This has the side benefit of efficiently mopping up damaging molecules produced by inflammation of any cause, which may explain bats' uniquely long lifespans. Smaller animals with faster heart rates and metabolism typically have shorter lifespans than larger animals with slower heartbeats and slower metabolism, presumably because high metabolism leads to more destructive free radicals. But bats are unique in having far longer lifespans than other mammals of the same size: Some bats can live 40 years, whereas a rodent of the same size may live two years.

This rapid tamping down of inflammation may also have another perk: tamping down inflammation related to antiviral immune response. One key trick of many bats' immune systems is the hair-trigger release of a signaling molecule called interferon-alpha, which tells other cells to "man the battle stations" before a virus invades.

Brook was curious how bats' rapid immune response affects the evolution of the viruses they host, so she conducted experiments on cultured cells from two bats and, as a control, one monkey. One bat, the Egyptian fruit bat (Rousettus aegyptiacus), a natural host of Marburg virus, requires a direct viral attack before transcribing its interferon-alpha gene to flood the body with interferon. This technique is slightly slower than that of the Australian black flying fox (Pteropus alecto), a reservoir of Hendra virus, which is primed to fight virus infections with interferon-alpha RNA that is transcribed and ready to turn into protein. The African green monkey (Vero) cell line does not produce interferon at all.

When challenged by viruses mimicking Ebola and Marburg, the different responses of these cell lines were striking. While the green monkey cell line was rapidly overwhelmed and killed by the viruses, a subset of the rousette bat cells successfully walled themselves off from viral infection, thanks to interferon early warning.

In the Australian black flying fox cells, the immune response was even more successful, with the viral infection slowed substantially over that in the rousette cell line. In addition, these bat interferon responses seemed to allow the infections to last longer.

"Think of viruses on a cell monolayer like a fire burning through a forest. Some of the communities -- cells -- have emergency blankets, and the fire washes through without harming them, but at the end of the day you still have smoldering coals in the system -- there are still some viral cells," Brook said. The surviving communities of cells can reproduce, providing new targets for the the virus and setting up a smoldering infection that persists across the bat's lifespan.

Brook and Boots created a simple model of the bats' immune systems to recreate their experiments in a computer.

"This suggests that having a really robust interferon system would help these viruses persist within the host," Brook said. "When you have a higher immune response, you get these cells that are protected from infection, so the virus can actually ramp up its replication rate without causing damage to its host. But when it spills over into something like a human, we don't have those same sorts of antiviral mechanism, and we could experience a lot of pathology."

The researchers noted that many of the bat viruses jump to humans through an animal intermediary. SARS got to humans through the Asian palm civet; MERS via camels; Ebola via gorillas and chimpanzees; Nipah via pigs; Hendra via horses and Marburg through African green monkeys. Nonetheless, these viruses still remain extremely virulent and deadly upon making the final jump into humans.

Brook and Boots are designing a more formal model of disease evolution within bats in order to better understand virus spillover into other animals and humans.

"It is really important to understand the trajectory of an infection in order to be able to predict emergence and spread and transmission," Brook said.

https://www.sciencedaily.com/releases/2020/02/200210144854.htm

First childhood flu helps explain why virus hits some people harder than others

Researchers also report that travel-related screening for coronavirus will identify less than half of those infected

February 4, 2020

Science Daily/University of California - Los Angeles

Why are some people better able to fight off the flu than others? Part of the answer, according to a new study, is related to the first flu strain we encounter in childhood.

Scientists from UCLA and the University of Arizona have found that people's ability to fight off the flu virus is determined not only by the subtypes of flu they have had throughout their lives, but also by the sequence in which they are been infected by the viruses. Their study is published in the open-access journal PLoS Pathogens.

The research offers an explanation for why some people fare much worse than others when infected with the same strain of the flu virus, and the findings could help inform strategies for minimizing the effects of the seasonal flu.

In addition, UCLA scientists, including Professor James Lloyd-Smith, who also was a senior author of the PLoS Pathogens research, recently completed a study that analyzes travel-related screening for the new novel coronavirus 2019-nCoV.

The researchers report that screening travelers is not very effective for the 2019 coronavirus -- that it will catch less than half of infected travelers, on average -- and that most infected travelers are undetectable, meaning that they have no symptoms yet, and are unaware that they have been exposed. So stopping the spread of the virus is not a matter of just enhancing screening methods at airports and other travel hubs.

