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Cerebral edema, the dangerous brain swelling that occurs after traumatic brain injury (TBI), can increase risk of death tenfold and significantly worsen prospects for recovery in brain function. In extreme cases, surgeons will remove a portion of the skull to relieve pressure, but this has significant risks and is not viable for the vast majority of TBI cases. Physicians have very few tools at their disposal that are effective in treating cerebral edema, which is one of the leading causes of in-hospital deaths, and is associated with long-term neurological disability.
New research appearing today in the journal Nature could change all that, showing that a cocktail of drugs already approved to treat high blood pressure quickly reduces brain swelling and improves outcomes in animal models of brain injury.
“Our research shows that cerebral edema is the consequence of impaired fluid flow through the glymphatic system and its associated lymphatic drainage,” said Maiken Nedergaard, MD, DMSc, co-director of the University of Rochester Center for Translational Neuromedicine and senior author of the study. “This impairment is under adrenergic control, and can therefore be rescued pharmacologically by broadly inhibiting adrenergic receptors. Because these drugs are already being used clinically and have observed neurological benefits, there is the potential to move quickly to clinical studies to confirm these findings.”
Manipulating fluid flows in the brain to release post-TBI brain pressure
The glymphatic system was first described by Nedergaard’s lab in 2012 as the brain’s unique waste removal process. Since then, a growing understanding of the mechanics of the system-aided by advanced imaging technologies and AI-driven models of fluid dynamics — has allowed researchers to better predict and manipulate the movement of cerebrospinal fluid (CSF) in the central nervous system. This research has opened new possibilities to treat Alzheimer’s and other neurological disorders and more effectively deliver and distribute drugs in the central and peripheral nervous system, including the inner ear.
The new study points to the potential to repurpose the glymphatic system to act as an emergency pressure release valve. Cerebral edema is a common consequence of moderate and severe cases of TBI. “In other parts of the body, edema helps with tissue repair, but because of the skull, the brain has limited capacity for expansion. As a result, pressure increases, blood supply decreases, and debris and toxic proteins are trapped at the injury site, compounding the damage and impairing recovery,” said Rashad Hussain, PhD, an assistant professor in the Center for Translational Neuromedicine and first author of the study.
One of the main triggers of cerebral edema is noradrenaline, a neurotransmitter that floods the brain immediately after TBI. Noradrenaline is typically associated with the flight-or-fight response, but in TBI this “adrenergic storm” impairs the flow of CSF in and out of the brain.

The researchers describe how noradrenaline interferes with the function of the glymphatic system. Specifically, it restricts the movement of fluid through the section of the system’s plumbing where CSF drains from the brain and flows into the meningeal and cervical lymph nodes in the neck. This observation led the team to speculate whether reopening these gates to the lymph nodes could flush excess CSF from the brain, thereby relieving pressure.
Blood pressure medications suppress adrenaline “storm” and restart fluid flow
To accomplish this, the team used a cocktail of drugs, including prazosin, atipamezole, and propranolol. This combination of alpha- and beta-blockers collectively suppress the different receptors used by cells to take up noradrenaline. Previous research in Nedergaard’s lab has shown that this combination of drugs ramps up the glymphatic system, replicating the level of activity experienced when we sleep, which is when the system is most efficient in manipulating CSF flow to remove waste.
In the new study, the same drug cocktail was administered to mice soon after TBI. Using fluorescent microspheres, the researchers traced CSF originating from the site of the swelling as it exited in bulk from the brain via lymphatic vessel, carrying with it debris from the injury to the lymph nodes. The result was an almost immediate elimination of cerebral edema and a sustained return to normal intracranial pressure in the animals. The treatment resulted significant recovery of cognitive, behavioral, and motor function.
“These findings show that the adrenergic storm, the resulting edema and intracranial pressure, and retention of neural debris, can all be reversed by broad adrenergic inhibition, with subsequent improvement in recovery in injured mice,” said Nedergaard.
The authors point to several clinical studies that demonstrate the safety profiles and observed neurological benefits of these drugs, early indications that this approach could also benefit humans. Atipamezole reduces post-traumatic seizures, prazosin is effective in treating the post-traumatic stress associated with TBI, and beta-blockers reduce in-hospital mortality and improve functional outcome of TBI patients. Additionally, Nedergaard and her colleagues at the University of Copenhagen have shown that individuals who take beta-blockers for hypertension are at lower risk for Alzheimer’s.
Additional co-authors in the study include: Jeffrey Tifhof, Wei Wang, Arokoruba Cheetham-West, Wei Song, Weiguo Peng, Qian Sun, Sisi Peng, and Doug Kelley with the University of Rochester; Bjorn Sigurdsson and Pia Weikop with the University of Copenhagen; Virginia Pla, Hajime Hirase and Steve Goldman with both with the Universities of Rochester and Copenhagen; Daeyun Kim with the University of Minnesota; Jorge Castorena-Gonzalez with the Tulane University; and Michael Davis with the University of Missouri. The research was supported with funding from the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the National Institute of Neurological Disorders and Stroke, the Burroughs Wellcome Fund, the Joint Programme — Neurodegenerative Disease Research, the Novo Nordisk Foundation, the Lundbeck Foundation, and the US Army Research Office.

