Mothers' sleep apnea may increase risk of autism-like changes in their male offspring

Sleep apnea in pregnancy may increase the risk for brain and behavioral changes associated with autism, especially in males, according to a study in rats by Amanda Vanderplow, Michael Cahill, and colleagues at the University of Wisconsin-Madison, and publishing Feb. 3 in the open-access journal PLOS Biology. The findings support evidence in humans of a link between sleep apnea and neurodevelopmental disorders, and provide a potential mechanism to explain the link.
During episodes of sleep apnea, breathing is partially or completely interrupted, often hundreds of timers per night, causing intermittent hypoxia, or decreased blood oxygenation. The incidence of sleep apnea during pregnancy is on the rise, in line with the obesity epidemic, and occurs in about 15% of uncomplicated pregnancies and more than 60% of high-risk pregnancies by the third trimester. Sleep apnea during pregnancy is known to have detrimental effects on the newborn, but the impacts on neurodevelopment have not been well studied.
To investigate such impacts, the authors subjected pregnant rats to intermittent low oxygen levels during times of rest, during the second half of their gestational period. The treatment induced hypoxia in the mothers, but (as expected) not in the fetuses. Behavioral abnormalities in the offspring were observed beginning shortly after birth, including altered distress vocalization patterns in both males and females. Maternal hypoxia also impaired cognitive and social function in male, but not female, offspring, both of which persisted into adulthood. Effects included reduction in working memory and longer-term memory storage, and reduced interest in socially novel situations.
These behavioral changes were accompanied by significant abnormalities in the density and morphology of dendritic spines, the outgrowths on neurons that receive and integrate signals from other neurons. In adolescents of both sexes, but much more so in males, the density of dendritic spines was elevated compared to age-matched control animals, an increase due mainly to lack of spine “pruning,” or reduction, a process that begins in childhood and is critical for normal brain development. How maternal hypoxia induced these changes in fetuses not themselves experiencing hypoxia remains unclear.
The authors found that affected offspring had excessive activity of a cell signaling pathway known as the mTOR pathway, a feature identified in the cortex of humans with autism, and that treatment with rapamycin, an mTOR inhibitor, partially mitigated the behavioral effects of maternal hypoxia in the offspring.
“To our knowledge, this is the first direct demonstration of the effects of maternal intermittent hypoxia during gestation on the cognitive and behavioral phenotypes of offspring,” Cahill says. “Our data provide clear evidence that maternal sleep apnea may be an important risk factor for the development of neurodevelopmental disorders, particularly in male offspring.”
Cahill adds, “Based on clinical correlations, maternal sleep apnea during pregnancy has been theorized to potentially increase risk for autism diagnosis in her offspring; however, functional studies are lacking. Here we show that sleep apnea during gestation produces neuronal and behavioral phenotypes in rodent offspring that closely resemble autism, and demonstrate the efficacy of a pharmacological approach in fully reversing the observed behavioral impairments.”
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New highly virulent and damaging HIV variant discovered in the Netherlands

