Publisher Health

Coronavirus vaccines provided strong protection against infection for essential workers earlier this year, but became less effective as the highly contagious Delta variant became the dominant form of the virus, according to a study published on Tuesday by federal health officials.It was not clear whether the decline in protection was caused by the emergence of the Delta variant or the lengthening period of time since the inoculations were begun. Vaccine effectiveness showed possible signs of decline starting four months after vaccinations were first rolled out.“What we were trying to figure out is: is this Delta, or is this waning effectiveness?” Dr. Fowlkes said. “Our conclusion is that we can’t really tell.”Researchers followed thousands of first-responders, health care workers and others who could not work remotely in eight locations in Arizona, Florida, Oregon, Texas, Utah and Minnesota. The participants were tested for coronavirus infection every week for 35 weeks, as well as any time they developed Covid-like symptoms.Most of the workers who were vaccinated received the Pfizer-BioNTech vaccine; one-third received the Moderna vaccine, and 2 percent received the Johnson & Johnson vaccine.Overall, the vaccines reduced infections among vaccinated workers by 80 percent from Dec. 14, when the U.S. vaccination campaign began, to Aug. 14, compared with unvaccinated workers. (The results were adjusted for factors including occupation, demographic characteristics, frequency of close social contact and mask use.)But while the shots reduced infections by 91 percent before the emergence of the Delta variant, their protectiveness dropped to 66 percent as the variant became dominant in each region.“We really wanted to let people know that we were seeing a decline in the effectiveness of the vaccine in protection against any infection, symptomatic or asymptomatic, since the Delta variant became dominant,” said Ashley Fowlkes, an epidemiologist on the Covid-19 response team at the Centers for Disease Control and Prevention, and the study’s lead author.“But we also want to reinforce that 66 percent effectiveness is a really high number,” she added. “It’s not 91 percent, but it is still a two-thirds reduction in the risk of infection among vaccinated participants.”The drop-off in effectiveness “should be interpreted with caution,” however, because the observation period while Delta was dominant was short, Dr. Fowlkes said, and the overall number of infections was small..css-1xzcza9{list-style-type:disc;padding-inline-start:1em;}.css-3btd0c{font-family:nyt-franklin,helvetica,arial,sans-serif;font-size:1rem;line-height:1.375rem;color:#333;margin-bottom:0.78125rem;}@media (min-width:740px){.css-3btd0c{font-size:1.0625rem;line-height:1.5rem;margin-bottom:0.9375rem;}}.css-3btd0c strong{font-weight:600;}.css-3btd0c em{font-style:italic;}.css-w739ur{margin:0 auto 5px;font-family:nyt-franklin,helvetica,arial,sans-serif;font-weight:700;font-size:1.125rem;line-height:1.3125rem;color:#121212;}#NYT_BELOW_MAIN_CONTENT_REGION .css-w739ur{font-family:nyt-cheltenham,georgia,’times new roman’,times,serif;font-weight:700;font-size:1.375rem;line-height:1.625rem;}@media (min-width:740px){#NYT_BELOW_MAIN_CONTENT_REGION .css-w739ur{font-size:1.6875rem;line-height:1.875rem;}}@media 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a:hover{-webkit-text-decoration:none;text-decoration:none;}Another C.D.C. study released on Tuesday analyzed infections and hospitalizations in Los Angeles County between May 1 and July 25 of this year. The researchers concluded that while vaccinated individuals became infected, infection rates among the unvaccinated were 4.9 times higher, and the hospitalization rate was 29 times higher among the unvaccinated.Of 43,127 known infections in Los Angeles County among residents aged 16 and older, 25 percent were in fully vaccinated individuals, 3.3 percent were in partially vaccinated individuals, and 71.4 percent were in unvaccinated people. (The proportion of fully vaccinated Los Angeles County residents increased to 51 percent on July 25, from 27 percent on May 1.)Three percent of vaccinated individuals needed to be hospitalized, 0.5 percent were admitted to intensive care and 0.2 percent required mechanical ventilation. The comparable rates for unvaccinated individuals were 7.6 percent, 1.5 percent and 0.5 percent, the study reported.Those who were hospitalized despite vaccination were also older, on average, than the unvaccinated who were hospitalized. The death rate among the vaccinated was lower: 0.2 percent, compared with 0.6 percent among the unvaccinated. The median age at death was also higher among the vaccinated, at 78, compared with a median age of 63 among the unvaccinated.