Researchers from the University of B.C. and the BC Provincial Toxicology Centre (BCPTC) have developed a more efficient way to find out which new ‘designer drugs’ are circulating in the community.
In a study published today in Analytical Chemistry, they showed how high-resolution mass spectrometry can be used to analyze urine samples at scale and uncover molecules from emerging designer drugs that have been missed by conventional testing.
The approach can support public health and safety by enabling swift identification of new substances, potentially saving lives and guiding timely clinical responses to drug-related emergencies.
“We were able to detect a number of drugs circulating in B.C. that were not being detected by existing tests. Any time such drugs emerge locally, that’s important information for clinicians and public health officials to have,” said Dr. Michael Skinnider, the study’s lead author who conducted the research as an MD/PhD student at UBC and is now an assistant professor at Princeton University.
Designer drugs have proliferated in the past two decades in the unregulated market. They tend to be modified versions of other drugs, with similar effects but just enough structural changes to get around drug laws. The drugs do not undergo proper testing or regulation. Some can poison or even kill users.
The BCPTC at the BC Centre for Disease Control (BCCDC) has identified over 20 different drugs of concern while monitoring for them since 2020.
To confirm whether a drug is present in a sample, a lab must first know what they’re looking for and obtain that drug in synthetic form. This becomes their “reference standard,” and it’s used to develop a repeatable laboratory test that leaves no doubt about the substance’s presence.

However, reference standards can be hard to acquire. Sometimes the drugs are so new that a reference standard simply doesn’t exist. Sourcing hundreds of reference standards for drugs that may or may not show up in the community is expensive and impractical, so laboratories instead make educated guesses about which ones to acquire.
The goal of the UBC/BCPTC study was to find a better way to prioritize acquisition of reference standards.
To do this, the researchers used high-resolution mass spectrometry to re-analyze more than 12,000 urine samples collected in B.C. from 2019 to 2022. If you imagine a urine sample to be a jigsaw puzzle with all its pieces scattered in the form of molecules, mass spectrometry can precisely determine the weight and shape of each puzzle piece, which helps researchers figure out which ones fit together in combinations that are typical of illicit drugs.
If a laboratory anywhere in the world has published data about new drug molecules found in their samples, a lab in B.C. can compare its data with theirs and determine which drugs are most likely showing up locally.
It’s not a definitive confirmation, but it’s enough to point the lab toward the right reference standards for more thorough testing.
The retrospective analysis of B.C. samples at BCPTC surfaced new synthetic opioids, benzodiazepines and stimulants that had eluded identification during initial screening. One of them, fluorofentanyl, is a modified version of fentanyl that was absent from samples before mid-2022 and then spiked during the final few months of the study. This suggests it was introduced to the local drug supply quite suddenly.

A few of the other drugs also had distinct peaks during the two-year study period.
“Applying this process on a regular basis will allow us to respond much more quickly to the emergence of new drugs and greatly reduce the time between a drug’s introduction to the community, and our ability to test for it in a rigorous way,” said Dr. Aaron Shapiro, the study’s senior author who is a clinical assistant professor in UBC’s department of pathology and laboratory medicine, and associate scientific director of the PTC.
The BCCDC is in the process of implementing this new tool into its clinical urine drug screen and hopes to apply it to other datasets in the future.
Researchers from the chief medical examiner’s office in San Francisco and St. Paul’s Hospital in Vancouver also contributed to the study.

