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People who have more disrupted sleep in their 30s and 40s may be more likely to have memory and thinking problems a decade later, according to new research published in the January 3, 2024, online issue of Neurology®, the medical journal of the American Academy of Neurology. The study does not prove that sleep quality causes cognitive decline. It only shows an association.
“Given that signs of Alzheimer’s disease start to accumulate in the brain several decades before symptoms begin, understanding the connection between sleep and cognition earlier in life is critical for understanding the role of sleep problems as a risk factor for the disease,” said study author Yue Leng, PhD, of the University of California, San Francisco. “Our findings indicate that the quality rather than the quantity of sleep matters most for cognitive health in middle age.”
The study involved 526 people with an average age of 40. They were followed for 11 years.
Researchers looked at participants’ sleep duration and quality. Participants wore a wrist activity monitor for three consecutive days on two occasions approximately one year apart to calculate their averages. Participants slept for an average of six hours.
Participants also reported bedtimes and wake times in a sleep diary and completed a sleep quality survey with scores ranging from zero to 21, with higher scores indicating poorer sleep quality. A total of 239 people, or 46%, reported poor sleep with a score greater than five.
Participants also completed a series of memory and thinking tests.
Researchers also looked at sleep fragmentation, which measures repetitive short interruptions of sleep. They looked at both the percentage of time spent moving and the percentage of time spent not moving for one minute or less during sleep. After adding these two percentages together, researchers found that participants had an average sleep fragmentation of 19%.

Researchers then divided participants into three groups based on their sleep fragmentation score.
Of the 175 people with the most disrupted sleep, 44 had poor cognitive performance 10 years later, compared to 10 of the 176 people with the least disrupted sleep.
After adjusting for age, gender, race, and education, people who had the most disrupted sleep had more than twice the odds of having poor cognitive performance when compared to those with the least disrupted sleep. There was no difference in cognitive performance at midlife for those in the middle group compared to the group with the least disrupted sleep.
“More research is needed to assess the link between sleep disturbances and cognition at different stages of life and to identify if critical life periods exist when sleep is more strongly associated with cognition,” Leng said. “Future studies could open up new opportunities for the prevention of Alzheimer’s disease later in life.”
The amount of time people slept and their own reports of the quality of their sleep were not associated with cognition in middle age.
A limitation of the study was that due to the small sample size, researchers were unable to fully investigate potential race or gender differences.
The study was funded by the National Institute on Aging and the National Heart, Lung, and Blood Institute.

Hearing loss affects approximately 40 million American adults, yet only one in 10 people who need hearing aids use them, research shows.
Those who don’t use hearing aids but should may want to make wearing them one of their New Year’s resolutions, according to a new study from Keck Medicine of USC published today in The Lancet Healthy Longevity.
“We found that adults with hearing loss who regularly used hearing aids had a 24% lower risk of mortality than those who never wore them,” said Janet Choi, MD, MPH, an otolaryngologist with Keck Medicine and lead researcher of the study. “These results are exciting because they suggest that hearing aids may play a protective role in people’s health and prevent early death.”
Previous research has shown that untreated hearing loss can result in a reduced life span (as well as other poor outcomes such as social isolation, depression and dementia). However, until now, there has been very little research examining if the use of hearing aids can reduce the risk of death. The study represents the most comprehensive analysis to date on the relationship between hearing loss, hearing aid use and mortality in the United States, according to Choi.
Choi and her fellow researchers used data compiled by the National Health and Nutrition Examination Survey between 1999-2012 to identify almost 10,000 adults 20 years and older who had completed audiometry evaluations, a test used to measure hearing ability, and who filled out questionnaires about their hearing aid use. Researchers followed their mortality status over an average follow-up period of 10 years after their evaluations.
A total of 1,863 adults were identified as having hearing loss. Of these, 237 were regular hearing aid users, which were characterized as those who reported wearing the aids at least once a week, five hours a week or half the time, and 1,483 were identified as never-users of the devices. Subjects who reported wearing the devices less than once a month or less frequently were categorized as non-regular users.
Researchers found that the almost 25% difference in mortality risk between regular hearing aid users and never-users remained steady, regardless of variables such as the degree of hearing loss (from mild to severe); age, ethnicity, income, education and other demographics; and medical history. There was no difference in mortality risk between non-regular users and never users, indicating that occasional hearing aid use may not provide any life-extending benefit.

While the study did not examine why hearing aids may help those who need them live longer, Choi points to recent research linking hearing aid use with lowered levels of depression and dementia. She speculates that the improvements in mental health and cognition that come with improved hearing can promote better overall health, which may improve life span.
Choi hopes this study will encourage more people to wear hearing aids, even though she acknowledges that factors, including cost, stigma and difficulty finding devices that fit and function well, are barriers to use.
Choi can personally relate to these challenges. She was born with hearing loss in her left ear, but did not wear a hearing device until her 30s. It then took her several years to find ones that worked effectively for her.
She is currently working on an AI-driven database that categorizes hearing aid choices and tailors them to individual patient needs. She also advocates for larger studies to further understand the link between regular hearing aid use and a lower mortality risk and to promote hearing care.

