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Scientists find evidence that novel coronavirus infects the mouth’s cells

“When infected saliva is swallowed or tiny particles of it are inhaled, we think it can potentially transmit SARS-CoV-2 further into our throats, our lungs, or even our guts.”

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Photo by Kelsey Curtis from Unsplash.com

An international team of scientists has found evidence that SARS-CoV-2, the virus that causes COVID-19, infects cells in the mouth. While it’s well known that the upper airways and lungs are primary sites of SARS-CoV-2 infection, there are clues the virus can infect cells in other parts of the body, such as the digestive system, blood vessels, kidneys and, as this new study shows, the mouth.

The potential of the virus to infect multiple areas of the body might help explain the wide-ranging symptoms experienced by COVID-19 patients, including oral symptoms such as taste loss, dry mouth and blistering. Moreover, the findings point to the possibility that the mouth plays a role in transmitting SARS-CoV-2 to the lungs or digestive system via saliva laden with virus from infected oral cells. A better understanding of the mouth’s involvement could inform strategies to reduce viral transmission within and outside the body. The team was led by researchers at the National Institutes of Health and the University of North Carolina at Chapel Hill.

“Due to NIH’s all-hands-on-deck response to the pandemic, researchers at the National Institute of Dental and Craniofacial Research were able to quickly pivot and apply their expertise in oral biology and medicine to answering key questions about COVID-19,” said NIDCR Director Rena D’Souza, D.D.S., M.S., Ph.D. “The power of this approach is exemplified by the efforts of this scientific team, who identified a likely role for the mouth in SARS-CoV-2 infection and transmission, a finding that adds to knowledge critical for combatting this disease.”

The study, published online March, 25, 2021 in Nature Medicine, was led by Blake M. Warner, D.D.S., Ph.D., M.P.H., assistant clinical investigator and chief of NIDCR’s Salivary Disorders Unit, and Kevin M. Byrd, D.D.S., Ph.D., at the time an assistant professor in the Adams School of Dentistry at the University of North Carolina at Chapel Hill. Byrd is now an Anthony R. Volpe Research Scholar at the American Dental Association Science and Research Institute. Ni Huang, Ph.D., of the Wellcome Sanger Institute in Cambridge, U.K., and Paola Perez, Ph.D., of NIDCR, were co-first authors.

Researchers already know that the saliva of people with COVID-19 can contain high levels of SARS-CoV-2, and studies suggest that saliva testing is nearly as reliable as deep nasal swabbing for diagnosing COVID-19. What scientists don’t entirely know, however, is where SARS-CoV-2 in the saliva comes from. In people with COVID-19 who have respiratory symptoms, virus in saliva possibly comes in part from nasal drainage or sputum coughed up from the lungs. But according to Warner, that may not explain how the virus gets into the saliva of people who lack those respiratory symptoms.

“Based on data from our laboratories, we suspected at least some of the virus in saliva could be coming from infected tissues in the mouth itself,” Warner said.

To explore this possibility, the researchers surveyed oral tissues from healthy people to identify mouth regions susceptible to SARS-CoV-2 infection. Vulnerable cells contain RNA instructions for making “entry proteins” that the virus needs to get into cells. RNA for two key entry proteins–known as the ACE2 receptor and the TMPRSS2 enzyme–was found in certain cells of the salivary glands and tissues lining the oral cavity. In a small portion of salivary gland and gingival (gum) cells, RNA for both ACE2 and TMPRSS2 was expressed in the same cells. This indicated increased vulnerability because the virus is thought to need both entry proteins to gain access to cells.

“The expression levels of the entry factors are similar to those in regions known to be susceptible to SARS-CoV-2 infection, such as the tissue lining the nasal passages of the upper airway,” Warner said.

Once the researchers had confirmed that parts of the mouth are susceptible to SARS-CoV-2, they looked for evidence of infection in oral tissue samples from people with COVID-19. In samples collected at NIH from COVID-19 patients who had died, SARS-CoV-2 RNA was present in just over half of the salivary glands examined. In salivary gland tissue from one of the people who had died, as well as from a living person with acute COVID-19, the scientists detected specific sequences of viral RNA that indicated cells were actively making new copies of the virus–further bolstering the evidence for infection.

Once the team had found evidence of oral tissue infection, they wondered whether those tissues could be a source of the virus in saliva. This appeared to be the case. In people with mild or asymptomatic COVID-19, cells shed from the mouth into saliva were found to contain SARS-CoV-2 RNA, as well as RNA for the entry proteins.

To determine if virus in saliva is infectious, the researchers exposed saliva from eight people with asymptomatic COVID-19 to healthy cells grown in a dish. Saliva from two of the volunteers led to infection of the healthy cells, raising the possibility that even people without symptoms might transmit infectious SARS-CoV-2 to others through saliva.