The NewsOn Saturday, after a 12-year effort, the Department of Veterans Affairs reached a long-term goal — it enrolled the millionth veteran in a genetic database, the Million Veteran Program.According to the V.A., the Million Veteran Program is the largest such database in the world. It includes not only genetic information but also is linked to the department’s electronic medical records and even contains records of diet and environmental exposure.The department says its data are available for now only to V.A. doctors and scientists, most of whom also have academic appointments. They have published hundreds of studies using what has already been collected.A U.S. Army veteran prepared to kayak during a Veterans Affairs health care network kayaking and sailing event on the Hudson River in August.Spencer Platt/Getty ImagesA Moment That Sums It Up: 3:46 p.m.The millionth vet joined the database on the afternoon of Nov. 11. Employees who had waited a dozen years for this moment wept.As the goal approached, the department had started an intensive email campaign, encouraging vets to sign up online or at V.A. medical centers. In the few weeks building up to the millionth vet, what had been a few hundred enrollees a day turned into thousands. The department created a ticker, which it posted online, showing the numbers.“This is a gift to the world,” said Denis McDonough, secretary of veterans affairs.The V.A. will continue to enroll more vets to the database, but this was a symbolic moment.Why It Matters: A diverse database yields disease insights.For years, researchers have been building large databases for genetic research. Using them they have found, for example, genes that appear to confer resistance to dementia and ones that most likely contribute to obesity. The discoveries provide paths to understanding these diseases and developing treatments.There are other large genetic databases, but they have mostly been built in Europe and include few minorities. The V.A. says its database offers a more diverse population: 175,000 people with African ancestry and 80,000 Hispanics joined the Million Veteran Program. The database also includes 100,000 women.“It’s a massive investment and scientific opportunity,” said Dr. Amit V. Khera, a genetic researcher at Massachusetts General Hospital. He is not a V.A. researcher, but he has used the data through collaborations with researchers who are affiliated with the department.As the database acquired participants, about 600 V.A. researchers registered to use it. The result so far has been more than 350 papers on diseases and disorders, including post-traumatic stress disorder, heart disease, high blood pressure and nonalcoholic liver disease.For example, said Dr. Sumitra Muralidhar, director of the Million Veteran Program, researchers found genes linked to having flashbacks of traumatic events, a feature of post-traumatic stress. Now, Dr. Muralidhar said, investigators can study those genes and the role they play, which may help in developing treatments for PTSD.The department also says it is being mindful of patient privacy. Although researchers can examine genetic and other data and links to medical records, fewer than 10 people at the V.A. have the links that tie records to individuals. Those records, Dr. Muralidhar said, are held at a facility in Boston that is “heavily secured.”What It Looks Like: Veterans hope the database will help.In 2019, a nurse at a V.A. hospital told Octavia Harris, 60, of San Antonio, about the Million Veteran Program. She signed up and said participating was a chance to help other vets and to help herself.Ms. Harris, who retired from the Navy in 2012 after 30 years of service, said three conditions run in her family — diabetes, high blood pressure and arthritis. She is hoping that with her genetic and health information added to that of so many others, researchers will make useful discoveries.In her family, Ms. Harris said, people died young.“We haven’t lived beyond the age of 70,” she said. “I want to go past 70.”

