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As anti-racism solidarity protests continue around the world, new research suggests mainstream media have a tendency to focus on the violence and spectacle of a protest rather than the substance. That mentality and approach need to change according to Summer Harlow, assistant professor of journalism at the University of Houston Jack J. Valenti School of Communication.

"How journalists cover protests and social movements matters because the more delegitimizing the coverage is the less likely the public is to support it," said Harlow, lead author of the study published online in the Journal of Journalism Studies. "Reporters should focus on the real issues, not just the violence you see on television or read about in newspapers between police and protestors or the inconvenience to bystanders. It hurts a movement's ability to be successful."

Harlow and co-authors Danielle Kilgo at the University of Minnesota; Ramón Salaverría at University of Navarra in Pamplona, Spain; and Victor García-Perdomo at the University of La Sabana in Bogotá, Colombia, examined the way protests are covered across mainstream, alternative and digital-only media outlets. The team analyzed more than 1,400 news articles in English and Spanish from 2015 spanning the globe related to human rights/justice, anti-government/corruption and socio-economic issues, among others. The articles had been shared on Twitter and Facebook allowing the researchers to consider the correlation between story characteristics and social media user engagement.

The researchers found the type of protest, location of protest and type of media outlet were significantly related to whether these stories stuck to the protest paradigm - a pattern of negative coverage of protests, especially when the events are anti-status quo, that demonizes protesters and marginalizes their causes.

"This goes back to traditional journalistic practices and values. If you are a journalist on a deadline, you rely on official sources such as law enforcement for information. As a result, protestors are seen as less credible and the reason why they are so upset gets lost in the coverage," explained Harlow, whose body of research centers on how news media cover protests and the relationship between journalists and activists.

Previous research shows news coverage that follows the paradigm uses four frames, three of which delegitimize the root of the cause: riot, a focus on the violence; confrontation, a focus on clashes between protestors and police; spectacle, a focus on the drama or emotions; and debate - a media frame that legitimizes viewpoints and demands by emphasizing the reasons for the protest.

In applying this framing to stories shared on social media, the study reveals articles published about socio-economic and human rights/justice protests in Europe, for example, focused less on confrontation and more on the debate. In Latin America/Caribbean and Asia, social media users leaned more towards the spectacle with a tendency to highlight the drama, oddity and circus of protests in these regions.

Harlow, who will teach a course about media and social justice this fall, says recent protests in the United States over the killing of George Floyd and in support of Black Lives Matter, offer opportunities for all media outlets to improve their coverage.

"George Floyd represents this moment where journalists can take what they've been doing all this time and change it," she said. "There's been this collective wake-up call among journalists who are now questioning the way it's always been done, and that maybe they haven't been doing it the right way."

NEW YORK, NY (June 24, 2020) -- More than 99.9% of seasonal coronaviruses present in airborne droplets were killed when exposed to a particular wavelength of ultraviolet light that is safe to use around humans, a new study at Columbia University Irving Medical Center has found.

"Based on our results, continuous airborne disinfection with far-UVC light at the current regulatory limit could greatly reduce the level of airborne virus in indoor environments occupied by people," says the study's lead author David Brenner, PhD, Higgins Professor of Radiation Biophysics at Columbia University Vagelos College of Physicians and Surgeons and director of the Center for Radiological Research at Columbia University Irving Medical Center.

The research was published today in Scientific Reports.

Background

Conventional germicidal UVC light (254 nm wavelength) can be used to disinfect unoccupied spaces such as empty hospital rooms or empty subway cars, but direct exposure to these conventional UV lamps is not possible in occupied public spaces, as this could be a health hazard.

To continuously and safely disinfect occupied indoor areas, researchers at Columbia University Irving Medical Center have been investigating far-UVC light (222 nm wavelength). Far-UVC light cannot penetrate the tear layer of the eye or the outer dead-cell layer of skin so it cannot reach or damage living cells in the body.

The researchers had previously shown that far-UVC light can safely kill airborne influenza viruses.

The new paper extends their research to seasonal coronaviruses, which are structurally similar to the SARS-CoV-2 virus that causes COVID-19.

Study details

In the study, the researchers used a misting device to aerosolize two common coronaviruses. The aerosols containing coronavirus were then flowed through the air in front of a far-UVC lamp. After exposure to far-UVC light, the researchers tested to see how many of the viruses were still alive.

The researchers found that more than 99.9% of the exposed virus had been killed by a very low exposure to far-UVC light.

Based on their results, the researchers estimate that continuous exposure to far-UVC light at the current regulatory limit would kill 90% of airborne viruses in about 8 minutes, 95% in about 11 minutes, 99% in about 16 minutes, and 99.9% in about 25 minutes.

Using far-UVC light in occupied indoor spaces

The sensitivity of the coronaviruses to far-UVC light suggests that it may be feasible and safe to use overhead far-UVC lamps in occupied indoor public places to markedly reduce the risk of person-to-person transmission of coronaviruses, as well as other viruses such as influenza.

Ongoing studies in SARS-CoV-2

In a separate ongoing study, the researchers are testing the efficacy of far-UVC light against airborne SARS-CoV-2. Preliminary data suggest that far-UVC light is just as effective at killing SARS-CoV-2.

"Far-UVC light doesn't really discriminate between coronavirus types, so we expected that it would kill SARS-CoV-2 in just the same way," Brenner says. "Since SARS-CoV-2 is largely spread via droplets and aerosols that are coughed and sneezed into the air it's important to have a tool that can safely inactivate the virus while it's in the air, particularly while people are around."

