Publisher Health

New research from the University of British Columbia is painting a clearer picture of the early signs of multiple sclerosis (MS), showing that people are nearly twice as likely to experience mental illness in the years leading up to the onset of the diseases.
The study, published in Neurology, the medical journal of the American Academy of Neurology, suggests that psychiatric conditions like anxiety and depression may be part of a prodromal phase of MS — a set of preliminary symptoms and clues that arise before classic MS symptoms.
“For a long time, it was thought that MS only really began clinically when a person experienced their first demyelinating event, such as in the form of vision problems,” said senior author Dr. Helen Tremlett, professor of neurology at UBC and member of the Djavad Mowafaghian Centre for Brain Health. “But we’ve come to understand there is a whole period preceding those events where the disease presents itself in more indirect ways.”
MS is an autoimmune disorder in which the immune system attacks the protective sheath (myelin) that covers nerve fibres, disrupting communications to and from the brain. Recognizing MS is often challenging for medical professionals because its symptoms are varied and easily mistaken for other conditions. For many patients, this means the journey toward a diagnosis can be long and filled with uncertainty.
Dr. Tremlett and her team have been working to better characterize the early stages of MS with the hopes of facilitating earlier detection and possible intervention. Prodromal periods are well established in other diseases such as Parkinson’s, where people experience symptoms such as constipation years before classical motor deficiencies begin.
“If we can recognize MS earlier, treatment could begin sooner. That has tremendous potential to slow disease progression and improve quality of life for people,” said Dr. Tremlett.
For the study, the researchers examined health records for 6,863 MS patients in B.C. They looked at the prevalence of mental health conditions, including depression, anxiety, bipolar disorder and schizophrenia, in the five years before patients developed classical, medically recognized signs of MS. These MS patients were compared to 31,865 patients without MS.

The NewsMany online marijuana dispensaries do not enforce age limits on purchases, and they have other lax policies that enable minors to buy cannabis on the internet, according to a new study published on Monday in The Journal of the American Medical Association Pediatrics.Robyn Beck/Agence France-Presse — Getty ImagesThe NumbersThe research examined the age-verification policies and other practices of 80 online dispensaries, based in 32 states, that sell marijuana to American customers.The study found that 18.8 percent of dispensaries, or nearly one in five, “required no formal age verification at any stage of the purchasing process.” And that more than 80 percent accepted “nontraceable” payment methods, like prepaid cards or cash, thus “enabling youth to hide their transactions,” the authors noted.Of the dispensaries studied, nearly one-third allowed delivery across state lines — and of those, 95 percent offered delivery to states with marijuana laws different from the home state of the online dispensary. Five percent of the dispensaries provided student discounts.The ContextHealth officials have expressed concerns about the effects of marijuana use on the developing brain, particularly in an era of increased drug potency and widespread legalization. According to a 2022 survey funded by the National Institutes of Health, 6.3 percent of 12th graders reported using cannabis daily in 2021, as did 2.1 percent of 10th graders and 0.7 percent of eighth graders.Periodic use was lower. About one-third of high school seniors had used marijuana at least once in 2021, along with 20 percent of 10th graders and 8.3 percent of eighth graders.The use of marijuana in these age groups fell during the pandemic; one theory is that young people had a harder time obtaining drugs, including marijuana, and consuming them outside supervision.What’s NextOnline marijuana sales, and the ease of shipping, would seem to make it easier for minors to access the drug, the study’s authors noted. “It is imperative,” they wrote in their conclusion, “to require strict age-verification procedures prior to cannabis purchases online and to establish stringent surveillance of online marijuana dispensaries to protect youth.”In the interim, they added, “pediatricians and caregivers must be aware of the widespread availability of online dispensaries and potential dissemination of marijuana to minors.”

