Publisher Health

A small molecule previously shown to enhance strength in injured or old laboratory mice does so by restoring lost connections between nerves and muscle fibers, Stanford Medicine researchers have found.
The molecule blocks the activity of an aging-associated enzyme, or gerozyme, called 15-PGDH that naturally increases in muscles as they age. The study showed that levels of the gerozyme increase in muscles after nerve damage and that it is prevalent in muscle fibers of people with neuromuscular diseases.
The research is the first to show that damaged motor neurons — nerves connecting the spinal cord to muscles — can be induced to regenerate in response to a drug treatment and that lost strength and muscle mass can be at least partially regained. It suggests that, if similar results are seen in humans, the drug may one day be used to prevent muscle loss of muscle strength due to aging or disease or to hasten recovery from injury.
It’s estimated that sarcopenia, or debilitating muscle frailty, affects about 30% of people over 80 and costs the United States around $380 billion each year.
“There is an urgent, unmet need for drug treatments that can increase muscle strength due to aging, injury or disease,” said Helen Blau, PhD, professor of microbiology and immunology. “This is the first time a drug treatment has been shown to affect both muscle fibers and the motor neurons that stimulate them to contract in order to speed healing and restore strength and muscle mass. It’s unique.”
Blau, the Donald E. and Delia B. Baxter Foundation Professor and director of the Baxter Laboratory for Stem Cell Biology, is the senior author of the study, which was published online Oct. 11 in Science Translational Medicine. Postdoctoral scholar Mohsen Bakooshli, PhD, and former postdoctoral scholar Yu Xin Wang, PhD, are the lead authors of the study. Wang is now an assistant professor at the Sanford Burnham Prebys Medical Discovery Institute in San Diego.
Addressing loss of strength
The finding is the latest from the Blau laboratory focused on understanding how muscles weaken from aging or disease, and whether it’s possible to combat this decline. In 2021, the group showed that blocking the activity of 15-PGDH in 24-month-old laboratory mice significantly enhances the animals’ leg strength and endurance when running on a treadmill. (Laboratory mice typically live about 26 to 30 months.) But it wasn’t clear exactly how.

Published20 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, Mary GriffinBy Dominic Hughes and Lucy WatkinsonBBC NewsA 12-year-old girl who suffered a lung collapse and spent four days in an induced coma has told the BBC that children should never start vaping. Sarah Griffin had asthma and was a heavy vaper when she was rushed to hospital with breathing problems a month ago.Her mum Mary told the BBC she feared she was going to lose her daughter.The UK government has announced plans to restrict the marketing and sale of vapes targeted at children.Prime Minister Rishi Sunak said the proposals – which are open for public consultation for the next eight weeks – would “reverse the worrying rise in youth vaping” by making vapes less colourful and less appealing to children.Speaking at the Labour Party conference, shadow health secretary Wes Streeting said a Labour government would come down like “tonne of bricks” on vaping companies pushing flavours like ‘rainbow burst’ at children.Sarah Griffin’s bedroom at her home in Belfast is like that of most 12-year-old girls – a dressing table littered with make-up, perfume bottles and hair straighteners, with some childhood cuddly toys on the bed.But this is where Sarah also used to hide her vapes from her mum – even cutting holes in the carpet to keep them out of sight.Sarah had started vaping when she was just nine.Her mum Mary tried to stop her – searching her when she came home, confiscating her phone – but nothing worked.By the summer, Sarah was getting through a 4,000-puff vape (a regulation vape contains 600 puffs) in just a few days.It was the first thing she did in the morning and the last thing she did at night – sleeping with the vape on her pillow.Even though it’s illegal to sell vapes to anyone under the age of 18, Sarah bought vapes over the counter and became addicted to the nicotine hit.Sarah’s asthma and the fact she was not good at using her preventative inhaler left her at risk of complications.In early September she also developed a head cold, and when combined with her vaping, it all added up to what Sarah’s doctor describes as a “perfect storm”.”A lot of risk factors were going in the wrong direction,” says Dr Dara O’Donoghue, consultant respiratory paediatrician at the Royal Belfast Hospital for Sick Children.Sarah became unwell and was taken to hospital, where an X-ray