Brenner continues, "Because it's safe to use in occupied spaces like hospitals, buses, planes, trains, train stations, schools, restaurants, offices, theaters, gyms, and anywhere that people gather indoors, far-UVC light could be used in combination with other measures, like wearing face masks and washing hands, to limit the transmission of SARS-CoV-2 and other viruses."

Below please find a summary and link(s) of new coronavirus-related content published today in Annals of Internal Medicine. The summary below is not intended to substitute for the full article as a source of information. A collection of coronavirus-related content is free to the public at http://go.annals.org/coronavirus.

Masks for Prevention of Respiratory Virus Infections, Including SARS-CoV-2, in Health Care and Community Settings

Researchers from Oregon Health & Science University reviewed multiple electronic databases, including the World Health Organization COVID-19 database and medRxiv preprint server to examine the effectiveness of N95, surgical, and cloth masks in community and health care settings for preventing respiratory virus infections, and effects of reuse or extended use of N95 masks. They found that evidence on mask effectiveness for respiratory infection prevention is stronger in health care than community settings. Current evidence suggests that use of N95 respirators might reduce SARS-CoV-1 risk versus surgical masks in health care settings, but applicability to SARSCoV-2 is uncertain. This is a living review, meaning that the article will be updated periodically, with updates appearing in the comments section. Read the full text: https://www.acpjournals.org/doi/10.7326/M20-3213.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. The lead author, Roger Chou, MD, can be reached through Erik Robinson at robineri@ohsu.edu.

In the face of a multipronged front to drive blood pressure up, including a high-salt diet, females are better able to keep their pressure down by increasing levels of a T cell that selectively dials back inflammation, scientists say.

Females have an innate ability to upregulate these anti-inflammatory cells, called Tregs, in response to a challenge, says Dr. Jennifer C. Sullivan, pharmacologist and physiologist, noting that the cell's levels are known to increase to help maintain a healthy pregnancy, for example, so the immune system does not attack the fetus, which has DNA from both parents.

"This is just a different challenge, but we are using those same protective pathways to do something else good for us," says Sullivan, professor in the Department of Physiology at the Medical College of Georgia at Augusta University, who studies sex differences in hypertension, the so-called 'silent killer" that is a key risk factor for heart disease and stroke.

Tregs are known to help protect us from an excessive immune response, like the cytokine storms causing so much destruction in COVID-19, as well as autoimmune diseases like rheumatoid arthritis, where our immune system attacks our own tissues, and are naturally associated with lower blood pressures and less organ damage.

Sullivan's most recent work, published in the journal Hypertension, supports the hypothesis that females rely heavily on Tregs for blood pressure control and this mechanism accounts for at least one of the sex differences in that control, she and her colleagues write.

Females, at least before menopause, tend to have lower blood pressures than males. "We think, based on studies in this and other models, that the ability of the female to maintain or upregulate those T regulatory cells is critical to their ability to maintain a lower pressure," she says.

"It's a compensatory response to an increase in blood pressure to help the overall cardiovascular impact," Sullivan says of this innate ability that could provide a promising new hypertension treatment strategy, particularly for females.

That compensatory role held when they turned Tregs down in this rapid hypertension-evoking environment called DOCA salt treatment in rats. When they used a neutralizing antibody to prompt about a 30-40% reduction in the number of Tregs, blood pressure went up in the females, essentially matching the measures found in the males. Sullivan suspects males and females likely make similar numbers of Tregs -- they have found similar numbers in the spleen, for example -- but differences may be in the recruitment and proliferation to organs key to blood pressure control like the kidneys, one reason she wanted to look specifically at Treg levels there.

Both sexes actually experienced increases in pro-inflammatory T cells, which contribute to infection fighting. Blood pressure increased significantly in both sexes by day two, but by the end of 21 days of treatment, male blood pressures were significantly higher. And, females experienced significantly more of the blood pressure-mitigating Tregs along with their lower pressures, the scientists report.

When given therapy to deplete Tregs, it essentially equalized Treg levels in the males and females but it significantly increased blood pressure only in females. The fact that decreasing Tregs in males did not affect blood pressure may indicate that male blood pressure is not as dependent on this mechanism during normal conditions, they write. However the clear impact in females supports the hypothesis that females are "highly dependent" on Tregs to maintain their blood pressure, they also write.

The hormone DOCA, or deoxycorticosterone acetate, prompts the kidneys to hold onto both more sodium and water, so there is a higher fluid volume in the blood vessels, which drives up blood pressure. Then, as with some humans, a high-salt diet magnifies the problem and so does the removal of a single kidney. This DOCA-salt model is a commonly used hypertension model, which provides scientists a good window for when hypertension sets in.

While they expected that like blood pressure, kidney damage also would be less in females following DOCA salt treatment, the scientists found in reality kidney damage was comparable in the sexes. While they are not yet certain what the surprise finding means, they are exploring ideas like protecting the kidney structure is simply not something Tregs do. Still they have found in similar studies in other rat strains, that kidney protection was afforded, and that in these new studies, even with significant blood pressure reductions in the females, blood pressures in both sexes were comparatively high compared with normal, so kidney damage may still result. They note that when they reduced Treg levels in females, which drove blood pressure up, it did not increase kidney damage further and investigators say more work needs to be done to understand what appear to be conflicting findings.

"If we can better understand how and why females are increasing their Tregs that could lead to therapies, potentially for both sexes, to also avoid or treat high-inflammation conditions like autoimmune and cardiovascular disease," Sullivan says. In fact, autologous Treg therapy is already showing promise in conditions where excessive inflammation is a factor like Crohn's disease and type 1 diabetes.

