Body

Nursing homes with the largest proportions of non-White residents experience 3.3 times more COVID-19 deaths than do nursing homes with the largest proportions of White residents, according to a new study from the University of Chicago. The paper, published in JAMA Network Open, suggests that these differences are likely due to nursing home size and the level of coronavirus spread in the local community, reinforcing the inseparability of long-term care facilities from society at large when it comes to bringing the COVID-19 pandemic to heel.

Since the start of the pandemic, between 35% and 40% of COVID-19 deaths have been associated with long-term care facilities. Senior author R. Tamara Konetzka, PhD, the Louis Block Professor of Public Health Sciences and the College at UChicago, wanted to bring her 25 years of experience studying nursing homes to ask why these facilities were experiencing such devastation from the coronavirus and if it was possible to predict which nursing homes were at highest risk.

Konetzka and her collaborator, Rebecca Gorges, PhD, a postdoc in the Department of Public Health Sciences, pulled together data sets from national sources, compiling information from over 13,000 nursing homes, to identify predictors of COVID-19 outcomes in nursing homes. The data represented COVID-19 outcomes during the first waves of the pandemic, beginning between January 1 and May 24 and ending September 23, 2020. "Very early on, we saw some striking relationships with the racial composition of a nursing home, where nursing homes serving more Black and brown residents seem to have more COVID cases and deaths," said Dr. Konetzka.

Nursing homes with the highest percentages of non-White residents had more than three times as many COVID-19 cases and deaths than nursing homes with the highest percentages of White residents. More than 60% of nursing homes with the highest percentages of non-White residents reported at least one COVID-19 death, with an average of 5.6 deaths, compared to only 20% of nursing homes with the highest percentages of White residents reporting at least one death, with an average of 1.7 deaths.

"There were theories floating around that maybe Black and brown residents are just sicker or are in low-quality homes, but we wanted to dig beneath these really alarming statistics and analyze why these outcomes were happening," said Konetzka.

To identify why these racial disparities between nursing homes existed, the investigators compared a number of characteristics of nursing homes to their COVID-19 outcomes, including: overall patient health, facility size, chain membership, ownership type, number of nursing hours, coronavirus spread in the local community, and facility star rating. After controlling for these factors, only two explained the difference in COVID-19 outcomes by race: nursing home size, and COVID-19 rates in the surrounding community.

"It's not about the underlying health of the residents or even the quality of the nursing homes by star rating," said Konetzka. "One factor is just the size of these facilities." Nursing homes with higher percentages of non-White residents tend to be larger than nursing homes with higher percentages of White residents. Large facilities are more likely to experience worse coronavirus outbreaks since their sheer size allows more opportunities for an outbreak to be seeded.

"The other important reason why we see these racial differences is the prevalence of the virus in the surrounding community," said Konetzka. "Black and non-White people in general tend to live in neighborhoods that have a high prevalence of the virus and even the staff who work in these facilities are more likely to live in these neighborhoods. It's about location and size, more than anything else."

These findings were not initially obvious to the investigators. At first, it seemed as if the disparities in COVID-19 outcomes might be explained by Black individuals being more likely to reside in lower quality nursing homes and entering these facilities in worse health than their White counterparts. However, neither of these explanations could account for the differences in COVID-19 outcomes, as it seems that the entire system was unprepared to weather the pandemic.

"I think it was surprising to everyone that low quality of nursing home care wasn't at the root of this. In fact, a few years prior to the pandemic, a lot was made of the fact that the majority of nursing homes had regulatory deficiencies in their infection control procedures. But it turns out even being cited by Medicare or Medicaid isn't predictive. The whole sector was just unable to deal with a crisis of this magnitude," said Konetzka.

According to her, the fundamental facts of how the coronavirus transmits and how nursing homes operate led to this system-wide failure. "The coronavirus can be spread asymptomatically and is airborne. Large nursing homes can have several residents per room and staff must go room to room to give care. COVID-19 is a perfect storm where it doesn't matter if a nursing home is high- or low-quality; all patients are at risk."

This research is part of a larger ongoing project by Konetzka to study the effects of COVID-19 on nursing homes. Her early work in the spring led to her testifying before the Senate Special Committee on Aging on why nursing homes were suffering from poor COVID-19 outcomes and how to improve the ability of the facilities to deal with the coronavirus. "This was really rewarding as an academic, because we do rigorous research about fundamental behaviors and this was an opportunity to directly influence policy and make a difference in people's lives," said Konetzka. While she believes that her and others' research has begun to shape the narrative around nursing homes during the pandemic, Konetzka says there is still more to study.

"There's also still a lot to learn about what works in terms of both state policy and federal policy," said Konetzka. "Nursing homes are a grossly underfunded area of our healthcare system, but they are still really connected to the rest of our system."

The paper's finding that the level of community spread accounted for some of the racial disparities underscores how intimately nursing homes are tied to the rest of society. "We can't just dissociate what's happening in nursing homes from the rest of the pandemic. Solving that problem is part of solving the entire pandemic."

Though there will be an end to the COVID-19 pandemic, Konetzka says the underlying issues in long-term care must still be addressed. "Getting old and needing long-term care is in all our futures. Selfishly, we should work towards a system that is safe and effective, and provides a high quality of life for people as they age. But, in the long run, if we want to prevent these nursing home deaths from happening again in the next pandemic, we have to seriously revisit the whole way we approach and fund long-term care."