Federal health officials and other experts have repeatedly sought to counter erroneous comments about the vaccines by Dr. Joseph Ladapo, Florida’s surgeon general.Florida’s surgeon general on Wednesday called for a halt to the use of Covid vaccines, citing widely debunked concerns that contaminants in the vaccine can permanently integrate into human DNA.“These vaccines are not appropriate for use in human beings,” Dr. Joseph Ladapo, the state’s surgeon general and highest-ranking health official, said in a statement released by the Florida Department of Health.Federal health officials and other experts have repeatedly sought to counter Dr. Ladapo’s erroneous comments about the vaccines, noting that careful review of the scientific evidence has found no basis for his declarations.The Food and Drug Administration said on Wednesday that it had not identified any “safety concerns related to the sequence of, or amount of, residual DNA.”The Covid vaccines made by Pfizer and Moderna use so-called messenger RNA, or mRNA, a type of genetic material, to direct the body to make immune molecules against the coronavirus.Dr. Ladapo’s latest statement amplifies Florida’s escalating anti-vaccine stance. He was appointed surgeon general in 2021 by Gov. Ron DeSantis, a Republican, and has since increasingly aligned himself with anti-vaccine claims that the shots cause serious harm.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? 

Published4 JanuaryShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Nick TriggleHealth correspondent@nicktriggleA six-day strike by junior doctors took place in England in January, causing huge disruption to services. The British Medical Association (BMA) says if the government makes a credible offer it will end the walkouts. But how much will it take to settle this dispute?Junior doctors started their industrial action later than many other workers. It was March 2023 by the time they first went on strike. By that point, walkouts had been going on for months in the NHS and other sectors.But their ask – a 35% pay increase – was the largest of all. Unlike most of the rest, it was not focused on the post-pandemic spike in inflation.Instead, it was about – in the words of the BMA – restoring lost pay after 15 years of below-inflation rises.How double pay rise for senior doctors is backfiringWhy talk of a UK doctor exodus is prematureThe union used a measure of inflation known as RPI, which includes housing costs, as the basis for its pay claim.This shows that between 2008-9 and 2021-22, pay for junior doctors had fallen by 26% once rising costs are taken into account. To reverse that drop would take a 35% increase.But that is just one measure of inflation. If the Office for National Statistics-favoured measure known as CPI is used, the drop in pay is lower.Regardless of which measure is used, much has happened both to inflation and the pay of junior doctors since those sums were done.Junior doctors have in fact received two pay rises. One in 2022-23 was worth 2%, while another in the current 2023-24 year was worth 8.8% on average (it was structured so the lower-paid junior doctors received the most – with those in their first year of training getting in excess of 10%). It brought the starting salary to more than £32,000, with those towards the end of their training receiving in excess of £63,000 currently.And that is just the basic pay. Junior doctors, like other NHS staff, receive extras on top and these can be worth 25% to 30% more for things such as unsocial hours and additional work. The junior doctor contract stipulates that they can be asked to work up to 48 hours a week rather than the standard 40.So, given this, what would it take for junior doctors to stop their strike action? Walkouts were paused between early October and December to allow talks to take place. As well as pay, these involved discussions on working conditions as well – a long-standing issue for junior doctors has been the amount of debt they build up while studying for five years at university, as well as the lack of control they have on where and when they are asked to work. It is not uncommon to find reports of people being rostered to work despite giving months of notice for big events like family weddings.It can also be difficult to put down roots, because they can find themselves doing placements in different parts of the country. All this and more was discussed during the talks, alongside the offer of an extra 3% pay award on top of the 8.8% that has already been given.The BMA’s junior doctor leaders, Dr Vivek Trivedi and Dr Robert Laurenson, made it clear this was not enough, and have been urging ministers to make a “credible” new offer. The demand for pay to be restored in one go has been toned down – they now say they would be happy to see it phased in over a number of years.The BMA says the pay rises seen over the last two years have made no dent in the amount of lost pay since 2008-09 because of what has been happening with inflation.Window of opportunityHowever, there is clearly scope for negotiation. In August, a pay deal was reached with junior doctors in Scotland. It included a 12.4% pay increase for 2023-24, which is in a similar ballpark to the 8.8% plus 3% that appeared to be on the table in England just a month ago. There are some key differences – junior doctors in Scotland received more than twice the 2% their peers in England got in 2022-23 and so started from a higher base, and the BMA says the Scottish deal included promises on future pay increases with a view to restoring pay – something the union says it has confidence in as there is no election there until 2026. Some in government believe the differences are small – and instead that the junior doctor leaders are being political. An interview Dr Laurenson gave to the BBC’s Today programme over the summer, in which he said the same deal as Scotland would not be accepted in England because the governments are different, has been cited by those close to the negotiations.Nonetheless, there is hope that once this walkout ends there will be a return to talks. Behind the scenes, there is a recognition on both sides that strike action cannot continue for much longer.More on this storyGive us credible offer and we’ll end strikes – BMAPublished3 JanuaryNHS consultant strike: How pay compares globallyPublished24 August 2023Junior doctor strikes return, after talks collapsePublished5 December 2023Nurses react with fury over doctor pay offerPublished28 November 2023Fresh pay offer could end NHS consultant strikesPublished27 November 2023Sunak to miss NHS target if doctors strike – AtkinsPublished3 December 2023Why talk of a UK doctor exodus is prematurePublished9 August 2023