For about a decade, scientists have been really interested in the immune system's control of blood pressure and the role of T cells in that control. Sullivan's lab did some of the early work looking specifically at calming Tregs. They have found, for example, in the spontaneously hypertensive rat model, the most commonly used hypertension model, that Tregs were "one of the most pronounced sex differences we saw between the males and females and it tracked most faithfully with changes in blood pressure," she says. They also saw that when a female's blood pressure goes up, so do her Treg levels, and those immune cells decrease when blood pressure does.

Normal blood pressure numbers also indicate sex differences. Generally women have lower blood pressure than men of a similar age; the advantage appears mostly lost after menopause when female pressures can creep even higher than males'.

Hypertension is the most common risk factor for cardiovascular disease, causing 18 million deaths a year, the investigators write, however mechanisms controlling blood pressure in either sex remains largely unknown. Genetic, dietary and environmental factors, like sodium intake and stress levels respectively, are considered causative.

Sullivan's laboratory has ongoing studies looking further at production of the anti-inflammatory cells, including the role of the short-lived gas and powerful blood vessel dilator nitric oxide, which has been associated with increased Treg levels in females. Estrogen increases nitric oxide production.

Sullivan reported last year that a high-fat diet also increased inflammation-promoting T cells and decreased inflammation-dampening Tregs in both sexes, but the females maintained higher percentages, just as they do normally.

WHAT:
Polycystic ovary syndrome (PCOS), an infertility disorder affecting at least 15% of reproductive-age women, may have at least two different subtypes, suggests a study funded by the National Institutes of Health. The findings could provide important information on the possible causes of PCOS and for developing more effective ways to treat the condition. The study appears in PLOS Medicine and was funded by NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and National Institute of Diabetes and Digestive and Kidney Diseases.

PCOS is characterized by irregular or missing menstrual periods (due to lack of or infrequent ovulation), high levels of androgens (male hormones) and small cysts on the ovaries. Women with PCOS are also at higher risk of diabetes and heart disease.

The current study analyzed the genes of nearly 900 women who had irregular menstrual periods. Researchers categorized them according to their body mass index (BMI) and levels of glucose, insulin and reproductive hormones, including androgens. Their analysis revealed two PCOS subtypes, each associated with distinct groups of gene variants. The reproductive subtype, about 23%, had higher levels of luteinizing hormone (LH), a pituitary hormone that regulates the ovaries, and sex hormone binding globulin (SHBG), a protein that transports estrogen and androgens. This subtype also tended to have a lower BMI and lower insulin levels than the others.

The metabolic group, roughly 37%, had a higher BMI, higher glucose and insulin levels and lower levels of SHBG and LH. The remaining women had no clear combinations of traits but had a greater frequency of gene variants associated with PCOS, suggesting that this group may be distinct from the others. Understanding the genes underlying these subtypes may yield new ways to diagnose PCOS and develop personalized treatments.

A new modeling study illustrates how accounting for factors such as age and social activity influences the predicted herd immunity threshold for COVID-19, or the level of population immunity needed to stop the disease's transmission. The model hints that herd immunity could potentially be achieved with around 43% of the population being immune, as opposed to the 60% threshold derived from previous models. However, the authors stress that their study serves mostly as a sketch of how population differences affect herd immunity, rather than as a precise estimate. As Science Editor-in-Chief Holden Thorp notes in a related Science Editor's blog post in which he discusses how the journal weighed potential costs and benefits of publishing this study, "Even if the model's most optimistic prediction of 43% as a herd immunity threshold is correct, none of the seroprevalence studies that we are aware of suggest that any country is close to achieving herd immunity. Continuing non-pharmaceutical interventions around the world is still of great importance." As health authorities grapple with how to respond to the COVID-19 pandemic and whether to lift restrictions, some have expressed fear that lifting restrictions before herd immunity is achieved could lead to a second wave of infections. Here, Tom Britton and colleagues simulated herd immunity using an epidemiological model that accounts for the influence of age and social activity on a person's susceptibility to COVID-19, in contrast to simpler models where all population members are equally susceptible to infection. Assuming that an infected person transmitted the virus to an average of 2.5 other people, their model predicted that a herd immunity level of 43% was sufficient to prevent a second major outbreak after lifting restrictions. Britton et al. call for further studies with more complex models, but speculate that lifting social restrictions gradually, rather than simultaneously, could help prevent a resurgence of infections.

Research led by Queen Mary University of London has revealed novel insights into the molecular circuitry controlling cancer cell growth and spread. The findings highlight new pathways involved in these key processes of cancer progression that may represent targets for therapies.

A complex communication network

The study, published today in Science Signaling, set out to uncover how a protein called MET drives cancer progression. Research has shown faulty or mutated versions of MET to be involved in cancer cell growth and spread in a variety of cancer types; however, the precise mechanisms by which it controls these processes are unknown.

MET belongs to a group of proteins called receptor tyrosine kinases (RTKs), which are key regulatory proteins involved in a variety of signalling pathways that control normal cellular processes. Abnormal changes to RTKs are implicated in the development and progression of many types of cancer, making them a popular target for cancer treatment.

The team, made up of researchers from the BCI, led by Dr Stéphanie Kermorgant, and The Institute of Cancer Research, London, including Dr Alexia Hervieu and Dr Paul Clarke, looked at cells and preclinical models in which MET was mutated. They found that the protein activated two distinct pathways to drive cancer cell growth and migration, by interacting with other key molecules that help MET to carry out these functions.

