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Irradiation May Help CAR-T Cell Therapy Work Better Against Solid Tumours

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New study shows focused irradiation helps immune cells keep cancer-fighting CAR T cells active and contained inside tumours

CAR-T cells (brown, arrowheads) infiltrating solid tumours. Left: unirradiated (0 Gy). Right: after focal irradiation (8 Gy).

Researchers from the Icahn School of Medicine at Mount Sinai have discovered a promising new way to improve CAR-T cell therapy for solid tumours such as lung cancer and melanoma. The study, published in Nature Cancer, found that focused irradiation, a targeted therapy that delivers high-energy beams to stun rapidly growing cells such as cancer, can help CAR-T cells survive longer and work more effectively inside tumours. 

CAR-T cell therapy involves removing the patient’s T cells (a type of immune cell), reprogramming them in the lab to fight cancer, and then infusing them back into the patient. It has transformed treatment for some blood cancers, but has not worked as well for solid tumours such as lung cancer and melanoma. Patients with solid tumours typically have bulky, treatment-resistant disease, and one of the central reasons CAR-T cells fail in this setting is that they do not persist or expand at the tumour long enough to eliminate it. Even when CAR-T cells initially reach the tumour, their numbers dwindle before they can finish the job. 

The research team discovered that tumour irradiation does something unexpected: it turns dendritic cells, the immune system’s most powerful antigen-presenting cells, into a local source of stimulation for CAR-T cells inside the tumour.  

In mouse models of advanced lung cancer and melanoma, irradiation promoted dendritic cells to capture intact tumour surface proteins and display them on their own membranes, a process called “antigen dressing.” These antigen-dressed dendritic cells then engaged the chimeric receptor on the CAR-T cells – the laboratory-engineered protein that gives these cells the ability to target specific proteins – keeping them alive and multiplying within the tumour over several weeks.  

The result was durable control of advanced lung tumors that CAR-T cells alone could not eliminate.  

“This study shows that irradiation can do more than kill cancer cells; it can enhance cell therapy,” said corresponding author Jalal Ahmed, MD, PhD, who led the study and is Assistant Professor of Immunology and Immunotherapy, and Radiation Oncology, at the Icahn School of Medicine at Mount Sinai. “We found that dendritic cells can dress themselves in tumor proteins and use them to directly expand CAR-T cells through the engineered receptor. This was completely unexpected – dendritic cells normally engage T cells through an entirely different mechanism.” 

A second finding addresses one of the most pressing safety challenges in the field. The researchers found that the CAR-T cell response stayed largely confined to the irradiated tumour. CAR-T cells expanded within the tumour but did not become more active in nearby healthy tissues, even when those tissues expressed the same protein targeted by the CAR-T cells. On-target activity against healthy organs has been one of the most serious safety barriers in solid tumour CAR-T cell therapy and has led to the termination of clinical trials. By selectively concentrating CAR-T cell activity at the tumour, focused irradiation may allow treatment of advanced tumours at lower and safer CAR-T cell doses.  

“What is striking is that irradiation does not just amplify the immune response – it tells the immune system where to act,” said study co-author Miriam Merad, MD, PhD, Robin Chemers Neustein Professor of Immunology and Chair of Immunology and Immunotherapy at the Icahn School of Medicine at Mount Sinai. “Confining CAR-T cell expansion to the tumour could open up a new generation of safer cell therapies for solid cancers.” 

This approach is particularly relevant for patients with metastatic solid tumours, who currently have few options. The irradiation treatment used in the study is available in cancer care centres around the world. This means the strategy could be tested in clinical trials without requiring new equipment, new drugs, or new infrastructure.  

“This work suggests that preparing the tumour environment is important to optimise the efficacy of CAR-T cells,” said study co-author Michel Sadelain, MD, PhD, who was previously at Memorial Sloan Kettering Cancer Center and is currently the founding director of Columbia University’s Institute for Cell Engineering and Therapy. “Irradiation may provide a practical way to help CAR-T cells succeed in solid tumours.” 

