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SharecloseShare pageCopy linkAbout sharingImage source, Getty ImagesA federal judge in Florida has struck down the Biden administration’s mask mandate for airplanes and other forms of public transit, calling it unlawful. US District Judge Kathryn Kimball Mizelle said the national public health agency had exceeded its legal powers in issuing the mandate. The US transit authority said it would now no longer enforce mask wearing. The US Centers for Disease Control and Prevention (CDC) just last week extended the mandate until 3 May.Judge Mizelle is based in Florida, but federal judges can issue rulings that block nationwide government policies.Her order on Monday effectively removes the masking requirement in all airports, trains, taxis and transit hubs.White House press secretary Jen Psaki called the decision “disappointing” and noted that the CDC still recommends travellers cover their mouths and noses. The CDC did not immediately respond to a request for comment to Monday’s ruling. Last week US Surgeon General Vivek Murthy said the mandate had been extended into May because of rising Covid-19 cases. The lawsuit was first brought in July 2021 by the conservative group Health Freedom Defense Fund (HFDF) and two Florida residents who said wearing masks increased their anxiety and panic attacks. The plaintiffs argued that the CDC mandate was “arbitrary and capricious” because it gave exemptions to certain groups – like children under two years of age – but not to others. In her ruling, Judge Mizelle, who was appointed by former President Donald Trump, found that the CDC had improperly invoked what is known as the “good cause exception”, allowing the agency to skip public notice and comment on the mandate.”Because ‘our system does not permit agencies to act unlawfully even in pursuit of desirable ends,'” Judge Mizelle wrote, invoking another case, “the Court declares unlawful and vacates the Mask Mandate.”Shortly after the legal decision was issued, the Transportation Security Administration – which runs US airport security – confirmed it would no longer enforce the mask mandate. United Airlines, Delta Air Lines, Alaska Airlines and American Airlines said face coverings would no longer be required on domestic flights and certain international flights.Since the CDC first issued a public health order in February 2021 requiring masks for travellers, more than 7,000 unruly passenger incidents have been reported – 70% of them involving masking rules, according to the Federal Aviation Administration.The Biden administration’s Covid-19 mandates have had mixed success in the court system.The Supreme Court in January blocked the White House from enforcing its sweeping vaccine-or-test rule for employees at large private companies.But the Biden administration’s requirement that all federal employees be vaccinated against Covid-19 was upheld on appeal earlier this month.More on this storyTime to remove face mask law – health secretaryWhat difference will lifting face mask laws make?

Studies linked to Cassava Sciences, once a stock market favorite, have been retracted or challenged by medical journals.A small biotech company that trumpeted an exciting new treatment for Alzheimer’s disease is now under fire for irregularities in its research results, after several studies related to its work were retracted or questioned by scientific journals.The company, Cassava Sciences, based in Austin, Texas, announced last summer that its drug, simufilam, improved cognition in Alzheimer’s patients in a small clinical trial, describing it as the first such advance in treatment of the disease. Cassava later initiated a larger trial.The drug’s potential garnered enormous attention from investors. Alzheimer’s disease affects roughly six million Americans, a number that is expected to double by 2050, and an effective treatment would be lucrative. Cassava’s stock soared, by more than 1,500 percent at one point. The company was worth nearly $5 billion last summer.But many scientists have been deeply skeptical of the company’s claims, asserting that Cassava’s studies were flawed, its methods opaque and its results improbable.Families of some trial participants have said they see improvements. But critics noted that the trial reporting better cognition due to simufilam lacked a placebo group, and asserted that the Alzheimer’s patients were not followed long enough to confirm that any improvements in cognition were genuine.Some experts went further, accusing the company of manipulating its scientific results.In response to the allegations, in December The Journal of Neuroscience published “expressions of concern” regarding two brain studies authored by the company’s chief collaborator, Hoau-Yan Wang, a professor at the City University of New York. One was co-written by Lindsay H. Burns, chief scientist at Cassava. The journal editors also noted errors in the images accompanying the latter study.