One molecule identified as a key player in these MET-driven processes was Rac1. It is widely understood that Rac1 is involved in cancer cell migration; however, the team found Rac1 to also be critical in driving cancer cell growth, via interaction with another protein called mTOR. This interaction occurs inside the cells (in structures called endosomes), followed by a relocation of the two molecules to the cell boundary - an unusual place for mTOR to be found. In a separate pathway, MET also communicates with another molecule, PI3K, to drive cell migration.

First author of the study Dr Hervieu, who did her PhD under Dr Kemorgant's supervision and is currently a postdoctoral researcher at The Institute of Cancer Research (ICR), said: "Grasping how MET controls cell behaviour in cancer is a crucial step towards improving treatment. The unexpected discovery of Rac1's role in this context expands our understanding of how MET deregulates cells and opens new opportunities for cancer research."

The research was primarily funded by Cancer Research UK and the Medical Research Council, with additional funding from the Rosetrees Trust, Breast Cancer Now and Pancreatic Cancer Research Fund.

Overcoming drug resistance

Cancer cell migration is key for metastasis - the spread of cancer cells from one site in the body to another. Metastatic disease is the leading cause of cancer mortality; however, there is currently no cure. Understanding the processes that drive metastasis and finding ways to stop these is vital for the development of more efficacious cancer treatments.

Drugs that target MET are being tested in clinical trials; however, patients often develop resistance to these drugs as the cancer can learn to activate the MET-driven pathways in other ways. The insights gained from this study may pave the way for the development of new treatment regimens; if drugs to target MET are used in combination with drugs that inhibit mTOR and PI3K, treatments may be effective for longer. Interestingly, drugs that inhibit mTOR and PI3K at the same time have recently been developed.

Dr Kermorgant said: "We are very excited with this discovery which suggests that MET, a major cancer target, may be co-targeted with existing drugs against two other major targets, PI3K and mTOR. This could be tested in clinical trials in a near future."

This study refines the current understanding of how MET controls the signalling pathways involved in cancer growth and spread, and identifies the key players involved in these processes. Targeting these molecules in combination may offer more efficacious treatment outcomes for patients with cancer.

A research group led by Professor Kenneth K.Y. Wong of the Department of Electrical and Electronic Engineering at the University of Hong Kong (HKU), in collaboration with Bielefeld University in Germany, has developed a compact fibre laser microscope that brought breakthroughs to analysing molecules in cells and clinical applications.

The newly innovated microscope generates far less noise than customary designs, and the compactness and stability make it suitable for use in operating rooms in hospitals. The innovation was presented in the journal 'Light: Science and Applications,' published by Springer Nature.

When investigating how tumors grow, or how pharmaceuticals affect different types of cells, researchers have to understand how molecules within a cell react - and interact. This is possible with modern fluorescence microscopy. However, molecules in cell specimens had to be labelled with fluorescent substances to make them visible, and this can distort the very behavior of the molecules. Also the staining with fluorescent markers is generally unsuitable for in vivo tissues.

Label-free microscopic imaging has always been a hot topic in biomedical research. The newly invented laser microscope does not require fluorescent markers to obtain a clear image of cell molecules. Instead, cell molecules with different level of characteristics are uniquely presented via a Raman Imaging System.

Professor Kenneth Wong, who led the research said: "We use fiber laser as the light source of the optical microscope to replace the traditional solid-state laser, which is a brand new concept. Traditionally, the laser needs to be amplified in a free space of several meters, so the instrument is very big. With fiber lasers, light is amplified and transmitted through glass fibers, and the instrument design becomes light and compact. The volume is only one-eighth to one-tenth of the traditional solid-state laser instrument. Due to the size of the instrument, there is a limitation on where it can be used currently, but this will no longer pose a problem in future."

Professor Wong explained: "Fiber lasers were previously not favorable for microscopes because they were less powerful and very noisy compared to solid state lasers. To obtain molecule-specific imaging with their microscope, the team used two synchronized optical resonators (laser cavities), both with short picosecond pulses - one picosecond being one thousand billionth of a second."

"One challenge here was to control the lasers so that both beams with different wavelengths are synchronized, and hit the specimen at exactly the same time and position," said Professor Thomas Huser in Germany, a biophysicist at Bielefeld University.

Professor Huser believes that the new microscope is likely to be used in clinical applications in the coming years. Preliminary studies in cooperation with the Evangelisches Klinikum Bielefeld Hospital in Germany are already underway to use the microscope to analyze liver tissue samples."

"Our project partners are amazed by what this microscope can do." said Professor Huser. "Label-free microscopy can be used, for instance, to investigate how various new types of cells develop from stem cells. It also allows for a tumor to be demarcated from normal tissue without staining. Furthermore, we can ascertain how pharmaceutical compounds react with molecules in the muscle tissue cells of the heart and liver, as well as other cells."

Professor Wong believes the new technology can be applied in many biomedical applications, such as the endoscopy of the intestines and digestive system, etc., to detect early tumors and lesions.

"Using fiber laser, the image clarity can be 100 times higher than that of traditional endoscopes. It can penetrate the surface of organs and reflect the condition of deeper tissues. The light source uses harmless infrared visible light and will not affect the human body. In the long run, since it is portable, unmarked and harmless, it can be clinically used in surgical operations, such as immediate pathological detection, to mark tumor borders during an operation, or to accurately mark different parts for precise cuts during brain surgeries."