Published15 NovemberShareclose panelShare pageCopy linkAbout sharingBy Aoife Walsh and Pria RaiBBC News and BBC ThreeA woman who was illegally sold a weight loss drug on social media told the BBC she ended up in A&E vomiting blood.Maddy, 32, fell seriously ill after using an unlicensed version of semaglutide – the active ingredient in Ozempic – from Instagram. A BBC investigation found unregulated sellers offering semaglutide as a medicine, without prescription, online.It also found the drug being offered in beauty salons in Manchester and Liverpool.Watch the full BBC3 documentary ‘The Skinny Jab Uncovered’ on iPlayerDoctors say drugs bought from unregulated sources are dangerous and could contain potentially toxic ingredients. Demand for Ozempic, a prescribed type 2 diabetes medication, spiralled last year after it hit the headlines for being Hollywood’s secret weight loss drug – nicknamed the skinny jab. The drug works by lowering blood-sugar levels and slowing down food leaving the stomach.Its soaring popularity led to a rise in off-label prescriptions for weight loss, which triggered global supply issues and created a shortage for diabetes patients in the UK. As pharmacies across the UK struggled to get hold of the medication, an illicit black market selling semaglutide “diet kits” began to flourish online.Delivered by post, these usually contain needles and two vials – one containing a white powder and the other a liquid – which have to be mixed together before the drug can be injected.That’s what came through Maddy’s letterbox after she searched for a “quick fix” on Instagram to help her lose weight ahead of an event. Weight loss drug semaglutide approved for NHS useGPs set to offer weight-loss jab to reduce obesityAppetite drug could mark ‘new era’ in obesity”I struggle in general with losing weight. I’m just not one of those people that can shift it easily,” she says.Maddy came across The Lip King, a company run by Jordan Parke. The Lip King’s Instagram feed was flooded with before-and-after transformation photos of women with newly slimmed physiques and screenshots of text messages from customers raving about his product. Maddy wanted in.After a brief message exchange with Mr Parke and a £200 bank transfer, Maddy was sold 10mg of semaglutide with no questions asked.She also received a video from him on WhatsApp instructing her how to mix and inject the drug, along with dangerous guidance advising her to take a higher dose than what health officials would recommend. After her first injection, Maddy was instantly “extremely ill, bed-bound, vomiting”.She says Mr Parke told her over text that vomiting was normal and to take anti-sickness tablets.A few weeks later, when the nausea had passed, Maddy tried the drug again – this time before bed.”I was woken up by the vomiting,” Maddy says. “It was bad. I was throwing up all night, to the point where I was throwing up stomach acid, blood, white foam.”She went to A&E the following afternoon, where she was put on a drip.”I can be a bit of a drama queen, but I thought I was dying. I was literally crunched over, bawling my eyes out to my mum. I was so angry, as well, because I was like, no-one told me that this was going to be a side effect,” she says. This video can not be playedTo play this video you need to enable JavaScript in your browser.”I did my own research, but I didn’t see anywhere that anyone was suffering to this level.”The BBC made several attempts to contact Mr Parke, but he did not respond. Removing websitesMr Parke is one of many illicit sellers peddling semaglutide through social media. To find out what is actually in the drugs, the BBC bought unlicensed semaglutide from several sellers and had them tested in the lab. The results showed inconsistencies in what was in each sample. Although most of the products contained semaglutide, vials from two different sellers had no semaglutide in them at all, and nearly all of them, including the one bought from the Lip King, did not contain the full dose that had been paid for. Ozempic is available on the NHS strictly for type 2 diabetes patients. Wegovy, another semaglutide drug prescribed specifically to treat obesity, will be offered on the NHS to those with a body mass index (BMI) of at least 35, and exceptionally, some people with a BMI of 30 and a weight-related health problem. Under UK law, it is illegal to sell semaglutide as a medicine without a prescription. Drugs manufacturer Novo Nordisk is the only company approved to sell and market semaglutide, branded as Ozempic and Wegovy, in the UK, but it is now battling against knock-off online sales. The firm says it is working with a third party to “proactively identify and remove websites, ads or social-media accounts selling counterfeit semaglutide”, and has been carrying out “in-depth investigations into copyright infringement, criminal networks and sellers illegally diverting our products”. But the BBC has discovered sellers that are closed down one day usually return the next under a new name. Online sellers attempt to get around the law by placing “not fit for human consumption” or “for research purposes only” on their product.Gerard Hanratty, a public law expert, says: “You can put lots of different things on a label. It doesn’t mean to say that it is then legal and you are compliant with the regulations.”He says sellers would need to be able to prove they are supplying the product for research purposes and not for human use in order for the warnings to be valid.Salon salesA BBC Three documentary The Skinny Jab Uncovered found the unapproved versions of the drug advertised in beauty salons on British high streets. Undercover investigators visited four salons in Manchester and Liverpool and received dangerous advice about mixing and dosages in some about how to use the drug. In one salon, a reporter was told: “Well, if you have too much, you just wouldn’t want to eat anything, and you might feel sick. It’s not going to be dangerous.”This video can not be playedTo play this video you need to enable JavaScript in your browser.The Medicines and Healthcare products Regulatory Agency (MHRA) says it has received reports of people ending up in hospital after using fake Ozempic pens, which are also flooding the market, with more than 300 seized since January.Prof Barbara McGowan, a consultant endocrinologist who co-authored a Novo Nordisk-funded study which trialled semaglutide to treat obesity, says licensed medications – like Ozempic and Wegovy – go through “very strict” quality controls before they are approved for use. She warns that buyers using semaglutide sourced outside the legal supply chain “could be injecting anything”. “We don’t know what the excipients are – that is the other ingredients, which come with the medication, which could be potentially toxic and harmful, [or] cause an anaphylactic reaction, allergies and I guess at worse, significant health problems and perhaps even death,” she says. Prof McGowan says that drugs like semaglutide can cause “significant side effects”, such as nausea, for some patients, which is why proper medical support is needed.”The important thing to understand is not just about the prescription. It’s about… all the wraparound care that one gets from senior health-care professionals,” she adds.’Huge health risks’Dale Dennis, a personal trainer from East Yorkshire, sells 10mg vials of the unofficial drug and pre-mixed pens.Mr Dennis sells the unlicensed drug on social media, encouraging buyers to message him on WhatsApp to place an order.His company, Raw Peptides Limited, is listed as a business involved in the sale of “new cars and light motor vehicles”.The BBC contacted Mr Dennis for comment, but after initially agreeing to speak to us, he cancelled our call and sent a text using an expletive, adding: “I definitely make your yearly salary weekly”. Dr Simon Cork, senior lecturer in physiology at Anglia Ruskin University, stresses that semaglutide is not a short-term weight loss solution and is suitable only for people with obesity.”That might be seen as being kind of selfish, because those people quite understandably want to lose some weight, but the drug is not tested or designed to help people in that position.”He says mixing and injecting weight loss drugs at home comes with “huge risks”. “The vast majority of the population are not qualified or trained to administer injectable drugs themselves. And the drugs you buy if you’re prescribed Wegovy or Ozempic, or one of the licensed drugs, those come in predefined amounts,” he says. “So you press a button and you get the correct dose of the medication. You’re not drawing up an amount into a needle that you’re then injecting into yourself.”The vials of semaglutide sold illegally online do not have the safeguards the official medication comes with to prevent patients from overdosing. Tilly, 22, decided to stop using semaglutide she bought on TikTok after she accidentally injected double the amount she was supposed to. “When it came, it didn’t have any instructions, which completely confused me… I messaged the company after being like ‘what am I meant to do with this?’ And she was like, ‘well, join a Facebook group’,” she says. “It felt like the worst hangover ever. I felt like I had a really bad headache. I felt sick, and I felt stressed about the fact that I’d taken too much,” she says. The medicines regulator says it will use its powers to protect the public by taking “appropriate enforcement action, including, where necessary, prosecuting those who put your health at risk”.The Medicines and Healthcare products Regulatory Agency’s chief safety officer, Dr Alison Cave, warns that buying semaglutide from illegal suppliers “means there are no safeguards to ensure products meet our quality and safety standards, and taking such medicines may put your health at risk”.”If you suspect you’ve had an adverse reaction to semaglutide or any other medicinal product, are worried about its safety or effectiveness, or suspect it is not a genuine product, please report it to our Yellow Card scheme,” she says. BBC Three investigates the black market in cut price ‘skinny jabs’ and asks: are they what they claim to be? And are they safe?Watch now on BBC iPlayer (UK Only)Sign up for our morning newsletter and get BBC News in your inbox.More on this storyWeight loss drug semaglutide approved for NHS usePublished8 MarchGPs set to offer weight-loss jab to reduce obesityPublished7 JuneAround the BBCBBC Three – The Skinny Jab Uncovered

