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The COVID pandemic appears to have triggered about a 44% increase in insomnia disorder among health care workers at a medical-school affiliated health system, with the highest rates surprisingly among those who spent less time in direct patient care, investigators say.

Another surprise was that about 10% of the group of 678 faculty physicians, nurses, advanced practice providers, like nurse practitioners and physician assistants, as well as residents and fellows, reported in a 17-question survey that their insomnia actually got better in the early months of the pandemic, says Dr. Vaughn McCall, chair of the Department of Psychiatry and Health Behavior at the Medical College of Georgia at Augusta University.

Still another surprise was the high reported insomnia rate among the group -- 44.5% -- pre-pandemic, McCall and his colleagues report in the Journal of Clinical Sleep Medicine.

"There are a lot of studies looking at sleep insomnia problems in response to natural disasters like an earthquake in Peru or a typhoon in Taiwan, but this is a universal stress," corresponding author McCall says of the year-plus old COVID pandemic.

While McCall, an expert in the trifecta of insomnia, depression and suicide, expected the pandemic to affect workers' sleep and rates of acute insomnia disorder to increase, the rate of the increase was still surprising: from 44.5% to 64%.

The May 15, 2020 survey, which investigators limited in scope so it wouldn't add to the burden of already overburdened health care workers, covered basics like demographics, work habits, mood and anxiety symptoms and indicators of acute insomnia disorder -- not just episodic problems with sleep that might commonly be referenced as insomnia. Respondents were 72% female, a mean age of 43 and included a lot of faculty physicians and staff nurses, McCall says. About 25% of the respondents were shift workers but sleep problem rates were similar regardless of whether they worked day- or night-shifts. Most were providing at least 30 hours of direct patient care weekly before and during the pandemic.

Survey takers were asked to reflect on work assignments for the two weeks before SARS-CoV-2 infections began to increase and impact the function of health care facilities and society, as well as the two weeks before the survey. On the May 2020 survey date, the health system had an average daily census of 21 COVID-19 patients, with four in intensive care. In mid-March, state leaders had asked that health care workers perform non-patient care duties at home.

The clear impact of insomnia on health care workers overall implies that health care leaders need to be aware of the association, both in staff on the frontline and working from home, the investigators report.

The combination of insomnia and anxiety over COVID-19 represents a potent risk for suicidal ideation, they write, and the medium number of insomnia symptoms indicates that severity was "of clinical significance" to the workers.

Previous studies have looked at the impact of COVID on more common sleep problems in health care workers, but the new study looked at more defined and potentially problematic acute insomnia disorder.

"Insomnia disorder is a patient complaint of poor sleep either in quantity or quality -- it can be both -- with daytime consequences of their poor sleep," McCall says. "They suffer in the daytime because of the nighttime," he says.

In this case, reported consequences included fatigue, malaise, reduced initiative, even gastrointestinal problems.
More than half the individuals in the survey reported at least one core symptom of depression, while at least one anxiety symptom was reported by nearly 65%.

"We see a lot of people who work too much at one job, or they hold down two jobs and there is simply not enough time to sleep," McCall says. "They don't have insomnia, if anything they have the opposite, which is sleep deprivation. Insomnia disorder requires that you at least have the opportunity to sleep," he says.

Insomnia disorder affects about 10% of the general population, and the acute insomnia disorder reported by health care workers is generally defined as a problem that stretches for weeks, while chronic insomnia disorder lingers for months or years. Acute insomnia may progress to a chronic disorder.

There are not good numbers on insomnia disorder rates among health care workers pre-COVID, McCall notes. The purposeful limit to the length of the survey also meant respondents did not provide insight on how long they had problems with insomnia pre-COVID or why, but there are logical factors like the ongoing stress and responsibility of caring for the sick and injured.

Investigators also logically presumed more time spent in the direct care of patients would mean increased risk/concern about COVID exposure, more worry and more insomnia, they write.

That's why one of the most interesting and surprising findings was that about 10% of respondents reported their insomnia had improved after the onset of COVID, potentially because working from home was a good fit for them, but again the survey did not ask for those kinds of details, McCall says.

Most of us complain about isolation, the inability to easily visit with our friends and family and go to restaurants, McCall says of social repercussions of the ongoing pandemic, and he is among them. "Isolation for most people has been bad, but there are people who love it."

Since those not involved in the direct care of patients had to work at home, the investigators hypothesized that for some of these individuals, working from home was not a good fit. Rather, trying to work while juggling the daily, online educational demands of school-age children as well as the ongoing needs of all their children was a significant, potentially insomnia-provoking stress.

He notes that the majority of respondents who spent 30 or more hours each week in direct patient care, tended to be younger than those who worked less, and age increases the overall insomnia risk. Fatigue resulting from those directly involved in hands-on care could also be a factor in promoting better sleep for those who remained on the frontline and help explain the surprising disparity.

The lack of a more typically structured day, with generally set times to work, be at home and sleep, might also be a factor. McCall notes the pandemic has also brought more college students into his practice who had to move back home and were struggling with staying up late and getting up late.

"If you work from home there is a risk that your sleep is going to fall apart because you don't have your schedule anymore," he says. "Most people don't self-regulate well."

He plans to survey the group again when the pandemic has subsided. Meanwhile, the MCG Department of Psychiatry and Health Behavior, under the direction of Dr. Lara Stepleman, chief of psychology and director of the MCG Office for Faculty Success, is offering phone, video or in-person consultations; confidential weekly online group meetings where they can discuss the issue with their peers; and short-term telehealth or in-person psychotherapy and medication management to their colleagues.

McCall notes that generally speaking insomnia is more common in females, as it was in the survey.

Insomnia is associated with the risk of developing mental health problems like depression, as well as increased risk of suicidal thoughts and behavior and overall poor quality of life, the investigators say.

Both good and bad personal life events, like an upcoming wedding or a divorce, respectively, can precipitate acute insomnia disorder.

(Media note: Interviews with Texas Biomed researchers are available with advanced notice. Photos and video of rhesus macaques and the Biosafety Level 3 & 4 laboratories at Texas Biomed are available upon request.)

SAN ANTONIO (April 27, 2021) - When the world was coming to grips with an emerging global pandemic a year ago, scientists at Texas Biomedical Research Institute sprang into action. The rhesus macaques at the Southwest National Primate Research Center (SNPRC) at Texas Biomed were quickly validated as models for studying vaccines designed to protect humans against SARS-CoV-2, the virus that causes COVID-19. The Pfizer-BioNTech COVID-19 vaccine was tested in this model at the Institute and has now been given to millions of people around the world.

