Publisher Health

Scientists at Duke-NUS Medical School have discovered new molecular details of how cells ensure that their energy supply is adjusted to meet energy demand. Their study, carried out in collaboration with researchers at the University of Melbourne in Australia and Duke University in Durham, North Carolina, USA, highlights the crucial role microproteins play in assembling larger protein complexes inside energy-generating cell components known as mitochondria.
Problems with mitochondria underlie a wide range of diseases, including common conditions such as heart failure, obesity, diabetes and cancer.
“Our long-term goal is to learn how to manipulate the microproteins we are investigating to combat mitochondrial dysfunction in patients,” said senior author Assistant Professor Lena Ho, from Duke-NUS’ Cardiovascular & Metabolic Disorders (CVMD) Programme. “The more immediate significance of the research is to reveal new details of how mitochondria function and are maintained in all cells. The work could add an important new level of understanding to this central aspect of cell biology.”
Mitochondria, often referred to as the powerhouses of the cell, are bounded by a double membrane. The inner of the two membranes hosts a series of proteins that transfer electrons along what is called the electron transport chain. This electron transport is a crucial part of the processes that extract chemical energy from nutrients and ultimately store it in energy-rich molecules of adenosine triphosphate (ATP).
The new insight from the Duke-NUS team reveals that small microproteins (also called peptides) play a previously unrecognised role in allowing the electron transport chain to form. Specifically, they appear to work together to assist and control the assembly of one of the central proteins of the chain, called Complex III. This role allows the microproteins to participate in regulating the levels of electron transport chain proteins, and therefore energy supply, in response to changes in energy demand.
“Microproteins have fascinated but also mystified biologists from diverse fields for a long time,” said Mr Liang Chao, co-first author of the study, who is a PhD candidate at Duke-NUS. “Our study provides an example of what they can do and how they participate in controlling energy metabolism at the deepest level of molecular detail.”
“Mitochondria are the batteries and factories of our cells, making not only energy but also many of the building blocks required for cells to multiply and stay alive,” said Dr Shan Zhang, formerly a research fellow with Asst Prof Ho’s Endogenous Peptides Lab, under Duke-NUS’ CVMD Programme, and now an Assistant Professor at Zhejiang University, China. “We clearly see that modulating the levels of these microproteins can lead to or protect against mitochondrial dysfunction, which is a feature that underlies almost all types of common diseases.”
The team now plans to move on from these initial findings at the cellular level to more fully investigate the roles and significance of the microproteins in preclinical models and ultimately in humans.
“These next stages will hopefully lead us towards learning how to target the microprotein activity to treat mitochondrial diseases,” Asst Prof Ho concluded.
“Innovations in healthcare and disease prevention benefit from advances in knowledge made possible by fundamental scientific research, such as this study by Assistant Professor Ho and her team,” said Professor Patrick Casey, Senior Vice-Dean for Research at Duke-NUS. “I look forward to seeing where the research leads us next.”
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What is the typical movement behaviour of visitors to large events, such as concerts, and what does this mean for the risk of spreading infectious diseases like COVID-19? A group of researchers from the Informatics Institute at the University of Amsterdam, together with an epidemiologist from the Utrecht University, set out to investigate using data from events in a large stadium in Amsterdam. Their results have now been published in the journal Nature Scientific Reports.
Following the outbreak of the COVID-19 pandemic, governments around the world responded with social distancing measures including the cancellation of events involving the gathering of large crowds. Although it is intuitively clear that crowded events present a high level of risk for the spread of an infectious disease like COVID-19, a lot depends on specifically how people move in crowds. Despite a large body of scientific research on both crowd dynamics and human mobility in the past decades, surprisingly little is known about human movement in the specific context of large, crowded events.
Intermittent pattern
As the pandemic was beginning, a small group of researchers from the Informatics Institute were finalising their analyses of movement patterns of visitors to large sports and dance events in the Johan Cruijff stadium in Amsterdam. In two separate publications, they investigate the movement patterns in terms of both space and time. The first of these two publications appeared in February 2021 and compared the movements of individuals in the crowd to the typical foraging patterns that were also present in our human hunter-gatherer ancestors.
Most importantly, they found that individuals were not constantly on the move. People stay in one place for some time, and then decide to go somewhere else, usually in one continuous effort. This leads to an intermittent pattern of movement and rest which is sometimes called ‘bursty’ in the scientific literature. This observation only comes about when people’s movements are studied over longer time spans, e.g. several hours.
Infection risks
The researchers realised that the movement patterns they had observed would have important consequences for the spread of a disease like COVID-19. They then collaborated with theoretical epidemiologist Hans Heesterbeek of Utrecht University. In the team’s new publication they reproduce the observed movement behaviour in so-called random walk models, on which they simulate the spread of an infectious disease. This second study appeared on 1 September in Nature Scientific Reports.
This new work exposes the perhaps counter-intuitive fact that the observed intermittent movement behaviour presents an increased level of risk compared to higher and more continuous levels of movement. One would expect that the more people move and encounter other people, the more individuals get infected. However, if the infection also needs time to be transmitted (instead of occurring instantly), the fact that people stop and spend time in proximity to each other increases the risk of infection. The first author of the study, PhD candidate Philip Rutten, comments: “This shows that, if the infection probability is time-dependent, an intermittently moving but freely mixing crowd may present the highest level of transmission risk.” The researchers emphasise that this type of crowd movement behaviour may be common to various kinds of events, such as music festivals, religious gatherings, and political demonstrations.