Published25 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, PA MediaBy Nick TriggleHealth correspondentNHS bosses have made more than 20 requests for striking junior doctors in England to be allowed to cross the picket line to help out services.None of the requests made on the first strike day have been granted so far by the British Medical Association (BMA).The union accused NHS bosses of misusing the system known as derogation and bowing to political pressure to undermine the strike.But NHS England said they were genuine requests for help.It said the health service was under huge pressure after the six-day walkout began on Wednesday, and NHS bosses were trying everything they could to protect patients and keep struggling services safe.”Given this period of industrial action coincides with the most difficult time of year for the NHS, it is to be expected that more senior medical leaders will ask for allowances to be made to ensure safe levels of cover,” the spokesman added.The requests are made by individual departments so some NHS trusts are thought to have made more than one request. Only one request is under active consideration. Most involve emergency care areas, such as A&E units.This is the ninth walkout – and longest ever -by junior doctors, and before this stoppage only a handful of requests had been made.Just one was granted – to Somerset’s Weston General Hospital in April – and that was only done temporarily as the BMA said it was misled about the scale of the problem.In a letter to NHS England boss Amanda Pritchard on Wednesday, BMA leader Prof Philip Banfield said in many cases insufficient information was being provided by the NHS to judge the merits of the request.He said this was “undermining” the derogation process and placing the BMA in an impossible position.”We are increasingly drawing the conclusion that NHS England’s change in attitude towards the process is not due to concerns around patient safety, but due to political pressure to maintain a higher level of service and undermine our strike action.”The trusts that made the requests are not being named.But it is clear a number of areas are facing difficulties.Routine services have been scaled back to allow senior doctors to be drafted across to emergency care to provide cover.But several NHS trusts reported significant waits in A&E, with some declaring a critical incident, meaning bosses were concerned they could not provide critical services for patients.How double pay rise for senior doctors is backfiring on governmentWhy talk of a UK doctor exodus is prematureHow much do junior doctors really get paid? Queen Alexandra Hospital in Portsmouth said its A&E department was “full” as it declared a critical incident – its third in three months.In Nottinghamshire, the entire Nottingham and Nottinghamshire NHS system declared a critical incident at 16:30 GMT.Cheltenham A&E has been closed with patients diverted elsewhere, and Bolton NHS Foundation Trust said it was facing “extreme pressure” with waiting times in A&E of “up to 11 hours”. Warwick Hospital warned it was under “extreme heightened pressure”, while Airedale Hospital said its emergency department was “exceptionally busy”.Health officials in East Sussex, South Tees, Gateshead, Greater Manchester, Berkshire, Rotherham and Harlow in Essex also reported being “busy”.Are you a junior doctor with a view on the strike? Are you a patient affected? Email haveyoursay@bbc.co.uk.Please include a contact number if you are willing to speak to a BBC journalist. You can also get in touch in the following ways:WhatsApp: +44 7756 165803Tweet: @BBC_HaveYourSayUpload pictures or videoPlease read our terms & conditions and privacy policy

If you are reading this page and can’t see the form you will need to visit the mobile version of the BBC website to submit your question or comment or you can email us at HaveYourSay@bbc.co.uk. Please include your name, age and location with any submission. More on this storyGive us credible offer and we’ll end strikes – BMAPublished2 hours agoFresh pay offer could end NHS consultant strikesPublished27 November 2023What is the NHS pay offer?Published2 May 2023Why talk of a UK doctor exodus is prematurePublished9 August 2023NHS pay deal signed off for one million staffPublished2 May 2023How much do junior doctors really get paid?Published11 August 2023