"This puts the onus on government officials and public health officials to follow up with travelers after they arrive, to isolate them and trace their contacts if they get sick later," said Lloyd-Smith, a UCLA professor of ecology and evolutionary biology. Many governments have started to impose quarantines, or even travel bans, as they realize that screening is not sufficient to stop the spread of the coronavirus.

One major concern, Lloyd-Smith said, is that other countries, especially developing nations, lack the infrastructure and resources for those measures, and are therefore vulnerable to importing the disease.

"Much of the public health world is very concerned about the virus being introduced into Africa or India, where large populations exist do not have access to advanced medical care," he said.

The researchers, including scientists from the University of Chicago and the London School of Tropical Hygiene and Medicine, have developed a free online app where people can calculate the effectiveness of travel screening based on a range of parameters.

Solving a decades-old question

The PLoS Pathogens study may help solve a problem that had for decades vexed scientists and health care professionals: why the same strain of the flu virus affects people with various degrees of severity.

A team that included some of the same UCLA and Arizona scientists reported in 2016 that exposure to influenza viruses during childhood gives people partial protection for the rest of their lives against distantly related influenza viruses. Biologists call the idea that past exposure to the flu virus determines a person's future response to infections "immunological imprinting."

The 2016 research helped overturn a commonly held belief that previous exposure to a flu virus conferred little or no immunological protection against strains that can jump from animals into humans, such as those causing the strains known as swine flu or bird flu. Those strains, which have caused hundreds of spillover cases of severe illness and death in humans, are of global concern because they could gain mutations that allow them to readily jump not only from animal populations to humans, but also to spread rapidly from person to person.

In the new study, the researchers investigated whether immunological imprinting could explain people's response to flu strains already circulating in the human population and to what extent it could account for observed discrepancies in how severely the seasonal flu affects people in different age groups.

To track how different strains of the flu virus affect people at different ages, the team analyzed health records that the Arizona Department of Health Services obtains from hospitals and private physicians.

Two subtypes of influenza virus, H3N2 and H1N1, have been responsible for seasonal outbreaks of the flu over the past several decades. H3N2 causes the majority of severe cases in high-risk elderly people and the majority of deaths from the flu. H1N1 is more likely to affect young and middle-aged adults, and causes fewer deaths.

The health record data revealed a pattern: People first exposed to the less severe strain, H1N1, during childhood were less likely to end up hospitalized if they encountered H1N1 again later in life than people who were first exposed to H3N2. And people first exposed to H3N2 received extra protection against H3N2 later in life.

The researchers also analyzed the evolutionary relationships between the flu strains. H1N1 and H3N2, they learned, belong to two separate branches on the influenza "family tree," said James Lloyd-Smith, a UCLA professor of ecology and evolutionary biology and one of the study's senior authors. While infection with one does result in the immune system being better prepared to fight a future infection from the other, protection against future infections is much stronger when one is exposed to strains from the same group one has battled before, he said.

The records also revealed another pattern: People whose first childhood exposure was to H2N2, a close cousin of H1N1, did not have a protective advantage when they later encountered H1N1. That phenomenon was much more difficult to explain, because the two subtypes are in the same group, and the researchers' earlier work showed that exposure to one can, in some cases, grant considerable protection against the other.

"Our immune system often struggles to recognize and defend against closely related strains of seasonal flu, even though these are essentially the genetic sisters and brothers of strains that circulated just a few years ago," said lead author Katelyn Gostic, who was a UCLA doctoral student in Lloyd-Smith's laboratory when the study was conducted and is now a postdoctoral fellow at the University of Chicago. "This is perplexing because our research on bird flu shows that deep in our immune memory, we have some ability to recognize and defend against the distantly related, genetic third cousins of the strains we saw as children.

"We hope that by studying differences in immunity against bird flus -- where our immune system shows a natural ability to deploy broadly effective protection -- and against seasonal flus -- where our immune system seems to have bigger blind spots -- we can uncover clues useful to universal influenza vaccine development."

Around the world, influenza remains a major killer. The past two flu seasons have been more severe than expected, said Michael Worobey, a co-author of the study and head of the University of Arizona's department of ecology and evolutionary biology. In the 2017-18 season, 80,000 people died in the U.S., more than in the swine flu pandemic of 2009, he said.