Published7 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, Sebastiao Moreira/EPA-EFE/REX/ShutterstockBy Kathryn ArmstrongBBC NewsRed alerts have been issued for almost 3,000 towns and cities across Brazil, which have been experiencing an unprecedented heatwave. Rio de Janeiro recorded 42.5C on Sunday – a record for November – and high humidity on Tuesday meant that it felt like 58.5C, municipal authorities said.More than a hundred million people have been affected by the heat, which is expected to last until at least Friday.Officials have attributed it to the El Niño phenomenon and climate change.The city of São Paulo saw average temperatures of 37.3C on Tuesday afternoon, the National Institute of Meteorology (Inmet) reported. “I’m exhausted, it’s hard,” Riquelme da Silva, 22, told AFP news agency on the streets there. “When I get home, it’s cold water, otherwise I can’t even get up because I’m so tired. It’s even hard to sleep.”Dora, a 60-year-old street vendor, described the heat as “unbearable” for those who worked outside. Image source, ReutersInmet has issued red alerts for a large part of the country. These indicate that temperatures may be 5C above average for longer than five days and could pose a serious danger to health. The heatwave, which comes more than a month before the beginning of summer in the southern hemisphere, has seen Brazil’s energy consumption soar to record levels as people try to keep themselves cool. Inmet research released last week showed that the average temperature in the country had been above the historical average from July to October. Extreme weather is becoming more frequent and more intense in many places around the world because of climate change.According to scientists, heatwaves are becoming longer and more intense in many places and this is expected to continue whilst humans keep releasing planet-warming greenhouse gases.Meanwhile, the Earth is currently in an El Niño weather phase, during which time global temperatures typically increase.Image source, AFPMore on this storyExtreme autumn heat sets up 2023 for recordPublished7 days agoStranded boats and dead fish: Amazon droughtPublished12 October

