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An analysis of workers’ compensation claims in New York found that 71 percent of claimants with long Covid needed continuing medical treatment or were unable to work for six months or more.Long Covid is having a significant effect on America’s work force, preventing substantial numbers of people from going back to work while others continue needing medical care long after returning to their jobs, according to a new analysis of workers’ compensation claims in New York State.The study, published Tuesday by New York’s largest workers’ compensation insurer, found that during the first two years of the pandemic, about 71 percent of people the fund classified as experiencing long Covid either required continuing medical treatment or were unable to work for six months or more. More than a year after contracting the coronavirus, 18 percent of long Covid patients had still not returned to work, more than three-fourths of them younger than 60, the analysis found.“Long Covid has harmed the work force,” said the report, by the New York State Insurance Fund, a state agency financed by employer-paid premiums. The findings, it added, “highlight long Covid as an underappreciated yet important reason for the many unfilled jobs and declining labor participation rate in the economy, and they presage a possible reduction in productivity as employers feel the strains of an increasingly sick work force.”The report, which analyzed Covid-related claims from patients exposed to the virus at work, filed between Jan. 1, 2020, and March 31, 2022, and paid by the agency, provides a snapshot of the problem. The agency, one of the 10 largest workers’ compensation insurers in the country, found that nearly a third of 3,139 Covid-related claims it paid met its definition of long Covid.Patients received coverage from the fund if they had a positive coronavirus test and the agency or a workers’ compensation board determined that they had a high risk of having been exposed to the virus while at work, typically in environments like hospitals, grocery stores or transit systems. The report classified a case as long Covid if, after infection, a patient required medical treatment for 60 days or more or lost 60 or more days of work.More on the Coronavirus PandemicAnnual Boosters: The Food and Drug Administration proposed that most Americans be offered a single dose of a Covid vaccine each fall, much as they are given flu shots.A Better Covid Winter: Some of the worst days of Covid in the United States have come as winters have settled in. But a surge in hospitalizations has yet to materialize this season.New Subvariant: A highly contagious version of the Omicron variant — known officially as XBB.1.5 or by its subvariant nickname, Kraken — is quickly spreading in the United States.Pfizer’s Boosters: Federal officials said that fears that the Covid booster shots made by Pfizer may increase the risk of strokes in people aged 65 and older were not borne out by an intensive scientific investigation.“It’s a pretty conservative estimate,” said Gaurav Vasisht, executive director and chief executive officer of the insurance fund. “It’s not capturing people who may have gone back to work and didn’t seek medical attention and may still be suffering, so you know, they’re just toughing it out.”During the time frame of the report, claims for the 977 people the fund designated as having long Covid cost about $17 million out of the approximately $20 million paid to all Covid patients, officials said, adding that the proportion for lost wages was slightly greater than for medical treatment. But Mr. Vasisht cautioned that the dollar amounts provided only a partial picture because it was unclear how long people would need medical care or time off for long Covid.He added that the cost to patients went beyond money. “The longer you’re out of work, the harder it is for you to get back to work, and that can stigmatize patients,” Mr. Vasisht said. “It could be highly disruptive to their family and professional lives.”Long Covid is defined by public health authorities as a constellation of symptoms that linger after the initial infection or that emerge weeks later and can include breathing problems, fatigue and brain fog. The Government Accountability Office estimated that long Covid has affected 7.7 million to 23 million people in the United States.A long Covid patient returned to part-time work after being diagnosed in 2021.Alex Wroblewski for The New York TimesKatie Bach, a nonresident senior fellow at the Brookings Institution who was not involved in the report, said the study showed that “we have a group of people who got long Covid and at least up until now have been unable to get back to work, and it is a nontrivial number of people.”She said the report reflects only a slice of the work force: employees with workplace exposure to the virus who are knowledgeable enough about workers’ compensation to file claims. It might include employees who are younger or sicker than the overall working population, while also missing other workers with long Covid, said Ms. Bach, whose own research suggests that about 500,000 people in the United States are currently not working because of long Covid.The New York report also found some optimistic signals. Since the pandemic’s first wave in early 2020, long Covid cases decreased as a percentage of workers’ compensations claims and of Covid-related claims. The decrease coincided with the advent of vaccines, which studies suggest reduce the risk of long Covid, and with new coronavirus treatments, supporting the idea that if people can avoid becoming severely ill from their initial infection, they are less likely to experience long-term symptoms.Still, Mr. Vasisht said the agency continued to receive claims for workers with long Covid, especially after surges in infections. The report also suggested that more employees than reflected in the data might have met the criteria for long Covid claims. The vast majority of all Covid-related claims, over 83 percent, were filed by essential workers — in occupations like health care, law enforcement and security services. But only 29 percent of their claims met the definition for long Covid, while 44 percent of nonessential workers met that definition.That could be because “essential workers might not have been able to stay home from work beyond the required quarantine period,” the report said. And health care workers might have “self-treated their symptoms” rather than seeking medical care, the report said, adding “essential workers may have long Covid rates higher than the data suggests, creating a blind spot for policymakers.”“A lot of people can’t afford to not work and so they’re working when they really shouldn’t be, continuing to work while they’re sick,” said Ms. Bach. She said that the experience of people with similar post-viral conditions like myalgic encephalomyelitis and chronic fatigue syndrome suggests that some people who work despite their long Covid may have harder recoveries. “When people who have a condition whose hallmark symptoms are fatigue and brain fog go into work, they’re not going to be as productive and they’re probably reducing their odds of improvement,” she said.And because 40 percent of claimants with long Covid returned to work within 60 days of becoming infected while still receiving medical treatment, Mr. Vasisht said employers might receive “more requests for reduced hours or other accommodations.”The study also found that doctors only used a specific long Covid diagnostic code in 30 cases, even though the code was added to the International Classification of Diseases in October 2021. “Physicians are underutilizing the I.C.D. code,” said Mr. Vasisht, adding that he believed his organization “can do a lot of good by conducting outreach to the physician community and letting them know about the research on long Covid and also about the existence of this I.C.D. code.”Other findings were consistent with previously identified long Covid patterns, including results of two 2022 studies that analyzed different workers’ compensation data sets. The most common long Covid symptoms included shortness of breath, fatigue, weakness, and cognitive and memory problems.Women appeared to be at greater risk than men, as were people who became sick enough from their initial infection to be hospitalized and those with previous conditions like lung disease, hypertension, obesity and depression. Adults older than 60 were less likely to resume working than younger employees, which might indicate that some long Covid patients are retiring early, adding to labor shortages, Ms. Bach said.Overall, said David Cutler, an economics professor at Harvard who has researched the cost of long Covid and was not involved in the study, “The report shows that even if Covid deaths are down, Covid is not over, and it won’t be for some time.”