Hospitalizations have ticked upward, and there are at least 1,200 Covid deaths each week. Americans should wear masks more often and get vaccinated, experts say. The holidays have come and gone, and once again Americans are riding a tide of respiratory ailments, including Covid. But so far, this winter’s Covid uptick seems less deadly than last year’s, and much less so than in 2022, when the Omicron surge ground the nation to a halt.“We’re not seeing the signs that would make me think that we’re heading into another severe wave,” said Caitlin Rivers, an epidemiologist at the Johns Hopkins Center for Health Security. “So far, we’re in relatively good shape.”Still, there are few masks in sight, and just a fraction of the most vulnerable people have received the latest Covid shots, she noted.“It’s not too late,” Dr. Rivers added. “We have not even reached peak yet for Covid, and once you reach peak, you still have to get down the other side.” That leaves plenty of time for the vaccine to provide some protection.Federal officials are relying on limited data to measure this year’s spread. After the end of the public health emergency in May, the Centers for Disease Control and Prevention stopped tracking the number of Covid infections. The agency now has only partial access to information from states about vaccination rates.But trends in wastewater data, positive tests, emergency department visits, hospitalization rates and deaths point to a rise in infections in all regions of the nation, according to the C.D.C. These patterns have prompted many hospitals to reinstate mask policies, after initially resisting a return to them this fall.As in previous years, the numbers have steadily been rising all winter, and are expected to increase further after holiday travel and get-togethers.Many of the infections are caused by a new variant, JN.1, which has rapidly spread across the world in recent weeks. “I think that there’s no doubt it’s helping drive, pretty substantially, this winter wave,” said Katelyn Jetelina, a public health expert and author of a widely read newsletter, “Your Local Epidemiologist.”“Unfortunately, it’s coming at the same exact time as us opening up our social networks due to the holidays,” she said, “so there’s kind of a perfect storm going on right now.”A billboard in New Mexico encouraged masks in 2020. Covid is still claiming about 1,200 lives per week.Ruth Fremson/The New York TimesSome scientists have pointed to rising levels of the virus in sewage samples as an indicator that infections are at least as high this year as they were at this time last year. But Dr. Rivers urged caution in interpreting wastewater data as a proxy for infections and said hospitalizations were a more reliable metric.In the week that ended on Dec. 23, hospitalizations rose by nearly 17 percent from the previous week. There were about 29,000 new hospital admissions, compared with 39,000 the same week last year and 61,000 in 2021.And weekly hospitalizations are increasing more slowly than in previous years, Dr. Rivers said.Covid is still claiming at least 1,200 lives per week. But that number is about one-third the toll this time last year and one-eighth that in 2021.“We are in this pretty big infection surge right now, but what’s really interesting is how hugely hospitalizations have and continue to decouple from infections,” Dr. Jetelina said.She said she worried most about hospitals buckling under the weight of multiple epidemics at once. Even in years before the pandemic, outbreaks of just influenza and respiratory syncytial virus could strain hospitals; rising Covid rates now overlap both illnesses, adding to the burden.The C.D.C. estimates that so far this season, there have been at least 7.1 million illnesses, 73,000 hospitalizations and 4,500 deaths from the flu.While Covid tends to be mild in children and young adults, influenza and R.S.V. are most risky for young children and older adults. All three diseases are particularly dangerous for infants.Emergency department visits for Covid are highest among infants and older adults. While R.S.V. has leveled off in some parts of the country, hospitalization rates remain high among young children and older adults.The JN.1 variant accounts for nearly half of all Covid cases in the United States, nearly six times the prevalence just a month ago. The variant has one mutation that gives it a greater ability to sidestep immunity than its parent, BA.2.86, which was limited in its spread.JN.1 may in fact be less transmissible than previous variants. But its immune evasiveness, coupled with the disappearance of preventive measures like masks, may explain its exponential growth worldwide, said Dr. Abraar Karan, an infectious disease physician and postdoctoral researcher at Stanford University.Still, JN.1 does not appear to cause more severe illness than previous variants, and the current vaccines, tests and treatments work well against all of the current variants.Experts urged all Americans — including those not at high risk of severe illness — to opt for vaccines against both Covid and flu, to use masks and air purifiers to prevent infections, to be tested and treated and to stay home if they become ill.Even those who do not become severely sick run the risk of long-term complications with every new viral infection, researchers noted.“I’m not at high risk, to be honest — I’m young and vaccinated,” Dr. Rivers said. “But I continue to take precautions in my own life because I do not want to deal with that disruption, and the risk that I could develop a longer-term illness.”Vaccination in Las Vegas in 2021. Experts say rates for the new Covid vaccine are low, in part, because many people don’t realize that they should get them even if they are not at high risk.Ethan Miller/Getty ImagesBut few Americans are following that advice. As of Dec. 23, only 19 percent of adults had received the latest Covid vaccine, and about 44 percent had opted for the annual flu shot. Just over 17 percent of adults aged 60 and older had received the vaccine for R.S.V.Even among those 75 and older, who are at highest risk from Covid, only about one in three have received the latest shot, according to the C.D.C.Many people don’t realize that shots that protect against the newest variants are available, or that they should be vaccinated even if they are not at high risk, said Gigi Gronvall, a biosecurity expert at the Johns Hopkins Center for Health Security.Even if the Covid vaccine does not prevent infection, it can shorten the duration and severity of illness, and minimize the risk of long-term symptoms, including brain fog, fatigue, movement problems and dizziness — collectively known as long Covid.“I’m sure also there are plenty of people who are actively hostile to the idea, but most of the people I encounter, they just don’t even know about it,” Dr. Gronvall said.Poor availability of the shots, particularly for children and older adults, has also limited the vaccination rates.Dr. Gronvall struggled to find a Covid vaccine for her teenage son. Dr. Jetelina has yet to find any for her young children. She said her grandparents, who are both in their mid-90s, also had “an incredibly challenging time.”One of them is in a nursing home and still hasn’t been immunized because she happened to be sick the one day the vaccines were offered.Many nursing home residents and staff members remain unvaccinated, because the staff doesn’t understand the benefits, said Dr. Karan, who worked with nursing facilities in Los Angeles County.Financial incentives can improve vaccine coverage, but the lack of awareness about the benefits “is a major problem,” he said.Experts also urged people who develop symptoms to take a test and ask for antiviral drugs — Tamiflu for influenza, Paxlovid for Covid — especially if they are at high risk of complications.Paxlovid is still available free of charge to most people, but many patients and even doctors avoid it out of a mistaken belief that it causes Covid symptoms to rebound, experts said. Recent studies did not find a relationship between antiviral drugs and symptom rebound.“For many viruses, including the flu, we know that earlier use of antivirals is going to be beneficial,” Dr. Karan said. “You stop viral replication quickly, you have less of an immune dysregulation thereafter.”