People who had their first bout of flu as children in 1955 -- when the H1N1 was circulating but the H3N2 virus was not -- were much more likely to be hospitalized with an H3N2 infection than an H1N1 infection last year, when both strains were circulating, Worobey said.

"The second subtype you're exposed to is not able to create an immune response that is as protective and durable as the first," he said.

The researchers hope that their findings could help predict which age groups might be severely affected during future flu seasons based on the subtype circulating. That information could also help health officials prepare their response, including decisions about who should receive certain vaccines that are only available in limited quantities.

The research was funded by the National Institutes of Health, the National Science Foundation, DARPA and the David and Lucile Packard Foundation. In 2018, the NIH's National Institute of Allergy and Infectious Diseases announced a strategic plan to develop a universal flu vaccine.

https://www.sciencedaily.com/releases/2020/02/200204094722.htm

Unique new antiviral treatment made using sugar

January 29, 2020

Science Daily/University of Manchester

New antiviral materials made from sugar have been developed to destroy viruses on contact and may help in the fight against viral outbreaks. This new development from a collaborative team of international scientists shows promise for the treatment of herpes simplex (cold sore virus), respiratory syncytial virus, hepatitis C, HIV, and Zika virus to name a few. The team have demonstrated success treating a range of viruses in the lab - including respiratory infections to genital herpes.

This new development from a collaborative team of international scientists shows promise for the treatment of herpes simplex (cold sore virus), respiratory syncytial virus, hepatitis C, HIV, and Zika virus to name a few. The team have demonstrated success treating a range of viruses in the lab -- including respiratory infections to genital herpes.

The research is a result of a collaboration between scientists from The University of Manchester, the University of Geneva (UNIGE) and the EPFL in Lausanne, Switzerland. Although at a very early stage of development, the broad spectrum activity of this new approach could also be effective against newly prevalent viral diseases such as the recent coronavirus outbreak.

So called 'virucidal' substances, such as bleach, are typically capable of destroying viruses on contact but are extremely toxic to humans and so cannot be taken or applied to the human body without causing severe harm. Developing virucides from sugar has allowed for the advent of a new type of antiviral drug, which destroys viruses yet is non-toxic to humans.

Current antiviral drugs work by inhibiting virus growth, but they are not always reliable as viruses can mutate and become resistant to these treatments.

Using modified sugar molecules the team showed that the outer shell of a virus can be disrupted, thereby destroying the infectious particles on contact, as oppose to simply restricting its growth. This new approach has also been shown to defend against drug resistance.

Publishing their work in the journal Science Advances the team showed that they successfully engineered new modified molecules using natural glucose derivatives, known as cyclodextrins. The molecules attract viruses before breaking them down on contact, destroying the virus and fighting the infection.

Dr Samuel Jones, from The University of Manchester and a member of the Henry Royce Institute for Advanced Materials, jointly led the pioneering research with Dr Valeria Cagno from the University of Geneva. "We have successfully engineered a new molecule, which is a modified sugar that shows broad-spectrum antiviral properties. The antiviral mechanism is virucidal meaning that viruses struggle to develop resistance. As this is a new type of antiviral and one of the first to ever show broad-spectrum efficacy, it has potential to be a game changer in treating viral infections." said Sam.

Professor Caroline Tapparel from the University of Geneva and Prof Francesco Stellacci from EPFL were both also senior authors of the study. Prof Tapparel declared: "We developed a powerful molecule able to work against very different viruses, therefore, we think this could be game changing also for emerging infections."

The molecule is patented and a spin-out company is being set up to continue pushing this new antiviral towards real-world use. With further testing the treatment could find a use in creams, ointments and nasal sprays or other similar treatments for viral infections. This exciting new material can work to break down multiple viruses making for cost-effective new treatments even for resistant viruses.

https://www.sciencedaily.com/releases/2020/01/200129143339.htm

To predict an epidemic, evolution can't be ignored

March 2, 2020

Science Daily/College of Engineering, Carnegie Mellon University

Whether it's coronavirus or misinformation, scientists can use mathematical models to predict how something will spread across populations. But what happens if a pathogen mutates, or information becomes modified, changing the speed at which it spreads? Researchers now show for the first time how important these considerations are.

When scientists try to predict the spread of something across populations -- anything from a coronavirus to misinformation -- they use complex mathematical models to do so. Typically, they'll study the first few steps in which the subject spreads, and use that rate to project how far and wide the spread will go.