More hospitals and medical practices have begun charging for doctors’ responses to patient queries, depending on the level of medical advice.To Nina McCollum, Cleveland Clinic’s decision to begin billing for some email correspondence between patients and doctors “was a slap in the face.”She has relied on electronic communications to help care for her ailing 80-year-old mother, Penny Cooke, who is in need of specialized psychiatric treatment from the clinic. “Every 15 or 20 dollars matters, because her money is running out,” she said.Electronic health communications and telemedicine have exploded in recent years, fueled by the coronavirus pandemic and relaxed federal rules on billing for these types of care. In turn, a growing number of health care organizations, including some of the nation’s major hospital systems like Cleveland Clinic, doctors’ practices and other groups, have begun charging fees for some responses to more time-intensive patient queries via secure electronic portals like MyChart.Cleveland Clinic said that its email volume had doubled since 2019. But it added that since the billing program began in November, fees had been charged for responses to less than 1 percent of the roughly 110,000 emails a week its providers received.“Billing a patient’s health insurance supports the necessary decision-making and time commitment of our physicians and other advanced professional providers,” said Angela Smith, a spokeswoman for the clinic.But a new study shows that the fees, which some institutions say range from a co-payment of as little as $3 to a charge of $35 to $100, may be discouraging at least a small percentage of patients from getting medical advice via email. Some doctors say they are caught in the middle of the debate over the fees, and others raised concerns about the effects that the charges might have on health equity and access to care.Dr. Eve Rittenberg, an internist in women’s health at Brigham and Women’s Hospital in Boston, examined the effects of medical correspondence with patients in a study that found that female practitioners shouldered a greater communications burden.“The volume of messaging combined with the expectation of quick turnaround is very stressful,” Dr. Rittenberg said. She recalled one day when she took her teenage daughter to the doctor but was distracted by responding to patient messages on her phone. She recently reduced her clinic schedule — and took a commensurate pay cut — to free up a few hours outside of office visits to cope with other tasks like patient messages.The U.S. Centers for Medicare and Medicaid Services first introduced Medicare billing codes in 2019 that allowed providers to seek reimbursement for writing messages through secure portals. The pandemic prompted the agency to broaden coverage for telemedicine and hospitals significantly expanded its overall use.The federal rules state that a billable message must be in response to a patient inquiry and require at least five minutes of time, effectively making it a virtual visit. Private insurers have widely followed Medicare’s lead, reimbursing health care practices for physicians’ emails, and may charge patients a co-pay. For several major hospital systems across the country, the increase in email fees has opened up a new revenue stream.More on the Coronavirus PandemicAnnual Boosters: The Food and Drug Administration proposed that most Americans be offered a single dose of a Covid vaccine each fall, much as they are given flu shots.A Better Covid Winter: Some of the worst days of Covid in the United States have come as winters have settled in. But a surge in hospitalizations has yet to materialize this season.New Subvariant: A highly contagious version of the Omicron variant — known officially as XBB.1.5 or by its subvariant nickname, Kraken — is quickly spreading in the United States.Pfizer’s Boosters: Federal officials said that fears that the Covid booster shots made by Pfizer may increase the risk of strokes in people aged 65 and older were not borne out by an intensive scientific investigation.Blue Cross Blue Shield said some of its state and regional plans reimburse for doctor emails. But David Merritt, a senior vice president for policy and advocacy for the insurer, expressed concern that the ability “to charge patients for what often should be routine email follow-up could easily be viewed and abused as a new revenue stream.”According to the Cleveland Clinic, Medicaid patients are not charged. Medicare beneficiaries without a supplemental health plan would owe a co-pay between $3 and $8. The clinic’s maximum charge, hitting those with high deductibles on private insurance plans or without coverage, would be $33 to $50 for each exchange.Ms. McCollum and other clinic patients are given the option of avoiding such fees by choosing to discontinue a query or request an appointment instead. Ms. McCollum kept on emailing on behalf of her mother: “I said, ‘Yes,’ because I need to reach her doctor.” She added, “It’s maddening.”“The volume of messaging combined with the expectation of quick turnaround is very stressful,” said Dr. Eve Rittenberg, an internist at Brigham and Women’s Hospital. She recently reduced her schedule to accommodate a few hours for patient messages.Sophie Park for The New York TimesNot all patient-doctor exchanges carry fees. Emails for simpler concerns largely remain free, including for prescription refills, appointment scheduling and follow-up care. According to several hospital systems and insurers, electronic communications that could prompt a bill would address, for example, medication changes, a new medical issue or symptom or shifts in long-term health conditions. Providers may only bill a patient once a week.Nearly a dozen of the nation’s largest hospital systems said they charged fees for some of their providers’ emails to patients or have started pilot programs, in response to an informal survey by The New York Times. In addition to Cleveland Clinic, this includes Houston Methodist; NorthShore University HealthSystem, Lurie Children’s, and Northwestern Medicine in Illinois; Ohio State University; Lehigh Valley Health Network in Pennsylvania; Oregon Health & Science University; University of California, San Francisco and U.C. San Diego; and the U.S. Department of Veterans Affairs.Other major hospitals are closely watching those at the vanguard of this new billing practice, according to A Jay Holmgren, an assistant professor in the Department of Medicine at U.C.S.F.The Health Insurance Portability and Accountability Act (HIPAA) permits doctors to send unencrypted emails or texts if they caution patients about the risks of unsecure channels. But to protect patient privacy, prevent hacking and comply with other HIPAA requirements, most health care companies and organizations discourage the use of anything other than the encrypted portals like MyChart that have become ubiquitous over the past decade.Hospital officials note that while young people may be the most tech-savvy and wedded to app-based correspondence, they are usually healthier and less apt to keep in touch with their doctors.