(An “expression of concern” indicates that the editors have reason to question the integrity and accuracy of a paper.)In March, the journal Neurobiology of Aging attached an expression of concern to another publication about Alzheimer’s authored by Dr. Wang and Dr. Burns, among others, that has been key to the company’s treatment hypothesis.The editors “did not find compelling evidence of data manipulation intended to misrepresent the results,” but went on to list a variety of methodological errors. Both journals said they would wait to take further action pending an investigation by Dr. Wang’s employer, CUNY.Dr. Wang did not respond to requests for comment. The university declined to confirm or deny that an investigation was underway.On March 30, another scientific journal, PLoS One, retracted five papers by Dr. Wang after a five-month investigation into “serious concerns about the integrity and reliability of the results,” according to a spokesman for the journal. Two of the papers, co-written by Dr. Burns, were about a brain protein targeted by Cassava’s drug.The New York Times contacted nine prominent experts for comment about the scientific underpinnings of Cassava’s trials. All said they did not trust the company’s methods, results or even the premise underlying the drug’s supposed effectiveness.Dr. Roger Nicoll, a neuroscientist at the University of California, San Francisco, said he was particularly angered that Cassava’s work is partly funded by taxpayers. In all, the company has received more than $20 million from the National Institutes of Health.“This drug should not be put into patients. It should never have been. Never,” he added. “The longer this goes on, the more outraged I am.”Remi Barbier, the company’s founder and chief executive, said many of Cassava’s critics were “bad actors” with financial conflicts of interest. He said the allegations of data manipulation were false, and noted that some were publicized by short sellers trying to drive down the company’s stock price.“They have gone, and continue to go, to unreal extremes to halt our progress,” Mr. Barbier wrote in an email. “The effort to besmirch Cassava Sciences appears endless.”Cassava is a newcomer to Alzheimer’s research. Until 2019, it was called Pain Therapeutics, and its product Remoxy — a gel form of the opioid oxycodone that was intended to deter drug abuse — was a favorite among investors.But the Food and Drug Administration repeatedly rejected the drug, and reprimanded the company for promoting Remoxy before approval.According to Cassava, simufilam restores the normal shape and functioning of a protein called filamin A that becomes warped in the brains of people with Alzheimer’s disease, and thereby slows dementia and improves cognition.But Alzheimer’s experts said they knew of no independent studies that supported this hypothesis or would explain the results.“The overall conclusions with regard to Alzheimer’s disease make no sense to me whatsoever,” said Dr. Thomas Südhof, a Nobel laureate and neuroscientist at Stanford.Cassava’s theories “are not in the mainstream of the field, and to me they seem implausible and contrived,” he said.In its papers, Cassava has said that the theory is supported by strong evidence. “But in fact, all the evidence seems to be from this lab,” said Dr. Lawrence Honig, an Alzheimer’s disease expert at Columbia.The criticisms and retractions have dented Cassava’s reputation. This month the company told investors it had enrolled only 60 of the 1,750 participants it needed for its Alzheimer’s trial. As of Monday, the company’s stock was trading at $25 per share, down from a high of $135 last summer.Cassava has indeed been the object of short-selling tactics. In August, two scientists filed a citizen’s petition to the F.D.A., using a law firm that represents whistle blowers and citing “grave concerns about the quality and integrity” of Cassava’s research. Its stock dropped by about 30 percent.Both scientists held a short position in Cassava’s stock and profited from its decline, which undercut the credibility of their petition. Both have since divested themselves of those financial positions.The F.D.A. denied the petition “solely on the grounds that your requests are not the appropriate subject of a citizen petition,” according to its statement.But F.D.A. officials also acknowledged the issues raised, and said its response did not represent “a decision by the agency to take or refrain from taking any action.”A spokeswoman told The Times that “the F.D.A., by policy, does not discuss possible or ongoing investigations.” The scientists, Dr. Geoffrey Pitt of Cornell and Dr. David Bredt, a neuroscientist, declined to comment, as did the lawyer who represented them.The Securities and Exchange Commission is investigating allegations that the company manipulated research results, The Wall Street Journal has reported. The National Institutes of Health is also investigating, Mr. Barbier acknowledged.Cassava said in a securities filing in November that it was cooperating with “certain government agencies” that had asked the company to provide them with corporate information and documents for ongoing investigations.