Finally, to explore the relationship between oral symptoms and virus in saliva, the team collected saliva from a separate group of 35 NIH volunteers with mild or asymptomatic COVID-19. Of the 27 people who experienced symptoms, those with virus in their saliva were more likely to report loss of taste and smell, suggesting that oral infection might underlie oral symptoms of COVID-19.

Taken together, the researchers said, the study’s findings suggest that the mouth, via infected oral cells, plays a bigger role in SARS-CoV-2 infection than previously thought.

“When infected saliva is swallowed or tiny particles of it are inhaled, we think it can potentially transmit SARS-CoV-2 further into our throats, our lungs, or even our guts,” said Byrd.

More research will be needed to confirm the findings in a larger group of people and to determine the exact nature of the mouth’s involvement in SARS-CoV-2 infection and transmission within and outside the body.

“By revealing a potentially underappreciated role for the oral cavity in SARS-CoV-2 infection, our study could open up new investigative avenues leading to a better understanding of the course of infection and disease. Such information could also inform interventions to combat the virus and alleviate oral symptoms of COVID-19,” Warner said.

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Study finds low-dose eye drops successful in managing adult myopia for 24 hours

A single low-dose atropine eye drop can produce daylong effects in managing myopia, or nearsightedness.

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Groundbreaking research from the University of Houston shows that a single low-dose atropine eye drop can produce daylong effects in managing myopia, or nearsightedness, which affects roughly one-third of U.S. adults.   

Professor of Optometry Lisa Ostrin and postdoctoral researcher Barsha Lal are reporting that even one drop in the eye of low-dose atropine (0.01%–0.1%) produces clear changes in pupil size and focusing ability that persist for at least 24 hours. Importantly, they also found that the drop shows no short-term structural effects on the eye, with only temporary changes in blood flow inside the retina. 

Ostrin’s latest research is published in the journal Eye and Vision. It adds to a growing body of vision research from David Berntsen, Golden-Golden Professor of Optometry at the University of Houston, who is co-leading a national $25 million NIH-funded clinical trial to delay the development of myopia in children by using the atropine drops. 

Low concentration atropine is widely prescribed to slow myopia progression in children, yet its short-term retinal and choroidal effects remain incompletely understood. Ostrin’s new study evaluated short-term effects of a range of low atropine concentrations on the length of the eye, the blood vessels in the retina and the thickness of the retina and choroid, which sits just behind the retina. These are important measurements because longer eye length is associated with myopia and as it gets longer, the retina and choroid are stretched.  

“These findings indicate that a single instillation of atropine does not alter axial length or retinal or choroidal thickness over 24 hours but may transiently affect superficial retinal perfusion in a time-dependent manner,” said Ostrin.  

In the double-masked, randomized study, twenty healthy adults received a single instillation of either a placebo or atropine in the right eye during five separate sessions. Researchers then checked the eye structure, thickness, and length in the central retina both one-hour and 24-hours later.  

“Characterizing these short-term effects is important for a better understanding of the physiological responses to atropine in clinical and research settings,” said Ostrin who previously published research results of a study investigating the short-term effects of a range of low-dose atropine concentrations on the pupils of young adults. In that study, she found similar results with a single drop of atropine inducing significant changes in the pupils. 

Together, the studies indicate that atropine induces early functional and vascular effects in the eye, in the absence of structural change.  

“By linking objective ocular responses with subjective visual experience, this work advances our understanding of how atropine works and supports more precise, evidence-based, and individualized approaches to myopia management,” said Ostrin. 

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Study: Egg consumption is associated with a lower risk of Alzheimer’s Disease

Compared to never eating eggs, eating at least five eggs per week can decrease risk of Alzheimer’s.

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Consumption of eggs is associated with a lower risk of being diagnosed with Alzheimer’s Disease for those 65 years and older, according to researchers at Loma Linda University Health

Eating one egg per day for at least five days a week reduces risk of Alzheimer’s by up to 27%, researchers found.

“Compared to never eating eggs, eating at least five eggs per week can decrease risk of Alzheimer’s,” said Joan Sabaté, MD, DrPH, a professor at Loma Linda University School of Public Health and the study’s principal investigator.

Even less frequent consumption of eggs significantly reduced the risk of Alzheimer’s. Researchers found that eating eggs 1 to 3 times per month had a 17% decrease in risk, while eating eggs 2 to 4 times per week had a 20% decrease in risk, Sabaté said.

The study, Egg intake and the incidence of Alzheimer’s disease in the Adventist Health Study-2 cohort linked with Medicare datawas published last week in the Journal of Nutrition.

Researchers said they embarked on the study because of a substantial knowledge gap in the relationship between modifiable dietary factors and risk of Alzheimer’s disease risk.