Found around the world, powdery mildew is a fungal disease especially harmful to plants within the sunflower family. Like most invasive pathogens, powdery mildew is understudied and learning how it affects hosts can help growers make more informed decisions and protect their crops.

Scientists at the University of Washington and the University of Central Florida inoculated 126 species of plants in the sunflower family with powdery mildew, growing 500 plants from seeds that were collected from the wild and provided from the USDA germplasm network. Through this large-scale study, they were able to measure the various plants' susceptibility to powdery mildew.

"We observed that the amount of disease present on a host can be dependent on where that host lies on the tree of life--that is, the evolutionary history of a host can predict how susceptible that host is to disease," explained Michael Bradshaw, a plant pathologist involved with the study.

They also measured common plant traits, such as biomass, trichome density, and chlorophyll content, and found that none of them were associated with the disease, underscoring the unimportance of commonly assessed host plant traits in powdery mildew severity and pointing further to the role that evolutionary history plays in plant susceptibility to disease.

"Any tools we can use to predict the severity of a disease can be valuable and improve management guidelines. Especially with fungal pathogens, where there is often a large lag time between the introduction of a pathogen and the formation of an epidemic," Bradshaw said. "I am hopeful that this research could spur future work and provide ideas and techniques for other researchers studying the evolution of disease."

This research provides information on species of sunflower plants that are resistant to powdery mildew disease, which can be beneficial to breeding programs. Bradshaw also hopes that this study will inspire other studies that mine the genome of different plant species involved to potentially locate genes involved with resistance.

Wearing a protective face mask has only a modest effect on the ability of healthy people to do vigorous exercise, according to a study published today (Monday) in the European Respiratory Journal [1].

Researchers carried out detailed testing on breathing, heart activity and exercise performance in a group of 12 people while they were using an exercise bike with and without a mask.

Although they found differences in some measurements between wearing a mask and not wearing a mask, they say that none of their results indicate any risk to health. This suggests that masks could be worn safely during intense exercise, for example to reduce COVID-19 transmission between people visiting an indoor gym.

The study was by a team of researchers including Dr Elisabetta Salvioni from Centro Cardiologico Monzino, IRCCS, Milan, Italy, and Dr Massimo Mapelli and Professor Piergiuseppe Agostoni from Centro Cardiologico Monzino and the University of Milan.

Dr Salvioni said: "We know that the main route of transmission for coronavirus is via droplets in the breath and it's possible that breathing harder during exercise could facilitate transmission, especially indoors. Research suggests that wearing a mask may help prevent the spread of the disease, but there is no clear evidence on whether masks are safe to wear during vigorous exercise."

To address this question, researchers worked with a group of healthy volunteers made up of six women and six men with an average age of 40. Each person took part in three rounds of exercise tests: once while not wearing a face mask, once wearing a surgical mask (blue, single-use mask) and once wearing a 'filtering face piece 2' or FFP2 mask (white, single use mask believed to offer slightly better protection than a surgical mask).

While the volunteers used an exercise bike, the researchers measured their breathing, heart rate, blood pressure and the levels of oxygen in their blood.

Results of the tests showed that wearing a face mask had a small effect on the volunteers. For example, there was an average reduction of around ten per cent in their ability to perform aerobic exercise (according to their 'peak VO2' which is a measurement of their highest possible oxygen uptake).

The results also indicate that this reduction was probably caused by it being slightly harder for the volunteers to breathe in and out through the masks.

Dr Mapelli said: "This reduction is modest and, crucially, it does not suggest a risk to healthy people doing exercise in a face mask, even when they are working to their highest capacity. While we wait for more people to be vaccinated against COIVD-19, this finding could have practical implications in daily life, for example potentially making it safer to open indoor gyms.

"However, we should not assume that the same is true for people with a heart or lung condition. We need to do more research to investigate this question."

The team are now studying the impact of wearing a face mask while carrying out daily activities, such as climbing the stairs or doing housework, in healthy people and those with heart or lung conditions.

Professor Agostoni added: "COVID-19 has hit our region and our hospital so hard, with devastating effects at a personal, professional and organisational level. Despite that, this was one of many studies carried out with enthusiasm by our young researchers.

"We are particularly proud of this work because it began spontaneously during our free time in the otherwise depressing period of the current pandemic and our findings demonstrate the necessity of clinical research, even during an emergency."

Professor Sam Bayat from Grenoble University Hospital, France, is Chair of the European Respiratory Society (ERS) Clinical Respiratory Physiology, Exercise and Functional Imaging Group and was not involved in the research. He said: "There are still gaps in our knowledge of how to limit the spread of COVID-19, but we believe face masks have a role to play and we are becoming accustomed to wearing face masks in public spaces such as shops, trains and buses.

"Although these results are preliminary and need to be confirmed with larger groups of people, they seem to suggest that face masks can also be worn safely for indoor sports and fitness activities, with a tolerable impact on performance."

Being able to make blind people see again sounds like the stuff of miracles or even science fiction. And it has always been one of the biggest challenges for scientists. Diego Ghezzi, who holds the Medtronic Chair in Neuroengineering (LNE) at EPFL's School of Engineering, has made this issue a research focus. Since 2015, he and his team have been developing a retinal implant that works with camera-equipped smart glasses and a microcomputer. "Our system is designed to give blind people a form of artificial vision by using electrodes to stimulate their retinal cells," says Ghezzi.