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Materials provided by Universiteit van Amsterdam. Note: Content may be edited for style and length.

A single research test has the potential to predict which patients treated with immunotherapies — which harness the immune system to attack cancer cells — are likely to have their cancer recur or have severe side effects, a new study found.
Published online September 15 in Clinical Cancer Research, the study revolved around the set of immune system signaling proteins called antibodies that recognize invading bacteria, viruses, and fungi. These blood proteins are designed to glom onto and inactivate specific bacterial and viral proteins, but in some cases “autoantibodies” also react to the body’s “self” proteins to cause autoimmune disease.
Led by researchers at NYU Grossman School of Medicine and its Perlmutter Cancer Center, the new study generated data suggesting that a newly identified a panel of autoantibodies, if found in patients’ blood before immunotherapy, has the potential to accurately predict whether a patient’s cancer would recur and if they would experience autoimmune side effects because of the treatment itself. The study patients had received adjuvant immunotherapy, where the aim is to keep cancer from returning after prior treatment.
To spare normal cells from autoimmune attack, immune cells have “checkpoint” sensors that turn them off when they receive an appropriate signal. The body recognizes tumors as abnormal, but cancer cells hijack checkpoints, including programmed death receptor 1 (PD-1), to turn off immune attack. As one type of immunotherapy, PD-1 inhibitors are effective against many cancers, and are used as adjuvant therapy in patients with resected melanoma. Nevertheless, some patients suffer recurrent disease or severe treatment-related side effects, researchers say
The research team theorized that certain patients might have higher levels of key autoantibodies prior to treatment but not enough to be detected as autoimmune disease. This hidden susceptibility, they hypothesized, would then be triggered by checkpoint inhibitors to cause greater immune-based side effects.
In the current work, the team identified a panel of distinct autoantibody signatures that could predict immune-related adverse effects upon treatment with two leading checkpoint inhibitors, nivolumab and ipilimumab, and for the combination of the two agents. Although their data support the predictive utility of the autoantibody scores by comparing them with data from clinical trials, the researchers say, more research is needed to validate the value of such a test in the clinic, and to better understand the relationship between autoantibodies, recurrence, and toxicity.
“Our results show that the new research test, by predicting whether a patient will respond to a treatment or experience side effects, has the potential to help physicians make more precise treatment recommendations,” says study first author Paul Johannet, MD. At the time of the study, Johannet was a postdoctoral fellow in the lab of senior study author Iman Osman, MD, the Rudolf L. Baer Professor of Dermatology in the Ronald O. Perelman Department of Dermatology and a member of Perlmutter Cancer Center. “With further validation, this composite panel might help patients to better balance the chances of treatment success against severe side effects.”
The researchers obtained blood samples from more than 950 patients enrolled in one of two Phase 3 randomized controlled trials of adjuvant checkpoint inhibitors in patients with advanced melanoma. Tumors in these patients had been surgically removed and blood samples collected before they received any treatment. The new test employs a microchip with 20,000 proteins attached in specific spots. When an antibody recognizes any of the proteins present in a blood sample, those spots glow with the signal intensifying as the concentration of antibody increases.
Based on the newly identified panel of autoantibodies, and using statistical modeling, co-senior author Judy Zhong, PhD, and colleagues developed a score-based prediction system for each treatment used. Patients with a high autoantibody recurrence score were found to have quicker disease return than those with a lower score, says Zhong, a professor in the Department of Population Health and the Department of Environmental Medicine at NYU Grossman School of Medicine. Similarly, patients with higher pre-treatment autoantibody toxicity scores were significantly more likely to develop severe side effects than those with lower scores.
“That we identified 283 autoantibody signals shows that the biological phenomena underlying recurrence and toxicity are complex, and cannot be driven one or two biomarkers” says Osman, also director of the Interdisciplinary Melanoma Cooperative Group at NYU Langone Health.
Moving forward the researchers plan to test the predictive value of autoantibody signatures in patients with the other cancer types for which checkpoint inhibitors are currently approved for use.