“No government agency has informed us that any wrongdoing has occurred by any party,” the company said.The most striking evidence of simufilam’s effectiveness was said to be an improvement in cognition in two-thirds of patients after taking the drug for a year. Some of the 50 patients had no neurological or psychiatric symptoms at all by that time, the company reported.But this study did not compare the medication to a mock treatment or placebo, other researchers noted. All of the participants in this trial received the drug and were aware of it, and their reported improvement could have been a result of their positive expectations — a so-called placebo effect, which has been particularly strong in Alzheimer’s trials.For a drug to improve cognition scores, it would have to have the “extraordinary effect of actually reversing neurodegeneration,” said Dr. Robert Howard, professor of old age psychiatry and an expert in clinical trial design at University College London.“Generally, in this area, we would regard slowing or stopping of cognitive decline as a win,” he said. To claim that patients are actually improving, on the basis of small numbers, “at the very least is implausible,” he added.Cassava reported that initial analysis of a trial that did include a placebo group showed “highly anomalous” data, so it had the data reanalyzed by an “outside” lab. The company later acknowledged that the second analysis was in fact conducted by its collaborator, Dr. Wang.“If the data is suspect in key papers, and not just minor mistakes, you can’t trust anything,” said George Perry, a neuroscientist at the University of Texas at San Antonio and editor in chief of The Journal of Alzheimer’s Disease, who serves on the boards of companies with other drug candidates. “It’ll have to be independently validated.”Experts also pointed to several methodological oddities in the company’s work. For example, Cassava has pointed to changes in the levels of certain molecules in cerebrospinal fluid, or C.S.F., as evidence of simufilam’s effectiveness.But the levels that the company reported are out of range for the testing method that was used, said Dr. William Hu, an expert on spinal fluid markers at Rutgers who works with a number of companies that develop such assays.One marker of inflammation was much higher than is typically reported for Alzheimer’s disease patients, he added. “There’s a clear discrepancy there for those of us who work with C.S.F. biomarkers,” Dr. Hu said. “That type of discrepancy really raises questions in terms of the rigor as well as the reliability of these results.”Dr. Honig said the company’s reliance on an outdated lab technique called Western blotting, used to detect proteins, was unusual because it does not have “the sensitivity or reproducibility or accuracy” of newer methods.In another set of experiments, Cassava reported data suggesting that its drug was able to restore the shape of most of the filamin A protein in the brain — a dramatic recovery that Dr. Südhof, who consults for drug companies and serves on the board of Sanofi, questioned.“There’s just no possibility, no rational way this could happen,” he said.Elisabeth Bik, a leading expert in image manipulation, became aware of the company last summer after short sellers filed the F.D.A. petition. In a series of twitter posts, posts on her blog and on the website PubPeer, Dr. Bik has pointed to signs that she said show some results had been copied and pasted from other experiments.“Those were of severe concern,” she said in an interview. Based on the pattern of irregularities in images in multiple papers, she believes “it is highly likely that there was some manipulation going on.”Charles Spruck, a cancer researcher at the Sanford Burnham Prebys Medical Discovery Institute in San Diego, who has more than 25 years of experience with the Western blot method, said he believed the anomalies in those images could be the result of simple mistakes or vagaries of the technique.Irregularities or errors in one or two images could be due to chance, but “when you see it again and again, it makes it unlikely that you could do it accidentally,” said Dr. David Vaux, deputy director of scientific integrity and ethics at the Walter and Eliza Hall Institute of Medical Research in Australia.Mr. Barbier dismissed the criticisms, saying that the irregularities did not impact the company’s research findings. “These background pixels have no impact on the data or its interpretation,” he said, adding “We stand by Professor Wang 100 percent.”Dr. Vaux and others bemoaned the limitations of peer review in identifying mistakes or manipulation, and said many scientific journals are reluctant to retract papers because of their fear of being sued, or damage to their own reputations.“It’s time for regulatory bodies to step in, as it seems that the peer review process has taken it as far as it can,” Dr. Hu said. “If the tide has shifted such that the science seems to not be there, I just don’t see how the clinical trials can proceed.”