Lead author of the study Dr Cihang (Sherry) Kong said: "The prototype of the microscope will now serve as the basis from which to build portable devices. Because the molecules do not first have to be labelled, the specimen does not take a long time to prepare compared with using other microscopes, and the labelling-induced toxicity can be avoided. "Dr Kong is a former PhD student in Professor Wong's group, and currently a post-doctoral researcher of Professor Thomas Huser.

Both the University of Hong Kong and Bielefeld University have pioneering research in the biomedical and health technology fields, while HKU's Engineering Faculty is especially focused in the research of imaging technologies. This research was supported by the Germany/Hong Kong Joint Research Scheme sponsored by the Research Grants Council of Hong Kong and the Germany Academic Exchange Service of Germany, the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Grant, project "DeLIVER", the Research Grants Council of the Hong Kong Special Administrative Region, China, the National Natural Science Foundation of China, and the Innovation and Technology Fund.

Syracuse, N.Y. - Syracuse University chemistry professor Dr. Robert P. Doyle has developed a new drug lead to treat type 2 diabetes in millions of patients who are seeking to better control their blood sugar without the common side effects of nausea, vomiting, and in select cases, undesired weight loss.

Doyle's research article, "Corrination of a GLP-1 Receptor Agonist for Glycemic Control without Emesis," was published recently in the peer-reviewed scientific journal Cell Reports.

A common group of drugs used to treat type 2 diabetes are glucagon-like peptide-1 receptor (GLP-1R) agonists. While they do lower blood sugar levels in diabetic patients, their side effects include nausea, vomiting, and weight loss.

Through grants from the National Institutes of Health (NIH), Doyle and his collaborators found a way to combine two molecules into a new substance that lowers blood sugar without those undesired side effects.

In technical terms, Doyle's team developed a new area of bioconjugation, a chemical technique used to combine two molecules. By binding together exendin-4 (Ex4), an FDA-approved GLP-1R agonist, to dicyanocobinamide (Cbi), which is a small piece of the complex vitamin B12 molecule, they produced Cbi-Ex4 in a technique they call "corrination" - a play, of course, on "coronation."

Data collected from testing Cbi-Ex4 in the musk shrew (Suncus murinus) - the mammal used in this study due to its ability to vomit (rodents and many mammals lack that ability) - revealed beneficial effects as evidenced by improved blood sugar levels during glucose tolerance tests and a profound reduction in vomiting compared to Ex4. Importantly, no weight loss was noted, again in stark contrast to the currently approved GLP-1R agonist, making this new drug ideal for patients who require glucoregulation without affecting their body mass index (BMI) levels.

This drug could therefore benefit diabetes patients who also live with cystic fibrosis, COPD, sarcopenia, cancer, or HIV, where weight-loss is counter-indicated.

The next step in the development of this groundbreaking drug is to move it through the pre-clinical phase into phase I human studies. Doyle and his team have submitted a new grant proposal to the NIH to fund this effort.

Alongside this work, Doyle has also been awarded a three-year, $3 million grant through the federal Department of Defense (DoD) to help military veterans with comorbid diabetes and obesity. Nearly 25 percent of veterans receiving care at VA medical centers are diagnosed with diabetes (compared to about 9 percent of the general population).

"This is what the military would call dual-use technology, applicable to all civilians if it works," Doyle said. "The grant is specifically aimed at making researchers look at major problems within the veteran community, and the hope is that we would see a significant weight loss method that is better than what is currently available.

"There's no treatment out there now that can keep weight off for a long period of time without illness behaviors such as nausea," Doyle added. "So, my group is pushing to expand on GLP-1R agonists to treat diabetes with obesity (DoD project) and then separately to treat diabetes without affecting nutritional status ('corrination')."

Doyle is the Laura J. and L. Douglas Meredith Professor in the Department of Chemistry in the College of Arts and Sciences at Syracuse University and an adjunct Associate Professor of Medicine at SUNY Upstate Medical University in Syracuse. Doyle's research was conducted in collaboration with the labs of Matt Hayes, professor from the Department of Psychiatry at the University of Pennsylvania; Bart C. De Jonghe, professor from the Department of Biobehavioral Health Sciences at the University of Pennsylvania; and Dr. Christian Roth, a pediatric endocrinologist and professor at Seattle Children's Hospital.

PHILADELPHIA - After examining the genes of more than 200,000 people all over the world who have type-2 diabetes, researchers from the Perelman School of Medicine at the University of Pennsylvania and the Veterans Health Administration's (VHA) Corporal Michael J. Crescenz Veterans Affairs Medical Center (CMCVAMC) found hundreds of genetic variants never before linked to the disease. The study also identified gene variants that vary by ethnicity, as well as variants tied to conditions related to type-2 diabetes like coronary heart disease and chronic kidney disease. This expansive genetic investigation, the largest of its kind, has the potential to dramatically impact care for millions of people worldwide who suffer from this disease. The study is published in the latest edition of the journal Nature Genetics.

Using data from the world's biggest biobank--the Million Veteran Program (MVP) in the VHA - plus the DIAGRAM Consortium, the UK Biobank, the Penn Medicine Biobank, and Biobank Japan, the researchers analyzed a study population of 1.4 million people around the world, of which almost 230,000 people had type-2 diabetes. From there, they broke down the genetic makeup of those hundreds of thousands of people and found 558 independent genetic variants that are differentially distributed between people with and without type-2 diabetes, 21 being European-ancestry-specific and seven African American-ancestry specific. Of the 588 variants found, 286 had never before been discovered. Researchers then set out to see if certain genetic variants among this group of people could be tied to specific type-2-diabetes-related diseases.