“In my own experience, most messages come from individuals in their 50s and 60s, likely because they are sufficiently familiar with technology to learn how to use messaging and are starting to have increasing needs, whether screening or illness-related,” said Dr. Daniel R. Murphy, an internist and chief quality officer at Baylor Medicine in Houston, which does not currently bill for emails.Before the pandemic, Dr. Murphy found in his research that primary care doctors spent about an hour a day managing their inbox. But a recent study led by Dr. Holmgren of data from Epic, a dominant electronic health records company, showed that the rate of patient emails to providers had increased by more than 50 percent in the last three years.“We’re at an inflection point with messaging,” Dr. Holmgren said. “How are we going to deliver care in the future as we continuously move away from all care being a discrete visit?”Many doctors and their assistants have little time during work hours for replying to patients. Doctors find themselves attending to such demands during “pajama time” before bed, according to Dr. Anthony Cheng, an associate professor of family medicine at Oregon Health & Science.“We know that this is a contributor to burnout,” Dr. Rittenberg said. “Burnout and resulting attrition in physicians’ work is becoming a crisis in our medical system.”Dr. Rittenberg teamed up with her husband, Jeffrey B. Liebman, an economist at the Harvard Kennedy School, to study electronic health record responsibilities among primary care doctors at Brigham. In an article published in the Journal of General Internal Medicine in January 2022, they reported that female doctors spent more time responding to messages and received more messages from both patients and staff members than their male colleagues. This difference, they surmised, could help explain greater burnout rates among women in medicine.Some doctors have reported examples of patients who communicate too frequently or insistently through the online portal.“People now have the expectation that these communications are like texts and that they should get a response right away,” Dr. Rittenberg said. But, she said she empathized with what might be driving such patients’ insistent inquiries: pandemic-era malaise.“People are very anxious and worried and isolated, and the doctor offers a connection,” she said.Attaching a monetary fee to doctor-patient emails may be a step toward recognition of the value of this particular practice. But the addition of another bill has primed simmering resentments among some Americans, who are experiencing “pandemic fatigue” and have strained household budgets because of inflation, including higher health care costs.Ms. McCollum, a marketing writer, has been trying to raise extra cash to help cover her mother’s care by selling some of Ms. Cooke’s belongings online.“It’s been a tough year and I don’t need the clinic making it any worse,” she added.Dr. Kedar Mate, chief executive at the Institute for Healthcare Improvement, a nonprofit in Boston, said charging for providers’ emails amounted to “a very complicated and slippery slope” and that it could exacerbate health inequities.“Increasing levels of communication and interactions with patients is a good thing,” Dr. Mate said. “And I worry about disincentivizing that by creating a financial barrier.”“Increasing levels of communication and interactions with patients is a good thing,” said Kedar Mate, chief executive at the Institute for Healthcare Improvement.Carlos Bernate for The New York TimesCaitlin Donovan, senior director of the Patient Advocate Foundation, said that even a small co-pay could prove alienating to people living paycheck to paycheck.“We write a lot of $5 checks in this organization,” she said, referring to subsidies for co-pays and other out-of-pocket medical expenses.Others pointed out that when a severe physician shortage left patients waiting months to see a specialist, exchanging messages was a time-efficient way to bridge those gaps.“It’s really been a win-win for our physicians and our patients,” said LeTesha Montgomery, senior vice president for system patient access at Houston Methodist, which rolled out a full billing plan beginning in September. “So, it actually helped us increase access for our patients,” she said.Some patients view billing for a provider’s time and expertise as only fair and a good use of their own time, as well.Kacie Lewis, 29, is among those who manage their health concerns electronically. Until recently, her Aetna insurance coverage had a high deductible, through her work as a product manager at a health care company. And since late 2021, she said, she had been billed $32 for each of three email threads, seeking treatments for psoriasis, eczema and a yeast infection from providers at Novant Health in Charlotte, N.C.“Time is money,” Ms. Lewis said. “And to be able to submit something super simple and communicate with your doctor over email is much better than driving 20 minutes one way, 20 minutes back the other way and potentially sitting in the waiting room.”In a paper published on Jan. 6 in JAMA, Dr. Holmgren and his colleagues reported that after U.C.S.F. Health started its email billing in November 2021, there was a slight drop in the number of patient emails to providers. The researchers suggested that might have been the result of patients’ reluctance to be charged a fee.In the first year, U.C.S.F. billed for 13,000 message threads, or about 1.5 percent of 900,000 threads and more than three million messages, according to the study. (Other hospitals told The Times they billed for no greater than 2 percent of threads.) From about $20 from Medicare and Medicaid and $75 from commercial insurers per bill, the email fees generated $470,000, compared with the system’s $5.6 billion in 2021 revenues.“This will hopefully be revenue-neutral,” Dr. Holmgren said. “We are not intending to make this a profitable enterprise.”Critics argue that billing for a small fraction of emails is not likely to reduce physician burnout substantially unless hospitals also set aside workday hours for patient queries and reward clinicians for those efforts. U.C.S.F. has begun giving “productivity points,” a metric used for compensation, for doctors’ correspondence.Jack Resneck Jr., president of the American Medical Association, said he supported insurance coverage for emailing as a way to adjust health care models to fast-changing times.“How do we reinvent the physician’s day and the care delivery system to actually recognize and support the broad array of ways that we deliver care?” Dr. Resneck asked.