As the ongoing coronavirus pandemic has demonstrated, new mutations in viral genetic sequences can have significant impacts on the virus’s transmissibility and the damage it causes. For many years, there have been concerns that this could arise in the HIV-1 virus, which already affects 38 million people worldwide, and has caused 33 million deaths to date. This has now been confirmed with the discovery of a new, highly virulent HIV strain in the Netherlands, in a study led by researchers from the University of Oxford’s Big Data Institute. The results are published in Science.
Individuals infected with the new “VB variant” (for virulent subtype B) showed significant differences before antiretroviral treatment compared with individuals infected with other HIV variants: Individuals with the VB variant had a viral load (the level of the virus in the blood) between 3.5 and 5.5 times higher. In addition, the rate of CD4 cell decline (the hallmark of immune system damage by HIV) occurred twice as fast in individuals with the VB variant, placing them at risk of developing AIDS much more rapidly. Individuals with the VB variant also showed an increased risk of transmitting the virus to others.Reassuringly, after starting treatment, individuals with the VB variant had similar immune system recovery and survival to individuals with other HIV variants. However, the researchers stress that because the VB variant causes a more rapid decline in immune system strength, this makes it critical that individuals are diagnosed early and start treatment as soon as possible.
Further research to understand the mechanism that causes the VB variant to be more transmissible and damaging to the immune system could reveal new targets for next-generation antiretroviral drugs. The VB variant is characterized by many mutations spread throughout the genome, meaning that a single genetic cause cannot be identified at this stage.
Lead author Dr Chris Wymant, from the University of Oxford’s Big Data Institute and Nuffield Department of Medicine, said: ‘Before this study, the genetics of the HIV virus were known to be relevant for virulence, implying that the evolution of a new variant could change its impact on health. Discovery of the VB variant demonstrated this, providing a rare example of the risk posed by viral virulence evolution.’
Senior author Professor Christophe Fraser from the University of Oxford’s Big Data Institute and Nuffield Department of Medicine, added: ‘Our findings emphasise the importance of World Health Organization guidance that individuals at risk of acquiring HIV have access to regular testing to allow early diagnosis, followed by immediate treatment. This limits the amount of time HIV can damage an individual’s immune system and jeopardise their health. It also ensures that HIV is suppressed as quickly as possible, which prevents transmission to other individuals.’
The VB variant was first identified in 17 HIV positive individuals from the BEEHIVE project, an ongoing study which collects samples from across Europe and Uganda. Since 15 of these people came from the Netherlands, the researchers then analysed data from a cohort of over 6,700 HIV positive individuals in the Netherlands. This identified an additional 92 individuals with the variant, from all regions of the Netherlands, bringing the total to 109.
By analysing the patterns of genetic variation among the samples, the researchers estimate that the VB variant first arose during the late 1980s and 1990s in the Netherlands. It spread more quickly than other HIV variants during the 2000s, but its spread has been declining since around 2010. The research team believe that the VB variant arose in spite of widespread treatment in the Netherlands, not because of it, since effective treatment can suppress transmission.
The individuals with the VB variant showed typical characteristics for people living with HIV in the Netherlands, including age, sex, and suspected mode of transmission. This indicates that the increased transmissibility of the VB variant is due to a property of the virus itself, rather than a characteristic of people with the virus.
The full paper, ‘A highly virulent variant of HIV-1 circulating in the Netherlands’, can be read in the journal Science.
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How to get chloride ions into the cell

For the first time, a molecular movie has captured in detail the process of an anion transported across the cell membrane by a light-fuelled protein pump. Publishing in Science, the researchers have unravelled the mystery of how light energy initiates the pumping process − and how nature made sure there is no anion leakage back outside.
Many bacteria and unicellular algae have light-driven pumps in their cell membranes: proteins that change shape when exposed to photons such that they can transport charged atoms in or out of the cell. Thanks to these pumps, their unicellular owners can adjust to the environment’s pH value or salinity.
One such bacteria is Nonlabens marinus, first discovered in 2012 in the Pacific Ocean. Among others, it possesses a rhodopsin protein in its cell membrane which transports chloride anions from outside the cell to its inside. Just like in the human eye, a retinal molecule bound to the protein isomerizes when exposed to light. This isomerization starts the pumping process. Researchers now gained detailed insight into how the chloride pump in Nonlabens marinus works.
The study was led by Przemyslaw Nogly, once a postdoc at PSI and now an Ambizione Fellow and Group Leader at ETH Zürich. With his team, he combined experiments at two of PSI’s large-scale research facilities, the Swiss Light Source SLS and the X-ray free-electron laser SwissFEL. Slower dynamics in the millisecond-range were investigated via time-resolved serial crystallography at SLS while faster, up to picosecond, events were captured at SwissFEL — then both sets of data were put together.
“In one paper, we exploit the advantages of two state-of-the-art facilities to tell the full story of this chloride pump,” Nogly says. Jörg Standfuss, co-author of the study who built up a PSI team dedicated to creating such molecular movies, adds: “This combination enables first-class biological research as would only be possible at very few other places in the world beside PSI.”
No backflow
As the study has revealed, the chloride anion is attracted by a positively charged patch of the rhodopsin protein in Nonlabens marinus’ cell membrane. Here, the anion enters the protein and finally binds to a positive charge at the retinal molecule inside. When retinal isomerizes due to light exposure and flips over, it drags the chloride anion along and thus transports it a bit further inside the protein. “This is how light energy is directly converted into kinetic energy, triggering the very first step of the ion transport,” Sandra Mous says, a PhD student in Nogly’s group and first author of the paper.
Being on the other side of the retinal molecule now, the chloride ion has reached a point of no return. From here, it goes only further inside the cell. An amino acid helix also relaxes when chloride moves along, additionally obstructing the passage back outside. “During the transport, two molecular gates thus make sure that chloride only moves in one direction: inside,” Nogly says. One pumping process in total takes about 100 milliseconds.
Two years ago, Jörg Standfuss, Przemyslaw Nogly and their team unravelled the mechanism of another light-driven bacterial pump: the sodium pump of Krokinobacter eikastus. Researchers are eager to discover the details of light-driven pumps because these proteins are valuable optogenetic tools: genetically engineered into mammalian neurons, they make it possible to control the neurons activities by light and thus research their function.
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Materials provided by Paul Scherrer Institute. Original written by Brigitte Osterath. Note: Content may be edited for style and length.