Goldman Sachs told employees on Tuesday that it will require anyone who enters the bank’s U.S. offices, including clients, to be fully vaccinated starting on Sept. 7, making it the most prominent Wall Street bank to issue such a broad requirement.The announcement, in a memo obtained by The New York Times, came a day after the Food and Drug Administration gave full approval for the Pfizer-BioNTech vaccine, a move that many large corporations had been seeking before making mandates.President Biden seized on the F.D.A.’s approval, urging private businesses to protect their workers through vaccinations.“If you’re a business leader, a nonprofit leader, a state or local leader, who has been waiting for full F.D.A. approval to require vaccinations, I call on you now to do that,” the president said on Monday. “Require it.”Companies have been consulting with advisers for months about whether to mandate vaccines, but have been wary of employee pushback and potential litigation. The quick spread of the highly contagious Delta variant and prominent first moves by large corporations like Walmart and the Walt Disney Company helped to expedite those talks. Now, the F.D.A. approval on Monday has finally given them some assurances they need to move forward.Goldman Sachs told employees on Tuesday that anyone in the United States who is not fully vaccinated by Sept. 7 must work from home. It will also require fully vaccinated employees to undergo weekly coronavirus testing.The bank, which employs roughly 20,000 in the United States, is reinstating mask requirements throughout office common areas as of Wednesday. At offices in San Francisco and Washington, masks will be required at all times, except while someone is eating or drinking.Other Wall Street banks have similar requirements. Citigroup said this month that it would require vaccinations for employees returning to its corporate offices in the New York area this fall, and Morgan Stanley said in June that it would require all employees and visitors to its New York offices to be vaccinated. JPMorgan Chase has so far strongly encouraged, but not required, vaccinations for its work force.The Goldman Sachs announcement followed several others this week. On Monday, Chevron said it was mandating vaccines for expats and employees who travel internationally, as well as for the offshore work force in the Gulf of Mexico and for some onshore support personnel. CVS Health said its pharmacists have until Nov. 30 to be fully vaccinated, while others who interact with patients, and all corporate staff, have until Oct. 31. Disney Cruise Line said Tuesday that it was requiring passengers over 12 years old to be fully vaccinated for sailings to the Bahamas.The F.D.A. approval also gives industry groups grounds to encourage vaccinations from their members — and lobby against legislation that may hinder those efforts. The U.S. Chamber of Commerce announced this month that it would mandate vaccines for its work force once the F.D.A. fully approved them. The Business Roundtable, an influential lobbying group, said Monday that it supported mandates.“Many companies have made the decision to mandate vaccines for some or all of their employees, and we applaud their decision,” the group, led by the Walmart chief executive Doug McMillon, said in a statement. “We also encourage policymakers, including at the state and local levels, to support — not impede — companies’ ability to make such a decision.”At least three states — Montana, Texas and Utah — that had banned vaccine requirements by law or executive order did so specifically because the three vaccines used in the United States were being administered under emergency-use authorizations, not full approval. Some companies, like Norwegian Cruise Line in Florida, have resisted such prohibitions, but most have largely stayed out of the fray so far.Over the past month, there have been signs that companies are showing an increased appetite for vaccine mandates. Earlier this month, United Parcel Service said that any employee returning to an office that serves a support function must be fully vaccinated, or have received one shot with a second scheduled, by Oct. 1. The policy does not apply to workers in operational roles, though they are being encouraged to get vaccinated..css-1xzcza9{list-style-type:disc;padding-inline-start:1em;}.css-3btd0c{font-family:nyt-franklin,helvetica,arial,sans-serif;font-size:1rem;line-height:1.375rem;color:#333;margin-bottom:0.78125rem;}@media (min-width:740px){.css-3btd0c{font-size:1.0625rem;line-height:1.5rem;margin-bottom:0.9375rem;}}.css-3btd0c strong{font-weight:600;}.css-3btd0c em{font-style:italic;}.css-w739ur{margin:0 auto 5px;font-family:nyt-franklin,helvetica,arial,sans-serif;font-weight:700;font-size:1.125rem;line-height:1.3125rem;color:#121212;}#NYT_BELOW_MAIN_CONTENT_REGION .css-w739ur{font-family:nyt-cheltenham,georgia,’times new roman’,times,serif;font-weight:700;font-size:1.375rem;line-height:1.625rem;}@media (min-width:740px){#NYT_BELOW_MAIN_CONTENT_REGION .css-w739ur{font-size:1.6875rem;line-height:1.875rem;}}@media (min-width:740px){.css-w739ur{font-size:1.25rem;line-height:1.4375rem;}}.css-9s9ecg{margin-bottom:15px;}.css-16ed7iq{width:100%;display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;-webkit-box-pack:center;-webkit-justify-content:center;-ms-flex-pack:center;justify-content:center;padding:10px 0;background-color:white;}.css-pmm6ed{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;}.css-pmm6ed > :not(:first-child){margin-left:5px;}.css-5gimkt{font-family:nyt-franklin,helvetica,arial,sans-serif;font-size:0.8125rem;font-weight:700;-webkit-letter-spacing:0.03em;-moz-letter-spacing:0.03em;-ms-letter-spacing:0.03em;letter-spacing:0.03em;text-transform:uppercase;color:#333;}.css-5gimkt:after{content:’Collapse’;}.css-rdoyk0{-webkit-transition:all 0.5s ease;transition:all 0.5s ease;-webkit-transform:rotate(180deg);-ms-transform:rotate(180deg);transform:rotate(180deg);}.css-eb027h{max-height:5000px;-webkit-transition:max-height 0.5s ease;transition:max-height 0.5s ease;}.css-6mllg9{-webkit-transition:all 0.5s ease;transition:all 0.5s ease;position:relative;opacity:0;}.css-6mllg9:before{content:”;background-image:linear-gradient(180deg,transparent,#ffffff);background-image:-webkit-linear-gradient(270deg,rgba(255,255,255,0),#ffffff);height:80px;width:100%;position:absolute;bottom:0px;pointer-events:none;}.css-uf1ume{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-box-pack:justify;-webkit-justify-content:space-between;-ms-flex-pack:justify;justify-content:space-between;}.css-wxi1cx{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-flex-direction:column;-ms-flex-direction:column;flex-direction:column;-webkit-align-self:flex-end;-ms-flex-item-align:end;align-self:flex-end;}.css-12vbvwq{background-color:white;border:1px solid #e2e2e2;width:calc(100% – 40px);max-width:600px;margin:1.5rem auto 1.9rem;padding:15px;box-sizing:border-box;}@media (min-width:740px){.css-12vbvwq{padding:20px;width:100%;}}.css-12vbvwq:focus{outline:1px solid #e2e2e2;}#NYT_BELOW_MAIN_CONTENT_REGION .css-12vbvwq{border:none;padding:10px 0 0;border-top:2px solid #121212;}.css-12vbvwq[data-truncated] .css-rdoyk0{-webkit-transform:rotate(0deg);-ms-transform:rotate(0deg);transform:rotate(0deg);}.css-12vbvwq[data-truncated] .css-eb027h{max-height:300px;overflow:hidden;-webkit-transition:none;transition:none;}.css-12vbvwq[data-truncated] .css-5gimkt:after{content:’See more’;}.css-12vbvwq[data-truncated] .css-6mllg9{opacity:1;}.css-qjk116{margin:0 auto;overflow:hidden;}.css-qjk116 strong{font-weight:700;}.css-qjk116 em{font-style:italic;}.css-qjk116 a{color:#326891;-webkit-text-decoration:underline;text-decoration:underline;text-underline-offset:1px;-webkit-text-decoration-thickness:1px;text-decoration-thickness:1px;-webkit-text-decoration-color:#326891;text-decoration-color:#326891;}.css-qjk116 a:visited{color:#326891;-webkit-text-decoration-color:#326891;text-decoration-color:#326891;}.css-qjk116 a:hover{-webkit-text-decoration:none;text-decoration:none;}As of Aug. 7, the share of job postings requiring vaccinations was up 90 percent from a month earlier, according to the job search company Indeed. Those that require vaccinations, though, are still a small fraction of the overall listings.F.D.A. authorization could also simplify negotiations with unions, whose mixed stance toward mandates has contributed to a class divide among workers. On Monday, Disney World said unions representing more than 30,000 employees had agreed to a mandate, citing the F.D.A.’s full approval, that would require workers to be vaccinated by Oct. 22.But the United Food and Commercial Workers International, a union that represents around 1.3 million workers in grocery stores, pharmacies and meatpacking plants, warned on Monday against mandates that did not take employees’ concerns into consideration.“With more employers considering vaccine mandates after this new F.D.A. approval, U.F.C.W. continues to urge all businesses to negotiate any vaccine requirements with their frontline workers,” the union’s president, Marc Perrone, said. The union had previously cited concerns about lack of regulatory approval in its negotiations with Tyson Foods over the meatpacker’s decision to require its entire work force to get vaccinated.Unions and other industry groups are grappling with continued hesitancy about the shot. In a recent poll, three out of 10 unvaccinated people said they would be more likely to get a fully approved F.D.A. shot, but some experts believe that this figure could be exaggerated.Some companies that previously cited approval status for the vaccines had no updates to share as of Tuesday. “It’s very difficult for us to come in and mandate a vaccine that isn’t even federally approved yet,” the chief executive of Delta Air Lines, Ed Bastian, told CNBC this month. “So stay tuned.”A spokesman for the airline told The Times that the airline’s plans were “status quo”: mandating vaccines for new hires and strongly encouraging them for existing employees.More regulatory action that could make vaccines easier to mandate is coming. Moderna’s application for full approval of its vaccine was filed in June, a month after Pfizer’s. Johnson & Johnson is expected to apply for full approval soon. The F.D.A. is also weighing whether to authorize booster shots for the fully vaccinated, another twist for corporate vaccine mandates.Niraj Chokshi