Published2 days agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesMinisters have rejected a proposal from MPs to introduce “menopause leave” pilots in England, arguing it could be “counterproductive”.It also dismissed a recommendation to make menopause a protected characteristic under the Equality Act.The suggestions came from the Women and Equalities Committee, which accused ministers of making “glacial progress” on menopause support. The government insisted it had an “ambitious” plan to improve help.In July 2022, the committee published a report which warned that the impact of menopause was causing the UK economy to “haemorrhage talent”.It said a lack of support was pushing women out of work and made 12 recommendations aimed at giving working women more rights. What is the menopause and what are the signs?Working women need greater menopause rights – MPsHRT explained: Is it right for me? ‘I went through the menopause before my mum did’ However, in its response to the report, published on Tuesday, the government rejected outright five of the committee’s proposals, including a recommendation for the government to work with a large public sector employer to “develop and pilot a specific menopause leave policy”.In its report, the cross-party group of MPs argued this could stop women being “forced out of work by insensitive and rigid sickness policies”.The government said it was focused on encouraging employers to implement workplace menopause policies, adding: “We are concerned that specific menopause leave may be counterproductive to achieving this goal.”It also said it would not launch a consultation on amending the Equality Act to introduce a new protected characteristic of menopause “including a duty to provide reasonable adjustments for menopausal employees”.The government expressed concern that such a move could have “unintended consequences which may inadvertently create new forms of discrimination, for example, discrimination risks towards men suffering from from long term medical conditions or eroding existing protections.” Ministers accepted “in principle” the committee’s recommendations to launch a public health campaign around menopause and to appoint a menopause ambassador to monitor progress made by businesses in this area. However, the Conservative chair of the committee Caroline Nokes condemned the government’s overall response as “a missed opportunity to protect vast numbers of talented and experienced women from leaving the workforce, and leaves me unconvinced that menopause is a government priority.Menopause and me: Too young to feel so oldLots of women don’t think about the menopause until they’re in their 40s. But it could start much earlier. Emma, Soe-Myat, Olivia and Elspeth share their experiences to help others cope with menopause at any age.Watch now on BBC iPlayer (UK Only)”For too long women have faced stigma, shame and dismissive attitudes when it comes to menopause. “The evidence to our inquiry was crystal clear that urgent action was needed across healthcare and work settings to properly address women’s needs, yet government progress has been glacial and its response complacent.” A government spokesperson rejected accusations of complacency arguing it had “put women’s health at the top of the agenda as part of the first-ever women’s health strategy for England”.”We are implementing an ambitious programme of work with the NHS to improve menopause care so all women can access the support they need.”According to a previous British Menopause Society survey, 45% of women indicated they felt their menopause symptoms had a negative impact on their work.More on this storyHouse of Commons vows to be ‘menopause friendly’13 June 2022Working women need greater menopause rights – MPs28 July 2022HRT explained: Is it right for me?8 September 2022‘I went through the menopause before my mum did’28 December 2022

Prostate cancer is the second most common cancer and the second leading cause of cancer death among American men. Now, researchers have discovered key molecular players that drive prostate cancer to progress into a highly aggressive form of the disease called neuroendocrine prostate cancer that currently has no effective treatment. The finding uncovers new avenues to explore for therapeutics to treat neuroendocrine prostate cancer.
“We have found novel pathways that promote neuroendocrine prostate cancer,” says senior author Lucia R. Languino, PhD, a professor in the department of Pharmacology, Physiology and Cancer Biology and director of the Genetics, Genomics, and Cancer Biology PhD Program at Thomas Jefferson University. She and her team published the new research online on November 7, 2022 in the journal Scientific Reports.
Most prostate cancers are a type of disease called prostate adenocarcinoma. Other types of prostate cancer, including neuroendocrine tumors, are rare. However, unlike prostate adenocarcinoma, neuroendocrine prostate cancer is very aggressive and can quickly spread to other parts of the body. Treatments that are effective for adenocarcinomas in the prostate do not work against neuroendocrine prostate cancers.
Adenocarcinoma prostate cancers can progress into neuroendocrine prostate cancer. Until now, how this transition occurs has been a mystery.
To better understand how neuroendocrine prostate cancer develops, Dr. Languino and colleagues looked for biomarkers of the disease. In previous work, they discovered that a molecule known as aVb3 integrin is abundant in mice and humans with neuroendocrine prostate cancer, but missing in prostate adenocarcinoma.
To look for molecules unique to neuroendocrine prostate cancer, the researchers found that aVb3 integrin expression in prostate cancer cells bumped up the expression of a known marker of neuroendocrine prostate cancer and significantly increased the expression of a molecule called Nogo receptor 2 (NgR2).

The finding “was a big discovery,” Dr. Languino says, who is also a researcher with the Sidney Kimmel Cancer Center — Jefferson Health. That’s because NgR2 is a protein found in nerve cells, where it contributes to neuronal functions. It has never before been studied in cancer, of any kind.
