Publisher Health

According to a new study, thawing of permafrost due to climate change could expose the Arctic population to much greater concentrations of the invisible, lung cancer-causing gas Radon.
Professor Paul Glover from the University of Leeds and his co-author suggest that permafrost has historically acted as a protective barrier, blocking radon from travelling to the surface and entering buildings there.
Radon is an invisible, odourless, naturally occurring radioactive gas. It causes approximately one in 10 lung cancer deaths and affects smokers much more than non-smokers. It causes higher death rates in sub-Arctic communities due to the prevalence of smoking.
Their study, published today in the AGU journal Earth’s Future, modelled radon production, its flow through soil, permafrost and model buildings — including those with sub-surface and surface basements and those built, more traditionally, on piles.
They show that in buildings with basements, the presence of radon gas can increase to more than 100 times its initial value for up to seven years, depending on the depth of the permafrost and how fast the permafrost thaws.
This demonstrates the importance of not only keeping the permafrost layer intact by limiting global warming, but also has significant implications for health provision, building codes and ventilation advice.

Many factors go into the success of surgery. A new analysis suggests that women may do better with female surgeons.There are many important issues to consider before going into surgery: your overall health and the necessity of the operation, the complexity of the surgery, how experienced the surgeon is, the quality of the hospital and its reputation for good follow-up care.But does it matter if your surgeon is a man or a woman? It might. A new study suggests that overall, female surgeons may get better results, and that choosing a female surgeon may be especially beneficial if you are a woman.For the study, an international team of scientists studied records of 559,903 men and 760,205 women who were operated on by 2,937 surgeons in Ontario, Canada, over a 12-year period. Among the men, roughly 91 percent had male surgeons and 9 percent had female surgeons. Of the women, 88 percent had male surgeons and 12 percent had female surgeons.The female surgeons were, on average, younger, performed fewer surgeries and operated on patients who were generally healthier than those treated by the men. The researchers controlled for these factors, and for patient characteristics such as age, income and whether they lived in a rural or urban area. They also considered whether the surgery was done at a community hospital or a major academic medical center.The study, published in JAMA Surgery, covered 21 common elective and emergency surgeries, including cardiac, orthopedic, urological, head and neck, thoracic, vascular, neurological and plastic surgery. Operations included coronary artery bypass grafting, appendectomy, carpal tunnel release, gastric bypass, spinal surgery, thyroid surgery and knee and hip replacement.Overall, about 15 percent of patients had postoperative problems: 8.7 percent had significant complications within 30 days of the operation; 6.7 percent were readmitted to the hospital; and 1.7 percent died. The researchers found that when the sex of the surgeon and patient were different, the surgery was slightly less successful: There was a roughly 8 percent increase in complications or death, although no difference in readmissions to the hospital. This trend was consistent across different types of surgery and patient characteristics.But the researchers also found that on the whole, women surgeons tended to be more successful than male surgeons. And the worst surgical outcomes occurred when female patients were treated by male surgeons. Compared with a female patient treated by a female surgeon, a woman treated by a male surgeon was about 15 percent more likely to have complications, be readmitted to the hospital or die within 30 days of the operation.The authors acknowledge that the study had limitations. It was observational, and the researchers were unable to control for the role of nurses and other operating room staff. In addition, the data excluded robotic operations, which were uncommon in Ontario at the time.Still, Dr. Margaret G. Mueller, a surgeon and associate professor of gynecology at Northwestern University who was not involved in the research, noted the study had a “smart design” and was well controlled, with a large database. “We now have some objective data showing that there are superior outcomes with female surgeons,” she said. “We just don’t know the reasons.”The lead author, Dr. Christopher J.D. Wallis, an assistant professor of urology at the University of Toronto, said that there was no reason to believe that there is any difference in technical skills between male and female surgeons. Rather, he suggested, the problem may lie in part in differing styles of communication and the ways that doctors talk to male and female patients.The second author on the study, Dr. Angela Jerath, an associate professor of anesthesiology at the University of Toronto, said that when she is working as an anesthesiologist with a woman surgeon, the atmosphere in the operating room tends to be different, more collegial, which may foster better communication and improve teamwork.“Female surgeons ask me more questions,” she said. “Maybe women are more collaborative. Maybe they are more detail oriented. Maybe they are more meticulous. We can’t answer these questions with our data.”Dr. Wallis said that after the surgery, too, doctors may treat men and women patients differently.“We know that women’s pain is not given as much credence as men’s pain,” he said. “In postoperative care, this can be complex. To some degree, pain is an expected outcome of surgery, but it can also suggest an early sign of a complication. Doctors must be able to read the symptoms and at the same time have a demeanor that welcomes patients to present information in a way that we can head off problems before they happen.”It is not only in surgery that the sex of the doctor and patient can make a difference. There are many studies, Dr. Wallis said, demonstrating that in various specialties higher death rates occur when male doctors treat female patients. As one example, he mentioned a 2018 study that found higher mortality among female heart attack patients treated by male physicians.Dr. Jerath had some advice for her colleagues. “I’d like surgeons to be able to take a step back,” she said. “ Be thoughtful — something is happening here. Let’s look at it and be open to solutions.”