A team of researchers at Massachusetts General Hospital (MGH), Boston University School of Public Health (BUSPH), and other institutions have identified more than two dozen genetic regions that may affect individuals’ food intake. The investigators hope that the discovery, which is described in Nature Human Behaviour, will point to new treatment strategies to curb the obesity epidemic.
The brain is influenced by various signals to affect people’s eating behaviors and regulate their bodies’ energy balance, for example by changing appetite and energy expenditure in response to blood levels of key metabolic hormones and nutrients. Therefore, genetic variation in these signals can lead to extreme hunger and obesity.
“People with obesity and diabetes are often stigmatized for making unhealthy food choices. While food intake is shaped by many factors including social, demographic, religious, or political forces, previous studies have shown that inherited individual differences contribute to what, when, why, or how much we eat,” says co-lead author Jordi Merino, PhD, a research associate at the Diabetes Unit and Center for Genomic Medicine at MGH and an instructor in medicine at Harvard Medical School. “These early studies are starting to identify brain regions and molecular processes that influence food intake, but there has been limited research in humans to identify molecular signatures underlying variable susceptibility to food choice behavior.”
To provide insights, Merino and his colleagues conducted a genetic analysis and examined the food consumption of 282,271 participants of European ancestry from the UK Biobank and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. The study is the largest to date to examine genetic factors related to food intake.
The team identified 26 genetic regions associated with increased preference for foods containing more fat, protein, or carbohydrate, and these regions were enriched for genes expressed in the brain. “Downstream computational analyses highlighted specific subtypes of specialized neurons distributed across the central nervous system that are responsive to protein, fat, or carbohydrate, and when activated may explain why people are more likely to prefer foods or meals with higher amount of fat, protein, or carbohydrate,” says Merino.
The researchers also found that two main groups of genetic variants were differently associated with obesity and coronary artery disease. “The joint analysis of fat, protein, and carbohydrate intake coupled with clustering analyses helped to define more homogeneous subsets of genetic variants characterized by specific nutritional profiles and with different metabolic signatures,” says co-lead author Chloé Sarnowski, PhD, an instructor of biostatistics at BUSPH at the time of the study, and now a faculty associate at the University of Texas Health Science Center at Houston.
The discovery of these genetic variants can be used in future analyses — such as Mendelian randomization, a causal inference approach — to determine whether diet composition is causally related to metabolic and other diseases. “While we know that diet composition is related to diseases, the causal link is harder to prove,” says co-senior author Josée Dupuis, PhD, chair and professor in the Department of Biostatistics at BUSPH. “These loci will allow for future Mendelian randomization analyses to determine the causal impact of diet on type 2 diabetes, obesity, and other metabolic diseases.”
The findings will also likely lead to a better biological understanding of why food consumption behavior differs among individuals, and they could provide new avenues for preventing and treating obesity and other metabolic diseases.”Our findings provide a starting point for functional research that might aid in the discovery of new molecular targets and drugs,” says co-lead author Hassan Dashti, PhD, an instructor in the Department of Anesthesia, Critical Care and Pain Medicine at MGH and instructor of Anesthesia at Harvard Medical School. “Our results could also help identify people more likely to follow specific dietary recommendations for the prevention of obesity or diabetes. For example, if someone has a higher genetic susceptibility for preferring fatty foods, this information can be used to help this individual to choose foods with higher amount of healthy fats rather than recommending other dietary approaches that might compromise adherence to these interventions.”