Scientists have found a surprising effect of some antibiotics on certain bacteria — that the drugs can sometimes benefit bacteria, helping them live longer.
Until now, it has been widely acknowledged that antibiotics kill bacteria or stop them growing, making them widely used as blanket medication for bacterial infections. In recent years, the rise of antibiotic resistance has stopped some antibiotics from working, meaning that untreatable infections could be the biggest global cause of death by 2050.
Now, researchers at the University of Exeter have shown for the first time that antibiotics can actually benefit bacteria and protect them from death. In research funded by EPSRC and published today in PNAS, the team found that certain antibiotics can alleviate stress and help prevent the decline of bacterial populations when they are dying out. This means more bacteria survive for longer compared to untreated populations.
Professor Robert Beardmore, lead author from the University of Exeter, said “The study began when we realised that surprisingly, some bacterial strains didn’t grow in the lab until we treated them with antibiotics. As a result, this is the first evidence that antibiotics can promote bacterial survival. To tackle antibiotic resistance worldwide, we need to understand far more about the impact of these drugs on the balance of bacterial ecosystems, like those in the gut microflora, or in rivers that are exposed to antibiotics. Our research is evidence of unseen side effects — we just don’t know how drugs are changing the balance of bacterial populations in those contexts.”
In real-world environments, bacteria undergo periods of rapid growth, punctuated by periods where growth stops because nutrients are scarce, so the bacteria die off. So far, little has been understood about how antibiotics mediate populations during those periods.
The researchers examined E.coli in lab experiments. They found that antibiotics targeting ribosomes — factories that help cells make protein from DNA — slowed bacteria down when they were growing but also stopped them from dying, meaning the bacteria survived for longer overall.
Dr Emily Wood said: “Many antibiotics slow the growth of bacteria, but we show that can help bacteria overcome stresses caused by a lack of nutrients that might otherwise kill them off, ultimately helping them to survive. In our experiments, this comes about because the antibiotics are antioxidants, meaning they help cells deal with some of the waste products they make as they grow. Importantly, the antibiotic-resistant bacteria we tested didn’t get the same benefits so in our study, treatment does not promote resistance, which is unusual. Our next step will be to measure how these findings alter the dynamics of multi-species bacterial communities.”

A team led by researchers at Johns Hopkins Bloomberg School of Public Health and the National Cancer Institute has developed a new algorithm for genetic risk-scoring for major diseases across diverse ancestry populations that holds promise for reducing health care disparities.
Genetic risk-scoring algorithms are considered a promising method to identify high-risk groups of individuals who could benefit from preventive interventions for various diseases and conditions, such as cancers and heart diseases. These risk-scoring algorithms are based on large-scale genetic studies that link certain DNA variants to higher or lower disease risks.
The vast majority of subjects in these genetic studies have been people of European ancestry. The resulting risk-scoring algorithms have not always performed well in other populations, due to genetic differences across populations.
The new method, described in a paper that appears online today in Nature Genetics, has been applied to data from genetic studies from 23andMe Inc. and other sources involving more than 5 million individuals across diverse populations to generate genetic scores for 13 traits, including health conditions like coronary artery diseases and depression, in five different ancestry categories: European, African, Latino, East Asian, and South Asian. The researchers also tested the new method in large-scale simulation studies.
“We showed that our method can help close the risk-scoring performance gap for non-European-ancestry populations,” says study senior author Nilanjan Chatterjee, PhD, Bloomberg Distinguished Professor in the Bloomberg School’s Department of Biostatistics. “At the same time, we also concluded that we can’t fully close the gap with new methods alone — we also need larger datasets on these populations.”
Many risk-scoring models derived from genetic studies in non-European-ancestry populations often fall short because those studies typically are relatively small in scale. This results in a performance gap in risk-scoring between European-ancestry and other-ancestry populations, which may contribute to health care disparities.
The new method — which the researchers call CT-SLEB — used a combination of AI techniques including machine learning and Bayesian statistical modeling. In addition to the 23andMe database, the researchers “trained” CT-SLEB on data from the Global Lipids Genetics Consortium, the National Institutes of Health’s All of Us research program, and UK Biobank.