"It feels great to have contributed to the development of this important vaccine," said Deepak Kaushal, Ph.D., Professor and the Director of the SNPRC. "This is one circumstance where we helped develop a vaccine within months of the emergence of this new disease. The vaccine has been shown to be highly effective in protecting against COVID-19. As long as everyone in the U.S. who can take a vaccine does so over the next few months, I think we could shut the door on this pandemic before more variants arise."

The work performed by dozens of scientists at Pfizer, BioNTech, Texas Biomed, the SNPRC and scientific partners around the world from April to July of 2020 is now published in the scientific journal Nature. In the paper titled "Immunogenic BNT162b vaccines protect rhesus macaques from SARS-CoV-2" published on Feb. 1, 2021, scientists noted that the vaccine candidate tested for Pfizer "protected the lower respiratory tract from the presence of viral RNA and with no evidence of disease enhancement."

"Texas Biomed and SNPRC have the resources and expertise necessary to support this type of work, and as the vaccine rollout continues and we continue to hear about vaccine hesitancy, we believe it is important to share how vaccines are developed," explained Dr. Larry Schlesinger, President/CEO of Texas Biomed. "While science moved quickly in a time of great global need, these vaccines - whether they be Pfizer, Moderna or any of the others that are authorized by the FDA for emergency use - they all undergo rigorous development, testing and review by regulatory authorities before roll out to the public. Preclinical testing is a critical step in the scientific process."

SARS-CoV-2 is spread when droplet particles containing the virus spread from one person to another by coughing, sneezing, talking or singing. The virus usually enters through the nose but can then travel into the lower respiratory tract of the lungs.

"The lungs become full of water," Kaushal explained. "Patients develop pneumonia and other kinds of lung abnormalities. This is what leads to the use of ventilators and subsequently bad outcomes, including death. By reducing or eliminating the virus from the lower respiratory tract, we can markedly reduce the severe effects of the disease."

During the three-month experiment, scientists used rhesus macaques to test two of the Pfizer-BioNTech vaccine candidates. Although macaques do not succumb to the disease, as reported in a study published in Nature Microbiology last year, they are very effective at replicating disease. These nonhuman primates share 93% of human DNA, making them excellent models for the study of infectious diseases.

"There is no nonhuman primate model yet that is exceptional for COVID-19," Kaushal explained. "None of the monkey species that have been studied develop end-stage or late-stage COVID, equivalent to the severe disease that is seen in humans. However, rhesus macaques are our best-known model for imaging of the lungs using PET/CT scanning. More importantly, the immunology of this species is very well documented."

"Our job was to test two messenger RNA vaccine constructs in the rhesus macaques," Kaushal said. "While both were similar in their effectiveness in our studies, Pfizer and BioNTech chose BNT162b2."

The effect of the two vaccine candidates was tested not only by measuring viral levels, but also with state-of-the-art imaging modalities and blood tests. The virus used in testing was the Seattle strain that emerged in the United States in early 2020. The sample was provided by Biomedical Engineering Institute Resources Repository, part of the National Institutes of Health. The virus was produced in a lab at Texas Biomed by viral specialist Ricardo Carrion, Ph.D., Professor and Director of Maximum Containment Contract Research.

"The messenger RNA vaccine developers were far ahead of most other competitors," Kaushal stated. "They had studied these types of viruses earlier with Middle East Respiratory Syndrome (MERS) a decade ago and SARS-1 which caused an outbreak centered in China 20 years ago."

The experience with these vaccine platforms beginning in the 1990s set the stage for the speed with which this vaccine was developed. Rapid therapy and vaccine development has been aided by the worldwide effort of scientists and resources who have made this crisis their top priority.

Texas Biomed to host Virtual Global Health Symposium

On April 29-30, 2021, Texas Biomed is teaming up with other world leaders in infectious disease to host a Virtual Global Health Symposium. As an independent nonprofit infectious disease research institute, Texas Biomed is focused on bringing together a range of thought leaders involved in global health, research, sustainability and policy.

Among the more than 50 speakers during ten session, Kaushal will be hosting a discussion with Isis Kanevsky, Ph.D., Director Bacterial Vaccines and pre-clinical research models at Pfizer. The two will discuss the research published in Nature and the implications for the current pandemic and diseases on the horizon. The timely event will provide an exclusive inside look at the creation of the COVID vaccine from the perspective of Pfizer and Texas Biomed. For more information about the upcoming event, click here.

"We train for moments like these," Kaushal said. "We may have fatigue in the sense that once this pandemic is under better control with more and more people vaccinated, we will want to go back to 'normal' and not worry about the next pandemic. However, I would argue that the next pandemic may not be ten years away. It may only be five years away. We must stay vigilant and informed, and be more prepared for the next infectious disease threat that comes our way."

Remdesivir is currently the only antiviral drug approved in the U.S. for treating COVID-19 patients. In a paper published this week in Cell Reports, researchers from The University of Texas at Austin, Rensselaer Polytechnic Institute (RPI) and the Icahn School of Medicine at Mount Sinai showed that four drugs used to treat hepatitis C render remdesivir 10 times better at inhibiting the coronavirus in cell cultures.

These results indicate that a mixture containing remdesivir and a repurposed hepatitis C virus (HCV) drug could potentially function as a combination antiviral therapy for SARS-CoV-2. Such an antiviral could provide an immediate treatment for unvaccinated people who become infected and for vaccinated people whose immunity has waned.

Because these hepatitis drugs are already approved for use and their potential side effects are known, such a combination therapy could be tested in humans more quickly than for a new drug. One big drawback with remdesivir, however, is that it must be administered intravenously, limiting its use to patients already admitted to the hospital.

"Our goal is to develop a combination of oral drugs that can be administered to outpatients before they are sick enough to require hospitalization," said Robert M. Krug, professor emeritus of molecular biosciences at UT Austin and co-author of the paper. "The HCV drugs that enhance remdesivir's antiviral activity are oral drugs. Ideally, we would need an oral drug that inhibits SARS-CoV-2 in the same way as remdesivir to develop an effective combination treatment."

Krug helped initiate the research project and collaborated on designing experiments, interpreting results and writing the paper. The laboratory studies were carried out by two groups of collaborators: Gaetano Montelione, professor of chemistry and chemical biology, and postdoctoral fellows Khushboo Bafna and Balasubramanian Harish, all of RPI; and Kris White and Adolfo García-Sastre, professors of microbiology at Mount Sinai.

Remdesivir targets a part of the SARS-CoV-2 coronavirus called the RNA polymerase, which allows the virus to replicate, or make copies of itself. The HCV drugs, on the other hand, target two other parts of HCV that are also critical for viral replication, called proteases.