In the first year of the pandemic, at least four people in Michigan were infected with a version of the coronavirus observed mostly in mink, the Centers for Disease Control and Prevention confirmed on Monday.The cluster, which previously included just three cases, represents the first known instance of possible animal-to-human transmission of the virus in the United States.Two of the infected were employees of a Michigan mink farm that experienced a coronavirus outbreak in October 2020. The other two had no known links to the farm, suggesting that the mink variant may have been circulating more widely among area residents at the time.Samples of the virus collected from all four people contained two mutations that scientists have hypothesized may be signs of adaptation to mink, Dr. Casey Barton Behravesh, who directs the C.D.C.’s One Health Office, said in an email on Monday.The mutations have previously been documented in farmed mink in Europe, as well as in people with connections to those farms.“This, in addition to the mink farm workers testing positive for Covid-19 after the mink herd had begun experiencing illness and increased mortality, suggests that the most likely hypothesis is that the workers were infected after contact with mink on the farm,” Dr. Barton Behravesh said.But that cannot be conclusively proved, she noted.“Because there are few genetic sequences available from the communities around the farm, it is impossible to know for sure whether the mutations came from mink on the farm or were already circulating in the community,” she said.National Geographic first reported the fourth human case, after obtaining government documents about the mink farm outbreak under the Freedom of Information Act.Last year, The Detroit Free Press and the Documenting Covid-19 project reported on the first three cases, which included the two farm workers and a taxidermist who had no known connection to the mink farm, according to emails obtained by the two organizations.On Monday, they reported that the fourth case had been the taxidermist’s wife.In early October 2020, Michigan officials announced that the virus had been detected in mink on a local farm and that several of the animals had died. Upon the state’s request, the C.D.C. deployed a team to help investigate the outbreak.The investigators collected samples from animals and human workers on the farm, as well as people in the surrounding community, Dr. Barton Behravesh said. In March 2021, the C.D.C. updated its website to note that a “small number of people” had contracted a version of the virus that “contained unique mink-related mutations.”“This suggests mink-to-human spread might have occurred,” the agency said, noting that all of the human patients had recovered.But the first human cases, in two workers on the affected mink farm, were identified as early as Nov. 4, months before the agency updated its website, National Geographic reported.“C.D.C. became aware of genetic sequencing data indicating possible mink-to-human transmission in late 2020,” Dr. Barton Behravesh said.The agency then worked with other federal and state officials to analyze that data, she added: “Information was published on the C.D.C. website as soon as it became clear there was possible mink to human spread.”Mink-to-human transmission has also been reported in Denmark, the Netherlands and elsewhere.Overall, transmission of the virus from animals to humans is believed to be rare. Humans are far more likely to spread the virus to one another, or to other species, than they are to catch it from animals, experts say.

A new study finds that a history of infertility is associated with increased risk of heart failure. Published in the Journal of the American College of Cardiology, researchers from Massachusetts General Hospital (MGH) revealed that women who had experienced infertility had a 16% increased risk of heart failure compared with women who did not have an infertility history.
“We are beginning to recognize that a woman’s reproductive history tells a lot about her future risk of heart disease,” says first author Emily Lau, MD, MPH, cardiologist and director of the Menopause, Hormones & Cardiovascular Clinic at MGH. “Whether a woman has difficulty becoming pregnant, what happens during her pregnancies, when she transitions through menopause all influence her risk of heart disease later in life.”
Infertility affects about 1 in 5 US women and includes a spectrum of conception difficulties, but its link with heart failure has not been well-studied until recently. Partnering with the Women’s Health Initiative (WHI), which was designed in the early 1990s and queried a woman’s reproductive history, Lau and colleagues studied postmenopausal women from the WHI and examined whether infertility was associated with development of heart failure.