Eggs are known to be a source of key nutrients that support brain health. Sabaté said. Eggs provide choline, a precursor to acetylcholine and phosphatidylcholine, both of which are critical for memory and synaptic function, the study stated. Eggs also contain lutein and zeaxanthin—carotenoids that accumulate in brain tissue and are associated with improved cognitive performance and reduced oxidative stress. Eggs also contain key omega-3 fatty acids, and yolks are particularly rich in phospholipids, which constitute nearly 30% of total egg lipids and are essential for neurotransmitter receptor function.

Researchers said they studied the consumption of eggs in visible ways — such as eating eggs in various forms, like scrambled, fried, boiled, etc. — and hidden ways, such as eggs included in baked goods and packaged foods.

The cases of Alzheimer’s Disease in the Adventist Health Study 2 cohort were diagnosed by physicians, according to Medicare records, among the study population of 40,000 subjects. Eligibility was determined using the Medicare Master Beneficiary Summary Files. The average follow-up period was 15.3 years.

The team emphasized that moderate egg consumption should be  part of a balanced diet.

“Research supports eggs as part of a healthy diet,” said Jisoo Oh, DrPH, MPH, an associate professor of epidemiology at Loma Linda University School of Public Health and the study’s lead author. “Seventh-day Adventists do eat a healthier diet than the general public, and we want people to focus on overall health along with this knowledge about the benefit of eggs.”

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Telling people they might lose motivates more than telling them they might win, research shows

How managers choose to frame problems directly influences employees’ motivation to speak up at work. For managers, this is an insightful approach for building more open and collaborative teams.

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Athletes say they hate to lose more than they love to win. New research finds the same sentiment is shared in organizations.

A Virginia Tech researcher and his colleagues discovered that when managers frame work problems as a potential loss, employees are more likely to take action than when those problems are framed as potential gains. The research also revealed that when the potential loss impacts a larger group, employees are more likely to take action in the form of speaking up to a supervisor in hopes of finding a solution. The findings were recently published in the Journal of Applied Psychology.

For managers, this research suggests that framing work problems as potential losses can influence employees to speak up more.

“Employee voice occurs when suggestions are made to improve organizational functioning,” said Phil Thompson, associate professor in the Pamplin College of Business Department of Management. “From an organizational perspective, the positive outcomes of employee voice include improved performance, effectiveness, and workplace safety. From an employee level, speaking up is positively related to creativity, innovation, engagement, and ethical behavior.”

At its core, this research shows that how managers choose to frame problems directly influences employees’ motivation to speak up at work. For managers, this is an insightful approach for building more open and collaborative teams.

“When managers say, ‘If we don’t get this done, not only will you lose the $5,000 bonus, but everybody in this work group is going to lose a $5,000 bonus,’ it magnifies an employee’s motivation to act in a proactive way,” said Thompson. “This suggests that framing work problems as what will be collectively lost – compared to what can be individually lost – makes employees want to speak up more.”

Thompson was part of a research team led by Jeffery Thomas and Jonathan Booth from The London School of Economics and Mark Bolino from Oklahoma University. Together they analyzed responses from nearly 2,000 full-time employees, MBA students, and employee-supervisor pairs for their experience in situations where work problems were framed as either a gain or a loss. Across three different studies, framing something as a loss yielded employees to voice a work suggestion more.

For example, a manager dealing with a reputational crisis of their team, such as a product quality issue, can frame the problem in a way to spark helpful employee suggestions on how to resolve the issue. For example, instead of saying “if this product has great quality, our company will look really good” a manager saying “if this product is not up to quality standards, our reputation will be damaged” carries more weight for the team. When this reputational risk is shared by everyone, employees are more willing to step forward to help the problem.

In the first study, participants were asked to think about a problem at work that was significant for them. From there, they were randomly assigned to write about the potential losses or gains from that problem. They were also asked to indicate how likely they were to talk about these problems to their supervisor. Participants who reflected on their potential losses showed a 16 percent higher willingness to speak up compared to those who focused on the potential gains.

When it came to the MBA students, they read a fictional performance review scenario where a workplace problem was described. They then rated how willing they would be to speak up about that scenario if they were in the situation. One example suggested that the entire team might fall short of its goals if an issue was not addressed. This specific scenario yielded the most likelihood of speaking up 35 percent more than the scenario’s suggesting that only they would miss their goal, supporting the research’s findings that an employee is more likely to speak up when the loss impacts more people.

The third study looked at employee-supervisor pairings to understand how these relationships play out in the real world. Using pairings from across three industries, employees reported a workplace problem they encountered and their supervisor rated how often that employee spoke up on the job. While the first two studies involved hypothetical scenarios, this real-world evidence showed that employees were 8-10 times more likely to speak up when issues were framed as a potential collective loss compared with a potential collective gain. 

“This research is really geared toward managers so they can facilitate and understand how and why their employees will speak up,” said Thompson. “You can talk about the issue, but it always ends in terms of how we frame things.” 

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