This research was motivated by the finding by Montelione and Bafna of a striking similarity between the structures of HCV proteases and one of the SARS-CoV-2 proteases, called the main protease. They wondered whether existing drugs that bind to and inhibit an HCV protease might also bind to and inhibit this SARS-CoV-2 protease.

Using a supercomputer to model how drugs bind to viral proteins, the RPI researchers predicted that 10 HCV drugs would bind snugly to a SARS-CoV-2 protease. Researchers at Mount Sinai tested seven of these drugs in a secure biocontainment facility for their ability to inhibit SARS-CoV-2 virus replication in monkey and human cells growing in culture.

All seven HCV drugs inhibited virus replication, but all the collaborators were surprised to find that four of them (simeprevir, vaniprevir, paritaprevir and grazoprevir) inhibited an entirely different type of SARS-CoV-2 protease, called the papain-like protease. And that difference proved to be important. When each of the seven HCV drugs was tested for virus inhibition in combination with remdesivir, only the four that targeted the unexpected protease boosted the efficacy of remdesivir, by as much as tenfold.

A combination of inexpensive oral medications may be able to treat fatigue-inducing anemias caused by chronic diseases and inflammation, a new discovery from the University of Virginia School of Medicine suggests.

This type of anemia is the second-most common kind, and it can be an added burden for organ-transplant recipients and people with autoimmune disorders, as well as patients battling cancer or kidney disease and others. In addition to causing severe fatigue, the anemia can trigger headaches, dizziness, rapid heartbeat and sweating.

"Not only do these anemias cause unpleasant symptoms, but they are also associated with functional impairment and shorter lifespan," said researcher Adam Goldfarb, MD, the chief of UVA Health's Division of Experimental Pathology. "Drawbacks of current therapies include their expense, tendency to lose of effectiveness and risk for serious side effects. This new therapeutic approach has potential to provide a low-cost, highly effective, safe alternative. A further benefit would be its easy applicability to resource-limited areas around the world."

Understanding Anemia

People with anemia have fewer red blood cells and less hemogloblin than normal. Red blood cells carry oxygen throughout the body, while hemoglobin is an iron-rich protein in the red blood cells that transports oxygen molecules.

There are several types of anemias, but anemia of chronic disease and inflammation is triggered by restricted iron delivery to the bone marrow cells that make red blood cells.

Goldfarb and his colleagues initially found that this inadequate availability of iron disrupts an important organelle inside our cells called the Golgi apparatus. This multi-layered organelle, which is shaped a bit like a ribbon candy, is responsible for packaging proteins and lipids (fats) vital to cells' healthy operations.

The researchers identified the underlying source of this problem as a breakdown of tiny microtubules, which provide critical scaffolding for Golgi assembly and for the intracellular transport machinery. Importantly, the researchers were able to pinpoint the trigger for this microtubule breakdown as the loss of a protein, ferritin, within the cell.

By knowing the root-cause of these cellular defects the scientists could tailor a targeted approach to reverse the problem in mouse models of anemia. Giving the lab mice a combination of two substances, isocitrate and fumarate, allowed ferritin recovery and microtubule regrowth, enabling long-term correction of anemia caused by inflammation.

This suggests that an inexpensive oral medication might one day help human patients, too. Pilot studies in patients with anemia associated with kidney disease are in the advanced planning phase.

"The need for new anemia therapies is highlighted by the abundance of new agents currently in early clinical trials," said Goldfarb, of UVA's Department of Pathology. "In defining a novel basic cellular response, our work has opened the door to a safe and simple therapy with unique potential for globally accessibility."

The COVID-19 pandemic has highlighted health disparities for people of color, who have been disproportionately affected by the pandemic. People with opioid use disorder (OUD) faced unique challenges when many mental health and addiction services were forced to scale back operations or temporarily close when social distancing guidelines were put in place.

A group of researchers in the College of Agriculture, Health and Natural Resources recently published their findings in the Journal of Substance Abuse and Treatment about the experiences of racial-ethnic minorities during the COVID-19 pandemic among people with OUD.

Doctoral candidate Colleen Mistler, professor Michael Copenhaver, and assistant professor Roman Shrestha, all from the Department of Allied Health Sciences, collaborated with colleagues at Yale University and Drexel University, as well as the UConn Institute for Collaboration on Health, Intervention and Policy (InCHIP) on this research.

This population was of particular interest to the research group, since people with OUD and of a racial/ethnic minority group are particularly vulnerable to COVID-19 and its adverse health outcomes. Additionally, the group was already working with this population on studies related to improving HIV and substance use prevention outcomes as part of research efforts led by Copenhaver and Shrestha.

"As the pandemic unfolded, experts started raising concerns about both the direct and indirect impacts of COVID-19 on people with OUD," Shrestha says.

The researchers distributed a survey to 110 patients taking medication for opioid use disorder - methadone in this sample - to treat opioid addiction. They asked respondents about their substance use, sexual behavior, mental health, economic impacts of the pandemic, and experience with COVID-19 and preventative measures. The researchers collected their data from May 2020 through June 2020.

This broad range of variables allowed the researchers to craft a more expansive view of the pandemic's impact on participants' lives.

"We wanted to see the whole picture of how it was affecting the individual," Mistler says.

The researchers found people of color were more likely to know someone who died from COVID-19, and were more likely to be concerned about COVID-19. Racial-ethnic minorities also reported more difficulty accessing COVID-19 testing than white participants.

The researchers also found increases in depression, anxiety, and frustration across all groups during the pandemic, which has cut many people off from friends and family due to social distancing and travel restrictions.

Participants of color reported greater reductions in substance use behavior during the pandemic than white participants, which was a positive finding for the researchers.

Respondents did not report changes in number of sexual partners or how often they have unprotected sex, which raises concerns about contracting COVID-19 as well as sexually transmitted infections, like HIV.

"When you're supposed to be social distancing, you still want those behaviors to change, to reduce. And a majority of people didn't change those behaviors," Mistler says.

The group published another paper, on which Mistler is the lead author, in the Journal of Community Health, highlighting how the pandemic led to a reduction in the proportion of people in this population taking pre-exposure prophylaxis (PrEP), a drug that protects against HIV infection. However, they did not find any significant reduction in people getting tested for HIV.

The researchers found participants were still accessing methadone treatment. The clinics they sampled from, including the syringe services program, in the New Haven area established services such as telehealth, mobile-clinics, take-home bottles of methadone, and remained open at a safely limited capacity.

"The continued availability of these services, although in a limited capacity, were really helpful, and may be the reason why we're not seeing a significant difference in the use of addiction treatment and HIV prevention services," Shrestha says.

These findings will hopefully guide clinics in serving their patients using innovative strategies, such as telehealth and mobile clinics, during the current, and future, public health crises.