The pharmaceutical industry finances about 75 percent of the agency’s drug division, through a controversial program that Congress must reauthorize by the end of this month.Every five years, top officials of the Food and Drug Administration go behind closed doors to negotiate the terms of its core budget — about $3 billion this year.But the F.D.A. is not at the table with members of Congress or with White House officials. Instead, it’s in dozens of meetings with representatives of the giant pharmaceutical companies whose products the agency regulates. The negotiations are a piece of the “user fee” program in which drug, device and biotech companies make payments to the agency partly to seek product approvals. The fees have soared since the program’s inception three decades ago and now make up nearly half of the F.D.A.’s budget and finance 6,500 jobs at the agency.The pharmaceutical industry funding alone has become so dominant that last year it accounted for three-quarters — or $1.1 billion — of the agency’s drug division budget.Details of the program are being debated in Congress as a Sept. 30 deadline for reauthorization nears. The powerful pharmaceutical lobby says its role in funding the agency has helped speed approvals of lifesaving drugs to the market by providing it with the resources to do the work. But advocates for patients and doctors say the agreements have enabled the industry to weaken the approval process meant to ensure that drugs are safe and effective.“It’s kind of like a devil’s bargain,” said Dr. Joseph Ross, a professor at the Yale School of Medicine who has studied F.D.A. policies, “that I think is not in the best interest of the agency, because it turns this every-five-year cycle into the F.D.A. essentially asking industry, ‘What can we do to secure this money?’ ”In recent weeks, the user fee bill in Congress became snagged by added provisions, including over an effort to speed approval of generic drugs that could cut into the big companies’ profits and make the drugs less expensive for consumers and insurers. A key Republican senator and the major pharmaceutical lobby opposed that provision.Versions of the bills in the House and Senate also included a raft of extra proposals that would require annual inspections of infant formula makers and increase oversight of cosmetics, diagnostic tests, dietary supplements and food packaging.Those measures may not survive final haggling over reauthorizing the program in Congress, where the drug and device industries spend hundreds of millions on lobbying and campaign contributions. Senator Richard Burr, Republican of North Carolina and the leading member of the main Senate committee overseeing the agency, opposed the amendment that would allow the F.D.A. to help generic drug makers replicate an off-patent drug with specifics on the ingredients, which for years had tended to be more of a guessing game.The Congressional Budget Office estimated that the generic drug measure could save taxpayers $546 million over 10 years by speeding those versions to market. But Mr. Burr argued that it would hamper innovation and, objecting to another amendment limiting drug exclusivity, voted against the bill in June. In July, he introduced a stripped-down user fee bill to reset negotiations.Senator Richard Burr of North Carolina, a leading member of the Senate committee that oversees the F.D.A., voted against a user fee bill in June.Al Drago for The New York TimesSenator Patty Murray, Democrat of Washington and chairwoman of the Senate committee that oversees the F.D.A., issued a statement Wednesday underscoring the urgency of the moment.“At every single phase in this process, I‘m laser focused on patients—and making sure F.D.A. works for families, not pharmaceutical companies’ bottom lines,” Ms. Murray said. “We absolutely can’t let Congressional inaction force F.D.A. to send out pink slips. But we also can’t, and I won’t, stop pushing for the kind of reforms families need to see from the drug industry and this critical agency.”In committee hearings this summer, senators debated the merits of the user fee program.Senator Bernie Sanders, an independent of Vermont and a longtime critic of the drug industry, suggested that the pharmaceutical companies’ tendency to charge “outrageous” prices was related to their significant role in funding and advancing policy goals of the F.D.A.’s drug division.“So the industry, in a sense, is regulating itself,” Mr. Sanders said during a hearing on June 14 of the Senate Health, Education, Labor & Pensions Committee. “May make sense to somebody — but not to me.”Mr. Burr, a business-focused conservative, complained that the program burdens companies with negotiating with the agency over the fees, which he predicted would rise even higher. He has also complained about how the high costs of the program limit opportunity for small businesses; new-drug application fees are $1.5 million to $3.1 million.“In a perfect world, I hope we would all be here lobbying that there are going to be no user fees paid to the F.D.A. by anybody,” he said during the hearing. Ultimately, the White House and Congress have final say over the agency’s priorities.Even Dr. Robert Califf, the F.D.A. commissioner, acknowledged in a news briefing this summer that the program was not ideal. “Philosophically, I wish the taxpayer paid for all the F.D.A. and there weren’t user fees,” he said.A spokeswoman for the F.D.A. said agency policy prohibited officials from commenting on pending legislation.The user fee program traces its roots to 1992, when AIDS activists pressed the F.D.A. to hasten drug approvals. About a decade later, drugs moved through the pipeline more quickly, averaging about 10 months from roughly 19 months.Over the years, the program’s scope and funding grew. Annual “performance reports” detail the F.D.A.’s efforts to make quick decisions, hold routine meetings with drug companies and approve products under fast-track pathways.User fees were added for medical devices, generic drugs and biologics, which include vaccines and gene therapies. (The tobacco division and its 1,200 employees are entirely user-fee funded, though the industry has no say in how the dollars are spent.) By 2012, drug companies accounted for half of the F.D.A. drug division budget, through fees for new-drug applications and annual payments for approved drugs.“Philosophically, I wish the taxpayer paid for all the F.D.A. and there weren’t user fees,” said Dr. Robert Califf, the F.D.A. commissioner.Anna Rose Layden for The New York TimesDr. Aaron Mitchell, an oncologist and researcher at Memorial Sloan Kettering Cancer Center, recently wrote that the fee program’s policy changes had “favored industry through decreasing regulatory standards, shortening approval times and increasing industry involvement in F.D.A. decision making.”He said he was surprised that user fee negotiations in 1997 led to reducing the number of clinical trials for drug approval to one, from the longtime standard of two trials. He said it was also notable that the 2012 user fee law allowed “fewer, smaller or shorter clinical trials” for therapies for life-threatening conditions.