But what happens if a pathogen mutates, or information becomes modified, changing the speed at which it spreads? In a new study appearing in this week's issue of Proceedings of the National Academy of Sciences (PNAS), a team of Carnegie Mellon University researchers show for the first time how important these considerations are.

"These evolutionary changes have a huge impact," says CyLab faculty member Osman Yagan, an associate research professor in Electrical and Computer Engineering (ECE) and corresponding author of the study. "If you don't consider the potential changes over time, you will be wrong in predicting the number of people that will get sick or the number of people who are exposed to a piece of information."

Most people are familiar with epidemics of disease, but information itself -- nowadays traveling at lightning speeds over social media -- can experience its own kind of epidemic and "go viral." Whether a piece of information goes viral or not can depend on how the original message is tweaked.

"Some pieces of misinformation are intentional, but some may develop organically when many people sequentially make small changes like a game of 'telephone,'" says Yagan. "A seemingly boring piece of information can evolve into a viral Tweet, and we need to be able to predict how these things spread."

In their study, the researchers developed a mathematical theory that takes these evolutionary changes into consideration. They then tested their theory against thousands of computer-simulated epidemics in real-world networks, such as Twitter for the spread of information or a hospital for the spread of disease.

In the context of spreading of infectious disease, the team ran thousands of simulations using data from two real-world networks: a contact network among students, teachers, and staff at a US high school, and a contact network among staff and patients in a hospital in Lyon, France.

These simulations served as a test bed: the theory that matches what is observed in the simulations would prove to be the more accurate one.

"We showed that our theory works over real-world networks," says the study's first author, Rashad Eletreby, who was a Carnegie Mellon Ph.D. student when he wrote the paper. "Traditional models that don't consider evolutionary adaptations fail at predicting the probability of the emergence of an epidemic."

While the study isn't a silver bullet for predicting the spread of today's coronavirus or the spread of fake news in today's volatile political environment with 100% accuracy -- one would need real-time data tracking the evolution of the pathogen or information to do that -- the authors say it's a big step.

"We're one step closer to reality," says Eletreby.

https://www.sciencedaily.com/releases/2020/03/200302153551.htm

Drug meant for Ebola may also work against coronaviruses

Drug meant for Ebola may also work against coronaviruses

Understanding how drugs work is an important step in developing new treatments for COVID-19

February 27, 2020

Science Daily/University of Alberta Faculty of Medicine & Dentistry

Researchers who have discovered why the drug remdesivir is effective in treating the coronaviruses that cause Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) expect it might also be effective for treating patients infected with the new COVID-19 strain.

A group of University of Alberta researchers who have discovered why the drug remdesivir is effective in treating the coronaviruses that cause Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) expect it might also be effective for treating patients infected with the new COVID-19 strain.

"Even if you know a drug works, it can be a red flag if you don't know how it works," said virologist Matthias Götte. "It is reassuring if you know exactly how it works against the target.

"We know the drug works against different coronaviruses, like MERS and SARS, and we know the novel coronavirus is very similar to SARS. So I would say I'm cautiously optimistic that the results our team found with remdesivir and MERS will be similar with COVID-19."

The study, published in the Journal of Biological Chemistry this week, is among the first in Canada to discuss the COVID-19 strain.

Until now, there has not been a published explanation of why remdesivir may work against coronaviruses, said Götte, who added his study is an important step in answering that question.

Developed by Gilead Sciences as a response to the 2014 West African Ebola virus epidemic, remdesivir was first used on a patient with the novel coronavirus earlier this year in the United States.

As reported in the New England Journal of Medicine, the patient was given the drug on the seventh day of illness, and showed marked improvement the following day, with symptoms eventually disappearing altogether. And at a recent press conference in Beijing, the assistant director-general of the World Health Organization, Bruce Alyward, said remdesivir is the only drug available that may have real efficacy against COVID-19.

"What our study showed was that remdesivir essentially mimics one of the natural building blocks for RNA synthesis necessary for genome replication of the virus. Enzymes within the virus are synthesizing the viral RNA genome with these building blocks, but they mix up the bits they need with the drug. Once the drug is incorporated into the growing RNA chain, the virus can no longer replicate,"explained Götte.

He said the next step is to wait for results from ongoing clinical trials with remdesivir, which are expected by the end of April. Even then, that won't be the end of the story, he cautioned.