Public health experts agree that school mask mandates should not last forever, but differ on whether the time has come to remove them.As the Omicron surge begins to recede in many regions of the country, the governors of New Jersey, Connecticut and Delaware have announced that they will lift school mask mandates in the coming weeks.But the move to loosen these politically charged restrictions has divided scientists and public health experts. Some cheered the change.“I think it’s entirely appropriate that we start lifting school mask mandates now,” said Joseph Allen, a Harvard University researcher who studies indoor environmental quality, including in schools. “We’re in a much better place than we were before, and it’s time to update our strategies to reflect the moment.”Others noted that the virus was still exacting a significant toll on the country, with cases about as high as during last winter’s peak and more than 2,500 Americans dying each day. Lifting school mask mandates too early could jeopardize the progress that the country has made over the last few weeks, some health experts said.“We’re just starting to get it back under control,” said Seema Lakdawala, a respiratory virus researcher at the University of Pittsburgh, noting that many young children remain unvaccinated. “I don’t think we should be abandoning the interventions we have that are still helpful.”Experts agreed that mask mandates should not last forever and that officials needed to clearly explain what criteria would be used in deciding when to lift them. But there is still debate over what those metrics should be and whether certain places in the country had met them.“I think we’re moving to a place where it will make complete sense to remove mask mandates,” said Justin Lessler, an epidemiologist at the University of North Carolina at Chapel Hill. “Maybe we’ll be there in two to three weeks. Personally, I would like to see people wait until cases are low rather than anticipating that they will be low at some future date.”School mask mandates have been among the most contentious public health measures implemented in response to the pandemic. Opponents of mask mandates have often pointed to the lack of randomized, controlled trials on the effects of masking in schools and have highlighted flaws with specific studies that have documented benefits of masking.They have noted, for instance, that schools that require universal masking may differ in many ways from those that don’t, and that in a world brimming with confounding factors, it is difficult to conclusively prove that mask-wearing reduces viral transmission in schools.But a growing body of evidence — from laboratory experiments to real world studies conducted around the world — suggests that masking provides benefits in a variety of settings, including schools, scientists agreed.Today’s 3 Key Reads About Covid1. How Americans Feel: The U.S. public is frustrated with the pandemic. A wave of new polls shows how much.2. J&J Vaccine: The company quietly paused vaccine production despite a persistent need in much of the developing world.3. Canada’s Trucker Protests: Demonstrations against vaccine mandates have turned into an occupation of Ottawa. Here’s the latest.“You can pick apart any one study,” said Linsey Marr, an aerosol scientist at Virginia Tech. But, she noted, “there’s overwhelming evidence that masking has a beneficial and small effect on reducing transmission in schools.” (Although the effect is small on average, individual students and teachers can gain more personal protection by wearing high-quality, well-fitting masks, she noted.)A growing body of evidence, from lab experiments to real world studies, suggests that masking provides benefits in a variety of settings, including schools.Sarah Blesener for The New York TimesEven the experts who believe that it is time to lift school mask mandates said that such policies have been an important strategy at certain phases of the pandemic. But, they note, the country is no longer in the same position it was in 2020 during the first waves of the pandemic in the United States.Vaccines are now widely available for all adults and for children 5 or older. And although Omicron can evade some of the body’s immune defenses, making breakthrough cases more likely, the vaccines continue to provide protection against hospitalization and death.In communities where vaccination rates are high and the Omicron wave is receding, it makes sense for officials to begin thinking about lifting mask mandates, including in schools, some scientists said.