A new Dartmouth study in the journal Science Advances suggests that how well people with diabetes manage their blood sugar depends on their experience with the condition and their overall success in controlling their glucose levels, as well as on the season and time of day. The findings could help physicians identify those patients who could benefit from more guidance in regulating their blood sugar, particularly at certain times of year.
The researchers accessed data from wearable glucose monitors that showed how 137 people in the U.S. aged 2 to 76 living primarily with type 1, aka juvenile, diabetes managed their blood sugar on a daily basis. By analyzing more than 91,000 days of data, the study provides the most detailed look yet at how diabetes management can vary by month, day, age, and even how experienced a patient is with the condition.
Patients in the study tended to maintain healthier blood sugar levels from April to September, the researchers found. In these warmer months when activity levels tend to be higher, glucose levels stayed in the healthy range through a larger part of the day than average. In the colder months from October to February, however, the time spent within the normal range was lower than average.
This effect was amplified during the holidays for participants of all ages, with New Year’s Day and Christmas topping the list of days when sugar levels strayed outside the desired target range more often. Despite being a warm-weather holiday, Independence Day was third on the list of days when poor glucose control was recorded.
“We’re looking for specific patterns that could potentially inform clinical guidelines and set the stage for targeted interventions,” says Temiloluwa Prioleau, assistant professor of computer science, one of the study co-authors. The authors note that the majority of their study participants had type 1 diabetes, so it is not clear how these findings might generalize to people with type 2 diabetes.
Some researchers and providers have hypothesized that changes in activity levels, lifestyle, and food intake during different seasons impact blood-glucose management, says co-author Prajakta Belsare, an assistant professor at James Madison University who worked on the study while she was a postdoctoral fellow in the Department of Computer Science.
Given the granularity of their data, the researchers also were able to investigate daily and weekly variations. They found that patients’ glucose levels were more likely to stay normal from Monday to Friday, and more so in the working hours from 9 a.m. to 5 p.m., than on weekends, suggesting that workweek routines have a positive effect.

A team of researchers at the University of Massachusetts Amherst has shown that a single, small strand of microRNA, or miRNA, known as let-7, governs the ability of T-cells to recognize and remember tumor cells. This cellular memory is the basis for how vaccines work. Boosting cellular memory to recognize tumors could help improve cancer therapies. The research, published recently in Nature Communications, suggests a new strategy for the next generation of cancer-fighting immunotherapies.
“Imagine that the human body is a fortress,” says Leonid Pobezinsky, associate professor of veterinary and animal sciences at UMass Amherst and the paper’s senior author, along with Elena Pobezinskaya, a research assistant professor also in veterinary and animal sciences at UMass. Our bodies have T-cells, which are white blood cells that specialize in fighting both pathogens, think of the common cold, and altered cells of the organism itself, like tumor cells. Most of the time, the T-cells are “naïve” — mustered out of duty and resting. But when they recognize foreign antigens after bumping into them, they suddenly wake up, turn into killer T-cells and attack whatever the pathogen may be, from the sniffles to COVID, or even cancer. After the killer T-cells have won their battle, most of them die.
“But,” says Pobezinsky, “somehow a few survive, transform into memory cells and form an elite task force called the ‘memory pool’ — they remember what that particular antigen looked like, so that they can be on the lookout for the next time it invades the body.”
This is one of the mechanisms behind how vaccines work: infect the body with a weakened dose of a pathogen — say, the chicken pox virus — and the memory cells will remember what that virus looks like, turn into killer T-cells, annihilate the virally infected cells and then transform back into memory cells, waiting for the next time the chicken pox virus shows up.
But it’s never been clearly understood just how T-cells form their memories.
Moreover, cancerous tumor cells work by tricking the killer T-cells, turning them off before they can attack and create a memory pool, leaving the cancer to metastasize unchecked.
“What we’ve discovered,” says Pobezinsky, “is that a tiny piece of miRNA, let-7, which has been handed down the evolutionary tree since the dawn of animal life, is highly expressed in memory cells, and that the more let-7 a cell has, the less chance that it will be tricked by cancerous tumor cells, and the greater chance it has of turning into a memory cell.” If the memory cell isn’t tricked by the cancer, then it can fight and, crucially, remember what that cancerous cell looks like.
“Memory cells can live for a very long time,” adds Pobezinskaya. “They possess stem-cell-like features and can live for 70 years.”
“We are very excited, not only about the fundamental insights this research has provided, but also the translational impact it could have on next generation immunotherapies,” says lead author Alexandria Wells, a postdoctoral fellow at the Cancer Research Institute who completed the work as part of her Ph.D. training at UMass Amherst. “In particular, understanding how let-7 is regulated during treatment to enhance the memories and capabilities of our own immune systems is a promising avenue for further research.”
This work was supported by the National Institutes of Health.