“The faster you’re rushing to approval and the less clinical evidence that you’re requiring,” Dr. Mitchell said, “the greater the chances that you’re going to miss something” that could harm patients.Some F.D.A. drug approvals based on uncertain evidence have proved highly controversial. Medicare refused to routinely pay for the Alzheimer’s drug Aduhelm, citing little evidence of benefit and serious safety risks. Another approval of a medication for a deadly muscle disease — over the objections of agency experts — drew scrutiny when insurers refused to pay for it, calling the therapy “investigational.” The agency issued those approvals on the condition that further study prove a benefit, though such reviews take years to complete.For its part, the F.D.A. said the user fee process had given it authority to improve public health by expanding oversight of foreign drugmakers, allowing hearing aids to be sold over the counter and monitoring drug shortages.The user fee process “revolutionized” the F.D.A.’s drug approval process, Dr. Peter Marks, director of the agency vaccine and gene therapy division, told a Senate panel in April.“It’s not an understatement to say that there are many people with us today who would not be here without the program, which has dramatically reshaped drug development and approval in the United States,” Dr. Marks said.Those testifying from industry groups PhRMA, AdvaMed and BIO, which represents the biotech industry, have noted the program’s value in ensuring the F.D.A. has the staff and technology to review a growing number of rapidly changing gene and cell therapies, novel medical devices and rare-disease therapies. The Pharmaceutical Research Manufacturers of America, known as PhRMA, called the program a “success” and said the funding made the F.D.A. a global leader in approving three-fourths of new medicines before any other nation.The growth of the program “reflects the robust innovation and timely access to safe and effective medicines required for an appropriately staffed and funded F.D.A.,” Priscilla VanderVeer, PhRMA vice president of public affairs, said in a statement.“It’s a great example of a meaningful public, private collaboration to get patients the products that they need,” said Scott Whitaker, president of AdvaMed, which represents medical device makers.Dr. Reshma Ramachandran, a professor of medicine at Yale University, said doctors often don’t recognize the pressure the drug industry exerts over the F.D.A.Christopher Capozziello for The New York TimesThe pace of approvals often appears too hasty for Dr. Sanket Dhruva, a cardiologist and an assistant professor of medicine at the University of California, San Francisco. One cardiac device he recently encountered was approved after a study followed patients for only 30 days and offered no comparison against the standard treatment. It was not enough information for him to use the device on the patients he treats, he said.Generally, he said that doctors could earn more money by adopting the newest technologies and that hospitals liked to advertise them, though clear evidence of safety and effectiveness was often lacking.“What we end up going on is hype,” Dr. Dhruva said.Dr. Mitchell expressed concern that new cancer drugs had been approved using tests that compared a new treatment with a placebo, a practice that F.D.A. guidance has deemed unethical, instead of testing them against standard therapies. That leaves him uncertain whether the new drugs for the cancer patients he treats are better than the old ones.Dr. Reshma Ramachandran, co-director of the Yale Collaboration for Research Integrity and Transparency, said that doctors were not trained to sift through F.D.A. records to scrutinize the quality of the studies that led to approvals. Nor do many recognize the pressure the drug industry exerts on the F.D.A. to meet approval decision deadlines.“And that just seems like the wrong metric to care about,” said Dr. Ramachandran, who has tracked the user fee process and testified to Congress for Doctors for America. “It should be: ‘Are patients healthier? Are patients safe?’ And that just seems like an afterthought.”The latest negotiation cycle over prescription drug user fees involved about 100 meetings between the F.D.A. and drug company representatives and six meetings with groups like Dr. Ramachandran’s.The concerns expressed about the imbalance of access — that the drug and device industries hold outsize sway compared with patient groups and public-interest advocates — have led to calls for Congress to find a way to fully fund the agency through a tax on sales or by federal appropriations.While few see that change as likely, Dr. Mikkael Sekeres, a former F.D.A. oncology adviser who is a professor of medicine at the University of Miami, said that the F.D.A. should match its brisk pace of approvals with a system that could identify problems just as quickly.“They don’t have a good mechanism to monitor the side effects of these drugs once they’re on the market,” said Dr. Sekeres, who recently wrote a book about the F.D.A. “So the post-marketing approval surveillance mechanism isn’t as good as it should be to guarantee the safety of the public.”

In one of his most extensive interviews since having a stroke, John Fetterman said he was fully capable of handling a campaign that may decide who controls the U.S. Senate.Four months after suffering a stroke he described as a “near-death experience,” Lt. Gov. John Fetterman of Pennsylvania acknowledges lingering problems with his speech and hearing that sometimes cause verbal miscues. He has relied on closed captions or the help of staff members to smooth his interactions with voters and reporters as he runs for Senate.But in one of his most extensive interviews since the stroke in May, Mr. Fetterman said he was fully capable of handling the rigors of a campaign that may decide the balance of power in the U.S. Senate. He described driving his children to school, walking several miles a day and rapidly improving his auditory processing — while also lacing into his opponent, the celebrity television physician Mehmet Oz, who trails in the polls and whose campaign has mocked Mr. Fetterman’s health challenges.“I’m running a perfectly normal campaign,” Mr. Fetterman said in a 40-minute interview with The New York Times, conducted by video on Tuesday. He added at another point, “I keep getting better and better, and I’m living a perfectly normal life.”Indeed, Mr. Fetterman’s campaign has seemed increasingly normal in many ways.The candidate, whose personality-driven political style has inspired an unusual degree of fandom for a Senate hopeful, speaks at raucous rallies, jokes about his opponent at private fund-raisers and makes occasional news media appearances. His onetime Democratic rivals have moved to show a united front with their party’s nominee. Several Democratic officials who have interacted with Mr. Fetterman closely also said recently that they were encouraged by his progress. On Wednesday, he committed to debating Dr. Oz late next month.Yet in other respects, clashes over health and transparency have shaped the contest to a remarkable degree, fueled by attacks from the Trump-backed Dr. Oz and Republicans promoting out-of-context clips of Mr. Fetterman — and by the realities of Mr. Fetterman’s personal situation.He suffered a stroke on the Friday before the May primary election, though he waited until Sunday to disclose it. On Primary Day, he had a pacemaker and defibrillator implanted, which his campaign described at the time as a standard procedure that would help address “the underlying cause of his stroke, atrial fibrillation.” In a statement in June, his doctor said he also had a serious heart condition called cardiomyopathy.Mr. Fetterman thanked his supporters in a