Read more: https://actu.epfl.ch/news/a-retinal-implant-that-is-more-effective-against-b/

Star-spangled sky

The camera embedded in the smart glasses captures images in the wearer's field of vision, and sends the data to a microcomputer placed in one of the eyeglasses' end-pieces. The microcomputer turns the data into light signals which are transmitted to electrodes in the retinal implant. The electrodes then stimulate the retina in such a way that the wearer sees a simplified, black-and-white version of the image. This simplified version is made up of dots of light that appear when the retinal cells are stimulated. However, wearers must learn to interpret the many dots of light in order to make out shapes and objects. "It's like when you look at stars in the night sky - you can learn to recognize specific constellations. Blind patients would see something similar with our system," says Ghezzi.

Running simulations, for now

The only catch is that the system has not yet been tested on humans. The research team first needs to be certain of their results. "We aren't yet authorized to implant our device in human patients, since obtaining the medical approval takes a long time. But we came up with a process for testing it virtually - a type of work-around," says Ghezzi. More specifically, the engineers developed a virtual reality program that can simulate what patients would see with the implants. Their findings have just been published in Communication Materials.

Field of vision and resolution

Two parameters are used to measure vision: field of vision and resolution. The engineers therefore used these same two parameters to evaluate their system. The retinal implants they developed contain 10,500 electrodes, with each one serving to generate a dot of light. "We weren't sure if this would be too many electrodes or not enough. We had to find just the right number so that the reproduced image doesn't become too hard to make out. The dots have to be far enough apart that patients can distinguish two of them close to each other, but there has to be enough of them to provide sufficient image resolution," says Ghezzi.

The engineers also had to make sure that each electrode could reliably produce a dot of light. Ghezzi explains: "We wanted to make sure that two electrodes don't stimulate the same part of the retina. So we carried out electrophysiological tests that involved recording the activity of retinal ganglion cells. And the results confirmed that each electrode does indeed activate a different part of the retina."

The next step was to check whether 10,500 light dots provide good enough resolution - and that's where the virtual reality program came in. "Our simulations showed that the chosen number of dots, and therefore of electrodes, works well. Using any more wouldn't deliver any real benefits to patients in terms of definition," says Ghezzi.

The engineers also performed tests at constant resolution but different field-of-vision angles. "We started at five degrees and opened up the field all the way to 45 degrees. We found that the saturation point is 35 degrees - the object remains stable beyond that point," says Ghezzi. All these experiments demonstrated that the system's capacity doesn't need to be improved any further, and that it's ready for clinical trials. But the team will have to wait a little longer before their technology can be implanted in actual patients. For now, restoring vision remains in the realm of science fiction.

What The Study Did: The objectives of this study were to examine the characteristics and outcomes among adults hospitalized with COVID-19 at U.S. medical centers and analyze changes in mortality over the initial six months of the pandemic.

Authors: Ninh T. Nguyen, M.D., of the University of California, Irvine Medical Center, in Orange, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2021.0417)

Editor's Note: The article includes conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Approximately 15-to-30 percent of patients with metastatic breast cancer have brain metastasis (BM), with basal-like breast cancer (BLBC) metastasizing to the brain most frequently. The prognosis for BLBC-BM patients is poor, as the blood-brain barrier prevents most therapeutics from reaching the brain. Testing candidate therapies in clinical trials is also challenging because animal models that mimic BM are limited. In a new study, researchers from Brigham and Women's Hospital and collaborators engineered a bimodal tumor-suppressing and killing molecule that can be delivered to the brain by stem cells. They tested the therapy in three new mouse models of BLBC-BM that imitate human cancers and found that it successfully prolonged the lifespan of the mice. Findings are published in Science Advances.

"When breast cancer patients get metastasis to the brain, there's often not much we can do because therapeutics for brain metastatic cancer are scarce," said corresponding author Khalid Shah, MS, PhD, of the Center for Stem Cell Therapeutics in the Brigham's Department of Neurosurgery. "Given the urgent need and magnitude of the problem, we set out to not only work on the development of a new therapeutic approach, but also to develop it in a way that maximizes the likelihood that our findings will be clinically translatable."

The researchers began their work by analyzing tissue from breast tumors and metastatic tumors in the brain from human patients with BM. They pinpointed key targets that appeared to drive tumor growth: an excess of epidermal growth factor receptor (EGFR) and death receptors 4 and 5 (DR4/5). With this knowledge, the investigators genetically engineered a bi-functional molecule, EvDRL, to target EGFR and DR4/5 simultaneously and induce cell death in the tumors.

Because breast cancer can metastasize to the brain in numerous patterns, the researchers spent three years building BM mouse models to reflect the range and complexity of human disease. One mouse mimics metastasis that takes the form of a solid tumor in the middle of the brain (macro-metastasis), the second mimics a more scattered metastasis (perivascular niche micro-metastasis), and the third mimics one that appears in the back of the brain (leptomeningeal metastases). Armed with these models, they could more accurately determine the efficacy of the therapeutic molecule, EvDRL.

To introduce EvDRL to the brains of the metastasis mouse models, the researchers developed a stem-cell-based delivery platform. Stem cells have the advantage of being able to cross the BBB and home in on tumors in the brain. Allogeneic stem cell therapies, which use donor tissue samples to create large batches of cells, can produce stem cells efficiently, making them a readily available, "off-the-shelf" technology for administering therapies. In all three mouse models, the researchers observed improved survival rates.