"Ultimately, three were linked to coronary heart disease, two to acute ischemic stroke, four to retinopathy, two to chronic kidney disease, and one to neuropathy," said Marijana Vujkovic, PhD, a biostatistician at both the Perelman School of Medicine at the University of Pennsylvania, VHA's CMCVAMC and a co-leader for the VHA's national MVP Cardiometabolic Working Group. "Building on this research, the scientific community can assess which of the surrounding genes nearby the identified genetic variants is likely to be the causal gene that alters the risk of type-2 diabetes, and that could lead to early interventions to limit controllable risks of developing the condition."

While so many genetic variants were found in people with type-2 diabetes, no one variant was implicated as the "worst" or "most dangerous," said co-senior author Benjamin F. Voight, PhD, an associate professor of Systems Pharmacology and Translational Therapeutics at Penn, and a co-leader for the VHA's national MVP Cardiometabolic Working Group. "However, just like heart disease, schizophrenia, or obesity, it is the accumulation of a large number of these variants that can add up to a considerable increase in risk. We hope this study can not only help find that subset of patients with substantial risk, but also to motivate new, future studies for treatments based on these findings."

These Penn and VHA researchers say more knowledge about genetic variants related to type-2 diabetes may help identify potential therapeutic targets for type-2 diabetes. They also say it can help guide treatment plans for people with the condition who may also be predisposed to specific diabetes complications.

"Knowing the genetic susceptibility for diabetes complications in a patient already diagnosed with type-2 diabetes, for example through a cumulative genetic risk score, could help guide that patient's care," said co-senior-author Kyong-Mi Chang, MD, a professor of Medicine at Penn, Associate Chief of Staff for Research at VHA's CMCVAMC and the Co-PI for the VHA's MVP Merit Award that supported this work. "As clinicians, we hope that these findings can ultimately be applied to improve the health outcomes for our patients including veterans."

Following the patients from this analysis over the long term will help illuminate the risk associated with these genetic variants, the study authors say. Accordingly, they are planning to do a long-term examination of how genetics influence disease progression among patients with type-2 diabetes and associated metabolic disorders. The summary statistics from this work also have been released via dbGaP repository for public use to facilitate further discoveries. In addition, the researchers are currently using the list of newly-discovered genes to investigate medication interactions.

WHAT:

More than 300 scientists and clinicians from the federal government, industry and academia published a report of their conclusions and recommendations on COVID-19 serology studies online in Immunity. The group gathered for an online workshop in May to discuss the role of serology testing in understanding and responding to the COVID-19 public health crisis and to explore strategies to address key scientific knowledge opportunities and gaps in the emerging field. Serology tests for COVID-19 are designed to detect antibodies against SARS-CoV-2, the virus that causes COVID-19. While such tests do not diagnose active infection, they can indicate prior infection with SARS-CoV-2 that may have been missed because a person did not experience significant symptoms or access testing while infected.

The COVID-19 Serology Studies workshop was convened by an interagency working group comprised of experts from the U.S. Department of Health and Human Services--including scientists at the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute (NCI), and the National Heart, Lung and Blood Institute (NHLBI), parts of the National Institutes of Health, as well as the Centers for Disease Control and Prevention and the Biomedical Advanced Research and Development Authority--and the Department of Defense. Attendees assessed efforts to better understand the implications of serology test results, to produce and validate test kits, and to quantify undetected cases of SARS-CoV-2 infection.

Attendees recommended that additional research is needed to determine if and to what extent a positive antibody test means a person may be protected from reinfection with SARS-CoV-2. Attendees emphasized that until such data is available, serology tests should not be used as a stand-alone tool to make decisions about personal safety related to SARS-CoV-2 exposure. Researchers are now pursuing studies in humans and in animal models to better understand SARS-CoV-2 immunity. Attendees noted that such understanding could help identify optimal donors of convalescent plasma that potentially could be used to help treat those with severe COVID-19.

Researchers from NCI reviewed progress in their effort to independently validate SARS-CoV-2 serology tests on behalf of the U.S. Food and Drug Administration. Attendees also proposed strategies to expand the accuracy and capacity of these tests to distinguish between naturally acquired and vaccine-induced antibodies, which will be critical to evaluating COVID-19 vaccine candidates.

Both community-based and large-scale serology surveillance efforts--such as the RESPONSE study sponsored by NIAID and NHLBI--are collecting critical data to improve epidemiological models and inform public health decision-making. Ideally, attendees noted, federal partners will expand this activity to establish an interactive serological database that will help public health officials monitor and quickly respond to changes in SARS-CoV-2 infection patterns.

LA JOLLA, CA--Some common strains of influenza have the potential to mutate to evade broad-acting antibodies that could be elicited by a universal flu vaccine, according to a study led by scientists at Scripps Research.

The findings highlight the challenges involved in designing such a vaccine, and should be useful in guiding its development.

In the study, published in Science, the researchers found evidence that one of the most common flu subtypes, H3N2, can mutate relatively easily to escape two antibodies that were thought to block nearly all flu strains. Yet they found that it is much more difficult for another common subtype, H1N1, to escape from the same broadly neutralizing antibodies.

One of the main goals of current influenza research is to develop a universal vaccine that induces broadly neutralizing antibodies, also known as "bnAbs," to give people long-term protection from the flu.