The researchers caution that the findings are still preclinical and must be tested in human clinical trials. The team is now working to define the molecular mechanism of antigen dressing, identify the signals dendritic cells use to sustain CAR-T cells, and translate the approach into trials for patients with advanced solid tumours. 

Source: Mount Sinai

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Brain Region Linked to Transcranial Magnetic Stimulation’s Antidepressant Effects

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Source: Pixabay

A circuit that runs from the prefrontal cortex near the front of the brain to a deeper brain structure called the insular cortex appears to mediate the antidepressant effects of a newer form of transcranial magnetic stimulation (TMS), according to a study led by Weill Cornell Medicine investigators. The discovery could lead to more effective TMS treatment of depression.

In the study, published May 7 in Cell, the researchers developed mice whose brains can be stimulated artificially in a prefrontal region to mimic the antidepressant effect of a widely used—but not well understood—TMS technique. The researchers showed that this antidepressant effect in the mice depends heavily on the indirect stimulation of a connected region, the insular cortex.

“We’re excited about this work because it advances our understanding of the antidepressant effects of TMS, and points to more effective ways of delivering this therapy,” said study senior author Dr. Conor Liston, the Robert Michels, M.D. Professor of Psychiatry in the Department of Psychiatry and a professor of neuroscience in the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine. Dr. Shane B. Johnson, Dr. Devin Rocks and Dr. Laura Chalencon, postdoctoral associates in psychiatry at the time of the study, were co-first authors of the study.

Depression is one of the most commonly diagnosed illnesses in the modern world, and its prevalence has been increasing in recent decades. In the United States alone, tens of millions of people are treated for depression annually, according to the National Institute of Mental Health. Antidepressant drugs called selective serotonin reuptake inhibitors are the most common treatments but can take weeks to work and frequently have side effects.

TMS treatments, though they involve clinic visits, have the advantage of being more targeted, with few if any side effects, and are increasingly used for patients who do not respond to drug therapy. One new TMS protocol called accelerated intermittent theta-burst stimulation (aiTBS) has been found to reduce or abolish depression symptoms in many patients after only a few days of treatment. But exactly how TMS works and how it could be optimized have been notoriously difficult to study.

“There’s a lot of variation in how you can deliver TMS, which makes it very hard to test systematically in humans,” said Dr. Liston, who is also a psychiatrist at NewYork-Presbyterian/Weill Cornell Medical Center. “The variables include the duration of treatment in each session, the specific pulse rhythm, the interval between sessions and the specific brain area targeted, among others.”

The researchers developed a mouse model to explore and optimize aiTBS. The optogenetic mouse model allows the researchers to use light pulses to stimulate specific groups of neurons, with the same rhythms used in aiTBS. The team showed that stimulating the same prefrontal region targeted by aiTBS reverses stress-induced, depression-like behaviors in the mice.

Next, the scientists identified the specific prefrontal neurons that mediate this effect, and revealed changes that occur in these neurons, including denser growths of connections between brain cells in response to the stimulation. They then traced these neurons’ connections, finding that a connection to the insular cortex is necessary for the antidepressant effect.

The functions of the insular cortex, or ‘insula’, are complex and not completely understood; but they include processing bodily sensations – such as hunger and pain – and integrating them with emotion-related signals.

“The insula hasn’t been covered much in TMS research, in part because it is too deep in the brain to reach with ordinary TMS protocols, but it is one of the most consistently altered brain regions in studies of patients with depression,” Dr. Liston said.

Experiments in mice don’t always translate to humans. So, the researchers used functional magnetic resonance imaging to map brain connections and electroencephalography to measure neuronal responses in consented patients receiving TMS. They found that TMS stimulation of the prefrontal cortex does have a downstream effect on the insula in these patients.

The results overall suggest that aiTBS’s antidepressant effect might be improved by maximising its downstream stimulation of the insula – a prospect that Dr Liston and his colleagues now plan to investigate further using their mouse model and in future clinical trials.

The identification of the neurons that are important for aiTBS’s effects and the changes that occur in them could also lead to new drug therapies targeting those neurons, Dr Liston said.