There are two types of heart failure: heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). Ejection fraction is a measurement related to the volume percentage of blood that is pumped from the left ventricle of the heart during each beat. An ejection fraction less than 50% is commonly viewed as abnormal or reduced.
The team found an association between infertility and overall heart failure, specifically with HFpEF, a form of heart failure that is far more common in women regardless of fertility history. Among the 38,528 postmenopausal women studied, 14% of the participants reported a history of infertility. Over a 15-year follow up period, the researchers noted that infertility was associated with 16% future risk of overall heart failure. When they examined heart failure subtypes, they found that infertility was associated with a 27% increased future risk of HFpEF.
Over the past decade, HFpEF (where the heart muscle does not relax well) as opposed to HFrEF (where the left ventricle does not pump well), has become the dominant form of heart failure in both men and women. But it remains more common in women. “It’s a challenging condition because we still do not completely understand how HFpEF develops and we do not have very good therapies to treat HFpEF,” says Lau.
“I think our findings are particularly noteworthy because heart failure with preserved ejection fraction is more prevalent in women,” says Lau. “We don’t understand why we see HFpEF more in women. Looking back in a woman’s early reproductive life may give us some clues as to why.” Of note, the team observed that the link persisted regardless of whether an individual eventually conceived or had a live birth.
The increased risk was independent of traditional cardiovascular risk factors and other infertility-related conditions. “There has been some suggestion in previous studies that women with infertility do have more cardiometabolic risk factors,” says Lau, but the team did not find that cardiometabolic risk factors explained the link between infertility with heart failure in this study. They also looked to see if other infertility-related conditions like thyroid disease, irregular menses, and early menopause explained the association between infertility and heart failure but did not evidence to support that hypothesis either.
“So it really begs the question: what are the mechanisms driving the association between infertility and heart failure,” says Lau. Is it shared risk factors, or is infertility on the causal pathway? She mentions vascular and endothelial dysfunction may be involved and plans on eventually clarifying the mechanism underlying the link between infertility and heart failure. In the future, Lau hopes to conduct a prospective study of women with an infertility history involving exercise parameters, vascular measures, and more, to solve the mystery.
“We as scientists and doctors are beginning to recognize how important a woman’s reproductive history is for their future risk of heart disease. Infertility is one of many cardiovascular risk factors, such as hypertension and high blood pressure, but reproductive history is not routinely considered as part of the cardiovascular risk assessment,” says Lau. Since people do not tend to develop heart failure until well in their 60s and beyond, and infertility is mostly experienced in the 20s, 30s, and 40s, many physicians are not thinking about the connection. “We cannot change a woman’s history of infertility, but if we know a woman has had a history of infertility, we can be more aggressive about counseling her about other modifiable risk factors including high blood pressure, high cholesterol, smoking, and beyond.”
This research was supported in part by the National Institutes of Health and American Heart Association.

Sodium is an essential micronutrient, but the amount we need is small. Three slices of bread or one teaspoon of table salt will do it, and chances are your daily sodium intake is far greater. More than 90% of Americans consume too much sodium, which can lead to hypertension, high blood pressure, and increased risk of heart disease and stroke.
Most of the excess sodium comes from processed and packaged foods, so the food industry and food scientists continuously look for ways to reduce sodium. A new paper from the University of Illinois provides a comprehensive review of scientific literature on sodium reduction strategies in food production.
“Sodium overconsumption is a huge health concern, and the FDA has recommended sodium reduction in food since the 1980s, but we haven’t succeeded yet. While the unit volume of salt in the food supply has not increased, the amount of sodium consumption has gone up, because we just consume a lot of food,” says Soo-Yeun Lee, professor in the Department of Food Science and Human Nutrition (FSHN) at U of I and co-author on the paper.
We only need around 450 milligrams (mg) of sodium per day, and the recommended maximum amount is 2,300 mg, or 1,500 mg for those at risk for hypertension. But average consumption exceeds 3,000 to 3,500 mg per day — or 50% to 100% above the upper limit. More than 70% of our sodium intake comes from processed and packaged foods, primarily cured meats, bread, cheese, and soups.