"These are essential services we should definitely advocate for," Mistler says.

People with certain blood types are more likely to have blood clots or bleeding conditions, kidney stones, or pregnancy-induced hypertension, suggests a study published today in eLife.

The study confirms previously identified connections between certain blood types and the risk of blood clots and bleeding, and makes a new connection between kidney stones and having type B blood as compared to O. The discoveries may lead to new insights on how a person's blood type may predispose them to developing a certain disease.

Previous studies have found that people with blood type A or B were more likely to have cardiovascular disease or experience a blood clot than people with type O blood, and that people with type O blood were more likely to have a bleeding condition. Others have suggested that people with certain blood types may be more susceptible to some infectious diseases.

"There is still very little information available about whether people with RhD-positive or RhD-negative blood groups may be at risk of certain diseases, or how many more diseases may be affected by blood type or group," says first author Torsten Dahlén, a PhD student in the Department of Medicine, Solna, at Karolinska Institutet in Stockholm, Sweden. "To help fill this gap, we used an unbiased approach to investigate the link between ABO blood types and RhD groups and more than 1,000 diseases."

Dahlén and colleagues scanned Swedish health registries with information on more than five million people for links between ABO blood type or RhD-positive or RhD-negative blood groups and more than 1,000 diseases. They found 49 diseases that were linked to ABO blood types, and one that was linked to the RhD group.

Their findings confirmed that people with type A blood were more likely to experience a blood clot and that those with type O blood were more likely to experience a bleeding disorder. They also verified that women with type O blood were more likely to experience pregnancy-induced hypertension.

Additionally, they found a new connection between having type B blood and a lower risk of developing kidney stones. And women who were RhD-positive were more likely to experience pregnancy-induced hypertension.

The authors say that more studies are needed to confirm the results and to determine how different blood types or groups may increase the risk of certain diseases, or whether there are alternative explanations for these relationships.

"Our findings highlight new and interesting relationships between conditions such as kidney stones and pregnancy-induced hypertension and blood type or group," concludes senior author Gustaf Edgren, Associate Professor of Epidemiology at Karolinska Institutet, and a physician in the Department of Cardiology at Södersjukhuset Hospital, Stockholm, Sweden. "They lay the groundwork for future studies to identify the mechanisms behind disease development, or for investigating new ways to identify and treat individuals with certain conditions."

TROY, N.Y. -- When combined with drugs currently used to treat hepatitis C, the antiviral remdesivir is 10 times more effective in treating cells infected with SARS-CoV-2, the virus that causes COVID-19.

Published this week in Cell Reports, this finding -- from Gaetano Montelione, a professor of chemistry and chemical biology at Rensselaer Polytechnic Institute, and his collaborators at the Icahn School of Medicine at Mount Sinai and the University of Texas at Austin -- raises the potential for repurposing available drugs as COVID-19 antivirals in cases where a vaccine isn't practical or effective.

Remdesivir, which blocks viral replication by interfering with a viral polymerase, must be administered intravenously, limiting its use only to patients sick enough to be admitted to a hospital. However, the efficacy of the drug combination would extend to other polymerase inhibitors, of which at least one orally administered version is under development, making possible an oral drug combination that could be taken at home.

"Nearly 3 million people have died worldwide from COVID-19. There are situations where the vaccine isn't the best option and it would be helpful to have orally available antivirals," said Montelione, a member of the Rensselaer Center for Biotechnology and Interdisciplinary Studies (CBIS). "Here we see a promising synergy that, if confirmed through additional research and clinical trials, could provide a new antiviral to combat COVID-19."

Repurposed drugs, already approved for use as therapeutics for a different disease, could potentially be approved for clinical use more rapidly than newly developed, more specific, and potent drugs. Remdesivir itself is a repurposed antiviral drug, originally developed to treat hepatitis C, Ebola virus disease, and other viral infections.

"Repurposed drugs have the potential to be tested and approved quickly for safe use, while more effective therapies are under development" said Robert Krug, virologist and professor emeritus at the University of Texas at Austin, who helped to initiate the collaboration, interpret the results, and write the paper.

The Cell Reports paper identifies four hepatitis C drugs, simeprevir, grazoprevir, paritaprevir, and vaniprevir, which exhibited a synergistic effect - an effect that is greater than the sum of its parts. For example, when administered at low doses to virus-infected cells in the presence of simeprevir, 10 times less remdesivir is needed to inhibit 90% of the virus than when remdesivir is used on its own. Increasing the efficacy of the polymerase inhibitor remdesivir reduces the dosage required, and therefore could be more effective, and also reduce unwanted side effects in treating COVID-19.

The researchers discovered the synergistic effect as part of an effort to identify existing drugs that could be used against COVID-19. Remdesivir and the hepatitis C drugs inhibit viral replication, but they target different aspects of the process. The RNA that the virus injects into the cell causes it to make two polyproteins, which are then cut into more than two dozen smaller pieces that help to replicate the virus, and make excellent targets for antivirals that block their activity. Remdesivir targets a polymerase cluster, but many antivirals target viral proteases, enzymes that are required for the life cycle of the virus.

In earlier work, Montelione, Krug, and Khushboo Bafna, a postdoctoral fellow at Rensselaer, used a bioinformatics approach to identify existing proteins that resemble the coronavirus protease structures. The search identified a "striking similarity" with a protease from the hepatitis C virus, which is the target of several approved drugs. This similarity between the structures of key proteases of the two viruses raised the possibility that existing drugs that bind and block the hepatitis C protease would have the same effect on at least one of the proteases, called Mpro, in SARS-CoV-2. That possibility was borne out by multiple subsequent studies, including Bafna's docking simulations using supercomputer facilities at the Rensselaer Center for Computational Innovations, predicting the effect of various hepatitis C drugs on the SARS-CoV-2 Mpro.

In Cell Reports, the team performed protein binding and viral replication studies with the SARS-CoV-2 virus, remdesivir, and 10 hepatitis C drugs, some of which are already approved by the Food and Drug Administration. Seven of the drugs, tested in a secure biocontainment facility at Mount Sinai, inhibit Mpro and suppress the replication of SARS-CoV-2 virus. These studies were enabled by specialized expertise in the laboratories of research collaborators Adolfo García-Sastre and Kris White at Mount Sinai.

But a careful analysis of the data revealed that three hepatitis C drugs were acting not only on Mpro, but also on second viral protease, the papain-like protease, called PLpro. It is this activity that creates the synergy with the polymerase inhibitor remdesivir. These results indicate that PLpro is an important target for future antiviral drug development, especially for virus variants that are resistant to vaccine-generated antibodies.