of her lungs showed only one was working properly – and she was not responding to treatment.Within a few hours she was in intensive care – and shortly after that was put into an induced coma, in the hope that her condition would stabilise.For Mary, it was a moment of desperation.”There is absolutely no words to describe when you think your child is going to die.”After four days, Sarah was gradually brought round and is now recovering – but she has been left with permanent damage to her lungs.”She’s doing lung exercises and stuff you know, you’d expect an 80-year-old to be doing, not someone who is 12,” says her mum.”People open your eyes, because this is happening all round, and possibly your child too.”No matter what you’re thinking, people like to think their kids aren’t doing these things but the reality is very, very different.”Sarah hopes her experience will help others her age wake up to the dangers posed by vaping.”Don’t start doing it, because once you start doing it, you don’t stop doing it,” she says.”You only stop when you basically have to, when it’s a life or death situation.”Image source, Mary GriffinDr O’Donoghue called youth vaping “a healthcare emergency” which had to be addressed “urgently”.”We need to be wary about vapes because the healthcare problems associated with vapes are only emerging.” Recent figures suggest that one in five children aged 11-17 have now tried vaping – three times as many as in 2020.Vaping among younger children is also rising, with nearly one in ten 11- to 15-year-olds using them, according to a 2021 survey.Many countries around the world are experiencing similar trends in youth vaping.Fidelma Carter, from the charity Northern Ireland Chest, Heart and Stroke, says 70% of young vapers are doing it regularly.”Young people are taking up vaping because they assume there is no risk, there’s no dangers. “And we want to challenge the misconceptions and raise awareness that vaping can impact on your health and wellbeing,” she said.The government has announced a UK-wide consultation on its proposals to crack down on vaping among young people. The proposals include: restricting the flavours and descriptions of vapes so they are no longer targeted at children keeping vapes out of sight of children in shops regulating vape packaging so they are not targeted at children exploring whether increasing the price of vapes will reduce the number of young people using themconsidering restricting the sale of disposable vapes, which ministers say are clearly linked to the rise in vaping in children and are incredibly harmful to the environment.Sarah Woolnough, from charity Asthma + Lung UK, said she wanted to see restrictions on the marketing of vapes so that they did not target children.”Disposable vapes at their current pocket money prices, with cartoons and bubble-gum flavour options, are far too attractive and easy for children to access,” she said.Professor Chris Whitty, England’s chief medical officer, said marketing vapes or e-cigarettes to children was “utterly unacceptable”.But he said vaping could be useful as a way for smokers to quit tobacco, and that vaping was “less dangerous than smoking”.More on this storyWill Rishi Sunak’s plan to ban smoking in UK work?Published6 days agoVaping safety message luring in children – expertPublished26 SeptemberTeen vaping: ‘I’ll have puffs as I’m falling asleep’Published4 SeptemberHigh lead and nickel levels found in illegal vapesPublished23 May

New guidance has been issued for clinicians on the determination of brain death, also known as death by neurologic criteria. A new consensus practice guideline, developed through a collaboration between the American Academy of Neurology (AAN), the American Academy of Pediatrics (AAP), the Child Neurology Society (CNS), and the Society of Critical Care Medicine (SCCM) is published in the October 11, 2023, online issue of Neurology®, the medical journal of the American Academy of Neurology.
This guideline updates the 2010 AAN adult practice guidelines and the 2011 AAP/CNS/SCCM pediatric practice guidelines on the determination of brain death. Because of a lack of high-quality evidence on the subject, the experts used an evidence-informed consensus process to develop the guideline.
“Until now, there have been two separate guidelines for determining brain death, one for adults and one for children,” said author Matthew P. Kirschen, MD, PhD, FAAN, of the Children’s Hospital of Philadelphia, and a member of the Child Neurology Society and the Society of Critical Care Medicine. “This update integrates guidance for adults and children into a single guideline, providing clinicians with a comprehensive and practical way to evaluate someone who has sustained a catastrophic brain injury to determine if they meet the criteria for brain death.”