The blood-brain barrier blocks the entry of antibodies into the brain. This limits the potential use of antibody therapeutics to treat brain diseases, such as brain tumors.
Elsewhere in the body, more than 100 United States Food and Drug Administration-approved therapeutic antibodies are used by medical teams to treat cancers and autoimmune, infectious and metabolic diseases. Finding ways to transport therapeutic antibodies across the blood-brain barrier — from the peripheral blood stream into the central nervous system — could create effective treatments that act in the brain.
In a study published in the journal Frontiers in Cell and Developmental Biology, researchers at the University of Alabama at Birmingham report that the site-directed addition of an FDA-approved, biodegradable polymer at the hinge and near hinge regions of the therapeutic antibody trastuzumab effectively facilitated the brain delivery of this human monoclonal IgG1 antibody. Trastuzumab is used to treat breast cancer and several other cancers.
Preliminary work on this novel platform included in vitro and mouse-model experiments. Researchers say the delivery system still needs to be optimized and tested further, yet note their simple methodology converts antibody therapeutics to a brain-deliverable form that maintains the antibody’s medical functionality.
“The concerns of brain-entry haunt the development of brain-disease-targeting antibody therapeutics, impeding the medical translations of laboratory-generated antibodies to clinical practices,” said Masakazu Kamata, Ph.D., leader of the study and an associate professor in the UAB Department of Microbiology. “In this context, this simple methodology has great potential to serve as the platform to not only repurpose the current antibody therapeutics, but also encourage the design of novel antibodies, for the treatment of brain diseases.”
The biocompatible polymer used was poly 2-methacryloyloxyethyl phosphorylcholine, or PMPC, with chain lengths of 50, 100 or 200 monomers. The researchers had already discovered that this non-immunogenic polymer, which the FDA has approved as a coating material for transplantable devices, could bind to two receptors on brain microvascular endothelial cells composing the blood-brain barrier, and those cells could then move the polymer across the blood-brain barrier by transcytosis. Transcytosis is a specialized transport whereby extracellular cargo is brought inside the cell, shuttled across the cytoplasm to the other side of the cell, and then released.
The UAB researchers were able to cleave four interchain disulfide bonds in the trastuzumab IgG1 hinge and near hinge regions, creating thiol groups. Each thiol group was then conjugated to a chain of the PMPC to create trastuzumab molecules with one of the three chain lengths, which they denoted as Tmab-PMPC50, Tmab-PMPC100 and Tmab-PMPC200.

Each of these modified antibodies still maintained trastuzumab-specific binding to cells expressing the HER2 antigen, the target of trastuzumab. Both the Tmab-PMPC50 and the Tmab-PMPC100 were internalized into HER2-positive cells and promoted antibody-dependent cell death, which is the medical functionality by which trastuzumab kills HER2+ breast cancer cells.
The researchers then showed that PMPC conjugation of trastuzumab enhanced blood-brain barrier penetration through the epithelial cells on the blood-brain barrier via the transcytosis pathway. The translocatable Tmab-PMPC100 was the best at efficient blood-brain barrier penetration while retaining trastuzumab’s epitope recognition, the ability of the antibody to bind to its antigen target.
In a mouse model, both Tmab-PMPC100 and Tmab-PMPC200 were about fivefold better at brain penetration than native trastuzumab. In preliminary in vitro and mouse-model experiments, the polymer-modified trastuzumab did not induce neurotoxicity, did not show adverse effects in the liver, and did not disrupt the integrity of the blood-brain barrier.
“Those findings collectively indicate that PMPC conjugation achieves effective brain delivery of therapeutic antibodies, such as trastuzumab, without induction of adverse effects, at least in the liver, the blood-brain barrier or the brain,” Kamata said.
Others have also investigated ways to get cargos like antibodies across the blood-brain barrier, the researchers noted.
In work that led to the current study, the UAB researchers for the current study had shown they could wrap various macromolecular cargos within PMPC shells, and these nanocapsules demonstrated prolonged blood circulation, reduced immunogenicity and enhanced brain delivery in mice and non-human primates.