"Building these models was essential to testing our therapies because we wanted to mimic what happens in the patients," Shah said. "We started our research by bringing findings in patients to mice, and now we are planning to go back to the patients."

Beijing, 26 February 2021: the journal Cardiovascular Innovations and Applications (CVIA) has just published the third issue of Volume 5. This issue brings together important research from authors in the USA and China, including several important papers concerned with the various cardiological implications of COVID-19.

Papers in the issue are as follows.

RESEARCH PAPERS

Diyu Cui, Yimeng Liao, Jianlin Du and Yunqing Chen
A Meta-analysis of Major Complications between Traditional Pacemakers and Leadless Pacemakers
(http://ow.ly/CgYO30rz3eA)

Yue Wu, Guoyue Zhang, Rong Hu and Jianlin Du
Risk of Target Organ Damage in Patients with Masked Hypertension versus
Sustained Hypertension: A Meta-analysis (http://ow.ly/x63E30rzjEp)

Jing Li, Lijie Sun, Fang Wang, Bing Liu, Hui Li, Guodong Tang, Zhigang Chang, Aihua Liu, Chunyi Fu,
You Lv, Jing Gao and Jing Li
Relation between Cardiac Injury and Elevated Levels of Inflammatory Biomarkers
in Patients with Severe COVID-19 (http://ow.ly/C2Ch30rzjJD)

Yao Dong, Jun-E Liu and Ling Song
Risk Factors for Intraoperative Pressure Injury in Aortic Surgery: A Nested Case-Control Study (http://ow.ly/wozk30rzkhF)

Hai Zou and Shengqing Li
ECMO/CRRT Combined Support in the Treatment of Critically Ill SARS-CoV-2 Pneumonia Patients (http://ow.ly/G6DO30rzkiz)

Zhuzhi Wen, Jingying Hou, Zun Mai, Huifen Huang, Yangxin Chen, Dengfeng Geng and Jingfeng Wang
Predictive Value of Blood Pressure, Heart Rate, and Blood Pressure/Heart Rate Ratio in a
Chinese Subpopulation with Vasovagal Syncope (http://ow.ly/d3Hm30rzkj9)

CASE REPORTS

Yu Zhang, Wen-Long Dai, Can-Can Lin, Qiao-Yuan Li and Cheng-Jun Guo
Implantation of an S-ICD in a Patient with a DDD Pacemaker and Congenitally Corrected
Transposition of the Great Arteries (http://ow.ly/7Nk530rzkjw)

Wen-Yuan Ding, Jia-Min Li, Fei Zheng, Li-Li Wang, Xin-Yi Wei and Guo-Hua Li
The Challenges of Treating Acute Myocardial Infarction due to Variant Angina: Lesson from
an Interesting Case (http://ow.ly/vELU30rzkjM)

Yachao Li, Zengming Xue, He Ma, Wei Zhang, Shaoping Nie and Changsheng Ma
Pseudoaneurysm with Median Nerve Injury Caused by Right Radial Artery Puncture:
A Case Report (http://ow.ly/Oiyq30rzkk6)

COMMENTARY

C. Richard Conti
Coronavirus 19 (some thoughts about the Disease) (http://ow.ly/qQUL30rzkkj)

A new review of existing evidence proposes eight hallmarks of environmental exposures that chart the biological pathways through which pollutants contribute to disease: oxidative stress and inflammation, genomic alterations and mutations, epigenetic alterations, mitochondrial dysfunction, endocrine disruption, altered intercellular communication, altered microbiome communities, and impaired nervous system function.

The study by researchers at Columbia University Mailman School of Public Health, Ludwig Maximilian University, and Hasselt University is published in the journal Cell.

"Every day we learn more about how exposure to pollutants in air, water, soil, and food is harmful to human health," says senior author Andrea Baccarelli, MD, PhD, chair of Environmental Health Sciences at Columbia Mailman School. "Less understood, however, are the specific biological pathways through which these chemicals inflict damage on our bodies. In this paper, we provide a framework to understand why complex mixtures of environmental exposures bring about serious illness even at relatively modest concentrations."

We are continually exposed to a mixture of pollutants, which lead to changes in our bodies in multiple domains, from conception to old age. They govern gene expression, train and shape our immune systems, trigger physiological responses, and determine wellbeing and disease.

The paper summarizes evidence for eight hallmarks of environmental insults:

1. Oxidative stress and inflammation: When antioxidant defenses are depleted, inflammation, cell death, and organ damage occur.

2. Genomic alterations and mutations: An accumulation of DNA errors can trigger cancer and other chronic diseases.

3. Epigenetic alterations: Epigenetic changes alter the synthesis of proteins responsible for childhood development and regular function of the body.

4. Mitochondrial dysfunction: A breakdown in the cellular powerplant may interfere with human development and contribute to chronic disease.

5. Endocrine disruption: Chemicals found in our environment, food, and consumer products disrupt the regulation of hormones and contribute to disease.

6. Altered intercellular communication: Signaling receptors and other means by which cells communicate with each other, including neurotransmission, are affected.

7. Altered microbiome communities: An imbalance in the population of bacteria and other microorganisms in our body can make us susceptible to allergies and infections.

8. Impaired nervous system function. Microscopic particles in air pollution reach the brain through the olfactory nerve, and can interfere with cognition.