video at his election-night party in May. He has not tended to take questions from the news media at events since the stroke.Maddie McGarvey for The New York TimesIn Tuesday’s interview, Mr. Fetterman said, “We have never been hiding any of the health issues.”Those issues have plainly shaped how Mr. Fetterman campaigns now. He has not tended to take questions from the news media at his events, in contrast to his approach right before his stroke. He is still using closed captioning to conduct video conversations, as he did in the interview on Tuesday. And in some appearances over the last month, he jumbled a few words, a problem he has acknowledged.At a Labor Day event last week, he had to restart an occasional sentence, and he promised to “champion the union way of life in Jersey — excuse me, in D.C.,” after he sought to cast Dr. Oz as more comfortable in New Jersey, his longtime principal residence, than in Pennsylvania.For in-person appearances, Mr. Fetterman has sometimes relied on staff members to repeat questions he has trouble hearing over background noise.Many voters appear untroubled: A CBS News/YouGov poll released this week found that 59 percent of registered Pennsylvania voters surveyed believed Mr. Fetterman was healthy enough to serve.A cutout of Mr. Fetterman at his campaign rally in Erie, Pa., in August. A doctor found the candidate’s results on neurocognitive tests reassuring.Jeff Swensen for The New York TimesOn Wednesday, his campaign said he had taken neurocognitive tests, mentioning two: the Saint Louis University Mental Status Examination, administered on July 14, and the Repeatable Battery for the Assessment of Neuropsychological Status, or RBANS, taken on Wednesday morning. The campaign said his score on the St. Louis test was 28 out of 30. That score is typical for people with at least a high school education.His score on the RBANS was within the normal range for his age, according to his campaign.Stroke patients often undergo many neurocognitive tests, including brief ones administered by speech therapists and hourslong cognitive evaluations, said Dr. Lee Schwamm, a stroke expert at Massachusetts General Hospital.Dr. Schwamm found Mr. Fetterman’s scores reassuring but added that they “don’t preclude the possibility that his performance is lower than it might have been before his stroke.”But, Dr. Schwamm said, the emphasis on Mr. Fetterman’s cognitive tests plays into what he sees as a bias against people who have had strokes. “It is playing on the fear that a stroke made him vulnerable, weak, incapable of leadership,” he said. “Judge the guy on his merits.”Mr. Fetterman’s campaign said he continued to take all the medications he was prescribed, including the blood thinner rivaroxaban. The campaign also said he had exhibited no stroke symptoms or bleeding since the stroke.Mr. Fetterman’s campaign did not make his doctors available for interviews, and efforts to reach them independently were unsuccessful. Dr. Ramesh Chandra of Alliance Cardiology signed the June letter about Mr. Fetterman’s heart condition. Dr. Chandra’s office said health privacy laws prohibited him from discussing patients without their permission.Mr. Fetterman returned to the campaign trail last month with a splashy rally in Erie, Pa. He has held a number of big campaign events since, including a large one on Sunday, when, The Philadelphia Inquirer noted, “he stumbled over very few words compared with previous speeches.”Mr. Fetterman greeted a large crowd in Blue Bell. Even in appearances when he has halting moments, he can come across as high-energy.Hannah Beier for The New York TimesBy his campaign’s count, he has held more than two dozen fund-raisers since his stroke, conducted dozens of political meetings both in person and over video, and held or attended a number of public events. Even in appearances when he has halting moments, he can come across as high-energy, sometimes adopting the cadence of a stand-up comic to rip into Dr. Oz. He has also used his personal health challenges to bond with voters, asking at events for a show of hands from those who have experienced health problems in their families.“Who has someone, maybe personally, yourself, has ever had a big, major health challenge? OK, all right, how about any of your parents?” Mr. Fetterman said on Sunday. “I’m so sorry. I mean, I certainly have. And I hope, I truly hope for each and every one of you, you didn’t have a doctor in your life making fun of it.”Asked for comment, Barney Keller, an Oz campaign consultant, said that the Fetterman campaign “hasn’t been transparent at all about his health challenges.”Representative Mary Gay Scanlon, a Pennsylvania Democrat who attended the rally and a fund-raiser with Mr. Fetterman on Sunday, said he had strong exchanges at the private event.“There were no closed captions,” Ms. Scanlon said. “He fielded questions and had a sense of humor and was entirely what one would hope for for the next senator from Pennsylvania.”The issue of Mr. Fetterman’s health intensified in recent weeks as Dr. Oz used the matter of debate participation to question Mr. Fetterman’s fitness to serve. Mr. Fetterman’s campaign said Wednesday that he would debate on Oct. 25, two weeks before Election Day, noting that it had held conversations with several TV stations to determine how to accommodate his lingering auditory challenges.Shanin Specter, a Philadelphia lawyer and son of the late Senator Arlen Specter of Pennsylvania, said in an interview some voters might regard one debate as insufficient.“The recent indication of agreement to one debate in late October may be seen by voters as too little and too late, especially for those who vote by mail,” said Mr. Specter, who donates to candidates in both parties. He said at another point, “He hasn’t done much campaigning. The film of that which he’s done has been unreassuring. The drip, drip lack of forthrightness about his problems has been corrosive.”Mr. Specter said he supported the Democratic nominee for governor, Josh Shapiro, but was not involved in the Senate race.Dr. Mehmet Oz showed a photo of Mr. Fetterman from a Democratic debate before his stroke. Dr. Oz’s campaign has mocked his rival’s health challenges.Kriston Jae Bethel for The New York TimesShould he win, Mr. Fetterman, 53, would be far younger than many leaders in Washington, including President Biden (79), House Speaker Nancy Pelosi (82) and a number of octogenarian U.S. senators, some of whom have faced scrutiny over their mental acuity.“The goal posts for John keep moving. John is already healthier and more articulate than about 80 percent of the Senate, and he’s getting better every day,” said Rebecca Katz, a senior adviser to the Fetterman campaign.Senator Ben Ray Luján, a New Mexico Democrat who suffered a stroke earlier this year, has been in touch with Mr. Fetterman since his illness and said he had no doubt that Mr. Fetterman could handle the demands of the office.“If anyone wants to see what a stroke survivor looks like, they can just take a look at me,” the senator said, noting his participation in an all-night voting session. “He’s strong. He’s working. He’s connecting with constituents. He’s going to keep doing that.”Mr. Fetterman, for his part, suggested the health scare had given him a new perspective.“I had to be faced with the idea that this could have ended my life when I have three young children,” he said. “That’s 10 times harder than anything that I’m having, dealing with, right now.”