Brain death is a state in which there is complete and permanent cessation of function of the brain in a person who has suffered catastrophic brain injury.
“Brain death means that clinicians cannot observe or elicit any clinical signs of brain function,” said author David M. Greer, MD, FAAN, FCCM, of Boston University in Massachusetts. “Brain death is different from comatose and vegetative states. People do not recover from brain death. Brain death is legal death.”
The consensus practice guideline outlines the standardized procedure for trained clinicians to evaluate people for brain death. As part of this procedure, clinicians perform an evaluation to determine whether there is any clinical functioning of the brain and brainstem, including whether the person breathes on their own. Brain death is declared if a person has a catastrophic brain injury, has no possibility of recovering any brain function, is completely unresponsive, does not demonstrate any brain or brainstem function, and does not breathe on their own.
This guideline includes updates on the prerequisites for brain death determination, the examination and the examiners, apnea testing and ancillary testing.

Among people who report memory and thinking problems, some show no signs of a problem on standard tests, while others have subtle declines on their tests. A new study shows that people who have subtle problems with these tests may have an increased risk of developing mild cognitive impairment, which can be a precursor to dementia. The study is published in the October 11, 2023, online issue of Neurology®, the medical journal of the American Academy of Neurology.
“Several studies have found that people with subjective cognitive decline have an increased risk of dementia,” said study author Michael Wagner, PhD, of the German Center for Neurodegenerative Diseases in Bonn. “Our results now suggest that people with subjective cognitive decline who also have minor test deficits, or early signs of memory and thinking problems not yet reaching the diagnosis of mild cognitive impairment, may be more likely to progress to memory disorders. Testing for these deficits in people with self-reported decline could help identify people at a higher risk for progressing to mild cognitive impairment.”
The study involved 439 people with subjective cognitive decline with an average age of 71 who did not have dementia or mild cognitive impairment.
Participants completed a series of tests to assess thinking and memory skills. Tests included memorizing lists, copying a drawing, correctly identifying time frames and current location. Minor test deficits was defined as having a score of at least 0.5 standard deviations below the average score.
Mild cognitive impairment was diagnosed by a panel of researchers who reviewed each participant´s performance across several tests. A test score of at least 1.5 standard deviations below the average was necessary for a diagnosis of mild cognitive impairment.
Of those with subjective cognitive decline, 13 %, or 55 people, had minor test deficits at the start of the study and 87%, or 384 people, did not have the minor deficits. Then the participants were followed for an average of three years to see who developed mild cognitive impairment.
After adjusting for age and sex, researchers found that people with subjective cognitive decline who also had minor test deficits were more than four times more likely to progress to mild cognitive impairment compared to people without minor deficits.

Pleural mesothelioma (PM) is mainly caused by asbestos exposure and characterized by poor prognosis and limited therapeutic options. A recent research study led by Karin Schelch and Michael Grusch from MedUni Vienna identified the oncoprotein YB-1 as an attractive therapeutic target in PM and demonstrates that indirect targeting of YB-1 is a promising approach to enhance sensitivity to chemo- and radiotherapy. The study results were published in the medical journal “Cancer Letters.”
The study follows on from findings published earlier this year by the research group led by Michael Grusch (Center for Cancer Research at MedUni Vienna and Comprehensive Cancer Center at MedUni Vienna and University Hospital Vienna), according to which the oncoprotein YB-1 is involved in regulating multiple traits of pleural mesothelioma (PM) such as cell growth, cell death and migration. The current study proves its relevance also in drug response. Accordingly, YB-1 knockdown via siRNA resulted in significantly reduced tumor growth and furthermore enhanced the sensitivity to cisplatin and radiation.