Dr. Languino and her colleagues wanted to find out what this molecule, a neuronal protein, is doing in cancer.
An initial experiment revealed that NgR2 binds the aVb3 integrin. The scientists also saw that in mice with neuroendocrine prostate tumors, aVb3 integrin and NgR2 were both present in the primary tumor and in cancerous lesions that had formed in the lungs of the animals. A follow-up experiment made it clear that both aVb3 integrin and NgR2 are necessary for neuroendocrine prostate cancers.
When Dr. Languino and her team lowered the amount of NgR2 in neuroendocrine prostate cancer cells, neuroendocrine markers also decreased. The results suggest that NgR2 plays a role in the development of neuroendocrine prostate cancer. Lowering the amount of NgR2 also reduced the ability of cancer cells to grow and move, indicating that NgR2 may have a hand in cancer spreading to other parts of the body, in a process known as metastasis. Metastases are often what makes cancers fatal.
“These two molecules, aVb3 integrin and NgR2, seem to create a combination that is lethal,” Dr. Languino says.
She and her colleagues are now looking for a molecule or antibody that would block the effect of NgR2, or the aVb3 integrin/NgR2 complex, to inhibit their ability to promote neuroendocrine prostate cancer growth and development, and make the cancer more susceptible to therapy.
All funding sources and support as well as competing interests and ethics declarations are listed at the end of the article cited below.

In advance of a scientific meeting on Thursday, officials proposed offering new shots to Americans each fall, a strategy long employed against the flu.Americans may be offered a single dose of a Covid vaccine each fall, much as they are given flu shots, the Food and Drug Administration announced on Monday.To simplify the makeup and timing of the shots, the agency also is proposing to retire the original vaccines and to offer only bivalent doses for primary and booster shots, according to briefing documents published on Monday.The proposal took some scientists by surprise, including a few of the F.D.A.’s own advisers. They are scheduled to meet on Thursday to discuss the country’s vaccine strategy, including which doses should be offered and on what schedule.“I’m choosing to believe that they are open to advice, and that they haven’t already made up their minds as to exactly what they’re going to do,” Dr. Paul Offit, one of the advisers and director of the Vaccine Education Center at Children’s Hospital of Philadelphia, said of F.D.A. officials.There was little research to support the suggested plan, some advisers said.“I’d like to see some data on the effect of dosing interval, at least observational data,” said Dr. Eric Rubin, one of the advisers and editor in chief of the New England Journal of Medicine. “And going forward, I’d like to see data collected to try to tell if we’re doing the right thing.”More on the Coronavirus PandemicLong Covid: An analysis of workers’ compensation claims in New York found that 71 percent of claimants with long Covid needed continuing medical treatment or were unable to work for six months or more.Annual Boosters: The Food and Drug Administration proposed that most Americans be offered a single dose of a Covid vaccine each fall, much as they are given flu shots.A Better Covid Winter: Some of the worst days of Covid in the United States have come as winters have settled in. But a surge in hospitalizations has yet to materialize this season.New Subvariant: A highly contagious version of the Omicron variant — known officially as XBB.1.5 or by its subvariant nickname, Kraken — is quickly spreading in the United States.Still, Dr. Rubin added, “I’d definitely be in favor of something simpler, as it would make it more likely that people might take it.”Only about 40 percent of adults aged 65 and older, and only 16 percent of those 5 and older, have received the latest Covid booster shot. Many experts, including federal officials, have said that the doses are most important for Americans at high risk of severe disease and death from Covid: older adults, immunocompromised people, pregnant women and those with multiple underlying conditions.In its briefing documents, the F.D.A. addressed the varying risks to people of different ages and health status.“Most individuals may only need to receive one dose of an approved or authorized Covid-19 vaccine to restore protective immunity for a period of time,” the agency said. Very young children who may not already have been infected with the virus, as well as older adults and immunocompromised people, may need two shots, the documents said.But some scientists said there was little to suggest that Americans at low risk needed even a single annual shot. The original vaccines continue to protect young and healthy people from severe disease, and the benefit of annual boosters is unclear.Most people are “well protected against severe Covid disease with a primary series and without yearly boosters,” said Dr. Céline Gounder, an infectious disease physician and senior fellow at the Kaiser Family Foundation.The F.D.A. advisers said they would like to see detailed information regarding who is most vulnerable to the virus and to make decisions about future vaccination strategy based on those data.“How old are they? What are their comorbidities? When was the last dose of vaccine they got? Did they take antiviral medicines?” Dr. Offit said. At the moment, the national strategy seems to be, “‘OK, well, let’s just dose everybody all the time,’” he said. “And that’s just not a good reason.”According to the F.D.A.’s suggested plan, officials would choose the annual vaccine’s composition each June, targeted to fight whatever variant is circulating.But this year, the booster was quickly outpaced by newly evolved variants. It might make more sense to develop vaccines that target parts of the coronavirus other than the so-called spike protein, which changes less frequently, some researchers said.They also criticized the agency’s proposal to use the current “bivalent” vaccine, which was designed to counter both the original Wuhan variant and the BA.4 and BA.5 Omicron variants that were circulating last summer, when the agency decided on the makeup of the booster doses.Some studies have suggested that combining both variants in the booster dose has undermined their effectiveness. Because of a biological phenomenon called imprinting, preliminary research suggests the bivalent vaccine elicits a stronger immune response to the ancestral variant than to the newer variants.A monovalent vaccine targeted only to the newer variants might have been more powerful, experts said.“This makes no sense, based on what we’ve learned from the current bivalent vaccine and imprinting,” Dr. Gounder said of the F.D.A.’s proposal. “Why not switch to a monovalent Omicron vaccine?”The F.D.A. advisers said they hoped the meeting on Thursday would allow for robust discussion of those questions. But others were more skeptical.The voting questions “are framed in such a way as to force a certain outcome,” Dr. Gounder said.