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Pre-infection deficiency of vitamin D is associated with increased disease severity and mortality among hospitalized COVID-19 patients

Vitamin D is most often recognized for its role in bone health, but low levels of the supplement have been associated with a range of autoimmune, cardiovascular, and infectious diseases. Early on in the pandemic health officials began to encourage people to take vitamin D, as it plays a role in promoting immune response and could protect against COVID-19.
In a study published in the journal PLOS ONE researchers from the Azrieli Faculty of Medicine of Bar-Ilan University in Safed, Israel and the Galilee Medical Center in Nahariya, Israel show a correlation between vitamin D deficiency and COVID-19 severity and mortality.
The study is among the first to analyze vitamin D levels prior to infection, which facilitates a more accurate assessment than during hospitalization, when levels may be lower secondary to the viral illness.
The records of 1,176 patients admitted between April 2020 and February 2021 to the Galilee Medical Center (GMC) with positive PCR tests were searched for vitamin D levels measured two weeks to two years prior to infection.
Patients with vitamin D deficiency (less than 20 ng/mL) were 14 times more likely to have severe or critical case of COVID than those with more than 40 ng/mL.
Strikingly, mortality among patients with sufficient vitamin D levels was 2.3%, in contrast to 25.6% in the vitamin D deficient group.
The study adjusted for age, gender, season (summer/winter), chronic diseases, and found similar results across the board highlighting that low vitamin D level contributes significantly to disease severity and mortality.
“Our results suggest that it is advisable to maintain normal levels of vitamin D. This will be beneficial to those who contract the virus,” says Dr. Amiel Dror, of the Galilee Medical Center and Azrieli Faculty of Medicine of Bar-Ilan University, who led the study. “There is a clear consensus for vitamin D supplementation on a regular basis as advised by local health authorities as well as global health organizations.”
Dr. Amir Bashkin, an Endocrinologist who participated in the current study, adds that “This is especially true for the COVID-19 pandemic when adequate vitamin D has an added benefit for the proper immune response to respiratory illness.”
“This study contributes to a continually evolving body of evidence suggesting that a patient’s history of vitamin D deficiency is a predictive risk factor associated with poorer COVID-19 clinical disease course and mortality,” said study co-author Prof. Michael Edelstein, of the Azrieli Faculty of Medicine of Bar-Ilan University. “It is still unclear why certain individuals suffer severe consequences of COVID-19 infection while others don’t. Our finding adds a new dimension to solving this puzzle.”
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NFTs offer new method to control personal health information

NFTs, or nonfungible tokens, created using blockchain technology, first made a splash in the art world as a platform to buy and sell digital art backed by a digital contract. But could NFT digital contracts be useful in other marketplaces? A global, multidisciplinary team of scholars in ethics, law and informatics led by bioethicists at Baylor College of Medicine wrote one of the first commentaries on how this new emerging technology could be repurposed for the healthcare industry.
In a new publication in the journal Science, the researchers propose that the tool could help patients gain more control over their personal health information. NFT digital contracts could provide an opportunity for patients to specify who can access their personal health information and to track how it is shared.
“Our personal health information is completely outside of our control in terms of what happens to it once it is digitalized into an electronic health record and how it gets commercialized and exchanged from there,” said Dr. Kristin Kostick-Quenet, first author of the paper and assistant professor at the Center for Medical Ethics and Health Policy at Baylor. “NFTs could be used to democratize health data and help individuals regain control and participate more in decisions about who can see and use their health information.”
“In the era of big data, health information is its own currency; it has become commodified and profitable,” said Dr. Amy McGuire, senior author of the paper and Leon Jaworski Professor of Biomedical Ethics and director of the Center for Medical Ethics and Health Policy at Baylor. “Using NFTs for health data is the perfect storm between a huge market place that’s evolving and the popularity of cryptocurrency, but there are also many ethical, legal and social implications to consider.”
The researchers point out that NFTs are still vulnerable to data security flaws, privacy issues, and disputes over intellectual property rights. Further, the complexity of NFTs may prevent the average citizen from capitalizing on their potential. The researchers believe it is important to consider potential benefits and challenges as NFTs emerge as a potential avenue to transform the world of health data.
“Federal regulations already give patients the right to connect an app of their choice to their doctor’s electronic health record and download their data in a computable format,” said Dr. Kenneth Mandl, co-author of the paper, director of the Computational Health Informatics Program at Boston Children’s Hospital and Donald A.B. Lindberg Professor of Pediatrics and Biomedical Informatics at Harvard Medical School. “It’s intriguing to contemplate whether NFTs or NFT-like technology could enable intentional sharing of those data under smart contracts in the future.”
Dr. Timo Minssen, I. Glenn Cohen, Dr. Urs Gasser and Dr. Isaac Kohane also contributed to this publication. They are from the following institutions: Boston Children’s Hospital, Harvard Medical School, Harvard Law School, University of Copenhagen and Technical University of Munich. See the publication for a full list of funding for these researchers.
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Neuroscientists use deep learning model to simulate brain topography