Co-authors include Jacqueline M. Lane, Petar V. Todorov, Miriam S. Udler, Yanwei Song, Heming Wang, Jaegil Kim, Chandler Tucker, John Campbell, Toshiko Tanaka, Audrey Y. Chu, Linus Tsai, Tune H. Pers, Daniel I. Chasman, Martin K. Rutter, Jose C. Florez and Richa Saxena.
Funding for the study was provided by the American Diabetes Association, the European Commission Horizon 2020 programme, the National Institutes of Health, the MGH Research Scholar Fund, the Novo Nordisk Foundation, and the Lundbeck Foundation.

Previous research has shown that the spike (S) protein of -CoV-2 binds to a host cell receptor, facilitating viral entry. Research has also shown that SARS-CoV-2 variants that lose the furin cleavage site at the spike protein (S gene mutants) emerge rapidly during propagation in Vero cells (lineage of cells used in cell cultures).
Now, new research published in mBio, an open-access journal of the American Society for Microbiology, shows that hamsters inoculated with S gene mutants show resistance to subsequent infection with both the parental strain and the currently emerging SARS-CoV-2 alpha and gamma variants (B.1.1.7 variant, first identified in the U.K. and P.1. variant, first identified in Brazil, respectively). The research highlights the potential benefits of S gene mutants as immunogens (antigens that can trigger an immune response).
“SARS-CoV-2 S gene mutants may be used as immunogens for live-attenuated vaccines, similar to the current yellow fever vaccine,” said Hirofumi Sawa, Ph.D., M.D., study principal investigator in the Division of Molecular Pathobiology, International Institute for Zoonosis Control, at Hokkaido University, in Sapporo Japan, and with One Health Research Center at Hokkaido University.
In the new study, researchers set out to further characterize SARS-CoV-2 S gene mutants properties through animal experiments using hamsters. All infected animals were maintained in isolators at the biosafety level-3 facility. “Our experiments were conducted in accordance with set guidelines. Because we had to move animals with the isolators into the safety cabinet to monitor the animals, we did a lot of heavy lifting on a daily basis,” said lead study author Michihito Sasaki, Ph.D., D.V.M., a lecturer in the Division of Molecular Pathobiology, International Institute for Zoonosis Control, at Hokkaido University.
The researchers found that the SARS-CoV-2 S gene mutants are weakened variants but can induce protective immunity against infection with clinical strains of SARS-CoV-2. “Because these variants rapidly emerge through SARS-CoV-2 propagation in some cell lines, including Vero cells, researchers should be alert to the possibility of unexpected contamination with these variants,” said Dr. Sasaki.
The researchers say their next steps are to uncover the mechanism of severe COVID-19 and develop new therapeutic strategies for COVID-19. “To overcome the COVID-19 pandemic, a multisectoral and transdisciplinary approach under the ‘One Health’ umbrella is needed,” said Dr. Sawa. “At our International Institute for Zoonosis Control, we endeavor to establish effective strategies for prediction, prevention and control of zoonotic diseases, including COVID-19.”
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An enzyme with an elusive role in severe inflammation may be a key mechanism driving COVID-19 severity and could provide a new therapeutic target to reduce COVID-19 mortality, according to a study published in the Journal of Clinical Investigation.
Researchers from the University of Arizona, in collaboration with Stony Brook University and Wake Forest University School of Medicine, analyzed blood samples from two COVID-19 patient cohorts and found that circulation of the enzyme — secreted phospholipase A2 group IIA, or sPLA2-IIA — may be the most important factor in predicting which patients with severe COVID-19 eventually succumb to the virus.
sPLA2-IIA, which has similarities to an active enzyme in rattlesnake venom, is found in low concentrations in healthy individuals and has long been known to play a critical role in defense against bacterial infections, destroying microbial cell membranes.
When the activated enzyme circulates at high levels, it has the capacity to “shred” the membranes of vital organs, said Floyd (Ski) Chilton, senior author on the paper and director of the UArizona Precision Nutrition and Wellness Initiative housed in the university’s College of Agriculture and Life Sciences.