Not all environmental exposures are harmful. The researchers note that exposure to nature has been reported to have beneficial impacts on mental health.

These eight hallmarks are by no means comprehensive and do not capture the full complexity of the chemical and physical properties of environmental exposures, including mixtures of exposures over the short and long-term. Further research is needed to understand the complex mechanisms by which exposures affect human biology, and how altered processes interact and contribute to disease or confer health benefits, across the life course.

"We need research to expand our knowledge of disease mechanisms going beyond genetics.

Advances in biomedical technologies and data science will allow us to delineate the complex interplay of environmental insults down to the single-cell level," says Baccarelli. "This knowledge will help us develop ways to prevent and treat illness. With the serious environmental challenges like air pollution and climate change, most of all, we need strong local, national, and inter-governmental policies to ensure healthy environments."

Scientists at Walter Reed Army Institute of Research, in a collaboration with Duke University, have confirmed that monoclonal antibodies can be an effective tool in the global fight against malaria.

The study, led by Dr. Sheetij Dutta, chief of the Structural Vaccinology Laboratory at WRAIR, showed that mAbs such as CIS43 were most effective in a culture-based assay that measured malaria parasites’ ability to infect a human liver cell, while another mAb 317 showed the best activity in a mouse infection model. Dutta added “difference in assay outcomes for mAbs could reflect distinct sites on the circumsporozoite protein that can be exploited for developing improved vaccines.” The study results were published today in Nature Scientific Reports.

Despite decades malaria vaccine research, current vaccine candidates have shown low efficacy in field trials conducted in several countries in Africa. Many researchers from around the world have now focused their attention on using monoclonal antibodies against the circumsporozoite protein of the parasite.

Unlike vaccines, where protective responses can take multiple doses and many months to develop, mAbs may offer months of protection immediately after administration of a single injectable dose and can be developed at a fraction of the cost of developing new drugs.

Army Col. Jason Regules, MD, director of WRAIR’s Malaria Biologics Branch, added, “this was a critical study and will help to guide our future work in isolating monoclonal antibodies of unique specificity and activity from ongoing clinical trials of the FMP013 and FMP014 malaria vaccines that were developed at the WRAIR, in collaboration with our malaria research partners.”

Malaria, spread by infectious mosquitoes, causes over 200 million cases and kills hundreds of thousands of people every year, with a disproportionate allocation of morbidity and mortality distributed amongst children and pregnant women living in the most impoverished and resource-limited areas of the world. Malaria-naïve travelers to malaria-endemic regions must employ anti-malarial countermeasures or also be at risk of grave illness or death. The armamentarium against malaria is limited. Anti-malarial drug effectiveness, a cornerstone for prevention and treatment, can be sub-optimal due to ever-emerging resistance, the need for frequent administration, and difficulties with compliance. The WRAIR’s Malaria Biologics Branch has well-established capability to rigorously testing malaria vaccines and antibody-based products including human trials involving exposure to malaria infection.

The work was performed as part of a collaboration between Dr. Sheetij Dutta, Malaria Biologics Branch, WRAIR, Dr. Georgia Tomaras, Duke University, and Dr. Gordon Joyce of the Emerging Infectious Disease Branch, WRAIR.

About the Walter Reed Army Institute of Research

Headquartered in Silver Spring, Maryland, the Walter Reed Army Institute of Research is the oldest and most mission-diverse biomedical research laboratory in the Department of Defense. WRAIR provides unique research capabilities and innovative solutions to a range of force health and readiness challenges currently facing U.S. Service Members, along with threats anticipated during future operations. With research units in the state of Washington, Africa, Asia and the Caucasus region, WRAIR houses three centers, the Center for Infectious Disease Research, the Center for Military Psychiatry and Neuroscience and the Center for Enabling Capabilities.

Journal

Scientific Reports

DOI

10.1038/s41598-021-84622-x

If you are going to buy a face mask to protect yourself and others from COVID-19, make sure it's a three-layered mask. You might have already heard this recommendation, but researchers have now found an additional reason why three-layered masks are safer than single or double-layered alternatives.

While this advice was originally based on studies that showed three layers prevented small particles from passing through the mask pores, researchers have now shown that three-layered surgical masks are also most effective at stopping large droplets from a cough or sneeze from getting atomized into smaller droplets. These large cough droplets can penetrate through the single- and double-layer masks and atomize to much smaller droplets, which is particularly crucial since these smaller droplets (often called aerosols) are able to linger in the air for longer periods of time. Researchers studied surgical masks with one, two and three layers to demonstrate this behavior.

The researchers reported their results in Science Advances on March 5.

The team notes that single and double-layer masks do provide protection in blocking some of the liquid volume of the original droplet and are significantly better than wearing no mask at all. They hope their findings on ideal mask pore size, material thickness, and layering could be used by manufacturers to produce the most effective masks designs.

Using a droplet generator and a high-speed time-lapse camera, the team of engineers from the University of California San Diego, Indian Institute of Science and University of Toronto found that, counterintuitively, large respiratory droplets containing virus emulating particles (VEPs) actually get atomized when they hit a single-layer mask, and many of these VEPs pass through that layer. Think of it like a water droplet breaking into smaller droplets as it's being squeezed through a sieve. For a 620 micron droplet--the size of a large droplet from a cough or sneeze--a single-layer surgical mask only restricts about 30 percent of the droplet volume; a double-layer mask performs better, restricting about 91 percent of the droplet volume; while a three layer mask has negligible, nearly zero droplet ejection.