Damage to a part of the brain that processes visual information — the inferotemporal (IT) cortex — can be devastating, especially for adults. Those affected may lose the ability to read (a disorder known as alexia), or recognize faces (prosopagnosia) or objects (agnosia), and there is currently not much doctors can do.
A more accurate model of the visual system may help neuroscientists and clinicians develop better treatments for these conditions. Carnegie Mellon University researchers have developed a computational model that allows them to simulate the spatial organization or topography of the IT and learn more about how neighboring clusters of brain tissue are organized and interact. This could also help them understand how damage to that area affects the ability to recognize faces, objects and scenes.
The researchers — Nicholas Blauch, a Ph.D. student in the Program in Neural Computation, and his advisors David C. Plaut and Marlene Behrmann, both professors in the Department of Psychology and the Neuroscience Institute at CMU — described the model in the Jan. 18 issue of the Proceedings of the National Academy of Sciences.
Blauch said the paper may help cognitive neuroscientists answer longstanding questions about how different parts of the brain work together.
“We have been wondering for a long time if we should be thinking of the network of regions in the brain that responds to faces as a separate entity just for recognizing faces, or if we should think of it as part of a broader neural architecture for object recognition,” Blauch said. “We’re trying to come at this problem using a computational model that assumes this simpler, general organization, and seeing whether this model can then account for the specialization we see in the brain through learning to perform tasks.”
To do so, the researchers developed a deep learning model endowed with additional features of biological brain connectivity, hypothesizing that the model could reveal the spatial organization, or topography of the IT.

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Poor sleep and stress exacerbate each other among nurses who work night shift, study finds

Nurses who work the night shift report more sleep disturbances and are more likely to suffer from psychological and physical health symptoms including PTSD, insomnia and inflammation, a recent study from an Oregon State University researcher found.
Though effective interventions exist for many different sleep disorders, including insomnia and nightmares, those techniques are often not widely known or offered to patients such as nurses who could benefit from them.
“I think the main finding here is that sleep is important and should not be overlooked when we’re considering the picture of someone’s health, especially in fields that require a lot of attention and care and emotional involvement, like nursing,” said Jessee Dietch, co-author on the study and an assistant professor of psychology in OSU’s College of Liberal Arts.
The study, conducted in 2018, involved 392 nurses who reported their sleep experiences in daily sleep diaries for 14 days, noting duration, quality, efficiency — how long they were in bed versus how long they were asleep — and nightmare severity.
Researchers also took blood samples at the halfway point to test for general immune response and inflammation.
Based on the results, the researchers sorted participants into three sleep classes: 80.4% reported good overall sleep; 11.2% had poor overall sleep; and 8.4% were in the “nightmares only” group, with mostly average sleep but above average levels of nightmare severity.

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Study finds high levels of depression, anxiety among disabled people during COVID-19 pandemic

A new study from Oregon State University confirms what many in the disabled community already know: People with disabilities have been experiencing high levels of depression and anxiety during the COVID-19 pandemic.
Social isolation was the main predictor for both depression and anxiety, said Kathleen Bogart, co-author on the study and an associate professor of psychology at OSU.
“We know that people with disabilities were more socially isolated before the pandemic, so for a variety of reasons, the pandemic has amplified that disparity,” she said.
People with disabilities are often immunocompromised or have comorbidities that would cause more severe infection from COVID-19, requiring more strict isolation at home to avoid exposure to the virus.
The study, published in Rehabilitation Psychology, examined survey responses from 441 adults between October and December 2020 who self-identified as having a disability. In total, 61% of participants met the criteria for probable major depressive disorder and 50% for probable generalized anxiety disorder.
That’s much higher than the pre-pandemic baseline among people with and without disabilities, Bogart said. Previous research in the field has found that about 22% of people with disabilities are diagnosed with depression during their lifetime. According to the Anxiety & Depression Association of America, in an average year, roughly 7% of all U.S. adults have major depressive disorder and 3% have generalized anxiety disorder.