“Once you don’t have a lot of virus, and you have a highly vaccinated community, you move from masking required to masking optional,” said Dr. Carlos del Rio, an infectious disease specialist at Emory University.Dr. del Rio recommended that communities also pay close attention to local hospitalization rates and capacity when making decisions about masking policies. If local hospitalization rates are below 10 new Covid admissions per 100,000 residents per day and I.C.U.s are less than 80 percent full, it makes sense to remove mask mandates, he said.Dr. Allen, the Harvard researcher, noted that hospitalization rates, which were already low for children, have fallen in the Northeast, with 0.4 admissions per 100,000, according to data from the Centers for Disease Control and Prevention. That is lower than the hospitalization rate for vaccinated adults, who are now typically able to dine out mask-free.“But for kids with the same risk, even unvaccinated kids with the same risk, we’re keeping more strict policies in place,” he said.Keeping mask mandates in place beyond when they are necessary risks undermining the public’s trust in health officials, Dr. Allen said. In the event of future surges, officials may need to renew school mask mandates, but they should lift them when conditions are better, he said.“Kids can tolerate this, and when it’s necessary to do so, it’s fine for them to mask,” Dr. Allen said. “But we shouldn’t do it for one second longer than necessary.”Ideally, local officials should be prepared to lift and reimpose school mask mandates as conditions change, experts said.Zoe McLaren, a health policy expert at the School of Public Policy at the University of Maryland, Baltimore County, recommended that school officials do regular surveillance testing to monitor whether the virus is prevalent within the school population — and be prepared to adjust their mask policies accordingly.“If schools are well-ventilated and there’s low transmission in the schools, then they’ll have few cases,” she said. “Then lifting a mask mandate in that school would make more sense.”But officials tend to be reluctant to make these kinds of frequent shifts, she noted.States that lift school mask mandates now may find it difficult to reimpose them in the future, said Julia Raifman, a health policy expert at Boston University who leads the Covid-19 U.S. State Policy database.The Coronavirus Pandemic: Key Things to KnowCard 1 of 4Mask mandates ending.

For some couples on the brink of divorce, taking the illegal psychedelic drug was a last resort — but it ended up being the only thing that worked.After 10 years of marriage, Ree, 42, and her husband were ready to call it quits. Even their therapist had given up, she said, in part because her husband “was so closed off, just unable to open up.”“We loved each other a lot and we were very compatible, however, we didn’t know how to deal with conflict,” Ree said. She was often anxious about their relationship and could be “a little neurotic at times,” but the more she pushed her husband to connect, the more withdrawn he became. Their sex life suffered.Then a friend suggested that they try the illegal drug MDMA, popularly known as Ecstasy or Molly.For Ree — who, along with her husband, requested anonymity to speak about drug use, and is referred to by a nickname — the answer was an “immediate no.” MDMA, long associated with rave culture, is currently categorized as a Schedule I drug — meaning it has a high potential for abuse and no accepted medical use in the United States.“We are about as strait-laced as you can come,” she said. “We’re not people who break laws or do drugs.”Six months later, after reading “How to Change Your Mind,” the best-selling book by Michael Pollan that details his transformative experience with psychedelics, Ree reconsidered. And that’s how they found themselves in a secluded area of Utah at a large, rented house with a beautiful view of the mountains to trip on MDMA with five other couples.“We literally said on the drive to this house, ‘If this doesn’t work, we’re done,’” Ree said.In recent years, clinical trials have shown that MDMA, when combined with talk therapy, can bring relief to those suffering from post-traumatic stress disorder, a finding that has elevated MDMA’s reputation from party drug to potential therapeutic. Some couples, drawn to the drug’s ability to produce feelings of empathy, trust and compassion, have started using unregulated MDMA on their own in an effort to help them reconnect, improve communication and have better sex.But experts warn that MDMA, an amphetamine derivative, can have serious side effects. And although MDMA is known for enhancing empathy, there is very little research on couples who use it together, which makes it difficult to know how beneficial or long-lasting its effects are or in what instances the drug might be effective for people having relationship