Yet this system had drawbacks. The nanocapsules required the addition of targeting ligands to bring them to their disease target and degradable crosslinkers that would allow release of the cargo at that site. Unfortunately, disease-associated microenvironments often lack conditions that can trigger degradation of the crosslinkers.
Other researchers seeking to breech the blood-brain barrier have investigated various ligands other than PMPC to boost transport, such as ligands derived from microbes and toxins, or endogenous proteins like lipoproteins. These generally have had undesirable surface properties — such as being highly immunogenic, highly hydrophobic or charged. PMPC does not exhibit those undesirable traits.
Co-authors with Kamata in the study, “Site-oriented conjugation of poly(2-methacryloyloxyethyl phosphorylcholine) for enhanced brain delivery of antibody,” are Jie Ren, Chloe E. Jepson, Charles J. Kuhlmann, Stella Uloma Azolibe and Madison T. Blucas, UAB Department of Microbiology; Sarah L. Nealy and Eugenia Kharlampieva, UAB Department of Chemistry; Satoru Osuka, UAB Department of Neurosurgery; and Yoshiko Nagaoka-Kamata, UAB Department of Pathology.
Support came from National Institutes of Health grants CA232015 and MH130183, an O’Neal Comprehensive Cancer Center at UAB Pre-R01 award, and National Science Foundation grant DMR-2208831.
At UAB, Microbiology, Neurosurgery and Pathology are departments in the Marnix E. Heersink School of Medicine, and Chemistry is a department in the College of Arts and Sciences.

A groundbreaking study published in the American Journal of Respiratory and Critical Care Medicine provides new insights into the treatment of obstructive sleep apnea (OSA) and its associated health impacts.
Researchers at the University of Missouri School of Medicine and the Marshall University Joan C. Edwards School of Medicine led by David Gozal, M.D., M.B.A., Ph.D. (Hon), vice president of health affairs at Marshall University and dean of the Joan C. Edwards School of Medicine, explored innovative therapeutic strategies that could greatly advance the understanding and management of OSA-related morbidities. Obstructive sleep apnea is a widespread condition affecting nearly one billion people around the world. It is linked to accelerated biological aging and various end-organ health issues, such as cardiovascular, cognitive and metabolic morbidities. While current treatments like continuous positive airway pressure (CPAP) have demonstrated limited success in reversing such outcomes, this recent research delves into adjunct therapies, particularly the use of senolytics, to alleviate the burden of OSA.
The study assessed whether targeting senescence, a treatment that targets aging cells, coupled with a simulated approach that imitates good adherence to the most common treatment for sleep apnea (CPAP) could improve physiological outcomes in mice exposed to chronic intermittent hypoxia (IH), a hallmark feature of OSA. The study found that combining partial normoxic recovery with the senolytic Navitoclax (NAV) significantly reduced sleepiness during the dark phase, the usual sleeping time for rodents. The combined therapy also showed notable improvements in cognitive function. Such findings were not apparent when only “CPAP” was administered.
“Our findings suggest that the reversibility of end-organ morbidities induced by OSA goes beyond normalizing oxygenation patterns,” said Gozal, corresponding author on the study. “Targeting accelerated senescence appears to be a promising avenue for improving treatment outcomes in individuals with OSA.”
“It is quite evident in our preclinical model of OSA that recovering normal oxygenation patterns seen in traditional treatments, namely continuous positive airway pressure, is ineffective in preventing or mitigating multiple end-organ dysfunctions” said Mohammad Badran, Ph.D., assistant professor at the University of Missouri School of Medicine. “Adjuvant therapies, in this case senolytics, have the potential of becoming valuable and effective treatments targeting OSA-induced morbidities.”
In addition, the therapy demonstrated positive effects on coronary artery function, glucose and lipid metabolism and reduced intestinal permeability. The combination of simulated adherent CPAP treatment and NAV effectively reduced senescence in multiple organs, indicating a potential reversal of OSA-induced cellular aging processes.
This research could open new doors in understanding the deleterious processes involved in OSA-associated morbidities and formulate novel approaches aimed at reversing the multifaceted impact of OSA on health. Development of safe senolytics specifically focused on OSA along with clinical studies are warranted to validate these findings in human subjects and explore potential applications in the field of sleep medicine.
In addition to Gozal and Badran, co-authors on the study from the University of Missouri include Clementine Puech, Ph.D., post-doctoral fellow; Abdelnaby Khalyfa, Ph.D., associate professor; Rene Cortese, Ph.D., assistant professor in the Department of Child Health and the Department of Obstetrics, Gynecology and Women’s Health; Kylie Cataldo, research specialist; and Zhuanhong Qiao, senior research consultant.