The researchers conducted a scoping review including primary studies, literature reviews, book chapters, and patents covering sodium reduction in food products. They focused on studies that included sensory data with human subjects, because palatability is essential for consumer acceptance.
“In this review, we looked at different food systems. The way you would reduce salt in a solid system, like a topical application on snack foods, such as salted peanuts or salted chips, would be very different from embedded application in semi-solid foods like cheese or bread. And in a liquid system like soup, where it is completely dissolved, it would be really different in the way we could reduce salt yet provide the palatability it gives,” Lee states.

Results of a new multicenter study published in the New England Journal of Medicine found that vaccination with a primary series of the Pfizer-BioNTech mRNA COVID-19 vaccine reduced the risk of COVID-19-associated hospitalizations in children ages 5-11 years by two-thirds during the Omicron period. Among adolescents ages 12-18 years who were vaccinated with a primary series of Pfizer-BioNTech vaccine, protection against COVID-19-associated hospitalization during the Omicron period was lower than during the Delta period, similar to what has been previously shown among adults. Levels of protection against critical COVID-19 requiring life-supporting interventions remained high in vaccinated adolescents during both the Delta and the Omicron periods.
“Our study results are reassuring that COVID-19 vaccination in eligible children and adolescents continues to protect against the most severe outcomes associated with COVID-19, regardless of variant type,” said study co-author Bria Coates, MD, critical care physician at Ann & Robert H. Lurie Children’s Hospital of Chicago and Assistant Professor of Pediatrics at Northwestern University Feinberg School of Medicine. “It is difficult to predict whether the vaccine will be as effective against the current subvariant of Omicron, but most likely the level of protection would be similar. Our results reinforce the importance of COVID-19 vaccination, including receiving a booster dose for those ages 12 years and older, to protect against critical illness.”
During the Omicron period (December 19, 2021-February 17, 2022), vaccination reduced the risk of COVID-19-associated hospitalization by 68 percent in children ages 5-11 years. Vaccine effectiveness against any type of COVID-19-associated hospitalization in adolescents ages 12-18 years who received a primary series declined from 92 percent during the Delta (July 1, 2021-December 18, 2021) period to 40 percent during the Omicron period. Protection against COVID-19 requiring life-supporting interventions remained high for adolescents during Delta (96 percent) and Omicron (79 percent).
Due to the low numbers of hospitalized children ages 5-11 years in the study, researchers could not analyze vaccine effectiveness by disease severity for this age group but will continue to monitor as these data are collected. Data in this age group was not available for the Delta period, since younger children were not eligible for the vaccine at that time.
Protection against hospitalization in adolescents during the Delta period remained consistent for more than 6 months after receipt of a primary series. Levels of protection during Omicron, although lower, also stayed consistent over time after completing the primary series.
“This consistency in vaccine effectiveness during each variant suggests that the decline in protection among adolescents between the Delta and Omicron periods might be because the Omicron variant is more likely to escape control by the immune system, rather than waning immunity since vaccination,” said Dr. Coates, who also is the Crown Family Research Scholar in Developmental Biology. “However, more data are needed to answer this question.”
The study was funded by the Centers for Disease Control and Prevention (CDC).
Research at Ann & Robert H. Lurie Children’s Hospital of Chicago is conducted through Stanley Manne Children’s Research Institute. The Manne Research Institute is focused on improving child health, transforming pediatric medicine and ensuring healthier futures through the relentless pursuit of knowledge. Lurie Children’s is ranked as one of the nation’s top children’s hospitals by U.S. News & World Report. It is the pediatric training ground for Northwestern University Feinberg School of Medicine.