"While it is expected that large solid particles in the 500-600-micron range should be stopped by a single-layer mask with average pore size of 30 micron, we are showing that this is not the case for liquid droplets," said Abhishek Saha, professor of mechanical and aerospace engineering at UC San Diego and a co-author of the paper. "If these larger respiratory droplets have enough velocity, which happens for coughs or sneezes, when they land on a single-layer of this material it gets dispersed and squeezed through the smaller pores in the mask."

This is a problem. Droplet physics models have shown that while these large droplets are expected to fall to the ground very quickly due to gravity, these now smaller, 50-80 micron-sized droplets coming through the first and second layer of a mask will linger in the air, where they can spread to people at larger distances.

The team of engineers-- which also includes Professors Swetaprovo Chaudhuri from University of Toronto, and Saptarshi Basu of the Indian Institute of Science-- were well-versed in this type of experiment and analysis, though they were used to studying the aerodynamics and physics of droplets for applications including propulsion systems, combustion, or thermal sprays. They turned their attention to respiratory droplet physics last year when the COVID-19 pandemic broke out, and since then, have been studying the transport of these respiratory droplets and their roles in transmission of Covid-19 type diseases.

"We do droplet impact experiments a lot in our labs," said Saha. "For this study, a special generator was used to produce a relatively fast-moving droplet. The droplet was then allowed to land on a piece of mask material--that could be a single layer, double, or triple layer, depending on which we're testing. Simultaneously, we use a high-speed camera to see what happens to the droplet."

Using the droplet generator, they're able to alter the size and speed of the droplet to see how that affects the flow of the particle.

Going forward, the team plans to investigate the role of different mask materials, as well as the effect of damp or wet masks, on particle attrition.

Mount Sinai Researchers find a new way to prevent attention deficits associated with Fragile X, a leading genetic cause of autism, in an animal model

Corresponding Author: Hirofumi Morishita, MD, PhD, Department of Psychiatry, Neuroscience, Friedman Brain Institute, Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York.

Bottom Line: The adolescent maturation of the frontal cortex is important for establishing cognitive function, and disruption of this process is associated with neurodevelopmental disorders. This study uncovered a new molecular driver of frontal circuit maturation that is essential for cognitive function, and demonstrated, in an animal model, that this mechanism can be targeted to restore attention deficits caused by a leading genetic cause of autism.

Results: This study identified that neurotransmission (communication between neurons) via nicotinic receptors in the brain plays a major developmental role in establishing attentional circuitry and behavior. Although a naturally occurring neurotransmitter called acetylcholine is the usual activator of this brain receptor, it is also so-named the "nicotinic receptor," as it binds and responds to nicotine, thereby activating the receptor as well. They found that too much signaling via the nicotinic receptors in this circuit causes dysregulation of attention circuit development and subsequent attentional behavior deficit. This study also demonstrated that deficits in attentional circuitry and behavior in a mouse model of Fragile X syndrome can be prevented by selectively suppressing communication via nicotinic receptors in the frontal circuit, starting in adolescence.

Why the Research Is Interesting: This study provides novel insights into the pathophysiology of neurodevelopmental disorders by identifying that in a mouse model of Fragile X syndrome, a leading genetic cause of autism, there is failed top-down circuit maturation, leading to attention deficits due to excessive communication through nicotinic receptors. This study also points to regulation of neurotransmission via nicotinic receptors as a therapeutic target for attentional circuit impairments in neurodevelopmental disorders.

Who: A mouse model of Fragile X syndrome, a leading genetic cause of autism.

When: Animals were treated with molecular interventions from adolescence period and their frontal cortical circuit and behavior were studied in adulthood.

What: The study examined molecular and circuit alternations in frontal cortex and associated attentional behavior changes in a mouse model of Fragile X syndrome.

How: Neurons in frontal cortex projecting to visual cortex were characterized using electrophysiological, structural, and behavioral methodologies. Neuromodulatory signaling via nicotinic receptor was manipulated from adolescent period to examine the therapeutic potential.

Study Conclusions: Frontal sensory projection neurons undergo dynamic regulation of neurotransmission through nicotinic receptors from adolescent period to establish attentional circuit and behavior. A mouse model of Fragile X syndrome shows deficits in this attentional circuit and behavior, but these deficits can be prevented by the frontal circuit selective suppression of signaling via nicotinic receptors beginning in adolescence.

Paper Title: Nicotinic regulation of local and long-range input balance drives top-down attentional circuit maturation.

Said Mount Sinai's Dr. Hirofumi Morishita of the research: "For the last 20 years, developmental windows when synaptic connections are established for lifetime function, as well as their molecular controls, has been extensively studied in sensory areas. In contrast, very little is known about drivers of frontal cortical circuit maturation due to its complexity, making it difficult to relate molecular and synaptic changes to development of cognition. Our discovery of the drivers of circuit maturation in the context of cognitive behavior will likely point to therapeutic targets to reduce cognitive deficits shared across a range of disorders."

BUFFALO, N.Y. - New research using a nationally representative sample of more than 12,000 participants shows the collateral consequences victims are likely to confront following unfair treatment by police.

Michael Brown, George Floyd and Tamir Rice are just some of those who have died recently at the hands of police.