"It's likely we'll need more than one drug to properly fight emerging diseases like COVID-19, as we have with HIV and hepatitis C virus infections," Götte said.

"Ideally, we will have a couple of drugs because certain strains could be resistant to certain treatments."

Götte's study was supported by grants from the Canadian Institutes of Health Research and the Alberta Ministry of Economic Development, Trade and Tourism through the Major Innovation Fund Program and Antimicrobial Resistance -- One Health Consortium.

https://www.sciencedaily.com/releases/2020/02/200227122123.htm

Novel coronavirus (COVID-19) imaging features overlap with SARS and MERS

COVID-19's imaging features are variable and nonspecific, but the imaging findings reported thus far do show

February 28, 2020

Science Daily/American Roentgen Ray Society

Although COVID-19's imaging features are variable and nonspecific, the findings thus far do show ''significant overlap'' with those of severe acute respiratory syndrome and Middle East respiratory syndrome. The early evidence suggests that initial chest imaging will show abnormality in at least 85% of patients, with 75% of patients having bilateral lung involvement initially that most often manifests as subpleural and peripheral areas of ground-glass opacity and consolidation.

COVID-19 is diagnosed on the presence of pneumonia symptoms (e.g., dry cough, fatigue, myalgia, fever, dyspnea), as well as recent travel to China or known exposure, and chest imaging plays a vital role in both assessment of disease extent and follow-up.

As per her review of the present clinical literature concerning COVID-19, Melina Hosseiny of the University of California at Los Angeles concluded: "Early evidence suggests that initial chest imaging will show abnormality in at least 85% of patients, with 75% of patients having bilateral lung involvement initially that most often manifests as subpleural and peripheral areas of ground-glass opacity and consolidation."

Furthermore, "older age and progressive consolidation" may imply an overall poorer prognosis.

Unlike SARS and MERS -- where initial chest imaging abnormalities are more frequently unilateral -- COVID-19 is more likely to involve both lungs on initial imaging.

"To our knowledge," Hosseiny et al. continued, "pleural effusion, cavitation, pulmonary nodules, and lymphadenopathy have not been reported in patients with COVID-19."

Ultimately, the authors of this AJR article recommended CT for follow-up in patients recovering from COVID-19 to evaluate long-term or even permanent pulmonary damage, including fibrosis -- as seen in SARS and MERS infections.

https://www.sciencedaily.com/releases/2020/02/200228142018.htm

COVID-19 a reminder of the challenge of emerging infectious diseases

February 28, 2020

Science Daily/NIH/National Institute of Allergy and Infectious Diseases

The emergence and rapid increase in cases of coronavirus disease 2019 (COVID-19), a respiratory illness caused by a novel coronavirus, pose complex challenges to the global public health, research and medical communities, write federal scientists from NIH's National Institute of Allergy and Infectious Diseases (NIAID) and from the Centers for Disease Control and Prevention (CDC). Their commentary appears in The New England Journal of Medicine.

NIAID Director Anthony S. Fauci, M.D., NIAID Deputy Director for Clinical Research and Special Projects H. Clifford Lane, M.D., and CDC Director Robert R. Redfield, M.D., shared their observations in the context of a recently published report on the early transmission dynamics of COVID-19. The report provided detailed clinical and epidemiological information about the first 425 cases to arise in Wuhan, Hubei Province, China.

In response to the outbreak, the United States and other countries instituted temporary travel restrictions, which may have slowed the spread of COVID-19 somewhat, the authors note. However, given the apparent efficiency of virus transmission, everyone should be prepared for COVID-19 to gain a foothold throughout the world, including in the United States, they add. If the disease begins to spread in U.S. communities, containment may no longer be a realistic goal and response efforts likely will need to transition to various mitigation strategies, which could include isolating ill people at home, closing schools and encouraging telework, the officials write.

Drs. Fauci, Lane and Redfield point to the many research efforts now underway to address COVID-19. These include numerous vaccine candidates proceeding toward early-stage clinical trials as well as clinical trials already underway to test candidate therapeutics, including an NIAID-sponsored trial of the experimental antiviral drug remdesivir that began enrolling participants on February 21, 2020.

"The COVID-19 outbreak is a stark reminder of the ongoing challenge of emerging and re-emerging infectious pathogens and the need for constant surveillance, prompt diagnosis and robust research to understand the basic biology of new organisms and our susceptibilities to them, as well as to develop effective countermeasures," the authors conclude.