One University of Kentucky researcher has helped solve a 60-year-old mystery about one of the body’s most vital organs: The heart.
Kenneth S. Campbell, Ph.D., the director of translational research in the Division of Cardiovascular Medicine in the UK College of Medicine, helped map out an important part of the heart on a molecular level. The study titled “Cryo-EM structure of the human cardiac myosin filament” was published online in the journal Nature earlier this month.
The heart is made up of billions of cells. Each cell contains thousands of smaller structures, called sarcomeres. These are the building blocks of muscle. Within each block, are hundreds of myosin filaments. To put this microscopic level into perspective, if the heart is a continent, Campbell and fellow researchers are looking at single strands of hair.
“Each filament has roughly 2,000 molecules arranged in a really complicated structure that scientists have been trying to understand for decades,” said Campbell. “We knew quite a lot about the individual molecules and people thought the myosins could be arranged in groups of six that were called crowns, but not much beyond that.”
Campbell explained the most interesting discovery in the paper is that there are three different types of crowns. The interactions between them are shown in the second photo below.
“We think this means that heart muscle can be controlled more precisely than we had realized. We were also excited to see how myosin binding protein-C, another protein that is linked to genetic heart disease, sits within the structure. It gives us a new level of information about how the molecules are arranged in the heart,” said Campbell.
Working with researchers at the University of Massachusetts Chan Medical School, the group produced single-particle 3D reconstructions of the cardiac thick filaments. The pictures provide a new framework for interpreting structural, physiological and clinical observations.

“This study is important for discovering new drug therapies for heart disease which Kentucky desperately needs,” said Campbell. “It gives us a much better understanding of how the molecules in our hearts interact.”
Heart disease is the leading cause of death in Kentucky and puts the Commonwealth among the top 10 states with the highest death rate from the disease, according to the Centers for Disease Control and Prevention (CDC).
“We’re interested in therapies for different kinds of heart failure and myopathies, where the heart muscles don’t work very well,” said Campbell. “Our research is one of many projects underway at the university to help come up with better therapies for heart disease.”
The research team collected heart samples from the Gill Cardiovascular Biorepository, of which Campbell is the director. Samples are donated for research purposes from patients who receive cardiovascular care at UK.
“We started the Gill Cardiovascular Biorepository in 2008. With the help of a surgeon at UK HealthCare, we started collecting samples of myocardium from organ donors and from patients who were getting cardiac transplants,” said Campbell. “Now we’ve built a huge resource with roughly 15,000 samples from nearly 500 people.
“We also share these samples with research groups around the world. This study in Nature comes from one of those collaborations.”

For the first time, University of Queensland (UQ) researchers have shown how the tau protein, known for its role in dementias, behaves where communication in the brain takes place.
The study led by Dr Ramón Martínez-Mármol and PhD student Shanley Longfield from UQ’s Queensland Brain Institute used super-resolution microscopy to visualise individual tau proteins in motion while neurons are “talking” to each other.
Dr Martínez-Mármol explained that the team’s discovery is a big step towards understanding what triggers tau aggregation in disease states like Alzheimer’s disease.
“We discovered that tau in a healthy brain controls an important population of vesicles at the presynapse critical for neuronal communication,” Dr Martínez-Mármol said.
“These vesicles are like the words that neurons use to transmit information to other neurons.
“For the very first time, we’ve shed light on the mechanism by which tau acts in our nerve cells.
“By understanding tau’s role in a healthy context, we begin to fully understand what leads to the abnormal accumulation of tau in disease.”
Ms Longfield said that observing tau’s behaviour in healthy states provides clues to how these toxic aggregates start to form.

“Studying tau in a healthy brain is more challenging than studying it in a diseased brain, where changes in its molecular behaviour are far more prominent and obvious,” Ms Longfield said.
“But by visualising tau at the nanoscale and in this context, we can identify the molecular behaviours that precede the formation of toxic protein aggregates in disease.”
The team also discovered that tau molecules form tiny condensates, dense gel-like bodies within brain cells, which resemble oil droplets suspended in water.
“What we noticed is that these tau condensates are very fluid-like and dynamic and are tightly regulated by synaptic activity,” Ms Longfield said.
“In neurodegenerative disorders, these condensates get bigger and denser and eventually form aggregates, which are destructive to brain function.
“Our next challenge is to track diseased tau in brain cells to see how this new function is altered, leading to tau aggregation.”
This is a collaborative publication with The University of Sydney and i-Synapse.