Researchers from the University of Arizona Cancer Center have identified a new method of activating specific molecules to target cancer cells while leaving healthy cells unharmed.
In their recent study, published in the Journal of the American Chemical Society, Wei Wang, PhD, and his team developed a new strategy called click-release proteolysis targeting chimeras, or crPROTACs, that allows for the activation and release of PROTACs only in cancer cells.
“The studies open a new way to deliver anti-cancer drugs to cancer cells,” Wang said. “We are exploring the technology for the treatment of more challenging senescent cancer cells and other diseases.”
PROTACs are molecules that scientists designed to break down specific proteins in the body. They are now explored as a potential treatment for cancer; however, one of the challenges is that they can be harmful to healthy cells due to uncontrolled protein breakdown.
Wang’s research focuses on an existing metabolic pathway in the human system, the ubiquitin-proteasome pathway, that normally targets proteins for degradation and recycling. Wang’s strategy uses the pathway to specifically target cells at tumor sites, minimizing premature drug activation and unwanted side effects. The researchers found that the crPROTAC strategy successfully degraded proteins of interest in cancer cells.
“Unlike many other drug delivery strategies, this approach will be very precise in targeting just the tumor,” Wang said.
Wang’s approach stems from biorthogonal and click chemistry, which was originally developed by Carolyn Bertozzi, MS, PhD, for which she won the Nobel Prize in chemistry in 2022.
Wang is a professor at the R. Ken Coit College of Pharmacy’s Department of Pharmacology and Toxicology, co-director of Arizona Center for Drug Discovery, and member of the BIO5 Institute and UArizona Cancer Center. He recently received the inaugural UArizona Cancer Center Research Award for Basic Science for this research and publication.
Wang’s research team from the Wang Lab in the Coit College of Pharmacy included graduate students Mengyang Chang and Devin Pontigon; postdoctoral scholars Feng Gao, PhD, and Giri Gnawali, PhD; and postdoctoral research associate Hang Xu, PhD

To learn more about what causes the body to reject biomedical implants, a team at the University of Arizona College of Medicine — Tucson identified a protein that appears to help drive this response and hopes their discoveries will improve the design and safety of biomedical implants. The findings were published today in Nature Biomedical Engineering.
Biomedical implants, such as breast implants, pacemakers and orthopedic hardware, have transformed medicine, but a significant number are rejected by the body and need to be removed. The culprit is a little-understood immune reaction called foreign body response, or FBR, in which the body encapsulates the implant in scar tissue.
Senior author Geoffrey Gurtner, MD, FACS, department chair of surgery, and co-lead author Kellen Chen, PhD, assistant research professor of surgery, say their proposed approach is a departure from the conventional thought process for tackling implant failure, which thus far has relied on using so-called biocompatible materials that are better tolerated by the body but don’t completely remove the risk of FBR.
To understand why some immune systems build thick capsules around implants while others do not, the team gathered capsule samples from 20 patients whose breast implants were removed — 10 whose reactions were severe, and 10 whose reactions were mild. A protein called RAC2 was highly expressed in samples taken from patients with severe reactions.
“When we examined the severe fibrotic samples, RAC2 was one of the most important proteins we found,” Chen said. “Because it seemed to drive a lot of downstream pathways, we decided to explore a little more closely.”
In reaction to mechanical stress caused by the implants, immune cells activate RAC2 and other proteins, which summon additional immune cells, including types that can combine to attack a large invader.
“That foreign body, which is very stiff and causes stress on the external environment, activates these immune cells to aggregate to that area,” Chen said. “They start merging with each other, making massive cells that spit out fibrous proteins like collagen and other products.”
To confirm RAC2’s role in FBR, the team blocked the expression of RAC2 in animal models.