Story Source:

Materials provided by NIH/National Institute of Allergy and Infectious Diseases. Note: Content may be edited for style and length.

https://www.sciencedaily.com/releases/2020/02/200228142016.htm

COVID-19 vaccine development

February 26, 2020

Science Daily/Hong Kong University of Science and Technology

Scientists have recently identified a set of potential vaccine targets for SARS-CoV-2 coronavirus, to guide experimental efforts towards vaccine development against novel pneumonia (COVID-19).

A team of scientists at the Hong Kong University of Science and Technology (HKUST) has recently made an important discovery in identifying a set of potential vaccine targets for the SARS-CoV-2 coronavirus, providing crucial leads for guiding experimental efforts towards the vaccine development against the novel pneumonia (COVID-19) caused by the virus.

Like SARS-CoV, which caused the SARS (Severe Acute Respiratory Syndrome) outbreak in 2003, SARS-CoV-2 belongs to the same Betacoronavirus genus. By considering the genetic similarity between SARS-CoV-2 and SARS-CoV, the team leveraged experimentally-determined immunological data to identify a set of SARS-CoV- derived B cell and T cell epitopes that exactly match to SARS-CoV-2. Epitopes are biomarkers recognized by the immune system to trigger actions against the virus. As no mutation has been observed in the identified epitopes among the available SARS-CoV-2 genetic sequences, immune targeting of these epitopes may potentially offer protection against the novel pneumonia COVID-19.

The team, led by data scientists Prof. Matthew McKay and Dr. Ahmed Abdul Quadeer, expected that their work can assist in guiding experimental research towards the development of effective vaccines against SARS- CoV-2.

Prof. McKay highlighted that "Despite similarities between SARS-CoV and SARS-CoV-2, there is genetic variation between the two, and it is not obvious if epitopes that elicit an immune response against SARS-CoV will likely be effective against SARS-CoV-2. We found that only roughly 20% of the SARS-CoV epitopes map identically to SARS-CoV-2, and believe these are promising candidates."

"For the identified T cell epitopes, we also performed a population coverage analysis and determined a set of epitopes that is estimated to provide broad coverage globally as well as in China" said Dr. Quadeer. The estimated population coverage represents the percentage of individuals within the selected population that are likely to elicit an immune response to at least one epitope from the identified set.

Prof. McKay is a Professor in the Departments of Electronic & Computer Engineering and Chemical & Biological Engineering; Dr. Quadeer is a post-doctoral fellow in the Department of Electronic & Computer Engineering. Their findings were recently published in the scientific journal Viruses this month.

"Our objective was to try to assist with the initial phase of vaccine development, by providing recommendations of specific epitopes that may potentially be considered for incorporation in vaccine designs" Prof. McKay added. "More generally, our work is part of a global effort seeking to capitalize on data for COVID-19, made available and rapidly shared by the scientific community, to understand this new virus and come up with effective interventions."

The beginning of 2020 has seen the emergence of SARS-CoV-2 outbreak in mainland China, which has quickly spread to over 30 countries around the world, infecting over 80,000 people and causing over 2,600 deaths as of late February 2020.

https://www.sciencedaily.com/releases/2020/02/200226091227.htm

Remdesivir prevents MERS coronavirus disease in monkeys

February 13, 2020

Science Daily/NIH/National Institute of Allergy and Infectious Diseases

The experimental antiviral remdesivir successfully prevented disease in rhesus macaques infected with Middle East respiratory syndrome coronavirus (MERS-CoV), according to a new study from National Institutes of Health scientists. Remdesivir prevented disease when administered before infection and improved the condition of macaques when given after the animals already were infected.

The new report from NIH's National Institute of Allergy and Infectious Diseases (NIAID) appears in the Proceedings of the National Academy of Sciences.

MERS-CoV is closely related to the 2019 novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV) that has grown to be a global public health emergency since cases were first detected in Wuhan, China, in December.

Remdesivir has previously protected animals against a variety of viruses in lab experiments. The drug has been shown experimentally to effectively treat monkeys infected with Ebola and Nipah viruses. Remdesivir also has been investigated as a treatment for Ebola virus disease in people.