We’ve known for more than a century that women outlive men. But new research led by UC San Francisco and Harvard T.H. Chan School of Public Health shows that, at least in the United States, the gap has been widening for more than a decade. The trend is being driven by the COVID-19 pandemic and the opioid overdose epidemic, among other factors.
In a research paper, published Nov. 13, 2023, in JAMA Internal Medicine, the authors found the difference between how long American men and women live increased to 5.8 years in 2021, the largest it’s been since 1996. This is an increase from 4.8 years in 2010, when the gap was at its smallest in recent history.
The pandemic, which took a disproportionate toll on men, was the biggest contributor to the widening gap from 2019-2021, followed by unintentional injuries and poisonings (mostly drug overdoses), accidents and suicide.
“There’s been a lot of research into the decline in life expectancy in recent years, but no one has systematically analyzed why the gap between men and women has been widening since 2010,” said the paper’s first author, Brandon Yan, MD, MPH, a UCSF internal medicine resident physician and research collaborator at Harvard Chan School.
Life expectancy in the U.S. dropped in 2021 to 76.1 years, falling from 78.8 years in 2019 and 77 years in 2020.
The shortening lifespan of Americans has been attributed in part to so-called “deaths of despair.” The term refers to the increase in deaths from such causes as suicide, drug use disorders and alcoholic liver disease, which are often connected with economic hardship, depression and stress.
“While rates of death from drug overdose and homicide have climbed for both men and women, it is clear that men constitute an increasingly disproportionate share of these deaths,” Yan said.

Interventions to reverse a deadly trend
Using data from the National Center for Health Statistics, Yan and fellow researchers from around the country identified the causes of death that were lowering life expectancy the most. Then they estimated the effects on men and women to see how much different causes were contributing to the gap.
Prior to the COVID-19 pandemic, the largest contributors were unintentional injuries, diabetes, suicide, homicide and heart disease.
But during the pandemic, men were more likely to die of the virus. That was likely due to a number of reasons, including differences in health behaviors, as well as social factors, such as the risk of exposure at work, reluctance to seek medical care, incarceration and housing instability. Chronic metabolic disorders, mental illness and gun violence also contributed.
Yan said the results raise questions about whether more specialized care for men, such as in mental health, should be developed to address the growing disparity in life expectancy.
“We have brought insights to a worrisome trend,” Yan said. “Future research ought to help focus public health interventions towards helping reverse this decline in life expectancy.”
Yan and co-authors, including senior author Howard Koh, MD, MPH, professor of the practice of public health leadership at Harvard Chan School, also noted that further analysis is needed to see if these trends change after 2021.
“We need to track these trends closely as the pandemic recedes,” Koh said. “And we must make significant investments in prevention and care to ensure that this widening disparity, among many others, do not become entrenched.”

Monitoring brain injury biomarkers and glucose variation in patients who have suffered an acute cranial injury during the entire first week of hospitalisation can provide a more accurate picture of the pathological process. This is according to a paper by researchers at Karolinska Institutet in Sweden published in The Lancet Neurology. It is hoped that their findings can eventually lead to more personalised treatment.After samples of brain injury markers and glucose have been taken over the entire first week of intensive care, patients with traumatic brain injury can be divided into different groups with different disease trajectories and prognoses.
“This could one day be used to identify different therapies for these different groups, who currently receive effectively the same treatment,” says the study’s first author Cecilia Åkerlund, anaesthetist and intensive care specialist at Karolinska University Hospital in Solna and researcher at the Department of Physiology and Pharmacology, Karolinska Institutet, Sweden.
She shows in her study that an advanced clustering method can be used to divide patients into six groups by sample data. In the group with the best prognosis, only four per cent died after six months, as opposed to a full 65 per cent in the group with the worst prognosis after the same time – 41 per cent during the first week.
Many hospitals now use a model based on different factors from the patients’ day of admission to assess their prognoses.
“Our study shows that more information gathered over a longer time might be needed to assess the patients,” she says.
The variation between the highest and lowest glucose variation during the day was one of the key metrics used to characterise the patients, something to which little attention is paid today. The same is true of the relevant biomarkers, which are also generally ignored during the first week of admission. Karolinska University Hospital, however, is an exception:
“We clinically monitor certain brain injury biomarkers daily,” says Dr Åkerlund. “But we are one of few hospitals in the world to do so, as far as I’m aware.”
“Our study supports the notion that serial brain injury biomarkers can play an important part in monitoring the disease trajectory in our brain injury patients,” says the study’s last author David Nelson, consultant at Karolinska University Hospital’s neurocritical care unit and researcher at Karolinska Institutet.