“In the meantime, another exciting strategy with great potential is to pair drug treatment with TMS to accelerate the antidepressant response,” he said.

Source: Weill Cornell Medicine

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Can an Organ Transplant Really Change Someone’s Personality?

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Photo by Seb [ P34K ] Hamel on Unsplash

Adam Taylor, Lancaster University

Changes in personality following a heart transplant have been noted pretty much ever since transplants began. In one case, a person who hated classical music developed a passion for the genre after receiving a musician’s heart. The recipient later died holding a violin case.

In another case, a 45-year-old man remarked how, since receiving the heart of a 17-year-old boy, he loves to put on headphones and listen to loud music – something he had never done before the transplant.

A recent study suggests that heart transplant recipients may not be unique in experiencing personality changes. These changes can occur following the transplantation of any organ.

What might explain this? One suggestion could be that this is a placebo effect where the overwhelming joy of receiving a new lease on life gives the person a sunnier disposition. Other transplant recipients suffer from guilt and bouts of depression and other psychological issues that might also be seen as personality changes.

However, there is some evidence to suggest that these personality changes aren’t all psychological. Biology may play a role, too.

The cells of the transplanted organ will perform their expected function – heart cells will beat, kidney cells will filter and liver cells will metabolise – but they also play a role elsewhere in the body. Many organs and their cells release hormones or signalling molecules that have an effect locally and elsewhere in the body.

The heart seems to be most commonly associated with personality changes. The chambers release peptide hormones, including “atrial natriuretic peptide” and “brain natriuretic peptide”, which help regulate the balance of fluid in the body by affecting the kidneys.

Around two hundred heart transplants are performed in the UK each year. VesnaArt/Shutterstock

They also play a role in electrolyte balance and inhibiting the activity of the part of our nervous system responsible for the fight-or-flight response. The cells in charge of this are in the hypothalamus – a part of the brain that plays a role in everything from homeostasis (balancing biological systems) to mood.

So the donor organ, which may have a different base level of hormones and peptide production from the original organ, could change the recipient’s mood and personality through the substances it releases.

It has been shown that natriuretic peptide levels are higher following transplantation – and never return to normal. Although some of the elevation is probably a response to the trauma of surgery, it may not account for everything.

Memories stored outside the brain

The body stores memories in the brain. We access them when thinking or they can be triggered by sight or smell. But memories are basically neurochemical processes where nerves convey impulses to each other and exchange specialised chemicals (neurotransmitters) at the interface between them.

While in transplant surgery, many of the nerves that govern the function of the organ are cut and are not able to be reattached, this doesn’t mean that the nerves within the organ do not still function. In fact, there is evidence that they may be partially restored a year after surgery.

These neurochemical actions and interactions could feed into the nervous system of the recipient, enacting a physiological response that then affects the recipient’s personality according to memories from the donor.

We know that cells from the donor are found circulating in the recipient’s body and donor DNA is seen in the recipient’s body two years after the transplant. This again poses the question of where the DNA goes and what actions it may have.

One thing it does is stimulate immune responses. These immune responses may be enough to trigger personality changes as long-term, low-level inflammation is known to be able to change personality traits, such as extroversion and conscientiousness.

Whichever mechanism, or combination of mechanisms, is responsible, this area of research warrants further investigation so that recipients can understand the physical and psychological changes that could occur following surgery.

Adam Taylor, Professor and Director of the Clinical Anatomy Learning Centre, Lancaster University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Different Liquids Can Impact the Effectiveness of Certain Drugs

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Adrienn Demeter (r), Ph.D. student at the Faculty of Pharmaceutical Sciences of Semmelweis University and first author of the study. Photo: Boglárka Zellei – Semmelweis University

Some alkaline mineral and medicinal waters may weaken the enteric coating of medications within just a few minutes, potentially reducing their effectiveness, according to a new study by Semmelweis University. The study, published in Pharmaceutics, found that if the active ingredient is released too early in the stomach rather than in the intestinal tract, it may reduce – and, in extreme cases, even eliminate – the effectiveness of certain anti-reflux, gastroprotective, psychiatric, or anti-inflammatory pain-relief medications. 