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Hydrocephalus, or “water on the brain,” occurs when the cerebral ventricles — four interconnected cavities of the brain that are filled with cerebrospinal fluid — become enlarged, but its cause is unknown in many cases. A better understanding could lead to improved treatments for hydrocephalus, which is the leading reason for brain surgery in children and is associated with neurodevelopmental disability. To provide insights, a team led by investigators at Massachusetts General Hospital (MGH) and Yale University analyzed variations in genetic sequences and gene expression patterns in the brains of patients with congenital hydrocephalus. The research, which is published in Nature Neuroscience, indicates that hydrocephalus does not result from a defect of cerebrospinal fluid “plumbing” but rather arises because primitive cells in the brain do not behave properly during development.
In patients with hydrocephalus, continued accumulation of fluid dilates the cerebral ventricles, increases pressure in the skull, and compresses the surrounding brain structure. This compression can cause acute symptoms such as vomiting and headache, and even coma or even death. In the long-term, brain compression can lead to neurocognitive issues and neurodevelopmental disabilities in children, even when a medical device called a shunt is surgically placed in the brain.
“Neurosurgical shunting of cerebrospinal fluid addresses some consequences of the disease but does not target the underlying mechanisms,” says senior author Kristopher T. Kahle, MD, PhD, director of Pediatric Neurosurgery at MGH and director of the Harvard Center for Hydrocephalus and Neurodevelopmental. “Knowing the molecular cause of disease could be very helpful towards clinical decision making.”
To provide insights, Kahle and his colleagues genetically sequenced cells from 483 children with hydrocephalus and their unaffected parents, using a profiling technology that uncovers gene mutations in patients across the entire genome. By combining the genetic sequence data with gene expression data, the team found that many hydrocephalus-associated genes converge not in fluid circulation components but instead in neuroepithelial cells, which are the earliest stem cells of the brain that arise during the first several weeks of development. These cells go on to generate all of the neurons and support cells of the brain.
“This began to hint to us that rather than affecting fluid circulation, hydrocephalus gene mutations may be disrupting the earliest processes of human brain development to cause hydrocephalus,” says co-lead author Phan Q. Duy, an MD/PhD student at Yale University School of Medicine.
The most frequently mutated gene in the study’s patients — called TRIM71-codes for a protein that is part of a pathway that regulates the timing of stem cell development. When the investigators bred mice to express TRIM71 mutations, the mice developed fetal-onset hydrocephalus similar to human patients. Mechanistically, stem cells in the brains of the Trim71-mutated mice prematurely generated neurons, leading to a deficient pool of stem cells to support brain growth and development. This caused deficient expansion of brain tissue and underdevelopment of the cerebral cortex.
The scientists note that the resulting altered structure of the brain is not capable of holding the pressure exerted by cerebrospinal fluid, and thus the brain deforms and its ventricles passively expand. “The site of pathology is therefore not happening in the fluid itself, but rather the vessel — or the brain tissue — that’s holding the fluid,” says Duy.
The findings suggest that treatment strategies for hydrocephalus should go beyond draining fluid in the brain. “A more nuanced treatment approach may include not only cerebrospinal fluid diversion but also other approaches more tailored towards improving neurodevelopmental function,” says Kahle. “In the long-term, with continued gene discovery and better understanding of how other gene mutations disrupt brain development to cause hydrocephalus, we may be able to develop drug treatments or even gene therapy to correct the gene mutations months before the birth of patients.”
Beyond providing a better understanding hydrocephalus, this work may offer additional insights into other pediatric brain disorders. In fact, ventricular dilation is a common feature in developmental neuropsychiatric diseases such as autism and schizophrenia, and many of the processes involved with hydrocephalus may also be relevant for other structural brain malformations.
This work was supported by the National Institutes of Health, Rudi Schulte Institute, and the Hydrocephalus Association.
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Fighting cancer and chronic disease is tiring work for the immune system. When T cells are engaged in this kind of lengthy battle, they can become exhausted, or unable to function properly. One immunotherapy that revitalizes these cells by blocking an immune checkpoint protein called LAG3 was recently approved by federal regulators. But exactly how LAG3 works has remained a mystery — until now.
Published today in Nature Immunology, a new study pinpoints how LAG3 modulates T cell activity, providing important insights for development of other LAG3-blocking therapies for cancer and autoimmune disorders.