“It’s a bell-shaped curve of disease resistance versus host tolerance,” Chilton said. “In other words, this enzyme is trying to kill the virus, but at a certain point it is released in such high amounts that things head in a really bad direction, destroying the patient’s cell membranes and thereby contributing to multiple organ failure and death.”
Together with available clinically tested sPLA2-IIA inhibitors, “the study supports a new therapeutic target to reduce or even prevent COVID-19 mortality,” said study co-author Maurizio Del Poeta, a SUNY distinguished professor in the Department of Microbiology and Immunology in the Renaissance School of Medicine at Stony Brook University.

Opioids are powerful painkillers but their use is hindered because patients become tolerant to them, requiring higher and higher doses, and overdoses can cause respiratory depression and death. A recent study from researchers at the UC Davis Center for Neuroscience contradicts existing thinking about how opioid drugs cause tolerance and respiratory depression, and suggests a new, balanced approach to developing safer analgesics. The work was published July 13 in Neuropsychopharmacology.
“The holy grail of opioid research is to determine the ideal properties of an opioid analgesic for maximizing pain relief while reducing the adverse side effects,” said Jennifer Whistler, senior author on the paper and professor of physiology and membrane biology in the UC Davis School of Medicine. “This goal has become even more urgent in light of the devastation wreaked by the opioid overdose crises and the failure to identify other non-opioid targets for the treatment of severe and persistent pain.”
Whistler, who is associate director of the UC Davis Center for Neuroscience, has been researching the neurobiology of addictive disorders and their comorbidities and how to make safer opioids for more than 20 years.
Searching for new opioids with fewer side effects
Opioid drugs work by connecting to the mu opioid receptor (MOR) on cells. This receptor in turn signals through G-protein and can also engage a protein called arrestin-3. The prevailing view has been that engagement of the mu opioid receptor with arrestin-3 is responsible for the two treatment-limiting side effects of opioids: the respiratory depressive effects that cause overdose death and the development of analgesic tolerance that leads to dose escalation and increased risk of addiction and overdose death.
This doctrine has led to an almost two decades-long, highly visible search for new “ultra G protein biased” opioids that potently activate G protein but do not engage arrestins.

Emergency room patients who were flagged by an artificial intelligence algorithm for possibly having sepsis received antibiotics sooner and had better outcomes, according to a peer-reviewed study conducted by physician-researchers at Case Western Reserve University and MetroHealth.
Their findings were published August 20, in Critical Care Medicine, the journal of the Society of Critical Care Medicine.
“We showed that when providers had access to the early warning system, patients had better sepsis-related outcomes,” said Yasir Tarabichi, an assistant professor of medicine at the Case Western Reserve School of Medicine and the study’s principal investigator. “These patients got their antibiotics faster and had, on average, more days ‘alive and out of hospital’ than the group that had usual care. Taken together, the increase in survival rates and reduction in hospital stay improved with the implementation of the early warning system.”
Over five months in 2019, the study’s authors tracked nearly 600 patients who came into the emergency department. MetroHealth implemented an electronic health record-embedded early warning system for sepsis.
Patients 18 and older presenting to the emergency department were randomized to standard care for sepsis versus the pathway augmented by the early warning system.
The early warning system alerted both the physicians and pharmacists. This resulted in the patient who was flagged receiving antibiotics significantly faster than those patients whose alert was hidden, according to the study.
Collectively, those who received early antibiotics were measured to have more days alive and out of the hospital more than those in the standard care group.
“This study adds to the recent national discourse about sepsis early warning systems,” Tarabichi said. “Recent studies assessed how that score worked in isolation, which is not reflective of how it would actually be used in the real world. We envisioned the early warning system’s role as supportive to our health care team’s response to sepsis. Most importantly, we assessed the utility of the tool with the highest quality approach — a randomized controlled study. In fact, our work stands out as the first published randomized controlled evaluation of a model-based early warning system in the emergency room setting.”
MetroHealth Senior Vice President Brook Watts, a professor of medicine at the Case Western Reserve School of Medicine, said the study demonstrates that from an institutional level, MetroHealth is committed to working collaboratively to try new approaches to improve outcomes from patients.
“We rigorously validate and implement new tools that can help our patients,” said Watts, also an author of the study. “This was an integrated team-based response to sepsis, with augmentation by artificial intelligence. It demonstrates our focus on quality improvement. We have great providers and information service experts willing and interested in leveraging new technology to improve patient care.”