"These results show that in designing a universal flu vaccine or a universal flu treatment using bnAbs, we need to figure out how to make it more difficult for the virus to escape via resistance mutations," says the study's senior author Ian Wilson, DPhil, Hansen Professor of Structural Biology and Chair of the Department of Integrative Structural and Computational Biology at Scripps Research.

The promise of a universal vaccine

Influenza causes millions of cases of illness around the world every year and at least several hundred thousand fatalities. Flu viruses have long posed a challenge for vaccine designers because they can mutate rapidly and vary considerably from strain to strain.

The mix of strains circulating in the population tends to change every flu season, and existing flu vaccines can induce immunity against only a narrow range of recently circulating strains. Thus, current vaccines provide only partial and temporary, season-by-season protection.

Nevertheless, scientists have been working toward developing a universal flu vaccine that could provide long-term protection by inducing an immune response that includes bnAbs. Over the past decade, several research groups, including Wilson's, have discovered these multi-strain neutralizing antibodies in recovering flu patients, and have analyzed their properties. But to what extent circulating flu viruses can simply mutate to escape these bnAbs has not been fully explored.

In the study, first-authored by postdoctoral research associate Nicholas Wu, PhD, and staff scientist Andrew Thompson, PhD, the team examined whether an H3N2 flu virus could escape neutralization by two of the more promising flu bnAbs that have been discovered so far.

Known as CR9114 and FI6v3, these antibodies bind to a critical region on the virus structure called the hemagglutinin stem, which doesn't vary much from strain to strain. Because of their broad activity against different flu strains, they've been envisioned as antibodies that a universal flu vaccine should be designed to elicit, and also as ingredients in a future therapy to treat serious flu infections.

Using genetic mutations to methodically alter one amino acid building-block of the protein after another at the stem site where the bnAbs bind, Wu and colleagues found many single and double mutations that can allow H3N2 flu to escape the antibodies' infection-blocking effect.

The team also found a few instances of these "resistance mutations" in a database of gene sequences from circulating flu strains, suggesting that the mutations already happen occasionally in a small subset of ordinary flu viruses.

Escape skills vary by flu strain

Although experiments and analyses suggested that H3N2 viruses are broadly capable of developing resistance mutations, the same was not true for H1N1 viruses. The researchers tested several H1N1 viruses and found that none seemed able to mutate and escape, except for rare mutations with weak escape effects. The H3N2 and H1N1 subtypes account for most of the flu strains circulating in humans.

The researchers used structural biology techniques to show how differences in the hemagglutinin stem structure allow H3N2 flu viruses to develop resistance mutations to the two stem-binding antibodies more easily than H1N1 viruses.

"If it's relatively easy for H3N2 to escape those bnAbs, which are the prototype antibodies that a universal flu vaccine should induce, then we probably need to think more carefully and rigorously about the design of that universal flu vaccine against certain influenza subtypes," Wu says. "The good news is that a universal flu vaccine should at least work well against the H1N1 subtype."

The researchers now plan to conduct similar studies with other flu subtypes and bnAbs. They say that in principle, a vaccine eliciting multiple bnAbs that attack different sites on flu viruses or are more accommodating to changes in the virus could help mitigate the problem of resistance mutations.

A study published online as an accepted paper in the Journal of Clinical Sleep Medicine found that increased physical activity is associated with a lower risk of obstructive sleep apnea, a common sleep-related breathing disorder. The study is the largest to date focused on the relationship between sleep apnea and levels of physical activity in the general community.

Researchers reviewed lifestyle, medical, socio-demographic and sleep health data collected from more than 155,000 adults participating in the Ontario Health Study. Based on the physical activity of participants with and without sleep apnea, the investigators determined that a modest increase in physical activity, including walking, is associated with a 10 percent reduction in the risk of developing sleep apnea.

"Our results highlight the importance of physical activity as a preventive measure against developing sleep apnea," said senior author Lyle Palmer, who is professor of genetic epidemiology at the University of Adelaide in Australia. "One surprising finding was that not only vigorous physical activity but also just walking alone was associated with a decreased risk of sleep apnea."

The authors found that adding 20 minutes to a daily walk and increasing vigorous daily activity by eight minutes would be enough to achieve a lower sleep apnea risk. The finding is independent of other known risk factors for sleep apnea such as sex, age, ethnicity and obesity.

It is estimated that more than 29 million American adults have sleep apnea, many of them undiagnosed. Untreated sleep apnea is associated with an increased risk of heart disease, stroke, high blood pressure and other potentially serious conditions.

"The rates of sleep apnea in children and adults are continuing to rise. Therefore, understanding the role of modifiable protective factors for sleep apnea is important," said Palmer. "Exercise is one such protective factor and has many other positive effects on general health. Sleep health care professionals should be trying to get their patients to exercise more."

The cross-sectional, population-based study analyzed baseline questionnaire data from 155,448 adult residents of Ontario, Canada (60% women and 40% men). Their mean age was 46 years, and about 75% were white. About 6.9% of participants reported being told by a doctor that they have sleep apnea. Those with sleep apnea were more sedentary, sitting for a median of 4.4 more hours per week than those without sleep apnea.

Due to the cross-sectional nature of the study, the authors were unable to make temporal inferences on the observed associations between physical activity and sleep apnea. However, they report that previous studies also have suggested that physical activity can reduce the severity of sleep apnea.

In a related commentary, also published as an accepted paper in JCSM, Dr. Joyce Lee-Iannotti and Dr. James Parish write that the study's findings give sleep physicians another tool to treat mild to moderate sleep apnea that may be more appealing to patients.