difficulties.A ‘truth serum’ that lowers defensesBefore MDMA was banned in the United States in 1985, the psychiatrist Dr. George Greer conducted over 100 therapeutic MDMA sessions with 80 people and was an author on an informal, observational study featuring 29 of them.The participants didn’t volunteer with the intention of trying to heal a relationship, Dr. Greer said, but interestingly, every subject except one reported improved communication in their relationships after the MDMA session, either with a partner or someone else in their life.Now that MDMA is illegal, some providers resort to clandestine MDMA therapy sessions, at times with disastrous results. A recent essay in Slate detailed one man’s harrowing experience after an underground psychedelic coach gave him methamphetamine “cut with a bit of MDMA” instead of the pure MDMA he was expecting during a guided session in 2019.It is also risky for people to use MDMA on their own, experts warn.“This can include everything from a ‘bad trip,’ to reckless behavior to psychiatric symptoms like panic attacks or physical effects like hypertension or interactions with other medications,” said Dr. Smita Das, the chairwoman of the Council on Addiction Psychiatry at the American Psychiatric Association.Typical side effects of MDMA use include involuntary jaw clenching, nausea, racing heart and hot flashes or chills. And prolonged use can damage nerve cells in the brain that contain serotonin, a chemical that relays messages and helps regulate mood, sleep, pain, appetite and more.“There is more to taking MDMA than making sure the compound is pure,” said Rachel Yehuda, the director of the Center for Psychedelic Psychotherapy and Trauma Research at the Icahn School of Medicine at Mount Sinai. Some mental health providers are looking for ways to help patients without breaking the law. Last year the company Fluence, an organization that trains therapists to legally integrate psychedelics into their practice, taught more than 300 clinicians how to support clients using illegal psychedelics on their own, said Elizabeth Nielson, a psychologist and one of the company’s founders.Fluence tells therapists not to advise their clients on how to obtain an illegal drug or how to use it. But they can discuss why their clients want the drug, what they expect will happen when using it and how to reduce harm. Then they can work with clients after they take the drug to process their experience.Jayne Gumpel, a lead trainer at Fluence and a couples therapist who sees clients in Woodstock, N.Y. and New York City, said the public’s interest in psychedelics “is exploding.” Oregon, Washington, D.C. and a half-dozen municipalities have decriminalized psilocybin, and hundreds of ketamine clinics are popping up in the United States. To stay current, therapists need to have an understanding of these and other psychedelics, including MDMA, Ms. Gumpel added.Most of her couples who have tried MDMA say it deepens their connection, she said. But a few have had sought her help after having had “really challenging and difficult experiences,” because of tainted MDMA or unprofessional (and in some cases, nonexistent) guidance, she added. Charley Wininger, a psychotherapist in Brooklyn, N.Y., and the author of “Listening to Ecstasy: The Transformative Power of MDMA,” warned that the drug can serve as a “truth serum.”“What if a partner confesses an affair?” asked Mr. Wininger, who has often worked with couples that use MDMA on their own. Without a trained therapist present, he said, they may not have the tools to process the experience in a constructive way.Since the publication of his book, Mr. Wininger said couples interested in MDMA have “been coming out of the woodwork, seeking my assistance from all over the place.”During their first trip on MDMA, Ree said she and her husband tearfully discussed things they had trouble speaking about for the last decade: How his emotional withdrawal had affected her self-esteem, and how sorry she was that she had continually pushed him to open up without understanding the pain he held inside.“My husband started sharing with me for the first time all these thoughts and emotions,” Ree said. “It was him without the walls,” she added.They also cuddled in bed for hours, skin to skin, describing all the things they loved about one another.