Obese women who use oral contraceptives containing oestrogen and progestin have a 24-fold increased risk of venous thromboembolism (VTE) compared with non-obese women not using the drugs, according to a review paper published today in ESC Heart Failure, a journal of the European Society of Cardiology (ESC).
Study author Professor Giuseppe Rosano of the IRCCS San Raffaele Pisana, Rome, Italy said: “It is well established that both obesity and oestrogen-containing contraceptives are risk factors for VTE. Despite this, obese women continue to receive these drugs. The scientific evidence indicates that obesity and combined oral contraceptives have a synergistic effect on VTE risk and this should be considered in prescribing decisions. Progestin-only products, including pills, intrauterine devices, or implants are a safer alternative to the combined pill in women carrying excess weight.”
This review article highlights the latest evidence on the independent effects of obesity and contraceptives, and their synergistic effects, on VTE risk and provides clinical recommendations. VTE refers to a blood clot in a vein and includes two life-threatening conditions: deep venous thrombosis and pulmonary embolism.
The World Health Organization estimates that the global prevalence of obesity nearly tripled between 1975 and 2016 — with 15% of adult women being obese. The risk of VTE increases progressively with body mass index (BMI), and in obese women it is more than double that of non-obese women. Obesity has the most substantial impact on VTE women under 40 years of age, who have a five-fold increased risk compared with non-obese women. Professor Rosano noted: “The particularly high risk in obese women under 40 is important, since it is at this age that many seek contraception.”
Combined oral contraceptives are associated with an elevated likelihood of VTE, with users having a three- to seven-fold elevated likelihood of VTE compared with non-users. In contrast, progestin-only products are not associated with an increased risk of VTE.
The combination of overweight/obesity and use of combined oral contraceptives potentiates the likelihood of blood clots in women of reproductive age. For example, a large population-based study found that overweight and obesity were associated with 1.7-fold and 2.4-fold increased risks of VTE, respectively. However, in combined pill users, the risk of VTE was 12-fold higher in overweight women and 24-fold higher in obese women — when compared with normal weight non-users.
Professor Rosano said: “Obese women taking contraceptives are vulnerable to VTE and should take steps to limit their other predisposing factors for cardiovascular disease, for example by quitting smoking and increasing their physical activity levels.”
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Materials provided by European Society of Cardiology. Note: Content may be edited for style and length.

Published8 hours agoSharecloseShare pageCopy linkAbout sharingPakistani health officials are warning of a looming health crisis in the country after devastating recent floods.Thirty-three million people have been affected by the flooding, which has left nearly 1,500 dead since the middle of June. As rescue and evacuation efforts continue in parts of the country, health experts are reporting a surge in dengue, malaria and severe gastric infections. Many displaced people are living near stagnant water. Dengue fever is already claiming lives and cases are increasing by the day.Image source, ReutersAbout 3,830 cases of dengue fever have been reported by health officials in southern Sindh province, with at least nine deaths, but there are concerns this may be a conservative estimate. “Overall the situation in Sindh is very bad, we are organising medical camps all over the province. Most of the cases we are seeing now are of dengue patients followed closely by malaria,” Dr Abdul Ghafoor Shoro, secretary general of the Pakistan Medical Association, told the BBC.”The dengue burden is the same all over the province and it’s increasing daily. When we checked with the laboratories, the suspected cases are around 80% of tests being done.”Dr Shoro, who has been treating scores of dengue patients at Agha Khan hospital in Karachi, fears the situation is only going to worsen in the coming weeks.It’s been more than two months since the floods began and yet across Pakistan, thousands of villages are still submerged, leaving countless families displaced. With roads in many remote communities still unusable because of water damage, some communities are forced to rely on mobile vans for their health care, but those are few and far between. Muna Sajjad has brought her one-year-old, Sakina, to a mobile clinic near Sehwan in Sindh province, hoping she will finally get medical care. Sakina has been unwell for some days with a gastric infection. Her mother holds her tightly to her chest to try to settle her, but Sakina won’t stop crying – she is dehydrated, vomiting and in pain.”Two of my children are unwell, I don’t have any money to care for them, I lost everything in the floods,” says Muna. “If I had not made it to the clinic, I’m sure Sakina would have died. We have no food to even feed ourselves and our sick children.”Inside the packed van, there are sick children and adults everywhere and not enough hands to care for them. Doctors tell us they are overstretched. IN PICTURES: Pakistan floods: Images show huge scale of devastationON THE GROUND: ‘We spent the whole night running from the flood’WATCH: Bed frames used to pull victims over floodwaters”There are so many people, we are trying our best to get to everyone, but we do not have the capacity to help everyone,” says a senior medic, Khalid Khosa. “We are seeing hundreds of patients a day, but there are many more we cannot serve. It’s not just us that are overwhelmed, it’s like this across the province.” Dr Khosa is also a monitoring officer, looking into the scale of disease in the province. He tells us he is greatly concerned by the picture that is emerging.”We are trying our best, but my biggest fear is that we’re sitting with the makings of a human catastrophe. So many people are getting sick – it’s dengue cases, malaria and gastro problems and we can’t help them all.”So