Reaching the target
Histone deaceylase inhibitors (HDACi) have already been shown in trials to be effective in fighting tumor cells of different types. Since there are no pharmaceutical YB-1 inhibitors available, indirect targeting of YB-1 was achieved by the HDACi entinostat which also inhibits YB-1 deacetylation, thereby modifying its function. “Our findings provide the basis for the development of novel, clinically feasible therapy approaches” says principal investigator Michael Grusch from the Center of Cancer Research and Comprehensive Cancer Center, highlighting the study’s high clinical relevance.
Combination instead of single therapy
Entinostat proved to be very effective against PM cells and furthermore showed strong synergistic interactions with cisplatin chemotherapy, which was linked to significantly increased cellular platinum uptake. In a mouse model, the combination of cisplatin and entinostat also resulted in stronger growth inhibition than each treatment alone.
“These data go hand in hand with another study performed in parallel in Small Cell Lung Cancer where we showed similar synergistic effects between these two drugs” says Karin Schelch also from MedUni Vienna’s Center for Cancer Research, Comprehensive Cancer Center and Department of Thoracic Surgery at MedUni Vienna and University Hospital Vienna, first author of the present and last author of the parallel study recently published in Clinical Cancer Research.
Taken together, this study highlights YB-1 as an attractive target in PM and demonstrates that targeting YB-1 via entinostat is an urgently needed novel treatment approach for PM.

The prevalence of malaria infections among migrants from sub-Saharan Africa is considerably high (8%), while Asian and Latin American migrants have a much lower prevalence, according to a study by the Barcelona Institute for Global Health (ISGlobal), an institution supported by “la Caixa” Foundation. These findings can help inform screening strategies to combat malaria infections in migrant populations.
Malaria is often thought of as a tropical disease, but a systematic review led by ISGlobal has shed light on a lesser-known aspect of this mosquito-borne disease: its prevalence among migrants in non-endemic areas.
Migrant populations currently make up 10% of the total population in EU countries and many of them come from malaria-endemic regions. However, as ISGlobal researcher Ana Requena notes, “screening of migrants arriving in European countries is not usually done, so we do not know the true percentage of those infected with the malaria parasite, especially since many of the infections can be asymptomatic.”
To estimate the prevalence of malaria parasites in this population, Requena and her team searched several databases for studies conducted in Europe, USA, Canada, Australia or New Zealand where migrants had been systematically screened for malaria parasites. The researchers excluded studies in which people were tested because of malaria symptoms, as their aim was to capture asymptomatic infections.
Of the 1,819 studies initially identified, the review included 23 studies that met the criteria, with a total of 4,203 participants tested with PCR, 3,186 with microscopy, and 4,698 with rapid diagnostic tests (RDTs).
Regional variations
The prevalence of the malaria parasite varied widely between migrant groups. Sub-Saharan African migrants had the highest prevalence, with 8.3% testing positive by PCR, 4.3% by RDTs and 3.1% by microscopy. Prevalence was highest among those from Central Africa (9.3% by PCR) and those who had arrived in their host country within the last year (11.6% by PCR). In contrast, malaria parasite prevalence was much lower among Asian and Latin American migrants (0% and 0.4%, respectively, by PCR).
Not surprisingly, parasite prevalence based on PCR (which is much more sensitive) was two to three times higher than that detected by RDT or microscopy.
Implications for Public Health
These findings can help inform screening strategies and guidelines for malaria control in migrant populations. “By identifying at-risk populations, health authorities can better tailor interventions to prevent and treat malaria in these communities, ultimately contributing to global efforts to eliminate this devastating disease,” says Requena.

Scientists have uncovered why night shift work is associated with changes in appetite in a new University of Bristol-led study. The findings, published in Communications Biology, could help the millions of people that work through the night and struggle with weight gain.
Scientists from Bristol and the University of Occupational and Environmental Health in Japan, sought to understand how ‘circadian misalignment’ — a phenomenon commonly associated with ‘jet-lag’ whereby the body’s biological clock is disrupted — affects the hormones responsible for regulating appetite.