“Although LAG3 has been studied extensively as a potential immunomodulatory target, there hadn’t been an awful lot known about how it works. It truly was a black box,” said co-senior author Dario A.A. Vignali, Ph.D., distinguished professor and vice chair of immunology at the University of Pittsburgh School of Medicine. “I believe this is a landmark study because we finally know how LAG3 works. This will help the development of new LAG3-targeting therapeutics.”
T cells protect the body by eliminating threats such as cancer and infection. Molecules called antigens from cancer cells and pathogens are recognized by T cell receptors, activating these immune cells for battle. But exhausted T cells don’t engage normally with antigen-presenting cells because immune checkpoint proteins slow immune responses like brakes on a car.
Research on two immune checkpoints called PD-1 and CTLA-4 led to development of breakthrough drugs called immune checkpoint inhibitors more than a decade ago. These therapies work by releasing the immune system’s brakes and revving up T cell function.
In March 2022, the U.S. Food and Drug Administration approved the first LAG3 inhibitor for advanced melanoma, and 18 other LAG3-inhibitiors are in clinical trials — despite murkiness around how this checkpoint inhibits T cell function.

An analysis of more than 70,000 fossils indicates that mollusk communities were incredibly resilient to major climatic shifts during the last ice age.
Scientists from the Florida Museum of Natural History and several European research institutions tracked the history of Adriatic ecosystems through two warm periods that bookend the most recent glacial expansion. Their results show that major changes in temperature, salinity and sea-level had much less of an impact on mollusk communities than the current environmental crisis caused by human activity in the region.
“It is sobering to consider that about 120,000 years of major climate change did not affect these ecosystems nearly as much as the human-induced changes of the last few centuries,” said senior author Micha? Kowalewski, the Florida Museum Thompson chair of Invertebrate Paleontology.
Researchers have known for some time that modern Adriatic ecosystems are considerably altered compared to historical baselines.
“There are multiple human-driven stressors on these ecosystems, such as changes in land use that increase sedimentation rates,” said co-author Rafa? Nawrot, a postdoctoral researcher at the University of Vienna, formerly with the Florida Museum. “This has occurred as far back as the Roman Empire, when increased agriculture led to higher rates of erosion.”
While prior civilizations along the Italian peninsula have left a notable signature on Adriatic ecosystems, Nawrot explains that most of the changes have occurred within the last century. The influx of fertilizers into rivers and estuaries have sparked runaway reactions that deplete oxygen in marine and freshwater environments. Pollution from towns and cities creates a toxic mélange for sea life, and cargo vessels litter international shipping lanes with invasive stowaway species that disrupt native ecosystems. Perhaps most detrimental to Adriatic mollusks, commercial fisheries drag nets across the sea floor, scouring the basin for bottom-dwelling fish and bivalves.

Scientists have developed a new nanotechnology approach for locating and removing the painful and dangerous lesions associated with endometriosis, a common gynecological condition in women of childbearing age.
The research led by Oleh Taratula of the Oregon State University College of Pharmacy and Ov Slayden of the Oregon National Primate Research Center at Oregon Health & Science University involves magnetic nanoparticles — tiny pieces of matter as small as one-billionth of a meter.
The animal-model study, published today in the journal Small, shows that the iron oxide nanoparticles, injected intravenously, act as a contrast agent — they accumulate in the lesions, making them easier to see by advanced imaging such as MRI.
And when exposed to an alternating magnetic field, a non-invasive procedure, the nanoparticles’ temperature soars to more than 120 degrees Fahrenheit, high enough for lesion removal via heat.
“Endometriosis is a debilitating, systemic disease, and the need for an efficient, non-surgical method of removing the lesions is urgent,” Taratula said. “We invented targeted nanoparticles with extraordinary heating capabilities that enable the use of magnetic hyperthermia for the safe and efficient elimination of endometriosis lesions.”
The endometrium is the innermost layer of the uterus, and endometriosis occurs when endometrium-like tissue forms lesions outside of the uterine cavity — usually involving the ovaries, the fallopian tubes and the tissue lining the pelvis.