Their names are now tragically familiar, but thousands of other people who are unjustly stopped, searched or questioned by law enforcement will likely experience a range of detrimental outcomes associated with unfair police treatment, including depression, suicidal thoughts, drug use, and a loss of self-efficacy, according to Christopher Dennison, PhD, assistant professor of sociology in the University at Buffalo College of Arts and Sciences.

Previous work using small, non-random samples has suggested similar results, but Dennison's study leverages the National Longitudinal Study of Adolescent to Adult Health (Add Health), a powerful and illustrative data set that clearly shows how these unfortunate patterns are generalizable.

Controlling for variables including behavioral and socioeconomic indicators early in life, treatment by parents and perceived social support, the results showed that individuals who reported unfair police treatment were more likely to also report detrimental social-psychological and behavioral consequences, such as depression and suicide ideation, than those who reported no unfair police treatment.

When examining these relationships within each racial and ethnic group, however, the gap in predicted depressive symptoms and self-efficacy scores between white people with and without a history of unfair police treatment was significantly more pronounced compared with that of Black people.

Black people, and specifically Black men, were far more likely to report unfair police treatment than white people, but the consequences of such experiences were more apparent for white people, according to the findings.

"This effect we found among white people could be attributed to evidence suggesting how minority families are socializing their children to prepare for police encounters," says Dennison, the paper's corresponding author and an expert in life course criminology and social responses to crime.

"It's the realization of the 'experience of the expected hypothesis,'" he says. "For minorities, more generally, there's a belief that unfair treatment by police will likely happen at some point in their lives, while white people don't have that expectation. That preparation and lack of preparation might be responsible for the effects we see in this study."

The findings published in the journal Criminology broaden the understanding of unfair treatment by police by showing the tragedy is not limited to the incident itself. The detrimental effects of this type of injustice can become corrosively lodged in the life course of victims.

Transparency is critical to moderate the likelihood of the detrimental outcomes, and proactive police tactics, such as stop-and-frisk, should be eliminated, according to Dennison.

"The perception of these interactions is certainly consequential," says Dennison. "The Add Health data do not provide context. It asks only if someone has been unfairly treated by police. But context might not matter, because what someone perceives as unfair is indeed consequential."

Making law enforcement aware of these results can help motivate transparency, according to Dennison. It's critical that people know why something is happening in a police interaction to increase the perception of legitimacy.

"It's also important to be aware of how these findings reinforce structural inequalities," says Dennison. "These experiences involving police are leaning to the point of being normal and engrained.

"That's alarming and disturbing."

Dennison's research with Jessica Finkeldey, an assistant professor of criminal justice at SUNY Fredonia, relied on the fifth round of questioning from the Add Health data set.

Started in 1994, Add Health is a sample of 20,000 participants who were in grades 7-12 during the first round of data collection from participants and their parents relating to social, familial and behavioral areas.

For the fifth wave, roughly 12,000 participants were asked whether they had ever been treated unfairly by police.

"We controlled for many behaviors that might have generated inaccuracies, and the findings remain robust," says Dennison. "People who report these kind of interactions with police were much more likely to experience these detrimental outcomes."

Strong, collaborative relationships with principal investigators are a key factor of longevity in clinical research coordinator positions -- an essential, but increasingly transient job in executing treatment-advancing clinical trials, Vanderbilt University Medical Center researchers found.

Danielle Buchanan, BS, clinical translational research coordinator III in the Department of Neurology, and Daniel Claassen, MD, MS, chief of the Division of Cognitive Disorders and associate professor of Neurology, found the top factor for retention is a close working relationship between clinical research coordinators (CRCs) and the study's principal investigator that emphasizes respect and collaboration. Salary followed as the next factor for retention among 85 former or current CRCs who responded to a REDCap survey sent to 113 people from more than 30 academic medical centers across the U.S.

Survey results spotlight that compensation and a clear trajectory for career growth were significant predictors of retention among coordinators. More so, principal investigators are encouraged that establishing collegial relationships through hands-on involvement in clinical research trials were the greatest predictors of retention.

They published results in "Empowering the Clinical Research Coordinator in Academic Medical Centers" in the Mayo Clinical Proceedings: Innovation, Quality & Outcomes.

"Clinical research coordinators are the lynchpin of research teams. For patients, they are the constant face across a sometimes-difficult journey. We wanted to know what it takes to make this coordinator role a career, and not a steppingstone to another position. What does it take for coordinators to stay and thrive in an academic medical center? Can we transition from an 'in-and-out role' to a stable, honored position that has a trajectory in an academic system?" said Claassen, senior author.

"Over the last 10 years I've seen that hiring clinical research coordinators can become a challenge to principal investigators. I feel like the role is transient, in part because academic institutions have not invested in the role as long-term, respected positions. There is no clear trajectory for advancement and the salary structure is not incentivized," said Claassen.

The pair set out to examine what entices coordinators to stay in the role because while the position previously had longevity, it's evolved into a stopover role for people early in their careers. The transience carries costs for the research team and institution because filling the spot requires recruitment and training. For patients, turnover adds uncertainty and unfamiliarity to their clinical trial experience, said Buchanan, who has been a coordinator for eight years.

"Ultimately, we are here for the patient, especially the ones with chronic devastating diseases. When there is turnover, it is detrimental to the patient. I put together the survey because we wanted to look for that missing piece that tells us why people leave, or what makes them stay," said Buchanan, first author.