Prevalent in night shift workers, in this new study, the international team reveal how circadian misalignment can profoundly alter the brain’s regulation of hormones controlling hunger to the detriment of metabolic health.
The team focused on glucocorticoid hormones in the adrenal gland which regulate many physiological functions including metabolism and appetite. Glucocorticoids are known to directly regulate a group of brain peptides controlling appetitive behaviour, with some increasing appetite (orexigenic) and some decreasing appetite (anorexigenic).
In an experiment using animal models, comprising a control group and a out-of-phase ‘jet-lagged’ group, the team found misalignment between light and dark cues led the out-of-phase group’s orexigenic hypothalamic neuropeptides (NPY) to become dysregulated, driving an increased desire to eat significantly more during the inactive phase of the day.
Strikingly, the team discovered that rats in the control group ate 88.4% of their daily intake during their active phase, and only 11.6% during their inactive phase. In contrast, the ‘jet-lagged’ group consumed 53.8% of their daily calories during their inactive phase (without an increase in activity during this time). This equated to nearly five-times more (460% more) than what the control group consumed during the inactive phase. These results show that it is timing of consumption that has been affected.
This new discovery revealed how completely, and significantly, disordered the neuropeptides become when daily glucocorticoid levels are out of synch with light and dark cues. However, the authors suggest the neuropeptides identified in this study may be promising targets for drug treatments adapted to treat eating disorders and obesity.

Per- and polyfluoroalkyl substances (PFAS) have become ubiquitous throughout the environment, and increasing evidence has demonstrated their deleterious effects. A group of smaller, fluorinated compounds are becoming replacements for these “forever chemicals,” though research suggests the smaller versions could also be harmful. Now, a study in ACS’ Environmental Science & Technology reports that the levels of these substances in many indoor and human samples are similar to or higher than those of legacy PFAS.
Though PFAS have seen widespread use in consumer goods, including food packaging, period products and toilet paper, some governments are beginning to regulate their use. The most common are PFOS and PFOA — each are built with eight-carbon-long backbones and are considered to be perfluoroalkyl acids (PFAAs). “Short-chain” PFAAs, containing fewer than eight carbons, and “ultrashort-chain” PFAAs, with just two to three carbon atoms, have been thought to be suitable replacements for PFOS and PFOA. However, recent research has shown that their small size makes it easy for them to move throughout water supplies, and in vitro and in vivo tests have suggested that they could be more toxic than the longer compounds. So, Amina Salamova, Guomao Zheng and Stephanie Eick wanted to see if ultrashort PFAAs are accumulating in homes and in human bodies and understand how they might be getting there.
Over 300 samples of dust, drinking water, serum and urine were collected from 81 people and their homes in the U.S., then analyzed for 47 different PFAAs and their precursors. Of these fluorinated compounds, 39 were detected, including ultra-short and short-chain compounds. For instance: PFOS and PFOA were frequently detected in dust, drinking water and serum, but were less abundant than the shorter-chain PFAAs. In most dust, drinking water and serum samples, two-carbon-long trifluoroacetic acid was the most predominant PFAA, often followed by three-carbon long perfluoropropanoic acid. But in urine samples, the 5-carbon long perfluoropentanoic acid was the most abundant PFAA present.The researchers explain that the smaller PFAAs could slip through filters into drinking water or accumulate easily in household dust. Interestingly, dust samples from homes without carpets and homes that were vacuumed regularly contained substantially lower levels of PFAAs. From the data, the team determined that dust and water intake only contributed only about 20% of the total PFAA burden in these people. This result suggests that these compounds must primarily originate from other sources — many PFAA precursors can be found in consumer products, and some evidence suggests that they can break down into shorter-chain compounds in the environment or in the body. The researchers say that further investigation into ultra-short PFAA levels, their sources and their effects on human health is needed.

University of Virginia School of Medicine researchers have obtained new insights into how African-American and Hispanic-American people’s genes influence their ability to use Omega-3 and Omega-6 fatty acids for good health. The findings are an important step toward “precision nutrition” — where a diet tailored to exactly what our bodies need can help us live longer, healthier lives.