“For a person who has always had body image issues, to allow him to touch me — touch my stomach, the part of me I don’t love, was incredibly healing,” she said.They continued using MDMA about twice a year to help them have difficult conversations, and each kept a list of topics that they would discuss while tripping. Ree said they both started seeing therapists.Now, about three years after they first tried MDMA, the blend of therapy and MDMA has improved their relationship and sex life, she added, and they no longer need the drug to speak openly with one another.Where does MDMA go from here?Depending on the outcome of a Phase 3 trial currently underway, the Food and Drug Administration could approve MDMA for therapeutic use in people with PTSD as early as the end of next year. But few studies have examined how effective the drug might be for couples.A qualitative study published in January described how eight couples used MDMA privately to enhance their relationships, but to date there is only one published study in which couples received MDMA-assisted therapy in a clinical setting.In the study, which was conducted in Charleston, S.C., and included only six couples, at least one member of each pairing was required to have a PTSD diagnosis.The participants without PTSD also took the drug.By the end, five of the six people with PTSD no longer had symptoms and showed improvements in relationship satisfaction, the authors wrote.Anne Wagner, a clinical psychologist in Toronto and one of the lead researchers of the study, said she is now seeking approval for a clinical trial with as many as 60 couples. As with the pilot study, at least one member of each couple will need to have PTSD.When taking MDMA, “both people need to be prepared to actually dig in and communicate with each other, and not perceive it as ‘Oh, this is going to be a thing that fixes our relationship,’” Dr. Wagner said.Samuel, 33, and his wife, Chris, 29, (who asked that they be referred to by middle names when speaking about drug use) live in North Carolina and turned to MDMA because all of their conversations about starting a family had ended the same way: She wanted a baby and he did not.“There was this awful period of about two and a half months,” Samuel said, where “we would sometimes just look at each other and start crying.”Years earlier a friend had given Samuel some MDMA, explaining that he and his wife took it twice a year to strengthen their marriage. Samuel now suggested that they try it. Chris was hesitant, but after months learning about the drug, they decided to take it on New Year’s Eve 2020.Chris quickly felt nauseous. Samuel’s palms became sweaty, and Chris couldn’t stop laughing whenever she looked at them. But eventually, they started talking, and didn’t stop until hours later.“I was able to daydream about how cool it would be to have a kid,” he said. “It feels like everything that you’ve ever cared about or held onto that was getting stuck in your throat or making you anxious, just melts.”Then he began to realize that he had equated having a child with giving up everything that was important to him.They tried MDMA again months later, and then once more after that, Samuel purchasing it on the dark web and testing the crystals with a home kit to ensure they hadn’t been tainted with other substances, like methamphetamine.But MDMA alone didn’t solve their problems, he said. They committed to regular meditation and reflected on their experience in journals to figure out how to “bring that state of mind into our day-to-day-sober life, and be more present,” Samuel said.Chris said she and Samuel felt more empathy and understanding toward one another, and their conversations about having a baby were no longer so tense.Then, in late 2021, Chris unexpectedly got pregnant.“We were not actively and intentionally trying to start a family, but, on the other hand, for once I was not being as careful as I could have been,” Samuel said. “We kind of let it happen.”“I am still scared,” he added. “What is different now is that I’m more willing to be vulnerable and vocal about my needs.”

An FDA-approved drug that has been in clinical use for more than 70 years may protect against lung injury and the risk of blood clots in severe COVID-19 and other disorders that cause immune-mediated damage to the lungs, according to a preclinical study from researchers at Weill Cornell Medicine and Cold Spring Harbor Laboratory.
The researchers, whose report appears Feb. 8 in JCI Insight, found that the drug disulfiram protected rodents from immune-mediated lung injury in two separate models of this type of injury: infection with the SARS-CoV-2 coronavirus that causes COVID-19, and a lung failure syndrome called TRALI that in rare cases occurs after blood transfusion.
“As we learn more about the underlying biology of these lung injuries, we may be able to specifically target the processes that are damaging the lung tissue,” said senior co-author Dr. Robert Schwartz, an associate professor of medicine in the Division of Gastroenterology and Hepatology at Weill Cornell Medicine and a hepatologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.