"The identification of PLpro as an antiviral target that has a synergistic effect with remdesivir is a very important finding. We hope this work will encourage the development of specific SARS-CoV-2 PLpro inhibitors for inclusion in combination therapies with polymerase inhibitors to produce a highly effective antiviral cocktail that will also prevent the rise of resistance mutations," said Kris White, an assistant professor at Mount Sinai School of Medicine.

Adolfo García-Sastre, professor of virology at Mount Sinai emphasized, "Combined use of remdesivir with an inhibitor of the PLpro for the treatment of COVID-19 would also reduce the possibility of selecting SARS-CoV-2 resistant viruses."

Each year over 150,000 infants worldwide are infected with HIV in the womb, at birth, or through breastfeeding. Why transmission occurs in some cases but not others has long been a mystery, but now a team led by Weill Cornell Medicine and Duke University scientists has uncovered an important clue, with implications for how to eliminate infant HIV infections.

In a study published April 2 in PLoS Pathogens, the researchers found evidence linking mother-to-child transmission of HIV to rare variants of the virus in the mother's blood that are able to escape broadly neutralizing antibodies (bnAbs)--an emerging type of treatment that can be used to block a wide range of HIV strains. The scientists also found that these HIV variants tend to contain key genetic signatures.

The findings provide a possible way to predict whether mother-to-infant transmission of HIV will occur and point the way towards approaches that can help prevent such transmission, the researchers said. At the same time, the results hint that treating HIV-positive pregnant women or new mothers with bnAb therapies might have the unintended effect of promoting the evolution of variants that can resist these therapies and thus raising the risk of mother-to-child transmission.

"Our findings suggest that vaccines or treatments for HIV-infected pregnant and nursing women should be designed to prevent the development of these resistant variants, in order to reduce the chance of HIV transmission to the child," said senior author Dr. Sallie Permar, chair of pediatrics and Nancy C. Paduano Professor in Pediatrics at Weill Cornell Medicine and pediatrician-in-chief at NewYork-Presbyterian/Weill Cornell Medical Center.

Mother-to-newborn transmission of HIV has been puzzling because, even when the mother is infected and untreated, the chance of transmission to the child is less than 50 percent. Scientists have hypothesized that the factors determining whether transmission occurs lie in the mother's immune system and/or in the HIV variants circulating in her blood. But zeroing in on the source of transmission risk has been challenging, not least because antiretroviral (ART) drug treatment, which is now standard for most HIV-infected individuals, would be likely to confound the results of any study of current patients.

Dr. Permar and her colleagues circumvented this problem by evaluating a collection of samples from a study of HIV-infected mothers and their infants conducted three decades ago, before the age of ART.

In one set of experiments, Dr. Permar's team isolated the HIV variants that had been transmitted from the mothers to their infants, and found that these transmitted HIV variants--compared to non-transmitted variants from the mothers' blood--were about 30 percent less sensitive to the mothers' plasma--the antibody-containing fraction of the mothers' blood. In other words, the difference between transmission and non-transmission seemed to be due at least in part to HIV variations that allow escape from maternal antibodies.

Detecting those HIV escape variants in the mothers was not a simple matter. The researchers observed that HIV variants in transmitting mothers and HIV variants in non-transmitting mothers were, on the whole, just as sensitive to maternal plasma.

Ultimately the researchers analyzed genetic sequences in the HIV variants from transmitting and non-transmitting mothers and found that several genetic signatures were associated with transmission vs. non-transmission.

Most of these signatures were also associated with the rare ability to escape neutralization by some or all of a panel of bnAbs. The latter are antibodies that were originally isolated from a few HIV-positive individuals, are known to block a wide variety of HIV strains and are being developed as HIV therapies.

"This finding suggests that the presence of broadly neutralizing antibody-escape variants in the blood of HIV-infected mothers is a predictor of higher transmission risk to newborns," Dr. Permar said.

That in turn indicates that any vaccine or treatment given to HIV-infected pregnant or nursing mothers, as an adjunct to ART to reduce transmission risk, needs to be effective against HIV variants that can escape these special antibodies.

Moreover, the results suggest that simply vaccinating mothers to elicit broadly neutralizing antibodies, or delivering mixes of therapeutic bnAbs, might in some cases cause more mother-to-child transmission--if the presence of the potent antibodies promotes HIV evolution towards resistant variants.

Dr. Permar and colleagues are now working to understand better how to address this problem. Approaches worth investigating, Dr. Permar said, include giving pregnant, HIV-infected women high-dose, short-term combination bnAb therapy containing multiple types of these antibodies, in order to minimize escape risk; and also delivering a multi-bnAb therapy directly to babies at birth in the hope of curing any HIV infection that occurs during delivery and preventing subsequent HIV infection via breastfeeding.

The hormone prolactin has long been understood to play a vital role in breast growth and development and the production of milk during pregnancy. But a pair of recent studies conducted at VCU Massey Cancer Center finds strong evidence that prolactin also acts as a major contributor to breast cancer development and that the hormone could inform the creation of targeted drugs to treat multiple forms of the disease.

Hormones have proteins on their cell surface called receptors that receive and send biological messages and regulate cell function. Through research published in npj Breast Cancer, VCU Massey Cancer Center researcher Charles Clevenger, M.D., Ph.D., and his lab discovered a new, altered form of the prolactin receptor called the human prolactin receptor intermediate isoform (hPRLrI) that directly drives breast cancer. The researchers observed that this modified version of the prolactin receptor interacted with other forms of the receptor to turn benign breast cells into malignant ones, and the presence of hPRLrI in breast cancer cells was associated with triple negative breast cancer, a rapid rate of cell reproduction and poor outcomes.

"This research challenges the dogma that prolactin only functions in milk production and highlights the unique discovery that the hormone can contribute to breast cancer," said Clevenger, who is the associate director for precision oncology, Carolyn Wingate Hyde Endowed Chair in Cancer Research and member of the Cancer Biology research program at Massey as well as chair of the Department of Pathology at the VCU School of Medicine. "By understanding how the prolactin receptor correlates to breast cancer, novel therapeutic and prognostic agents can be developed to effectively treat the disease."

Clevenger said these findings support the argument that future approaches in drug design may need to specifically target hPRLrI, and could ultimately inform advanced diagnostic applications for breast cancer as well.

Through a separate study published in Endocrinology and prominently showcased on the journal's website as the Featured Article for a week, Clevenger's lab substantially prevented tumor growth in preclinical models of ER-positive breast cancer using an HDAC6 inhibitor, a drug that blocks a protein associated with prolactin.

Clevenger has previously found success in the lab stunting breast cancer growth by deactivating Stat5, the genetic pathway responsible for the production of prolactin.