The study was written by: Tarabichi; Aurelia Cheng; David Bar-Shain; Brian M. McCrate; Lewis H. Reese; Charles Emerman; Jonathan Siff; Christine Wang; David C. Kaelber; Watts; and Michelle T. Hecker.
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Materials provided by Case Western Reserve University. Note: Content may be edited for style and length.

A new gene that controls the completion of meiosis in spermatogenesis has been discovered by researchers from Kumamoto University. Until now, details of the mechanism that inactivates the expression of genes involved in the meiotic program during spermatogenesis had not been clarified. The researchers believe that this may lead to an advancement in reproductive medicine, like identifying causes for infertility from azoospermia or spermatogenic defects.
Meiosis is the special type of cell division that takes place in the ovaries and testes to produce eggs and sperm by reducing the number chromosomes to half the original. After meiosis is complete, DNA continues to be highly condensed and undergoes major morphological changes that are characteristic of spermiogenesis. This process inactivates the expression of many genes that were previously active in carrying out meiosis in spermiogenesis. However, the details of the mechanism that completes the meiotic program at the appropriate time are unknown, and although this is an important issue that is directly related to reproductive medicine, such as male infertility, it has remained an unresolved issue many years.
Professor Ishiguro’s group at Kumamoto University’s Institute of Molecular Embryology and Genetics (IMEG) previously discovered MEIOSIN, a gene that switches on meiosis and causes hundreds of genes involved in sperm and egg formation to activate simultaneously. Among them, many genes have functions that are still not fully understood. In their work to ascertain these functions, the researchers selected the ZFP541 gene to analyze in detail.
When the function of the ZFP541 gene in mice was eliminated using genome editing, male germ cells started meiosis but died in the process resulting in infertility since no sperm were produced. A detailed analysis of the testes of those mice revealed that the ZFP541 gene plays an essential role in the regulation of meiosis and is an important gene involved in sperm production.
Furthermore, ZFP541 is expressed in late meiotic prophase and binds to the regulatory regions (called promoters) of many meiosis-related genes. It is known that acetylated histones are present in the regulatory region of promoters as a marker for sustained activation of gene expression. Through mass spectrometry analysis, researchers found that ZFP541 binds to an unknown protein called KCTD19 and an enzyme called HDAC1 that has been shown by previous studies to remove acetyl groups from histones. These results show that ZFP541 and HDAC1 together eliminate the histone acetyl group, inactivate the expression of meiosis-related genes, and complete meiosis.
“This research is a follow-up to our discovery of MEIOSIN published in February of 2020 and reveals part of the function of a gene under the control of MEIOSIN whose function is still unknown,” said Dr. Yuki Takada, who led the study. “Although these results were verified in mice, ZFP541 is also known to exist in humans. There are many cases of infertility in humans where the cause is unknown, but we expect that this result will contribute to the elucidation of the pathogenesis of infertility, especially those related to sperm dysplasia.”
The researchers also believe that their research can be applied to the development of infertility treatment technology. By elucidating the functions of other genes in the process of egg and sperm formation, they hope to make a significant contribution to reproductive medicine.
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Materials provided by Kumamoto University. Note: Content may be edited for style and length.

As the country prepares to live in a post-Covid-19 world and car travel — including taxi and car-sharing services that mix households — returns to normal, new research from the University of Surrey has confirmed that keeping car windows open to draw in fresh air is key to reducing the risk of contracting the virus in vehicle environments — but there are trade-offs.
In a paper published by Environment International, Surrey’s renowned Global Centre for Clean Air Research (GCARE) explored what motorists must consider to make sure their in-car environments are as Covid-secure as possible.
The GCARE team used sensors to monitor pollution particles concentration, map how those particles varied during different settings in the vehicle and evaluate exposure dose per km of PM2.5 for three different ventilation settings (open window, air conditioning using fresh air, and air conditioning using air recirculation). The team also used sensors to monitor CO2 emission — a proxy used in the experiment for Covid-19.
The GCARE researchers found that maintaining a continuous intake of fresh air by keeping the windows open — while also wearing a mask — is the best way to guard against the transmission of Covid-19 — but this increases occupants’ exposure to toxic air pollution particles.
Motorists face a dilemma, since guarding against air pollution by keeping windows closed in turn aggravates the risk from Covid-19: the study found that the probability of Covid-19 transmission rate increased by 28.5 per cent when windows are closed and air recirculation is switched on.