Both types of lung injury are now known to be driven in part by immune cells’ formation of web-like structures called neutrophil extracellular traps, or NETs. These can trap and kill infectious organisms, but can also be harmful to lung tissue and blood vessels, causing the accumulation of fluid in the lungs (edema) and promoting the development of blood clots. Disulfiram blocks one of the steps in NETs formation.
The study was a collaboration between Dr. Schwartz’s research group and a group led by Dr. Mikala Egeblad, professor and cancer center co-leader at Cold Spring Harbor Laboratory.
Serendipity has attached to disulfiram almost from the start of its history as a medicine. The compound was originally used in the production of rubber, and was later investigated as an anti-parasite treatment. Incidental observations that people taking it became mildly sick whenever they drank alcohol led to its FDA approval in 1951 as a deterrent to alcohol consumption for people with alcohol use disorder.

A young adult in the U.S. could add more than a decade to their life expectancy by changing their diet from a typical Western diet to an optimized diet that includes more legumes, whole grains and nuts, and less red and processed meat, according to a new study publishing Feb. 8 in PLOS Medicine by Lars Fadnes of the University of Bergen, Norway, and colleagues. For older people, the anticipated gains to life expectancy from such dietary changes would be smaller but still substantial.
Food is fundamental for health and, globally, dietary risk factors are estimated to lead to 11 million deaths and 255 million disability-adjusted life-years annually. In the new study, researchers used existing meta-analyses and data from the Global Burden of Diseases study to build a model that enables the instant estimation of the effect on life expectancy (LE) of a range of dietary changes. The model is also now available as a publicly available online tool called the Food4HealthyLife calculator (https://food4healthylife.org/).
For young adults in the United States, the model estimates that a sustained change from a typical Western diet to the optimal diet beginning at age 20 would increase LE by more than a decade for women (10.7 [uncertainty interval 5.9-14.1] years) and men (13.0 [6.9-17.3] years). The largest gains in years of LE would be made by eating more legumes (females: 2.2 [1.0-3.4]; males: 2.5 [1.1-3.9]), more whole grains (females: 2.0 [0.7-3.3]; males: 2.3 [0.8-3.8]), and more nuts (females: 1.7 [0.8-2.7]; males: 2.0 [1.0-3.0]), less red meat (females: 1.6 [0.7-2.5]; males: 1.9 [0.8-3.0]) and less processed meat (females: 1.6 [0.7-2.5]; males: 1.9 [0.8-3.0]). Changing from a typical diet to the optimized diet at age 60 years could still increase LE by 8.0 (4.8-11.2) years for women and 8.8 (5.2-12.5) years for men, and 80-year-olds could gain 3.4 years (females: 2.1-4.7 and males: 2.1-4.8) from such dietary changes.
“Understanding the relative health potential of different food groups could enable people to make feasible and significant health gains,” the authors say. “The Food4HealthyLife calculator could be a useful tool for clinicians, policy makers, and lay-people to understand the health impact of dietary choices.”
Fadnes adds, “Research until now have shown health benefits associated with separate food group or specific diet patterns but given limited information on the health impact of other diet changes. Our modeling methodology has bridged this gap.”
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New research in mice for the first time draws a definitive causal connection between changes in the gut microbiome to behavioral and cognitive changes in an animal model of Alzheimer’s disease.
The study, published today in the journal Frontiers in Behavioral Neuroscience, suggests new avenues involving the use of probiotics to treat and potentially forestall symptoms of dementia associated with neurodegenerative diseases including Alzheimer’s.
The research was led by scientists at Oregon Health & Science University.
“We found that modulating the gut microbiome by fecal implants in germ-free mice induces behavioral and cognitive changes in an Alzheimer’s disease model,” said senior author Jacob Raber, Ph.D., professor of behavioral neuroscience in the OHSU School of Medicine. “To the best of my knowledge, no one has shown that before in an Alzheimer’s disease model.”
The work follows on a previous OHSU study in mice, published last year, that revealed a correlation between the composition of the gut microbiome and the behavioral and cognitive performance of mice carrying genes associated with Alzheimer’s.
In the new study, researchers carefully manipulated the digestive tract of mice using fecal implants.
They found changes in measures of behavior and cognition among three different genotypes and between males and females. Two of the genotypes involved mirror those associated with a predisposition to Alzheimer’s in people.