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Are scientists being fooled by bacteria?

For decades, a small group of cutting-edge medical researchers have been studying a biochemical, DNA tagging system, which switches genes on or off. Many have studied it in bacteria and now some have seen signs of it in, plants, flies, and even human brain tumors. However, according to a new study by researchers at the Icahn School of Medicine at Mount Sinai, there may be a hitch: much of the evidence of its presence in higher organisms may be due to bacterial contamination, which was difficult to spot using current experimental methods.
To address this, the scientists created a tailor-made gene sequencing method which relies on a new machine learning algorithm to accurately measure the source and levels of tagged DNA. This helped them distinguish bacterial DNA from that of human and other non-bacterial cells. While the results published in Science supported the idea that this system may occur naturally in non-bacterial cells, the levels were much lower than some previous studies reported and were easily skewed by bacterial contamination or current experimental methods. Experiments on human brain cancer cells produced similar results.
“Pushing the boundaries of medical research can be challenging. Sometimes the ideas are so novel that we have to rethink the experimental methods we use to test them out,” said Gang Fang, PhD, Associate Professor of Genetics and Genomic Sciences at Icahn Mount Sinai. “In this study, we developed a new method for effectively measuring this DNA mark in a wide variety of species and cell types. We hope this will help scientists uncover the many roles these processes may play in evolution and human disease.”
The study focused on DNA adenine methylation, a biochemical reaction which attaches a chemical, called a methyl group, to an adenine, one of the four building block molecules used to construct lengthy DNA strands and encode genes. This can “epigenetically” activate or silence genes without actually altering DNA sequences. For instance, it is known that adenine methylation plays a critical role in how some bacteria defend themselves against viruses.
For decades, scientists thought that adenine methylation strictly happened in bacteria whereas human and other non-bacterial cells relied on the methylation of a different building block — cytosine — to regulate genes. Then, starting around 2015, this view changed. Scientists spotted high levels of adenine methylation in plant, fly, mouse, and human cells, suggesting a wider role for the reaction throughout evolution.
However, the scientists who performed these initial experiments faced difficult trade-offs. Some used techniques that can precisely measure adenine methylation levels from any cell type but do not have the capacity to identify which cell each piece of DNA came from, while others relied on methods that can spot methylation in different cell types but may overestimate reaction levels.

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Medicare Will Soon Provide Free At-Home Coronavirus Tests

The announcement came after lawmakers and advocates argued that Medicare recipients had been passed over in the push to require insurers to cover the tests.Medicare, which covers roughly 60 million Americans, will provide free over-the-counter rapid coronavirus tests beginning in the spring, according to the federal government’s Medicare and Medicaid agency.The policy would “allow Medicare beneficiaries to pick up tests at no cost at the point of sale and without needing to be reimbursed,” the Centers for Medicare and Medicaid Services said, adding that it would be the first time Medicare covered the whole cost of an over-the-counter test.The announcement followed weeks of clamor from lawmakers and health care advocates, who argued that Medicare recipients had been passed over in the administration’s push to require private insurers to cover the tests.Under the plan, which will also apply to Medicare Advantage beneficiaries, Medicare will pay eligible pharmacies and health providers to offer the tests. The administration did not say how many pharmacies would participate.Enrollees will be able to get up to eight tests each month, the same number covered for privately insured Americans as part of a set of new requirements the Biden administration announced last month.The new Medicare program will not begin until the “early spring,” the administration said. The surge in cases caused by the Omicron variant, already declining, may have waned considerably by then. Even so, the tests could help Americans in possible future surges, perhaps driven by different variants, and as people begin to congregate more frequently with fewer virus cases around.The free tests covered by Medicare would go to some of the most vulnerable parts of the U.S. population. The vast majority of Medicare enrollees are 65 or older; others are younger people with disabilities.Because new treatments for the virus must be given early in the course of infection to be effective, testing and identifying cases quickly is critical to their use.After the Biden administration announced new guidelines for test reimbursement under private insurance plans, lawmakers called on the Centers for Medicare and Medicaid Services to extend coverage to Medicare enrollees. Frequent use of rapid tests, which typically cost around $10 each if paid for out of pocket and are usually packaged in pairs, can be prohibitively expensive for many Americans.“The cost of paying for tests and the time needed to find free testing options are barriers that could discourage Medicare beneficiaries from getting tested, leading to greater social isolation and continued spread of the virus,” Nancy LeaMond, an AARP official, said in a statement on Thursday commending the administration for the new policy.The Coronavirus Pandemic: Key Things to KnowCard 1 of 4The state of the virus in the U.S.

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