For the best chance of remaining safer from both Covid-19 and external air pollution, the GCARE team found that keeping the windows closed — which mitigates air pollution particles — while running air conditioning on ambient mode (drawing in fresh air from outside) to minimise exposure to Covid-19, is the optimal balance.
Professor Prashant Kumar, lead author of the study, Associate Dean (International) and Founding Director of GCARE at the University of Surrey, said:
“It’s vital that the scientific community provides society with the data it needs so we can learn from the painful experience of the past two years.
“Our research found that if your priority is to reduce the risk of contracting Covid-19, wearing a mask and keeping car windows open is the ideal approach.”
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A new study from Linköping University, Sweden, has shown that the tumour-inhibiting gene TET2 is silenced in a large fraction of cases of acute lymphoblastic leukemia (ALL) in children. The scientists show that the gene can be reactivated by treatment with an existing drug, 5-azacytidine. The results, published in the scientific journal PNAS, suggest that 5-azacytidine may function as targeted therapy for ALL in children.
“T-cell acute lymphoblastic leukemia (T-ALL) is a devastating disease for the affected children and their families. One of five children affected do not survive the disease. The ultimate goal of my research is to ensure that all children can be cured. Our discovery may pave the way for clinical studies of 5-azacytidine as a new therapy for this poorly understood disease. The more treatment options we have for T-ALL the more chance we have of beating this aggressive cancer,” says Colm Nestor, senior lecturer in the Department of Biomedical and Clinical Sciences at Linköping University, who has led the study.
One of the characteristics of cancer cells is that they lose their cellular identity. It’s as if they have forgotten that they should be, for example, a liver cell, brain cell, or cell of the immune system. One of the reasons for this loss of identity is that genes that should be active in a certain type of cell have been switched off (silenced), while other genes have been erroneously activated. The activation and deactivation of genes is controlled by a process known as epigenetic modification, in which small chemical groups are attached to and removed from DNA. One such epigenetic modification is DNA methylation. It has long been known that the pattern of DNA-methylation is often altered in cancer cells, and for this reason, drugs that change DNA-methylation are interesting as potential treatments for cancer.
In the recently published study, the researchers were interested in an enzyme, TET2, that removes methyl groups from DNA. The gene that codes for TET2 is often affected by mutations in adult leukemias. In contrast, harmful mutations in TET2 are very rare in T-ALL in children. This led the researchers to speculate whether the function of TET2 is affected in a different manner in child leukemias. They analysed the gene expression patterns in cancer cells from more than 300 patients with T-ALL, and found that the TET2 gene was silenced in a large fraction of cases.
It turned out that the TET2 gene was often silenced through methylation. The scientists therefore decided to treat tumour cells in culture with a drug, 5-azacytidine, that removes methyl groups from DNA. This drug is used to treat certain leukemias in adults.
“We found that one type of T-ALL cell, whose DNA seems to be highly methylated, is more sensitive to azacytidine than other cells that are not highly methylated. The drug actually turns silenced TET2 back on by demethylating it, so this might be a targeted therapy for a subset of cases. We suggest that azacytidine may have a doubled effect in these cells, since both the drug itself and TET2 kill cancer cells by demethylating the genome,” says Colm Nestor.
Since 5-azacytidine has already been approved as a drug, the researchers hope that the path from preclinical results in the laboratory to actually treating children with T-ALL will be much shorter than is required when developing a novel drug.
“Chemotherapy agents have a broad effect and can be used for many patients, but they kill also healthy cells and can give rise to serious undesired effects. Targeted treatment, on the other hand, only works for a small fraction of patients, but is extremely specific. We need an arsenal of drugs to use for patients who experience relapses, and for those whose cancer does not respond to chemotherapy,” says Colm Nestor.
The research is at an early stage. The LiU researchers will now continue with experiments to determine the effects of activating TET2 in these cancer cells. Another question is whether 5-azacytidine can function as targeted therapy in other types of cancer. The research group hopes that their discovery will inspire other researchers to test the therapy in clinical studies.
“The fact that we can target the loss of TET2 using the drug 5-azacytidine makes me hopeful that this treatment can help T-ALL patients in the future,” says Maike Bensberg, PhD student at Linköping University and one of the researchers behind the study.
Sources of funding for the study include the Swedish Cancer Society, the Swedish Childhood Cancer Foundation, the Swedish Research Council, and the Joanna Cocozza Foundation.
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Materials provided by Linköping University. Original written by Karin Söderlund Leifler. Note: Content may be edited for style and length.