Researchers found that changes in the gut microbiome clearly affected behavioral and cognitive changes measured in mice.
The study suggests possible avenues for forestalling dementia through targeted use of probiotics or fecal transplants, which already have been used to manipulate the gut microbiome in people. However, Raber said much more research needs to be conducted to ascertain the mechanism of these behavioral and cognitive effects, because the relationship between these effects and gut microbiome is influenced by genotype and sex.
“People can buy probiotics over the counter, but we want to make sure the right treatment is being used for each patient, and that it actually benefits them,” Raber said. “The gut microbiome is a complex environment. If you change one element, you’ll also change other elements, so you want to make sure to select a probiotic that promotes brain health and brain function for each patient, while limiting any negative side effects.”
The research was supported by the National Institutes of Health, awards R56 AG057495-01, RF1 AG059088, R21 AG065914, T32 AG055378, T32 ES007060, and the Collins Medical Trust.
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New research from the University of Georgia has shown, for the first time, that compounds used to fight fungal diseases in plants are causing resistance to antifungal medications used to treat people.
The study focused on Aspergillus fumigatus, the fungus that causes aspergillosis, a disease that causes life-threatening infections in 300,000 people globally each year. Published in G3: Genes, Genomes, Genetics, the study linked agricultural use of azoles — compounds used to fight fungal diseases in plants — to diminished effectiveness of the clinical azoles used to treat fungal infections in patients.
“Our results show that resistance to the compounds used to combat fungal infections in humans is developing in agricultural environments,” said Marin T. Brewer, a corresponding author of the study and an associate professor of mycology in the College of Agricultural and Environmental Sciences. “The samples that we collected in agricultural settings were resistant to both the azoles used in the environment and the clinical azoles used to treat people.”
Treatment-resistant fungus is widespread in agriculture industry
Fungi can be a menace for both people and plants, causing over 1.5 million human deaths annually and crop losses of 20%.
It’s not unusual to find A. fumigatus in the environment. It’s airborne, and it’s everywhere. Most people breathe it in without problem, but it can cause serious infections in people who have weakened immune systems.

Using data from over 100,000 malignant and non-malignant cells from 15 human brain metastases, UCSF researchers have revealed two functional archetypes of metastatic cells across 7 different types of brain tumors, each containing both immune and non-immune cell types. Their findings, published the February 17 issue of CELL, provide a potential roadmap for metastatic tumor formation that could be used to design therapies to improve the treatment of metastasized patients.
The UCSF researchers, led by first author Hugo Gonzalez, PhD, and senior authors, Jeroen Roose, PhD, and the late Zena Werb, PhD, analyzed metastatic tumor cells (MTCs) and identified eight functional processes expressed by MTCs across seven types of metastatic brain cancer. They found these specialized and complementary processes work together within single cells to shape two recurrent cell archetypes, one inflammatory and other proliferative that co-exist within each metastatic tumor and are both shaped by immune cells.
Brain metastasis is the most common form of brain cancer, occurring nearly ten times more often than cancer which begins in the brain. While treatment options for brain metastases have improved in recent years, there is still much left to understand about metastasis formation.
The team combined high-dimensional single-cell analyses of human brain tissue metastases from the different cancer types and experimental models to identify and understand the recurrent patterns that characterize the process of metastasis formation in patients. They also identified a comparable metastatic niche or microenvironment, and an immunosuppressive stroma enriched with T-cells and metastasis-associated macrophages that seem to play a role in the dynamics of the two archetypes.
“These archetypes co-exist within each metastatic tumor,” said Gonzalez. “For the MTCs that are not proliferating, these cells get reprogrammed to express genes for inflammation, stress, and other changing conditions. It’s likely that these tumor-immune interactions are shaping the state of the MTCs.”
“Zena Werb was the first person that saw the potential and feasibility of collecting human metastases and combining them with cutting-edge technologies such as single-cell transcriptomics and CyTOF,” said Gonzalez. “She believed that by analyzing human brain metastases, we could determine the relationship between these cellular processes orchestrated by MTCs and their specific microenvironments.”