In this new research, the scientists found that the prolactin-regulating function of Stat5 is dually dependent on the enzyme histone deacetylase-6 (HDAC6) and the gene HMGN2. They also discovered that the estrogen receptor (ER), a hormone widely believed to influence breast cancer development, was highly and almost exclusively interactive with Stat5 at sites where HDAC6 and HMGN2 were also present. This suggests that both the estrogen receptor and prolactin receptor can cooperate through the activation of Stat5 to initiate the development of breast cancer. Treating ER-positive breast cancer cells with an HDAC6 inhibitor drastically hindered tumor progression.

"Global analysis of gene expression again revealed that prolactin is closely associated with breast cancer growth and could be subdued by treatment with an HDAC6 inhibitor," Clevenger said.

Clevenger has dedicated a significant amount of his scientific career to understanding how prolactin might have implications in the growth and progression of breast tumors. In future studies, he plans to further test and develop breast cancer drugs using prolactin as a primary target.

A partnership between UC Davis and Maurice J. Gallagher, Jr., chairman and CEO of Allegiant Travel Company, has led to a new rapid COVID-19 test.

A recent study published Nature Scientific Reports shows the novel method to be 98.3% accurate for positive COVID-19 tests and 96% for negative tests.

"This test was made from the ground up," said Nam Tran, lead author for the study and a professor of pathology in the UC Davis School of Medicine. "Nothing like this test ever existed. We were starting with a clean slate."

The novel COVID-19 test uses an analytical instrument known as a mass spectrometer, which is paired with a powerful machine-learning platform to detect SARS-CoV-2 in nasal swabs. The mass spectrometer can analyze samples in minutes, with the entire process taking a total of about 20 minutes.

The accuracy matches or outperforms many of the current COVID-19 screening tests. The new testing method may allow for the rapid screening of large numbers of individuals for businesses, schools, venues and other large facilities. The project originated with Gallagher, a UC Davis alumnus and a longtime supporter of innovation and entrepreneurship at UC Davis.

Last year, when the pandemic brought the airline and hospitality industries almost to a standstill, he began conceptualizing approaches that would allow people to gather again safely.

Gallagher approached H. Rao Unnava, professor and dean of the UC Davis Graduate School of Management, who connected him with Tran at the School of Medicine.

Gallagher and UC Davis entered into a Sponsored Research Agreement, with support from Shimadzu Scientific Instruments, to develop an automated COVID-19 test on a mass spectrometer.

Mass spectrometers are essential analytic tools used by a wide variety of industries for research and testing.

This is the first test for COVID-19 that pairs mass spectrometry with robotics and a robust automated machine learning platform to rapidly deliver test results. The coupling of these unique elements not only allows testing for COVID-19 but may be able to quickly adapt to detect other diseases and perhaps future pandemic organisms.

"Mr. Gallagher, through his generosity as an alum, has shown how business and universities can work together in solving problems of critical importance to the world," said Unnava. "I am glad that this groundbreaking work will continue to build on the reputation of UC Davis as a place where you always 'Expect Greater.'"

Project builds on the prior success of MILO platform

The collaboration is part of a new center in the School of Medicine, the UC Davis Center for Diagnostic Innovation.

"This game-changing, rapid new COVID-19 test speaks to the deep expertise of our faculty and scientists to find novel solutions to pressing global health challenges," said Allison Brashear, dean of the UC Davis School of Medicine. "It's this kind of innovation and collaboration that has been the hallmark of our response to the pandemic."

To ensure support for the study's analytic portion, Tran enlisted Hooman Rashidi, a longtime collaborator and a professor in the Department of Pathology and Laboratory Medicine.

The machine, a mass spectrometer MALDI-TOF, or matrix-assisted laser desorption/ionization time-of-flight, uses a laser to create small particles -- ions -- from large molecules in the testing sample. These ionized particles create signals that can be used to identify many compounds, including those associated with microorganisms and pathogens.

For the study, 226 nasal swabs from UC Davis' biorepository of COVID-19 tests were ionized in the Shimadzu 8020. The swabs were from leftover samples and volunteers who consented to the study. Some of the participants had COVID-19 symptoms, and some were asymptomatic.

The hundreds of peaks and signals produced by the ionized test swabs were analyzed by the automated machine learning platform MILO (Machine Intelligence Learning Optimizer). Machine learning is a subset of artificial intelligence, or AI. Tran, Rashidi and Samer Albahra are the co-developers of MILO. The platform has previously been used to predict severe infections and acute kidney disease.

For the COVID-19 test, MILO finds distinguishing patterns among the many mass spectrometry peaks and signals and deciphers which patterns correspond to the presence or absence of the SARS-CoV-2 virus in the samples.

MILO accomplished the analysis in a fraction of the time that a non-automated machine-learning approach would have taken. "This meant drastically expediting the study without compromising any performance measures," said Rashidi.

Gallagher has launched a new startup, SpectraPass, to develop the rapid, automated system into a means to facilitate opening businesses and the economy.

Experts at UC Davis Health are helping guide the SpectraPass team through the scientific, machine learning and clinical steps needed to move the COVID-19 testing technology closer to emergency use authorization by the Food and Drug Administration (FDA).

"The COVID-19 pandemic not only brought the world's commerce and travel to a halt - it also took away our fundamental human interaction, our freedom to be together," said Gallagher. "This project has resulted in a real breakthrough that can not only provide instant, accurate information about COVID infection, but can be an important part of addressing other viruses and even developing therapies. The excitement of working with the team at UC Davis is in knowing we are helping make sure our children and grandchildren are better equipped to deal with potential pandemics in the future."

The partnership exemplifies the goals of Aggie Square, which brings together the university, community and industry to connect and collaborate.

"As a top-tier research university known for its excellence and disciplinary breadth, UC Davis is exceptionally well-positioned to work with our industry partners on groundbreaking innovations that benefit society," said Mary Croughan, provost and executive vice chancellor.

DALLAS, April 26, 2021 -- The hormonal therapies used to treat many breast and prostate cancers raise the risk of a heart attack and stroke, and patients should be monitored regularly and receive treatment to reduce risk and detect problems as they occur, according to a new American Heart Association scientific statement, published today in the Association's journal Circulation: Genomic and Precision Medicine.

"The statement provides data on the risks of each type of hormonal therapy so clinicians can use it as a guide to help manage cardiovascular risks during cancer treatment," said Tochi M. Okwuosa, D.O., FAHA, chair of the scientific statement writing group, an associate professor of medicine and cardiology and director of Cardio-Oncology Services at Rush University Medical Center in Chicago.