"I want to raise the prestige of the position so PIs, administrators and sponsors understand that coordinators are more than worker bees. We're ambassadors of hope to patients and families, and I'd love to change the mindset that this isn't a long-term career path," said Buchanan.

With three out of four newly emerging infectious human diseases originating in animals*, there is an urgent need to monitor the legal trade in wildlife, according to new research by Vincent Nijman, Professor in Anthropology at Oxford Brookes University.

Professor Nijman, who has been involved in monitoring and regulating the legal wildlife trade for over two decades, said: "Covid-19 more than anything else has put a spotlight on emerging infectious diseases and how this is linked to the trade in wild animals. Few people are aware of its scale. With literally hundreds of millions of live wild animals being shipped around the world each year, it seems unlikely that diseases are spread through illegal channels only. After all, parasites, bacteria and viruses do not read legal documents or check if they have received the correct stamp."

Dangerous to only focus on illegal wildlife trade

The illegal wildlife trade is often seen as one of the major gateways to zoonotic diseases, that spread from animals to humans. While the illegal trade in tigers, ivory, rhino horn, pangolins and primates is of paramount concern for public health, Professor Nijman says the legal wildlife trade should be of equal concern: "Given that in many instances the legal wildlife trade is several orders of magnitude larger than the illegal trade, it is ineffective and possibly dangerous to focus on the illegal wildlife trade only."

Lack of hygiene in wet markets could drive infection transmission

The Covid-19 pandemic threw attention onto wet markets, now associated closely with zoonotic diseases.
But in the wet market of Wuhan, the vast majority of non-domesticated animals (crocodiles, bats, civets, bamboo rats) were legally offered for sale. Professor Nijman notes that "a lack of appropriate hygiene conditions (handwashing, sanitation, separation of wildlife and their parts), make wildlife markets drivers for the transmission of infections."

Dr Chris R. Shepherd, an expert on wildlife trade and the Executive Director of the Monitor Conservation Research Society added: "This study clearly illustrates that there are incredibly serious risks associated with the trade in wildlife, regardless of whether the species involved are traded legally or illegally.

"Clearly the risk of spreading harmful zoonotic disease must be considered when regulating the trade in wildlife, and much more research and preventative measures are essential if we are to avoid further pandemics."

Administering zinc supplements to covid-19 patients with low levels of this element may be a strategy to reduce mortality and recovery time. At the same time, it could help to prevent risk groups, like the elderly, from suffering the worst effects of the disease. These are the findings of a study by physicians and researchers from the Hospital del Mar, Hospital del Mar Medical Research Institute (IMIM) and Pompeu Fabra University (UPF), led by Dr. Robert Güerri, a physician at the Infectious Diseases Service of Hospital del Mar, which has just been published in the journal Nutrients.

The study analysed the zinc levels of 249 adult patients treated at the centre between 9 March and 1 April 2020, with an average age of 65 years. The most common symptoms presented at the time of admission were fever, cough and dyspnea. In all cases, they analysed their blood zinc levels, considering those under 50 μ/dl as being low. As explained by Dr. Güerri, first author of the clinical study, they analysed this parameter because "zinc is an essential element for maintaining a variety of biological processes, and altering its levels causes increased susceptibility to infections and increased inflammatory response". For this reason, "given the comorbidities associated with zinc deficiency and its immunomodulatory and antiviral actions, zinc levels and zinc supplementation may prove useful tools to tackle the covid-19 crisis".

Higher mortality in patients with lower zinc levels

1 in 4 patients had low levels of zinc. This group had more severe symptoms and higher levels of inflammation as measured by two markers, C-reactive protein (CRP) and interleukin 6 (IL-6), which mediate the inflammatory response. On average, their length of hospital stay was three times longer than patients with higher levels of zinc (25 days compared to 8).

Regarding mortality, zinc levels were significantly higher in patients who survived the infection, 62 μ/dl, versus 49 μ/dl for those who died. Moreover, 1 in 5 patients with low zinc levels died. Conversely, the mortality rate of those presenting higher levels upon admission was 5%. The study reveals that a one-unit increase of zinc in blood plasma is directly linked to a 7% reduction of the risk of dying from covid-19. Dr. Güerri highlights that "we have shown the importance of zinc levels in patients' blood as an additional predictor of outcome in covid-19, as well as its potential as a therapeutic tool for treatment. We therefore propose this variable as a new parameter to predict the evolution of patients and we propose initiating clinical trials concerning zinc supplementation in patients with low levels admitted for covid-19 and implementing programmes to administer supplements to groups at risk of having low zinc levels to reduce the effects of the pandemic".

Effect of zinc on the replication of the coronavirus

The study involved the collaboration of the groups of Dr. Rubén Vicente and Dr. Juana Díez at UPF. Their efforts, using in vitro techniques, have focused on studying in parallel the effects of zinc levels on the virus's capacity to expand. The results confirm that the poor prognosis in patients with low concentrations of zinc is due both to the effect that a lack of zinc has on immune imbalance and the increase in viral load, as they found that low levels of zinc enhance the expansion of the virus in infected cells.

At the same time, the results indicate that an element must be sought to enable enhancing the activity of zinc in the cell to block viral replication, as their studies have shown that contrary to what had been speculated at the onset of the pandemic, chloroquine cannot perform this function.