Researchers at Semmelweis University studied how different liquids could affect enteric-coated medications. The study analysed 22 commonly consumed beverages, seven of which – including several mineral and medicinal waters, tap water, filtered water, and apple juice – were examined in detail under laboratory conditions. 

Alkaline bottled waters with high mineral content caused the greatest changes in the protective coating surrounding the active ingredient-loaded particles. According to the researchers, not only the water’s alkalinity but also its high mineral and ion content may have contributed to the faster dissolution of the protective coating, an effect that was particularly pronounced in some medicinal waters. In some cases, the enteric coating began to deteriorate after just five minutes, and after 15–30 minutes of pre-soaking, more than 90 percent of the active ingredient had been released prematurely. 

Enteric-coated medications are designed so that the active ingredient is not released in the stomach but later in the intestines. This is important because some active ingredients are broken down by stomach acid, while others may irritate the stomach lining. Such coatings are commonly used on certain reflux medications, anti-inflammatory pain relievers, and digestive enzyme products.

Acidic liquids are less impactful

By contrast, more acidic liquids caused less damage to the enteric coating of the medications. In apple juice, for example, almost no premature release of the active ingredient was observed at the start of the tests, indicating that the coating remained far more stable than in alkaline waters. 

“The small drug particle does not know whether it is already in the intestine or still sitting in a glass. If the pH of the surrounding environment is similar, the coating may begin to dissolve in the same way. Healthcare professionals generally assume that medications are swallowed with plain tap water, but that is not always obvious to patients today, given the wide variety of mineral and medicinal waters available on the market,” said Dr Nikolett Kállai-Szabó, Associate Professor at the Faculty of Pharmaceutical Sciences of Semmelweis University and senior author of the study. 

The researchers also analysed the Summary of Product Characteristics (SmPCs) of 103 enteric-coated medications. In 42 cases, the instructions did not specify what liquid should be used to take the medication. Another 31 mentioned only “liquid,” while 21 referred simply to “water” without further clarification. Only nine SmPCs provided specific guidance on what beverage to take or mix the medication with, such as apple juice or another mildly acidic liquid. 

This may be particularly important for people who open hard capsules because of swallowing difficulties and mix the capsule contents with liquids, yogurt, or applesauce. Older adults, children, and patients with a temporary sore throat or swallowing difficulties are more likely to find themselves in this situation. 

“In the pharmacy, we regularly see that many patients are unaware of how much it matters what they take their medication with. This can also affect whether the treatment works as intended,” said Adrienn Demeter, PhD student at the Faculty of Pharmaceutical Sciences of Semmelweis University and first author of the study. 

The researchers emphasize that the findings do not mean mineral or medicinal waters are inherently problematic. The key takeaway is that enteric-coated medications should preferably be taken with plain tap water, and patients should consult a pharmacist or physician before opening a capsule or splitting a tablet. 

Source: Semmelweis University

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Africa CDC update on the Bundibugyo Virus Disease Outbreak

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The Bundibugyo ebolavirus outbreak is currently affecting 27 health zones in the Democratic Republic of the Congo and one district in Uganda. A cumulative total of 681 confirmed cases and 126 deaths among confirmed cases have been reported across the Democratic Republic of the Congo and Uganda, representing a case fatality ratio of 18.5%.

The Democratic Republic of the Congo remains the main focus of the outbreak, with 662 confirmed cases and 124 deaths reported to date. Ituri Province continues to account for the majority of reported cases. In the last 24 hours, 29 new confirmed cases and five deaths among confirmed cases were reported in Ituri Province. Seven additional confirmed cases from North Kivu were also reported as part of a backlog from 8 June.

Uganda has reported 19 confirmed cases and two deaths to date. No new confirmed cases, deaths, suspected cases or recoveries were reported in Uganda in the last 24 hours. Uganda has now reported no new confirmed cases or deaths for five consecutive days.