Hormone-dependent cancers, such as prostate and breast cancer, are the most common cancers in the United States and worldwide not including skin cancers. As improvements in treatment - including increased use of hormonal therapies - allow people with these cancers to live longer, cardiovascular disease has emerged as a leading cause of illness and death in these patients.

Hormonal treatments for breast cancer include selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). SERMs block estrogen receptors in cancer cells so the hormone can't spur tumor growth, while letting estrogen act normally in other tissues such as bone and liver tissue; examples of SERMs include tamoxifen and raloxifene. Aromatase inhibitors lower the amount of estrogen produced in post-menopausal women and include exemestane, anastrozole and letrozole. Endocrine treatments for prostate cancer, called androgen deprivation therapy, include some medications that decrease production of testosterone by their action on the brain and others that block testosterone receptors found in prostate cells and some prostate cancer cells.

The writing group reviewed existing evidence from observational studies and randomized controlled trials and found that:

Tamoxifen increases the risk of blood clots, while aromatase inhibitors increase the risk of heart attack and stroke more than tamoxifen. For breast cancer patients who require more than one type of hormonal therapy because of developed resistance to the initial medication, , there is an improvement in cancer outcomes. However, treatment with multiple hormones is associated with higher rates of cardiovascular conditions such as high blood pressure, abnormal heart rhythms and blood clots.

Androgen deprivation therapy (to reduce testosterone) for prostate cancer increases cholesterol and triglyceride levels, adds body fat while decreasing muscle and impairs the body's ability to process glucose (which may result in type 2 diabetes). These metabolic changes are associated with a greater risk of heart attacks, strokes, heart failure and cardiovascular death.

The longer people receive hormonal therapy, the greater the increased risk of cardiovascular problems. Further research is required to better define the risks associated with duration of treatment.

The hormonal therapy-associated increase in CVD risk was highest in people who already had heart disease or those who had two or more cardiovascular risk factors - such as high blood pressure, obesity, high cholesterol, smoking or a family history of heart disease or stroke - when they began treatment.

"A team-based approach to patient care that includes the oncology team, cardiologist, primary care clinician, dietician, endocrinologist and other health care professionals as appropriate is needed to work with each patient to manage and reduce the increased risk of heart disease and strokes associated with hormonal therapy in breast and prostate cancer treatment," Okwuosa said.

There are currently no definitive guidelines for monitoring and managing hormonal therapy-related heart risks. The statement calls for clinicians to be alert for worsening heart problems in those with prior heart disease or risk factors, and to recognize that even those without pre-existing heart problems are at higher risk because of their exposure to hormonal therapies.

"For patients who have two or more cardiovascular risk factors, it is likely that referral to a cardiologist would be appropriate prior to beginning hormone treatment. For patients already receiving hormonal therapies, a discussion with the oncology team can help to determine if a cardiology referral is recommended," Okwuosa said.

The statement also calls for additional research in several areas, including:

Further evaluation of racial and ethnic disparities among breast and prostate cancer patients who have received hormone therapy. In the few studies that exist, racial and ethnic differences detected may be related to health inequities and other factors, and these are important areas to address.

Heart disease and stroke outcomes and risks should be added as primary endpoints in randomized trials of hormonal therapies.

Studies of specific hormonal medications are needed since each one may have different heart risks even if they work in the same way to treat breast or prostate cancer.

This scientific statement was prepared by the volunteer writing group on behalf of the American Heart Association's Cardio-Oncology Subcommittee of the Council on Clinical Cardiology and the Council on Genomic and Precision Medicine; the Council on Arteriosclerosis, Thrombosis and Vascular Biology; and the Council on Cardiovascular Radiology and Intervention.

A recent study provides insights on the COVID-19 pandemic’s effects on employment, anxiety, and financial distress among women who have gynecologic cancer and low income. The findings are published early online in CANCER, a peer-reviewed journal of the American Cancer Society.

For the study, Y. Stefanie Chen, MD, of Weill Cornell Medicine in New York City, and her colleagues conducted telephone interviews with 100 women with gynecologic cancer living in New York City who were covered by Medicaid health insurance.

Among the major findings:

31 percent of patients reported being employed prior to the pandemic, and 21 percent had a change in employment status due to the pandemic.

50 percent of patients reported that they felt more financial stress since the start of the pandemic, and 54 percent reported that they worry about future financial problems due to the pandemic.

49 percent of patients expressed increased anxiety about cancer since the start of the pandemic, and 83 percent expressed feeling increased anxiety in general.

Having an income less than $40,000 per year was the most common factor associated with increased financial distress, cancer worry, and anxiety. Early-stage cancer (stage I-II) was also a risk factor for increased financial distress.

"Patients with cancer are already financially vulnerable as many face changes in employment status when they undergo treatment, and also because cancer treatments can become costly as they accrue over time," said Dr. Chen. "Patients with low income may struggle to prioritize cancer care and treatments over other costs of daily living, especially when they face changes in employment not only due to their cancer diagnosis but also due to the changes in the job market caused by the pandemic."

Dr. Chen supports increased screening for anxiety and financial stress in these patients. "Understanding the complexity of finances, mental health, and cancer treatments in this population is crucial to the development of interventions and navigation strategies to ensure timely care and to promote survivorship among patients with all stages of cancer," she said.

The American Cancer Society announced earlier today in a press release that Suresh S. Ramalingam, MD, will join CANCER as the new Editor-in-Chief beginning on July 1, 2021. Dr. Ramalingam is the deputy director of Winship Cancer Institute at Emory University in Atlanta, Georgia, and has worked as a Section Editor for CANCER since 2011. Dr. Ramalingam succeeds Fadlo R. Khuri, MD, whose tenure as Editor-in-Chief concludes later this summer.

The CDC's opioid prescribing guideline has failed to reduce addiction and overdoses, significantly worsened the quality of pain care in the United States and should be revoked, according to a large new survey of patients and healthcare providers by Pain News Network, an independent, non-profit news organization.

Nearly 4,200 patients and providers participated in the online survey, which was conducted as the Centers for Disease Control and Prevention prepares to update and possibly expand its 2016 guideline, which discourages doctors from prescribing opioid pain medication.

Most survey respondents - nearly 75% -- believe the guideline should be withdrawn or revoked. Less than one in four (23%) believe changes can be made to make its recommendations more effective.

Although voluntary and only intended for primary care physicians, the guideline has become the standard of care for pain management in the U.S., with many doctors, insurers, pharmacies and regulators adopting its recommendations as policy. The goal of the guideline was to "improve the safety and effectiveness of pain treatment" and reduce the risk of opioid addiction and overdose.

But survey respondents overwhelmingly believe the CDC has failed to achieve its goals. Nearly 97% said the guideline has not improved the quality of pain care, and 92% believe it has not reduced opioid addiction and overdoses.