Researchers have developed a new tool and technique that uses “vortex ultrasound” — a sort of ultrasonic tornado — to break down blood clots in the brain. The new approach worked more quickly than existing techniques to eliminate clots formed in an in vitro model of cerebral venous sinus thrombosis (CVST).
“Our previous work looked at various techniques that use ultrasound to eliminate blood clots using what are essentially forward-facing waves,” says Xiaoning Jiang, co-corresponding author of a paper on the work. “Our new work uses vortex ultrasound, where the ultrasound waves have a helical wavefront.
“In other words, the ultrasound is swirling as it moves forward,” says Jiang, who is the Dean F. Duncan Professor of Mechanical and Aerospace Engineering at North Carolina State University. “Based on our in vitro testing, this approach eliminates blood clots more quickly than existing techniques, largely because of the shear stress induced by the vortex wave.”
“The fact that our new technique works quickly is important, because CVST clots increase pressure on blood vessels in the brain,” says Chengzhi Shi, co-corresponding author of the work and an assistant professor of mechanical engineering at Georgia Tech. “This increases the risk of a hemorrhage in the brain, which can be catastrophic for patients.
“Existing techniques rely in large part on interventions that dissolve the blood clot. But this is a time-consuming process. Our approach has the potential to address these clots more quickly, reducing risk for patients.”
CVST occurs when a blood clot forms in the veins responsible for draining blood from the brain. Incidence rates of CVST were between 2 and 3 per 100,000 in the United States in 2018 and 2019, and the incidence rate appears to be increasing.

“Another reason our work here is important is that current treatments for CVST fail in 20-40% of cases,” Jiang says.
The new tool consists of a single transducer that is specifically designed to produce the swirling, vortex effect. The transducer is small enough to be incorporated into a catheter, which is then fed through the circulatory system to the site of the blood clot.
For proof-of-concept in vitro testing, the researchers used cow blood in a 3D-printed model of the cerebral venous sinus.
“Based on available data, pharmaceutical interventions to dissolve CVST blood clots take at least 15 hours, and average around 29 hours,” Shi says. “During in vitro testing, we were able to dissolve an acute blood clot in well under half an hour.”
During any catheterization or surgical intervention there is a potential risk of harm, such as damaging the blood vessel itself. To address this issue, the researchers performed experiments applying vortex ultrasound to animal blood vein samples. Those tests found no damage to the walls of the blood vessels.
The researchers also conducted tests to determine whether the vortex ultrasound caused significant damage to red blood cells. They found that there was not substantial damage to red blood cells.
“The next step is for us to perform tests using an animal model to better establish the viability of this technique for CVST treatment,” Jiang says. “If those tests are successful, we hope to pursue clinical trials.”
“And if the vortex ultrasound ever becomes a clinical application, it would likely be comparable in cost to other interventions used to treat CVST,” says Shi.
The work was done with support from the National Institutes of Health under grants R01HL141967, R41HL154735, and R21EB027304; and the National Science Foundation, under grant number CMMI-2142555.

Bacteria of the genus Enterobacter are among the most dangerous bacteria associated with hospital infections worldwide. Some of their representatives are highly resistant to commonly used antibiotics, so that the reserve antibiotic colistin is increasingly used as a last resort therapy option. To avoid unnecessary reliance on colistin and risk increasing resistance, bacteria are tested for sensitivity or resistance to colistin before recommending treatment. However, commonly used tests for Enterobacter are not reliable. In a comprehensive study with broad participation within the German Center for Infection Research (DZIF), scientists have now resolved this problem. Based on these findings, they developed a simple, sensitive and robust test for the genus Enterobacter, which now enables targeted antibiotic therapy for the various Enterobacter species.
The currently used microbiological tests for colistin resistance and other antibiotic resistances did not allow accurate conclusions regarding the spread of resistance in different Enterobacter species. This was partly because the taxonomic classification of clinical Enterobacter isolates was imprecise, and partly because the error rate in determining resistance was high. The large-scale DZIF study has now achieved a breakthrough and clarified the relationships between the numerous Enterobacter species as well as optimised resistance testing. To this end, researchers at the Institute of Medical Microbiology of Justus Liebig University Giessen (Deep-iAMR project), together with DZIF scientists at the Research Center Borstel Leibniz Lung Center, analysed Enterobacter isolates collected at German university hospitals over a period of three years.
Using genome-based taxonomic studies, Enterobacter xiangfangensis was found to be the most frequently occurring species in German hospitals: From a data pool of over 3246 isolates worldwide — representing a collection from over twenty years — this species accounted for 68.7 percent of all Enterobacter detected.
Determination of antibiotic resistance profiles using phenotypic assays recommended by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) yielded mixed results with regard to colistin resistance.
“It turned out that many isolates were either not or barely resistant in these tests, even though the bacteria carried all the genes necessary for the expression of colistin resistance,” explains the study’s first author, Dr. Swapnil Doijad, of Friedrich Schiller University, Jena, Germany. A result that raised questions. The researchers obtained an initial answer by further investigating the isolates in which resistance was not clearly detectable using mass spectrometry.