what’s going to happen? Of course there are going to be deaths, and we have to try and save them.” Hundreds of people, including Muna and her young family, have made makeshift tents on a small piece of land in Lalbagh, one of the few places untouched by the water. But even here, the impact is being felt.The ground may be dry, but there is no food or clean drinking water. It’s a situation growing more desperate by the day.UN Secretary-General Antonio Guterres expressed concern about the situation during his visit to flooded areas last week, where he met families now left with nothing. He has described the world’s responsibility to helping Pakistan as a matter of justice, not generosity, but how would he get richer countries to listen, I asked him. Mr Guterres urged rich nations to help poor countries such as Pakistan to recover from tragedy. “We need a world in which peace and security can only be guaranteed if you reduce inequalities,” he told me.This video can not be playedTo play this video you need to enable JavaScript in your browser.”Pakistan is not responsible for this crisis, this was a product of climate change, this was caused by those that are populating the atmosphere with greenhouse gases. The G20, the biggest economies in the world, they represent 80% of the emissions, Pakistan less than 1%.”Officials now say it may take months before the water recedes in Sindh and life can resume. But many people here, like Muna, do not have that kind of time. She and others whom I’ve met in the last few weeks have had their lives destroyed – and it is becoming painfully clear that there will be no quick remedies to help flood survivors. It’s a desperate place to be. People in Pakistan are hoping the world hears of their anguish – and that those with the power to help them rebuild their lives will do so soon. More on this storyPakistan floods: Images show huge scale of devastation31 August’We spent the whole night running from the flood’3 September’The water came and now everything is gone’31 AugustPakistan floods are monsoon on steroids – UN30 August

Imagine you have 20 new compounds that have shown some effectiveness in treating a disease like tuberculosis (TB), which affects 10 million people worldwide and kills 1.5 million each year. For effective treatment, patients will need to take a combination of three or four drugs for months or even years because the TB bacteria behave differently in different environments in cells — and in some cases evolve to become drug-resistant. Twenty compounds in three- and four-drug combinations offer nearly 6,000 possible combinations. How do you decide which drugs to test together?
In a recent study, published in the September issue of Cell Reports Medicine, researchers from Tufts University used data from large studies that contained laboratory measurements of two-drug combinations of 12 anti-tuberculosis drugs. Using mathematical models, the team discovered a set of rules that drug pairs need to satisfy to be potentially good treatments as part of three- and four-drug cocktails.
The use of drug pairs rather than three- and four- drug combination measurement cuts down significantly on the amount of testing that needs to be done before moving a drug combination into further study.
“Using the design rules we’ve established and tested, we can substitute one drug pair for another drug pair and know with a high degree of confidence that the drug pair should work in concert with the other drug pair to kill the TB bacteria in the rodent model,” says Bree Aldridge, associate professor of molecular biology and microbiology at Tufts University School of Medicine and of biomedical engineering at the School of Engineering, and an immunology and molecular microbiology program faculty member at the Graduate School of Biomedical Sciences. “The selection process we developed is both more streamlined and more accurate in predicting success than prior processes, which necessarily considered fewer combinations.”
The lab of Aldridge, who is corresponding author on the paper and also associate director of Tufts Stuart B. Levy Center for Integrated Management of Antimicrobial Resistance, previously developed and uses DiaMOND, or diagonal measurement of n-way drug interactions, a method to systemically study pairwise and high-order drug combination interactions to identify shorter, more efficient treatment regimens for TB and potentially other bacterial infections. With the design rules established in this new study, researchers believe they can increase the speed at which scientists determine which drug combinations will most effectively treat tuberculosis, the second leading infectious killer in the world.
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High levels of mucosal antibodies in the airways reduce the risk of being infected by omicron, but many do not receive detectable antibodies in the airways despite three doses of the SARS-CoV-2 vaccine. These are the findings of a study published today in The New England Journal of Medicine, led by researchers at Karolinska Institutet and Danderyd Hospital in Sweden.
The COMMUNITY study enrolled 2,149 health care workers in the spring of 2020 at Danderyd Hospital, Sweden. Study participants and their immune responses against the coronavirus SARS-CoV-2 are since then followed up every four months. A sub-study between January and February 2022 screened 338 triple-vaccinated healthcare workers for SARS-CoV-2 infection. Antibody levels in blood and airways were determined at the start of the screening period, and one in six (57 participants) was subsequently infected with omicron during the four-week screening period. This allowed the research group to investigate immunity against omicron breakthrough infection as well as immune boosting following breakthrough infection.
The levels of mucosal IgA antibodies (immunoglobulin A) were measured in the airways because they play an important role in the protection against respiratory infections. All participants had high levels of systemic antibodies (e.g. in the blood) after three doses of the vaccine, but only 62 per cent had detectable mucosal airway antibodies (e.g in the nose). High levels of mucosal airway antibodies more than halved the risk of becoming infected with omicron.