Because same-sex sexual behavior does not result in offspring, evolutionary biologists have long wondered how the genes associated with this behavior have persisted in the human genome, and whether they will remain in the future.
A new University of Michigan-led study, scheduled for publication January 3 in the journal Science Advances, suggests that part of the explanation — specifically for male bisexuals — has to do with risk-taking behavior.
The U-M researchers analyzed data from more than 450,000 participants of European ancestry in the United Kingdom’s Biobank database of genetic and health information. Participants responded to a questionnaire that included the question, “Would you describe yourself as someone who takes risks?”
The U-M analysis revealed that male heterosexuals who carry the genetic variants associated with bisexual behavior, which are known as BSB-associated alleles, father more children than average. Furthermore, men who describe themselves as risk-takers tend to have more children and are more likely to carry BSB-associated alleles.
These and other observations suggest that male BSB-associated alleles confer reproductive benefits because of the shared genetic variants between male bisexual and risk-taking behaviors.
“Our results suggest that male BSB-associated alleles are likely reproductively advantageous, which may explain their past persistence and predict their future maintenance,” said U-M evolutionary biologist Jianzhi Zhang, the study’s senior author.
“These results also suggest that risk-taking behavior is the underlying cause of BSB-associated alleles’ promotion of reproduction in heterosexuals. That is, the reproductive advantage of BSB-associated alleles is a byproduct of the reproductive advantage of risk-taking behavior,” said Zhang, the Marshall W. Nirenberg Collegiate Professor in the Department of Ecology and Evolutionary Biology.

The first author of the new study is U-M graduate student Siliang Song.
Risk-taking propensity usually describes a tendency to engage in reward-seeking actions despite the possibility of negative consequences. Although the UK Biobank question on risk-taking did not specify the type of risk, it is likely that self-reported risk-taking includes unprotected sex and promiscuity, which could result in more children, Zhang said.
In their analysis of the genetic underpinnings of same-sex sexual behavior, the U-M researchers looked at both bisexual behavior and exclusive same-sex behavior, which they call eSSB.
When they compared the genetic basis of bisexual behavior to the genetic basis of eSSB, they found them to be significantly different. They found that eSSB-associated genetic variants are correlated with fewer children, which is expected to lead to a gradual decline in their frequency over time.
However, the authors stress that their study looks at the genetic underpinnings of same-sex sexual behavior and not the behaviors themselves, which are affected by both genetic and environmental factors.
In fact, the proportion of UK Biobank participants reporting same-sex sexual behavior has been on the rise in recent decades, likely due to growing societal openness toward it, according to the researchers.

In addition, the authors say their new results “predominantly contribute to the diversity, richness, and better understanding of human sexuality. They are not, in any way, intended to suggest or endorse discrimination on the basis of sexual behavior,” they wrote.
The new study is a follow-up to one published in May in Proceedings of the National Academy of Sciences by Song and Zhang. That study also sought to explain the persistence of genetic variants associated with same-sex sexual behavior.
In 2021, Australian biologist Brendan Zietsch and colleagues presented evidence that heterosexuals carrying same-sex-associated alleles have more sexual partners than those not carrying the variants. This could confer a genetic advantage, the authors suggested, because more sexual partners could translate into more children.
In their PNAS study, which also relied on UK Biobank data, Zhang and Song showed that while the mechanism proposed by Zietsch likely worked in pre-modern societies, it is not active today because the widespread use of contraception has decoupled the number of offspring from the number of sexual partners in heterosexuals.
The findings presented in that PNAS paper led Zhang and Song to search for other potential mechanisms for the genetic maintenance of human same-sex behavior. That led to the Science Advances study, which was supported by the U.S. National Institutes of Health.

Researchers have created a new brain imaging method that allows mild traumatic brain injuries (mTBIs) to be diagnosed, even when existing imaging techniques like magnetic resonance imaging (MRI) don’t show any structural abnormalities. The technique involves loading gadolinium, a standard MRI contrast agent, into hydrogel-based micropatches that are attached to immune cells called macrophages. mTBIs cause inflammation in the brain, which produces signals that attract macrophages to migrate there. Coupling the gadolinium contrast agent to these cells enables MRI to reveal brain inflammation and increase the number of correctly diagnosed mTBI cases, improving patient care. The method is described in a new paper in Science Translational Medicine.
“70-90% of reported TBI cases are categorized as ‘mild,’ yet as many as 90% of mTBI cases go undiagnosed, even though their effects can last for years and they are known to increase the risk of a host of neurological disorders including depression, dementia, and Parkinson’s disease,” said senior author Samir Mitragotri, Ph.D., in whose lab the research was performed. “Our cell-based imaging approach exploits immune cells’ innate ability to travel into the brain in response to inflammation, enabling us to identify mTBIs that standard MRI imaging would miss.”
Mitragotri is a Core Faculty member of the Wyss Institute at Harvard University and the Hiller Professor of Bioengineering and Hansjörg Wyss Professor of Biologically Inspired Engineering at Harvard’s John A. Paulson School of Engineering and Applied Sciences (SEAS).
Using immune cells to identify inflammation
Most of us know someone who has had a concussion (another name for an mTBI), sometimes even more than one. But the vast majority of people who experience an mTBI are never properly diagnosed. Without that diagnosis, they can exacerbate their injuries by returning to normal activity before they’re fully recovered, which can lead to further damage. Some studies even suggest that repeated mTBIs can lead to chronic traumatic encephalopathy (CTE), the neurodegenerative disease that has been found to afflict more than 90% of professional American football players.
Because the effects of mTBI are believed to be caused by “invisible” brain inflammation, members of the Mitragotri lab decided to leverage their experience with immune cells to create a better diagnostic. “Our previous projects have focused on controlling the behavior of immune cells or using them to deliver drugs to a specific tissue. We wanted to exploit another innate ability of immune cells — homing to sites of inflammation in the body — to carry imaging agents into the brain, where they can provide a visible detection signal for mTBI,” said first author Lily Li-Wen Wang, Ph.D.. Wang is a former Research Fellow in the Mitragotri Lab at the Wyss Institute and SEAS who is now a scientist at Landmark Bio.
The team planned to use their cellular backpack technology to attach gadolinium molecules to macrophages, a type of white blood cell that is known to infiltrate the brain in response to inflammation. But right away, they ran into a problem: in order to function as a contrast agent for MRI scans, gadolinium needs to interact with water. Their original backpack microparticles are compost of a polymer called PLGA, which is hydrophobic (meaning it repels water). So Wang and her co-authors started developing a new backpack made out of a hydrogel material that could be manufactured at a large scale in the lab.