Omega-3 and Omega-6 are “healthy fats.” We can get them from foods, but many people also take them as supplements. Omega-3 helps keep the immune system healthy and may lower the risk of heart disease, while Omega-6 promotes immune health and offers other benefits. These fatty acids also play important roles in the proper functioning of our cells. People with higher levels of the fatty acids circulating in their bloodstreams are thought to be at reduced risk of heart disease, type 2 diabetes, Alzheimer’s disease, breast cancer and other serious illnesses.
There has been substantial research into how genes influence the body’s ability to use Omega-3 and Omega-6 among people of European descent, but there has been much less study among Americans of Hispanic and African descent. UVA’s Ani W. Manichaikul, PhD, and colleagues set out to address that disparity. Their new findings reveal broad similarities among the groups but also some important differences — differences the researchers say highlight the need to conduct genetic studies in diverse groups of people.
“People of diverse ancestries have some distinct features in their DNA, and we can find this genetic variation if we include diverse participants in research,” said Manichaikul, of UVA’s Center for Public Health Genomics and Department of Public Health Sciences. “The results from this study bring us a step closer to considering a full spectrum of genetic variation to predict which individuals are at increased risk of fatty acid deficiencies.”
Genetic Influence on Fatty Acid Use
To better understand these genetic differences, Manichaikul and colleagues looked at data collected from more than 1,400 Hispanic-Americans and more than 2,200 African-Americans. This data was obtained through the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, an international group created to facilitate large-scale genetic analyses.
Manichaikul and colleagues report that prior genetic findings on fatty-acid metabolism in people of European ancestry often held true for Hispanic- and African-descended people. For example, one location on a particular chromosome had been identified as an important hub for the regulation of fatty acid use in Europeans, and that hub proved important for people of Hispanic and African descent too. There were several such shared genetic influences across the three groups.

Artificial intelligence, AI, which finds patterns in complex biological data could eventually contribute to the development of individually tailored healthcare. Researchers at Linköping University, Sweden, have developed an AI-based method applicable to various medical and biological issues. Their models can for instance accurately estimate people’s chronological age and determine whether they have been smokers or not.
There are many factors that can affect which out of all our genes are used at any given point in time. Smoking, dietary habits and environmental pollution are some such factors. This regulation of gene activity can be likened to a power switch determining which genes are switched on or off, witout altering the actual genes, and is called epigenetics.
Researchers at Linköping University have used data with epigenetic information from more than 75,000 human samples to train a large number of AI neural network models. They hope that such AI-based models could eventually be used in precision medicine to develop treatments and preventive strategies tailored to the individual. Their models are of the autoencoder type, that self-organises the information and finds interrelation patterns in the large amount of data.
To test their model, the LiU researchers compared it with existing models. There are already existing models of the effects of smoking on the body, building on the fact that specific epigenetic changes reflect the effect of smoking on the functioning of the lungs. These traces remain in the DNA long after a person has quit smoking, and this type of model can identify whether someone is a current, former or never smoker. Other models can, based on epigenetic markers, estimate the chronological age of an individual, or group individuals according to whether they have a disease or are healthy.
The LiU researchers trained their autoencoder and then used the result to answer three different queries: age determination, smoker status and diagnosing the disease systemic lupus erythematosus, SLE. Although the existing models rely on selected epigenetic markers known to be associated with the condition they aim to classify. However, it turned out that the LiU researchers’ autoencoders functioned better or equally well.
“Our models not only enable us to classify individuals based on their epigenetic data. We found that our models can identify previously known epigenetic markers used in other models, but also new markers associated with the condition we’re examining. One example of this is that our model for smoking identifies markers associated with respiratory diseases, such as lung cancer, and DNA damage,” says David Martínez, PhD student at Linköping University.
The objective of the autoencoder models is to enable compression of extremely complex biological data into a representation of the most relevant characteristics and patterns in data.