“It is not surprising that antibodies in the respiratory tract neutralise the virus locally, but these findings show, for the first time, that SARS-CoV-2 mucosal antibodies in the airways actually protect against omicron infection,” says lead author Charlotte Thålin, M.D. and associate professor at the Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet.
High mucosal antibodies in the airways were also associated with a lower viral replication among those infected with omicron. After omicron infection, a 40-fold increase in mucosal airway antibodies was found in the majority of participants, even if the infection had been mild.
The researchers also showed that participants with SARS-CoV-2 infection prior to vaccination had significantly higher levels of mucosal airway antibodies after vaccination compared with triple-vaccinated with no prior SARS-CoV-2 infection. This may explain why so-called hybrid immunity, the combination of infection and vaccine, provides stronger protection against infection than just vaccines.
“We are now in a situation with omicron infecting people despite having received several doses of today’s intramuscular vaccines,” says Charlotte Thålin. “It is tempting to think that a vaccine administered through the nose or mouth, where SARS-CoV-2 enters the body, could provoke a local immune response preventing infection at an earlier stage. Several vaccines in the form of a nasal spray are now being investigated in clinical trials with the hope of being able to reduce the spread of infection and thus reduce the risk of developing new virus variants.”
The COMMUNITY study continues with regular samplings from blood and mucosa, monitoring immune responses after repeated SARS-CoV-2 infections and vaccinations. The study is conducted in close collaboration between Danderyd Hospital, Karolinska Institutet, Uppsala University, the Public Health Agency of Sweden, KTH Royal Institute of Technology, and SciLifeLab.
The research has been funded by the Jonas and Christina af Jochnick Foundation, Region Stockholm, the Knut and Alice Wallenberg Foundation, Leif Lundblad and family, the Swedish Research Council, the Swedish Heart-Lung Foundation, the Bill and Melinda Gates Foundation, Karolinska Institutet and SciLifeLab.
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A combination of seven healthy lifestyle habits including sleeping seven to nine hours daily, exercising regularly and having frequent social contact was associated with a lower risk of dementia in people with type 2 diabetes, according to a study published in the September 14, 2022, online issue of Neurology®, the medical journal of the American Academy of Neurology.
“Type 2 diabetes is a worldwide epidemic that affects one in 10 adults, and having diabetes is known to increase a person’s risk of developing dementia,” said study author Yingli Lu, MD, PhD, of Shanghai Jiao Tong University School of Medicine in China. “We investigated whether a broad combination of healthy lifestyle habits could offset that dementia risk and found that people with diabetes who incorporated seven healthy lifestyle habits into their lives had a lower risk of dementia than people with diabetes who did not lead healthy lives.”
For the study, researchers looked at a health care database in the United Kingdom and identified 167,946 people 60 or older with and without diabetes who did not have dementia at the start of the study. Participants completed health questionnaires, provided physical measurements and gave blood samples.
For each participant, researchers calculated a healthy lifestyle score of zero to seven, with one point for each of seven healthy habits. Habits included no current smoking, moderate alcohol consumption of up to one drink a day for women and up to two a day for men, regular weekly physical activity of at least 2.5 hours of moderate exercise or 75 minutes of vigorous exercise, and seven to nine hours of sleep daily. Another factor was a healthy diet including more fruits, vegetables, whole grains and fish and fewer refined grains, processed and unprocessed meats. The final habits were being less sedentary, which was defined as watching television less than four hours a day, and frequent social contact, which was defined as living with others, gathering with friends or family at least once a month and participating in social activities at least once a week or more often.
Researchers followed participants for an average of 12 years. During that time, 4,351 people developed dementia. A total of 4% of the people followed only zero to two of the healthy habits, 11% followed three, 22% followed four, 30% followed five, 24% followed six and 9% followed all seven.
People with diabetes who followed two or fewer of the seven healthy habits were four times more likely to develop dementia than people without diabetes who followed all seven healthy habits. People with diabetes who followed all of the habits were 74% more likely to develop dementia than those without diabetes who followed all the habits.
For people with diabetes who followed all the habits, there were 21 cases of dementia for 7,474 person years or 0.28%. Person-years represent both the number of people in the study and the amount of time each person spends in the study. For people with diabetes who followed only two or fewer habits, there were 72 cases of dementia for 10,380 person years or 0.69%. After adjusting for factors like age, education and ethnicity, people who followed all the habits had a 54% lower risk of dementia than those who followed two or fewer. Each additional healthy habit people followed was associated with an 11% decreased risk of dementia. The association between healthy lifestyle score and dementia risk was not affected by medications people took or how well they controlled their blood sugar.
“Our research shows that for people with type 2 diabetes, the risk of dementia may be greatly reduced by living a healthier lifestyle,” Lu said. “Doctors and other medical professionals who treat people with diabetes should consider recommending lifestyle changes to their patients. Such changes may not only improve overall health, but also contribute to prevention or delayed onset of dementia in people with diabetes.”
A limitation of the study was that people reported on their lifestyle habits and may not have remembered all details accurately. Lifestyle changes over time were also not captured.
The study was funded by the National Natural Science Foundation of China, Shanghai Ninth People’s Hospital of Shanghai Jiao Tong University School of Medicine and other funders.
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Materials provided by American Academy of Neurology. Note: Content may be edited for style and length.