CORRECTION, 6/23/20, 12 p.m. CT: The five-year risk ratio of death associated with heart failure development after Type 2 diabetes diagnosis was three times higher in patients with diabetes than in patients without heart or kidney disease.

DALLAS, June 23, 2020 -- Heart failure posed the greatest 5-year risk of death for people newly diagnosed with Type 2 diabetes than any other heart or kidney diseases, according to new research published today in Circulation: Cardiovascular Quality and Outcomes, an American Heart Association journal.

People with Type 2 diabetes are 2 to 4 times more likely to develop heart failure - a condition in which the heart fails to efficiently pump oxygenated blood through the body - than people without diabetes. Research on cardiovascular disease in people with Type 2 diabetes has traditionally involved patients with a long duration of diabetes who are considered high-risk patients. This retrospective, longitudinal study aimed to learn more about the risk of heart failure in people with newly diagnosed Type 2 diabetes.

"With the emergence of novel treatments such as SGLT2 inhibitors and GLP-1 receptor antagonist medications for Type 2 diabetes, some of which are proven to reduce cardiovascular disease risk, clinicians are able to focus on cardiovascular disease and heart failure prevention in patients with Type 2 diabetes," said Bochra Zareini, M.D., Ph.D., principal investigator and research fellow at Herlev Gentofte University Hospital in Copenhagen, Denmark. "Our study highlights which subgroups of patients need and could benefit most from targeted risk evaluation, prevention and treatment."

The study identified patients who were age 18 and older without prior heart and kidney disease and were newly diagnosed with Type 2 diabetes in nationwide, Danish health registers. From 1998 to 2015, more than 153,000 patients were followed for approximately 10 years. During the median follow-up of 9.7 years, 45.1% of the patients (69,201) were diagnosed with a cardiovascular or kidney disease. Researchers estimated the five-year risk of death, the five-year risk ratios and the decrease in lifespan within five years associated with the development of any cardiovascular disease, such as heart failure, ischemic heart disease, stroke, peripheral artery disease and chronic kidney disease.

Researchers found:

heart failure in combination with any other diagnosis in the study was associated with the greatest risk of death and highest decrease in lifespan compared to combinations of other cardiovascular diseases and Type 2 diabetes;

the five-year risk ratio of death associated with heart failure development after Type 2 diabetes diagnosis was three times higher in patients with diabetes than in patients without heart or kidney disease;

risks were elevated regardless of when the patient developed cardiovascular disease after being diagnosed with Type 2 diabetes; and

the elevated risk of death was present in all subgroups based on the patient's age, gender and presence of other conditions.

The researchers also compared their findings to other similar, international studies focused on Type 2 diabetes and cardiovascular disease. They concluded their study has some limitations due to a lack of information surrounding clinical factors that would detail the severity of heart failure and Type 2 diabetes, and the progression and severity of Type 2 diabetes. The researchers also noted that they did not include the treatment effects of various new diabetes medications in the present study, thus, their findings should be interpreted with caution.

Newberry, Fla. -- Jun. 23, 2020 -- The American Society for Metabolic and Bariatric Surgery (ASMBS), the leading organization of bariatric surgeons and integrated health professionals in the nation, declared metabolic and bariatric surgery "medically necessary and the best treatment for those with the life-threatening and life-limiting disease of severe obesity" and called for the safe and rapid resumption of procedures, which have been largely postponed along with other surgeries deemed elective amid the COVID-19 pandemic.

In a new position statement entitled, "Safer Through Surgery," published online in the journal SOARD, the ASMBS strongly rejects classifying metabolic and bariatric surgery as "elective" and prefers the use of the term "Medically Necessary Time-Sensitive Surgery" or "Medically Necessary Non-Emergent Surgery" to better characterize the effectiveness of the intervention and the progressive nature of the many diseases it treats including obesity, type 2 diabetes, hypertension and heart disease.

"COVID-19 may be a factor for quite some time and the longer the treatment of obesity, type 2 diabetes and other related diseases are postponed, the greater the chance they will become worse," said Matthew M. Hutter, MD, MPH, president of the ASMBS and professor of surgery at Harvard Medical School. "Each state, doctor and patient must make a decision as to when conditions for metabolic and bariatric surgery are right, but the sooner it can be safely performed, the more quickly obesity, type 2 diabetes and other diseases can be reduced or resolved."

The ASMBS recommends that the precise timing for surgery be carefully considered based on factors including an individual patient's health status, local prevalence of COVID-19 and the availability of resources including hospital beds, ventilators and personal protective equipment (PPE).

The ASMBS statement concludes, "Before COVID-19 began, it was clear that patients with obesity were 'safer through surgery'. In the era of COVID-19, 'safer through surgery' for patients with obesity may prove to be even more important than before." Obesity has been identified as an independent risk factor for adverse outcomes including death among COVID-19 patients.

Metabolic/bariatric surgery has been shown to be the most effective and long-lasting treatment for severe obesity.1 Its safety profile is comparable to some of the safest and most commonly performed surgeries in the U.S. including gallbladder surgery, appendectomy and knee replacement.2

An estimated 252,000 bariatric surgeries were performed in the United States in 2018, which is approximately less than 1 percent of the population eligible for surgery based on BMI.3 The U.S. Centers for Disease Control and Prevention (CDC) reports 42.4 percent of Americans had obesity in 2017-2018.4 Obesity has been linked to more than 40 diseases including type 2 diabetes, hypertension, heart disease, stroke, sleep apnea, osteoarthritis and at least 13 different types of cancer.5,6,7