A new injectable solution that self-assembles into a gel under the right conditions could help manage HIV unlike any currently available methods, researchers have found.
The gel releases a steady dose of the anti-HIV drug lamivudine over six weeks, suggesting people living with HIV could have new therapy that doesn’t require a daily pill regimen to prevent AIDS.
“The primary challenge in HIV treatment is the need for lifelong management of the virus, and one way to address this is to reduce dosing frequencies to help patients stick to medical regimens,” said Honggang Cui, a Johns Hopkins University chemical and biomolecular engineer who led the research. “This new molecular design shows us a future in which drug hydrogelation can do that to improve HIV treatment.”
The research is set to publish in the Journal of the American Chemical Society.
Cui’s team demonstrated that in test tubes simulating the conditions of plasma, the liquid portion of blood, the gel quickly separates into molecules of lamivudine. By injecting the gel in the backs of mice, the researchers found one injection was sufficient to maintain effective and lasting drug concentrations for 42 days with nearly no side effects.
“Our goal is to help improve people’s quality of life,” Cui said. “The antiviral substance can be injected under the skin and remain in place over an extended period, releasing the therapeutic compound slowly and consistently — a critical need for individuals with HIV.”
For people living with HIV, the key is maintaining bloodstream drug levels at concentrations that suppress virus load in the body. But that can be difficult with traditional approaches because the body naturally rids itself of these chemicals, Cui said, which is why different treatments require different dosages and dosing frequencies to work.

A world-first discovery has revealed special immune cells called ‘killer T cells’ in older adults, directed against influenza viruses, closely resemble those found in newborns and children, but struggle to recognise infected cells — a finding that unlocks the potential for the development of better vaccines and therapies tailored to different age groups.
Killer T cells (also known as CD8+ T cells) play a critical role in the immune system by eliminating virus-infected cells. While much has been studied about these immune cells in adults, little was known about how they evolve and function across the human lifespan — until now.
In a pioneering research published in Nature Immunology and led by the Peter Doherty Institute for Infection and Immunity (Doherty Institute) and UNSW Sydney, researchers employed cutting-edge technologies to examine killer T cells in different age groups — newborns, school-aged children, adults and older adults (60+ years) — to understand how age shapes our immunity to influenza viruses.
University of Melbourne’s Dr Carolien van de Sandt, a Senior Research Fellow at the Doherty Institute and first author of the paper, said the team uncovered unexpected similarities in T cell responses between newborns/children and older adults.
“Based on previous studies, we expected to find that killer T cells in older adults were less effective because they had become exhausted or ‘fallen asleep’,” said Dr van de Sandt.
“However, to our surprise, the very efficient killer T cells that we detected in children and adults seemed to actually disappear and be replaced with suboptimal cells in older adults. It is almost as if you replace the sword of a Roman soldier with a kitchen knife; they can learn how to use it, but it will never be as efficient as the sword.
“One of the most intriguing findings of the study was that these cells, with a lower ability to recognise influenza viruses, displayed gene features closely similar to T cells found in newborns.”
University of Melbourne’s Professor Katherine Kedzierska, Head of the Human T cell Laboratory at the Doherty Institute and senior author on the paper, said this research greatly contributes to our understanding of how immunity changes over an individual’s lifespan, and has the potential to significantly advance the field of vaccinology.