At the same time, Dr Åkerlund acknowledges that more research is needed on both the biomarkers and the patient groupings before the method can be recommended on a broad front.
“These results need to be corroborated by larger studies and with other patient groups to show that the method is stable,” she says. “If we can do this, it will be an important step towards being better able to personalise the treatment of patients with primarily moderate and severe traumatic brain injuries.”
The study was financed by grants from the EU’s Seventh Framework Programme, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences Corporation and NeuroTrauma Sciences.
David K. Menon has reported financial relations with several pharmaceutical companies unrelated to this study; Shubhayu Bhattacharyay has reported research grants from the Gates Cambridge Foundation, Peter Smielewski software licence revenue, and Ewout Steyerberg royalties from Springer publishing house. All other researchers report no conflicts of interest.
Facts:
Acute cranial injury, or traumatic brain injury, affects men and women of all ages and for all types of reasons; however, patients are commonly in the younger age bracket following a traffic accident or the older following a fall. Seventy-five per cent are men. The study used data from the European multicentre study CENTER-TBI, the largest-ever observational study of traumatic brain injury. Frozen samples from over 1,700 patients were post-analysed. The researchers then used an advanced clustering method to create the different groups that best described the pathological process to optimise the groupings. Source: Cecilia Åkerlund.
Publication: “Clinical descriptors of disease trajectories in patients with traumatic brain injury in the intensive care unit (CENTER-TBI): a multicentre observational cohort study”, Cecilia A.I. Åkerlund, Anders Holst, Shubhayu Bhattacharyay, Nino Stocchetti, Ewout Steyerberg, Peter Smielewski, David K. Menon, Ari Ercole, David W. Nelson, The Lancet Neurology, online 14 November 2023, doi: 10.1016/S1474-4422(23)00358-7.

Waiting for two minutes or longer to clamp the umbilical cord of a premature baby soon after birth could help reduce the risk of death, compared with immediately clamping the umbilical cord, or waiting a shorter time before doing so. Delaying clamping could decrease the child’s risk of death by more than half relative to immediate clamping.
The new findings, published today in two companion papers in The Lancet, examined clinical trial data and outcomes of thousands of premature babies which had delayed cord clamping compared to those whose cord was clamped immediately after birth.
Delaying clamping of the umbilical cord allows blood to flow from the placenta to the baby whilst the baby’s lungs fill with air. This is thought to help ease the transition to breathing in the infant.
“Worldwide, almost 13 million babies are born prematurely each year and, sadly, close to 1 million die shortly after birth. Our new findings are the best evidence to date that waiting to clamp the umbilical cord can help save the lives of some premature babies,” says first author Dr Anna Lene Seidler at the NHMRC Clinical Trials Centre, University of Sydney.
“We are already working with international guideline developers to make sure these results are reflected in updated guidelines and clinical practice in the near future.”
Delayed cord clamping is now recommended routine practice for babies born at full term. However, whilst previous research , including trials led by University of Sydney, showed potential benefit for premature babies, best practice for this vulnerable group remained uncertain. Until recently, clinicians generally cut the cord of preterm babies immediately so urgent medical care could be given.
These uncertainties have led to different recommendations in national and international guidelines.

For instance, for preterm infants not requiring resuscitation at birth, the Australian and New Zealand Committee on Resuscitation (ANZCOR) suggest delaying cord clamping for at least 30 seconds.
The World Health Organization and the UK’s National Institute for Health and Care Excellence (NICE) recommend delayed umbilical cord clamping (not earlier than 1 min after birth) for improved maternal and infant health and nutrition outcomes.
For preterm babies requiring resuscitation, the WHO recommends immediate clamping, while ANZCOR make no recommendation due to insufficient evidence.
Largest delayed cord clamping dataset to date
The studies were the result of a massive global effort (the iCOMP collaboration) among more than 100 international researchers on umbilical cord management, who shared their original data with Dr Seidler and her team for analysis, including the large APTS trial led out of the University of Sydney.
This created one of the largest databases in this research field, with over 60 studies and including more than 9000 babies.

The first paper using data from 3,292 infants across 20 studiesfound delayed clamping of the umbilical cord, clamped 30 seconds or more after birth, likely reduced the risk of death in premature babies by a third compared to those whose umbilical cord was clamped immediately after birth.
In a subgroup of premature babies where infants were born before 32 weeks of pregnancy, 44.9 percent of the babies with immediate cord clamping experienced hypothermia after birth, compared to 51.2 percent of those with delayed clamping. The average difference in temperature between the deferred clamping group and the immediate clamping group was -0.13 °C.
“Our findings highlight that particular care should be taken to keep premature babies warm when deferring umbilical cord clamping. This could be done by drying and wrapping the baby with the cord intact, and then by placing the dry baby directly on the mother’s bare chest under a blanket, or using bedside warming trollies,” says Prof Lisa Askie, senior author of the study from the NHMRC Clinical Trials Centre.
The second paper analysed data from 47 clinical trials, which involved 6,094 babies, and found waiting at least two minutes before clamping the cord of a premature baby may reduce the risk of death compared with waiting less time to clamp the cord.
In comparing different timings, waiting two or more minutes to clamp the cord had a 91 percent probability of being the best treatment to prevent death shortly after birth.
Immediate clamping had a very low (