Werb, a well-known researcher in cancer biology, and associate director for basic science at the UCSF Helen Diller Family Comprehensive Cancer Center, transformed the field by highlighting the critical role of cells’ local “neighborhoods” in determining tumor growth and behavior. Over the course of four decades, her work laid the groundwork for the rise of immunotherapy and other modern approaches to cancer treatment. Werb passed away in 2020 at the age of 75, but her legacy lives on with her colleagues, for whom she was a mentor.
“From the beginning, she believed in this project and encouraged me to persevere even when the collection and processing of these rare and small samples were quite difficult,” said Gonzalez. “Zena also helped orchestrate fruitful collaborations with UCSF colleagues Joanna Phillips, MD, PhD, and Matthew Spitzer, PhD, who were critical for this large project.”
Roose added that Gonzalez’s work provided an important foundation for the team’s collaborative efforts with the UCSF Endeavor program, aimed at better understanding how metastases arise when cancer cells interact with host cells that surround the tumor.
Roose has found it extremely rewarding to see Hugo through the home stretch of this brain metastasis project. “I can just see Zena walk into my office, giving us a thumbs up and a big hug,” Roose said.
Funding: This work was supported by grants from the National Cancer Institute (CA057621, CA180039, CA199315, CA190851 and 5U01CA199315-05) and by grants from the NIH/NCI (R01 — CA187318), NIH/NIAID (R01-AI104789 and P01-AI091580), NIH/NHLBI (R01 — HL120724), and the Mark Foundation for Cancer Research (Endeavor). Additional funding information can be viewed in the study’s acknowledgments section.

Channels on the surface of bone cells called osteocytes help build stronger bones in response to mechanical stress, shows a study published today in eLife.
This discovery may help scientists develop new treatments for osteoporosis or other conditions that contribute to bone loss in patients.
Physical activities that exert mechanical stress on the bones stimulate new bone growth. Osteocytes, which make up 90-95% of all bone cells, help detect mechanical stress on the bone. They then regulate the breakdown of weakened bone by cells called osteoclasts and the build-up of new bone by cells called osteoblasts.
“Previous research has shown that mechanical stress on bones increases the number of channels on the surface of osteocytes, called connexin (Cx) 43 hemichannels,” explains first author Dezhi Zhao, a visiting PhD student at the University of Texas Health Science Center at San Antonio, Texas, US. “In this study, we wanted to examine the role that these channels play in responding to mechanical stress on bones.”
To do this, Zhao and the team studied two types of mouse models. In one, the connections between the bone cells, called gap junctions, were impaired but Cx43 hemichannels were strengthened. In the other, both gap junctions and Cx43 hemichannels were impaired. The team then tested what happened to the bone of these mice, as well as typical mice, when exposed to mechanical stress.
They found that a chemical called prostaglandin (PGE2) was produced in both the typical mice and the gap junction-impaired mice in response to mechanical stress, and their bones became stronger. On the other hand, this response was lacking in the Cx43 hemichannel-impaired mice.
To confirm that Cx43 hemichannels are essential to bone strengthening, the team then gave typical mice an antibody that blocks Cx43 hemichannel activity. They found that this also stopped the animals from releasing PGE2 and reduced bone strengthening in response to mechanical stress. But treating the same mice with PGE2 restored the bone-strengthening effects of mechanical stress.
Existing treatments for osteoporosis generally target osteoclasts that break down weakened bone and work by reducing bone turnover. This can inadvertently lead to more brittle bones over time and has been associated with some rare but serious side effects. The current study suggests that targeting Cx43 hemichannels on osteocytes might be an alternative treatment option that uses the body’s own response to mechanical stress.
“Our work highlights Cx43 hemichannels as a potential new target for medications to treat osteoporosis and other conditions that cause bone loss,” concludes senior author Jean Jiang, Professor and Zachry Distinguished University Chair, Department of Biochemistry and Structural Biology, UT Health Science Center at San Antonio. “Further studies are needed to verify these findings and explore the potential of drugs that target these channels. If they are one day proven to be safe and effective, such treatments could be particularly helpful for older patients who are less responsive to the bone-strengthening effects of movement.”
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