Opioid prescriptions were declining before the CDC guideline was released and now stand at their lowest level in 20 years. Most overdoses in the U.S. involve illicit fentanyl and other street drugs, not prescription opioids, yet many patients have been cut off from opioids or had their doses reduced.

"They have done immeasurable damage to chronic intractable pain patients all across America. There have been suicides, people have lost their jobs and their entire quality of life because of them," one patient said.

"In 40 years as a pain specialist, I have never seen patients with pain so mistreated, abandoned and unable to access pain treatment as a direct result of the CDC guidelines," a doctor wrote.

"Due to inadequate pain control many chronic pain patients, including myself, attempted suicide to get relief of intolerable pain. I wish I had succeeded," another patient wrote.

Other survey findings:

59% of patients were taken off opioids or tapered to a lower dose against their wishes

42% had trouble getting an opioid prescription filled at a pharmacy

36% were unable to find a doctor to treat their pain

29% were abandoned or discharged by a doctor

27% had a doctor who stopped prescribing opioids

35% have considered or attempted suicide due to poorly treat pain

10% have obtained prescription opioids from family, friends or the black market

9% have used illegal drugs for pain relief

"This is the fourth survey we've done on the CDC guideline. Each year the findings grow more disturbing, with patients desperate for pain relief or simply giving up on life," said Pat Anson, founder and editor of Pain News Network. "Nine out of ten patients say their pain levels and quality of life have grown worse since the guideline came out. Many of their stories are heartbreaking. Pain patients are the unrecognized victims of the opioid crisis and are being blamed for something they did not cause."

The CDC is currently in the process of updating and possibly expanding the guideline to include recommendations for treating short-term acute pain, migraine and other pain conditions such as fibromyalgia and low back pain. A draft version of the updated guideline is not expected until late this year.

(The survey was conducted online and through social media from March 15 to April 17. A total of 4,185 people in the United States participated, including 3,926 who identified themselves as chronic, acute or intractable pain patients; 92 doctors or healthcare providers; and 167 people who said they were a caretaker, spouse, loved one or friend of a patient. To see the full survey results, click here.)

Lung cancer is a major global cause of mortality, reportedly accounting for 1.7 million deaths each year. The most common form of lung cancer is non-small-cell lung cancer (NSCLC), and early-stage NSCLCs can often be surgically resected. Unfortunately, some patients still experience poor outcomes after surgical resection, prompting further research on the relationship between a patient's preoperative status and the likelihood of good postoperative outcomes.

Given this need for information, Dr. Shinya Tanaka from the Department of Rehabilitation and Prof. Naoki Ozeki from the Department of Thoracic Surgery, Nagoya University, and their colleagues decided to investigate. Previous studies had identified some risk factors for mortality after NSCLC resection, including sarcopenia, which is defined as the progressive loss of muscle mass and strength and predominantly occurs in older individuals. Another known risk factor for unfavorable postoperative outcomes is poor physical performance as measured with the 6-minute walking distance (6MWD) test, which involves measuring how far a patient can walk on a corridor in the span of 6 minutes.

To Dr. Tanaka and Prof. Ozeki, these past findings clearly pointed to "the importance of comprehensively assessing a patient's preoperative physical state in order to determine his or her risks of poor outcomes." However, no previous study of postoperative outcomes in patients with NSCLC had considered both sarcopenia and physical performance. Dr. Tanaka, Prof. Ozeki, and their colleagues therefore decided to conduct a study that addressed this gap in research. Their findings appear in a paper recently published in the Journal of Cachexia, Sarcopenia and Muscle.

The researchers analyzed data from 587 patients with NSCLC who underwent resection surgeries at Nagoya University Hospital between 2014 and 2017. They focused their analyses on determining how preoperative sarcopenia and exercise intolerance (defined as the inability to walk further than 400 meters on the 6MWD) influenced a patient's risk of mortality during the postoperative follow-up period, which lasted for 3.1 years on average.

The researchers' analyses showed that patients with preoperative sarcopenia had a 1.78-fold higher likelihood of death during follow-up than their peers without preoperative sarcopenia and exercise intolerance. Furthermore, patients with preoperative exercise intolerance had a 2.26-fold higher risk of death than patients without preoperative sarcopenia and exercise intolerance. However, the strongest effects emerged when sarcopenia and exercise intolerance coincided: patients who had preoperative sarcopenia and preoperative exercise intolerance had a 3.38-fold higher likelihood of death than patients who were free of sarcopenia and exercise intolerance prior to surgery.

These findings have important implications for the preoperative assessment of patients with NSCLC. In short, when oncologists are attempting to predict postresection prognoses, they should comprehensively consider a patient's physical status because variables like sarcopenia and exercise intolerance interact with each other to increase a patient's risk of mortality.

Dr. Tanaka and Prof. Ozeki hope that their findings "may contribute to the establishment of intervention methods to improve the prognoses of patients with NSCLC." More broadly, they hope that "more people will realize the importance of nutrition and exercise and try to lead healthier lives".

The paper, "Preoperative paraspinous muscle sarcopenia and physical performance as prognostic indicators in non-small-cell lung cancer," was published in Journal of Cachexia, Sarcopenia and Muscle on March 4, 2021, at DOI: 10.1002/jcsm.12691.

About Nagoya University, Japan

Nagoya University has a history of about 150 years, with its roots in a temporary medical school and hospital established in 1871, and was formally instituted as the last Imperial University of Japan in 1939. Although modest in size compared to the largest universities in Japan, Nagoya University has been pursuing excellence since its founding. Six of the 18 Japanese Nobel Prize-winners since 2000 did all or part of their Nobel Prize-winning work at Nagoya University: four in Physics - Toshihide Maskawa and Makoto Kobayashi in 2008, and Isamu Akasaki and Hiroshi Amano in 2014; and two in Chemistry - Ryoji Noyori in 2001 and Osamu Shimomura in 2008. In mathematics, Shigefumi Mori did his Fields Medal-winning work at the University. A number of other important discoveries have also been made at the University, including the Okazaki DNA Fragments by Reiji and Tsuneko Okazaki in the 1960s; and depletion forces by Sho Asakura and Fumio Oosawa in 1954.

Website: http://en.nagoya-u.ac.jp/

DOI

10.1002/jcsm.12691

What The Study Did: This simulation modeling study estimates the benefits of identifying silent COVID-19 infections among children as a proxy for their vaccination.

Authors: Alison P. Galvani, Ph.D., of the Yale School of Public Health in New Haven, Connecticut, 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.2021.7097)

Editor's Note: The article includes conflict of interest and funding/support 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.

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