“Depending on the particular Enterobacter species, we detected low levels of modified lipid A, the anchor structure of lipopolysaccharides (LPS) — a crucial component of the bacterial membrane and required for colistin resistance — even from bacteria grown in colistin-free medium,” comments the co-first author of the study, Dr. Nicolas Gisch of the Research Center Borstel Leibniz Lung Center. “These modifications of lipid A appear to be dependent on the bacterial species and are inherent, meaning their expression is embedded in a more complex regulation and not alone triggered by colistin,” he adds.
“The result suggests that there is species-dependent variation in the heteroresistance seen in Enterobacter: In routine test systems, the bacteria are sometimes resistant, sometimes not,” explains Dr. Can Imirzalioglu, co-author of the study and Acting Director for Clinical Microbiology and Diagnostics at the Institute of Medical Microbiology of Justus Liebig University Giessen.
Using further sophisticated methods, the authors were able to elucidate the phenomenon of heteroresistance in the genus Enterobacter. “Our analyses revealed that these bacteria have a sensor on their surface that responds to the pH value, i.e., the acidity in the environment, and regulates accordingly, either up or down, the genes required for the expression of colistin resistance,” explains Prof. Trinad Chakraborty, senior author and former director of the Institute of Medical Microbiology at Justus Liebig University Giessen. Genetic variations and interactions in this sensing pathway for environmental pH led to species-dependent differences regarding the extent of colistin resistance in the various Enterobacter species in conventional test systems.
Based on these findings, the researchers developed a simple new assay that eliminates heteroresistance effects and allows unambiguous and reliable determination of the true levels of colistin resistance for any isolate. The assay will avoid therapeutic failures when recommending the antibiotic, thereby paving the way for a targeted and economical treatment of Enterobacter species with this reserve antibiotic worldwide. A result that has come about not least through translational collaborations within the DZIF.

Researchers have found that the drug rilmenidine can extend lifespan and slow ageing.
Published in Aging Cell, the findings show that animals treated with rilmenidine, currently used to treat hypertension, at young and older ages increases lifespan and improves health markers, mimicking the effects of caloric restriction.
They also demonstrate that the healthspan and lifespan benefits of rilmenidine treatment in the roundworm C. elegans are mediated by the I1-imidazoline receptor nish-1, identifying this receptor as a potential longevity target.
Unlike other drugs previously studied for this purpose by the researchers, the widely-prescribed, oral antihypertensive rilmenidine has potential for future translatability to humans as side-effects are rare and non-severe.
To date, a caloric restriction diet has been considered the most robust anti-aging intervention, promoting longevity across species. However, studies of caloric restriction in humans have had mixed results and side effects, meaning finding medications like rilmenidine that can mimic the benefits of caloric restriction is the most reasonable anti-aging strategy.
Professor João Pedro Magalhães, who led the research whilst at the University of Liverpool and is now based at the University of Birmingham, said: “With a global ageing population, the benefits of delaying ageing, even if slightly, are immense. Repurposing drugs capable of extending lifespan and healthspan has a huge untapped potential in translational geroscience. For the first time, we have been able to show in animals that rilmenidine can increase lifespan. We are now keen to explore if rilmenidine may have other clinical applications.”
This study was undertaken by researchers from the University of Liverpool, ETH Zürich and Harvard Medical School, and funded by the Swiss National Science Foundation, LongeCity and the Biotechnology and Biological Sciences Research Council.

The transition to agriculture from hunting and gathering in pre-colonial North America led to changes in age-independent mortality, or mortality caused by factors that are not associated with age, according to a new study by a Penn State-led research team. The team found that the intensification of crop use occurred in two phases, the first of which led to a decline in human age-independent mortality, while the second is associated with a rise in it. The study is the first to tie patterns of age-independent mortality to food production.
“This study tells the story of our shared human experience,” said George Milner, distinguished professor of anthropology at Penn State and lead author. “We have several examples around the world where we see a move toward crop domestication as an independent event — eastern North America, particularly the midcontinent, being one of them, but so too the Fertile Crescent in the Middle East. Also, there are demographic changes happening. This paper addresses the relationship between the move toward agriculture and demographic change.”
The researchers examined previously published data to identify general trends in archaeobotanical samples, or the remains of plants in the archaeological record, and skeletal samples from sites across eight states stretching from Illinois to northern Alabama. They wanted to study the relationship between the domestication of crops and an index that uses skeletal data to capture the frequency of juveniles aged five to 19 years old relative to all individuals aged five or more. Anthropologists normally use the index to measure fertility rates and population growth, but the new work shows it is more responsive to age-independent mortality.
Mortality models, including those for pre-industrial societies, contain three components: juvenile mortality, which declines as children get older; adult mortality, where the probability of dying increases with advancing age; and age-independent mortality, an equal probability of dying for members of all age groups, which might occur in extreme events like food shortages, epidemics or warfare.
The researchers studied the archaeobotanical data to identify where the record showed an increase in the consumption of domesticated crops compared to foraged foods like nuts. They also examined skeletal data to identify decreases or increases in the indicator of age-independent mortality. The index focuses on individuals between five and 19 years old because in human populations that age range is characterized by low mortality relative to other age groups. Increases in mortality for this age group would indicate the occurrence of events like famines or conflict.
The researchers identified a strong correlation between crop domestication and changing age-independent mortality rates. Crop domestication happened in two stages in pre-colonial North America, with a decrease in age-independent mortality noted during the first stage of crop domestication and a rise during the second stage. The researchers reported their findings in the Proceedings of the National Academy of Sciences.

“What we’ve found is the index that has traditionally been interpreted as a fertility and population growth indicator is more tightly correlated to age-independent mortality, which reflects the number of deaths in the part of the age distribution where very few people die,” said Milner. “This means that the pattern of first adoption of agriculture, seen elsewhere in the world and observed in eastern North America as well, coincides with lower age-independent mortality. Basically, it’s good times, and that’s what we see culturally.”