The current study was conducted at NIAID's Rocky Mountain Laboratories in Hamilton, Montana. The work involved three groups of animals: those treated with remdesivir 24 hours before infection with MERS-CoV; those treated 12 hours after infection (close to the peak time for MERS-CoV replication in these animals); and untreated control animals.

The scientists observed the animals for six days. All control animals showed signs of respiratory disease. Animals treated before infection fared well: no signs of respiratory disease, significantly lower levels of virus replication in the lungs compared to control animals, and no lung damage. Animals treated after infection fared significantly better than the control animals: disease was less severe than in control animals, their lungs had lower levels of virus than the control animals, and the damage to the lungs was less severe.

The scientists indicate that the promising study results support additional clinical trials of remdesivir for MERS-CoV and COVID-19, the disease that SARS-CoV-2 causes. Several clinical trials of remdesivir for COVID-19 are under way in China, and other patients with COVID-19 have received the drug under a compassionate use protocol.

The Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services, also provided support for this study. Gilead Sciences, Inc., developed remdesivir, also known as GS-5734, and collaborated in the research.

MERS-CoV emerged in Saudi Arabia in 2012. Through December 2019, the World Health Organization had confirmed 2,499 MERS-CoV cases and 861 deaths (or about 1 in 3). Because about one-third of MERS-CoV cases spread from infected people being treated in healthcare settings, the scientists suggest that remdesivir could effectively prevent disease in other patients, contacts of patients, and healthcare workers. They also note the drug might help patients who are diagnosed with MERS or COVID-19 if given soon after symptoms start.

https://www.sciencedaily.com/releases/2020/02/200213160128.htm

Effectiveness of travel bans -- readily used during infectious disease outbreaks -- mostly unknown

February 13, 2020

Science Daily/University of Washington

While travel bans are frequently used to stop the spread of an emerging infectious disease, a new study of published research found that the effectiveness of travel bans is mostly unknown.

Because of the quick and deadly outbreak in late December of a novel coronavirus in Wuhan, China, now known as COVID-19 -- infecting tens of thousands and killing hundreds within weeks, while spreading to at least 24 other countries -- many governments, including the United States, have banned or significantly restricted travel to and from China.

And while travel bans are frequently used to stop the spread of an emerging infectious disease, a new University of Washington and Johns Hopkins University study of published research found that the effectiveness of travel bans is mostly unknown.

However, said lead author Nicole Errett, a lecturer in the UW Department of Environmental & Occupational Health Sciences in the School of Public Health, that's largely due to the fact that very little research into the effectiveness of travel bans exists.

"Some of the evidence suggests that a travel ban may delay the arrival of an infectious disease in a country by days or weeks. However, there is very little evidence to suggest that a travel ban eliminates the risk of the disease crossing borders in the long term," said Errett, co-director of the ColLABorative on Extreme Event Resilience, a research lab focused on addressing real-world issues relevant to community resilience.

The researchers combed through thousands of published articles in an effort to identify those that directly addressed travel bans used to reduce the geographic impact of the Ebola virus, SARS (Severe Acute Respiratory Syndrome), MERS (Middle East Respiratory Syndrome) and the Zika virus. They did not include studies of influenza viruses, for which travel bans have already been shown to be ineffective in the long term.

In the end, the researchers were able to identify just six studies that fit their criteria. Those six were based on models or simulations, not data from actual bans after they were implemented, to assess the effectiveness of travel bans in controlling outbreaks. Consequently, to improve research in this area, the study authors recommend that research questions, partnerships and study protocols be established ahead of the next outbreak so empirical data can be collected and assessed quickly.

"Travel bans are one of several legal options that governments have drawn on to mitigate a pandemic," said co-author Lainie Rutkow, a professor of health policy and management at Johns Hopkins Bloomberg School of Public Health. "As coronavirus spreads, our study raises the importance of understanding the effectiveness of legal and policy responses intended to protect and promote the public's health."

"When assessing the need for, and validity of, a travel ban, given the limited evidence, it's important to ask if it is the least restrictive measure that still protects the public's health, and even if it is, we should be asking that question repeatedly, and often," said co-author Lauren Sauer, an assistant professor of emergency medicine at Johns Hopkins University's School of Medicine and director of operations with the university's Office of Critical Event Preparedness and Response.

Consequently, the authors write, additional research is "urgently needed" to inform policy decisions, especially in light of the tremendous social, economic and political impacts of their implementation.

https://www.sciencedaily.com/releases/2020/02/200213175923.htm