After years of hard work, they finally created a new hydrogel backpack that could produce a strong gadolinium-mediated MRI signal, attach stably to both mouse and pig macrophages, and maintain their cargo for a sustained period of time in vitro. They named their new microparticles M-GLAMs, short for “macrophage-hitchhiking Gd(III)-Loaded Anisotropic Micropatches.” Now, it was time to test them in a more realistic setting, for which they partnered with researchers and clinicians at Boston Children’s Hospital.
First, they injected mouse M-GLAMs macrophages into mice to see if they could visualize them in vivo. They were especially interested to see if they accumulated in the kidney, as existing gadolinium-based contrast agents like Gadavist® can cause health risks for patients with kidney disease. Their M-GLAMs did not accumulate in the mice’s kidneys, but persisted in their bodies for over 24 hours with no negative side effects. In contrast, mice injected with Gadavist® showed substantial accumulation of the contrast agent in their kidneys within 15 minutes of injection, and the substance was fully cleared from their bodies within 24 hours.
Then, they tested porcine M-GLAMs in a pig model of mTBI. They injected the M-GLAMs into the animals’ blood two days after a mock mTBI, then used MRI to evaluate the concentration of gadolinium in the brain. They focused on a small region called the choroid plexus, which is known as a major conduit of immune cells into the brain. Pigs that received the M-GLAMs displayed a significant increase in the intensity of gadolinium present in the choroid plexus, while those injected with Gadavist® did not, despite confirmation of increased inflammation macrophage density in the brains of both groups. The animals showed no toxicity in any of their major organs following administration of the treatments.
“Another important aspect of our M-GLAMs is that we are able to achieve better imaging at a much lower dose of gadolinium than current contrast agents — 500-1000-fold lower in the case of Gadavist®,” said Wang. “This could allow the use of MRI for patients who are currently unable to tolerate existing contrast agents, including those who have existing kidney problems.”
The authors note that while M-GLAMs can indicate the presence of inflammation in the brain via the high concentration of macrophages entering it through the choroid plexus, their technique cannot pinpoint the exact location of injuries or inflammatory responses in brain tissue. However, if coupled with new treatment modalities like one they developed in , M-GLAMS could offer a more rapid and effective way to identify and reduce inflammation in mTBI patients to minimize damage and speed their recovery.
The researchers have submitted a patent application for their technology, and hope to be able to bring it to the market in the near future. They are currently exploring collaborations with biotech and pharmaceutical companies to accelerate it to clinical trials .
“This work demonstrates just how much potential is waiting to be unlocked within the human body for a variety of functions: monitoring health, diagnosing problems, treating diseases, and preventing their recurrence. I’m impressed with this team’s ingenuity in leveraging immune cells to improve medical imaging, and hope to see it in clinicians’ hands soon,” said Wyss Founding Director Donald Ingber, M.D., Ph.D. Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and the Hansjörg Wyss Professor of Bioinspired Engineering at SEAS.
Additional authors of the paper include Yongsheng Gao, Vineeth Chandran Suja, Suyong Shaha, Rick Liao, Ninad Kumbhojkar, Supriya Prakash, Kyung Soo Park, and Michael Dunne from the Wyss Institute and SEAS; Masen Boucher, Kaitlyn Warren, Camilo Jaimes, and Rebekah Mannix from Boston Children’s Hospital; Neha Kapate and Morgan Janes from the Wyss Institute, SEAS, and MIT; Bolu Ilelaboye, Andrew Lu, and Solomina Darko from SEAS; and former SEAS members Tao Sun and John Clegg.
This research was supported by the US Department of Defense under Grant No. W81XWH-19-2-0011 and the National Science Foundation Graduate Research Fellowship under Grant Nos. 1122374 and 1745302.