The first stage of agricultural intensification in North America, which includes the cultivation of plants such as squash, sunflower and other native plants, occurred approximately 2,000 years ago during the Middle Woodland period up to about A.D. 500, said Milner. Indigenous societies flourished during this time. They established long-distance exchange networks, had an incredibly rich ceremonial life, and constructed big mounds and earthwork complexes.
The archaeological record shows that in the centuries just before A.D. 1000, and from that time onward, there was an increase in warfare. During this time Indigenous societies began cultivating maize and beans, and a number of new cultural changes occurred, including the initial development of powerful chiefdom societies. Age-independent mortality increased during this period, presumably due to conflict and the spread of diseases from higher numbers of individuals living near one another.
“The overall pattern seen in the demographic picture of North American pre-European contact is similar to other datasets from around the world,” Milner said. “The entire story makes perfect sense in terms of agricultural productivity, demographic change and cultural developments, including change over time in conflict and sociopolitical systems.”
The study links, for the first time, a worldwide pattern to age-independent mortality and agricultural developments, according to Milner.
“It’s a convenient measure of what people were eating, but also other aspects of society,” he said. “You cannot adopt a new technology without changing other aspects of society, such as the distribution of people and communities across a landscape. This agricultural measure is a signal of other changes in society that we can measure or observe archaeologically. It’s really a bigger story about our shared human experience. What we’ve found here in North America parallels the experiences of people elsewhere around the world and reinforces the fact that we’re all in this together, no matter our backgrounds.”
Jesper L. Boldsen, ADBOU, University of Southern Denmark, also contributed to the study.

A potent plant toxin with a unique way of killing harmful bacteria has emerged as one of the strongest new antibiotic candidates in decades.
The antibiotic, called albicidin, is produced by the bacterial plant pathogen Xanthomonas albilineans, which causes the devastating leaf scald disease in sugar cane. Albicidin is thought to be used by the pathogen to attack the plant, enabling its spread. It has been known for some time that albicidin is highly effective at killing bacteria including E. coli and S. aureus. These superbugs, notorious for their growing resistance to existing antibiotics, have prompted a vital need for effective new drugs.
Despite its antibiotic potential and low toxicity in pre-clinical experiments, pharmaceutical development of albicidin has been hampered because scientists did not know precisely how it interacted with its target, the bacterial enzyme DNA gyrase (gyrase). This enzyme binds to DNA and, through a series of elegant movements, twists it up, a process known as supercoiling which is vital for cells to function properly.
Now, Dr Dmitry Ghilarov’s research group at the John Innes Centre, alongside the laboratories of Prof. Roderich Süssmuth at Technische Universität Berlin, Germany and Prof. Jonathan Heddle at Jagiellonian University, Poland, have exploited advances in cryo-electron microscopy to obtain a first snapshot of albicidin bound to gyrase.
It showed that albicidin forms an L-shape, enabling it to interact with both the gyrase and the DNA in a unique way. In this state gyrase can no longer move to bring the DNA ends together. The effect of albicidin is akin to a spanner thrown between two gears.
The way albicidin interacts with gyrase is sufficiently different from existing antibiotics that the molecule and its derivatives are likely to be effective against many of the current antibiotic resistant bacteria.

“It seems by the nature of the interaction, albicidin targets a really essential part of the enzyme and it’s hard for bacteria to evolve resistance to that,” said Dr Ghilarov. “Now that we have a structural understanding, we can look to further exploit this binding pocket and make more modifications to albicidin to improve its efficacy and pharmacological properties.”
This work has already begun: the team used their observations to chemically synthesise variations of the antibiotic with improved properties. In tests, these variants were effective against some of the most dangerous hospital-acquired bacterial infections including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Salmonella typhimurium.
Dr Ghilarov said: “We believe this is one of the most exciting new antibiotic candidates in many years. It has extremely high effectiveness in small concentrations and is highly potent against pathogenic bacteria — even those resistant to the widely used antibiotics such as fluoroquinolones.”
“This molecule has been around for decades,” continued Dr Ghilarov, “Now advances in cryo-electron microscopy has made it possible to determine structures of even the most elaborate protein-DNA complexes. To be the first person to see the molecule bound to its target and how it works is a huge privilege, and the best reward one can have as a scientist. But this work is a big team effort, and we would not have done it without our European colleagues.”
The next step for this research is to engage with academic and industrial collaborators, and to seek funding to take the research forward to human clinical trials. This could lead to the development of an urgently needed new class of antibiotics in the face of a global threat of antimicrobial resistance, AMR.

Albicidin — how does it work?
Albicidin targets an enzyme found in both plants and bacteria called DNA gyrase (or simply “gyrase”). This enzyme binds to DNA and, through a series of elegant movements, twists it up (a process known as supercoiling) — a vital process for cells to function properly. However, gyrase has an Achilles heel; to do its job it must momentarily cut the DNA double helix. This is dangerous, as broken DNA is lethal to the cell. Normally, gyrase quickly joints the two pieces of DNA back together again as it works, but albicidin prevents it from happening, resulting in broken DNA and bacterial death.
About Anti-Microbial Resistance (AMR)
Multi-drug resistant pathogens such as Escherichia coli, Pseudomonas aeruginosa and Salmonella typhimurium present a dangerous healthcare burden, exacerbated by the COVID-19 pandemic.
Infections by resistant pathogens are a leading cause of death in hospital intensive care units, with some strains becoming pan resistant. Gram-negative drug-resistant pathogens were a cause of 50,000 deaths in 2019.
Despite urgently needed new medicines to combat this threat, drug discovery programmes have yielded no new classes of antibiotics for several decades.