Across both countries, 25 recoveries have been reported, and 6,525 contacts have been listed for follow-up. Thirty-four healthcare workers have been infected, including 29 in the Democratic Republic of the Congo and five in Uganda.The outbreak is currently affecting 27 health zones in the Democratic Republic of the Congo and one district in Uganda.

Africa CDC continues to work closely with national authorities and partners to support surveillance, contact tracing, case management, infection prevention and control, risk communication and cross-border coordination.

Africa CDC and WHO continue to advise against unnecessary restrictions on travel and trade. Public health measures should remain evidence-based and aligned with the International Health Regulations.

Africa CDC urges communities in affected and at-risk areas to remain vigilant, follow guidance from health authorities, report symptoms early and cooperate with trained response teams.

Further updates will be shared as the situation evolves.

Distributed by APO Group on behalf of Africa Centres for Disease Control and World Health Organization

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MRI Approach Improves Assessment of Common Valve Disease

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Representative cine-CMR four-chamber image demonstrating severe tricuspid regurgitation. Courtesy of Dr Robert Zhang

A new cardiac magnetic resonance imaging-based measurement may improve how physicians assess a common heart valve condition, according to a study led by Weill Cornell Medicine and NewYork-Presbyterian investigators. The findings support the broader use and further study of the new metric known as effective right ventricular ejection fraction (eRVEF).

In the study, published in JACC: Cardiovascular Imaging, the researchers analysed deidentified clinical and cardiac imaging data, on nearly 800 patients who had the heart valve condition called tricuspid regurgitation. They found that eRVEF predicted mortality risk better than traditional risk markers for the disorder.

“Our goal in tricuspid regurgitation is to detect disease progression and intervene before irreversible heart dysfunction develops,” said study corresponding and co-senior author Dr. Jiwon Kim, associate professor of medicine in the Division of Cardiology and director of the Cardiovascular Imaging Program at Weill Cornell Medicine and a cardiologist at NewYork-Presbyterian/Weill Cornell Medical Center. “We believe this new measurement could help cardiologists identify high-risk patients earlier and make more informed treatment decisions.”

The tricuspid valve regulates the flow between the heart’s right atrium, which receives low-oxygen blood from major veins, and the right ventricle, which pumps this blood via the pulmonary artery into the lungs. When the tricuspid becomes dysfunctional, much of the blood pumped by the right ventricle flows back into the right atrium instead of going into the lungs. This loss of efficiency can lead to progressive right-sided heart failure.

“This investigation highlights the expanding role of cardiac MRI in the assessment of patients with valvular heart disease,” said co-senior author Dr Dipan Shah, professor of cardiology at Houston Methodist Research Institute and a professor of medicine at Weill Cornell Medicine. “Its unique ability to precisely quantify valvular heart lesions and the associated cardiac remodeling in both the left and right heart makes it an indispensable tool for comprehensive clinical evaluation.”

Conventional RVEF, a basic measure of the right ventricle’s pumping efficiency, is an estimate of right ventricular volume when filled and when fully compressed during pumping. But this measure cannot distinguish between normal blood outflow to the lungs and abnormal backflow to the right atrium. Thus, in patients with tricuspid regurgitation, RVEF may seem normal until the resulting heart dysfunction is relatively advanced.

“The tricuspid valve was once considered the ‘forgotten valve,’ managed primarily with medical therapy and occasionally treated surgically,” said study co-first author Dr Robert Zhang, an assistant professor of medicine at Weill Cornell Medicine and a cardiologist at NewYork-Presbyterian/Weill Cornell Medical Center. “Now we have less-invasive, catheter-based treatment options, which is incredibly exciting. But with that comes a new challenge: identifying the patients who are most likely to benefit and determining the right timing for intervention.”

Dr. Pablo Villar-Calle, an instructor of medicine at Weill Cornell, is the other co-first author on the paper.

The new measure, eRVEF, is derived from a more direct, magnetic resonance imaging-based estimate of blood flow from the right ventricle to the lungs. In principle, it enables a more accurate assessment of right ventricle function and the degree of tricuspid regurgitation.

The study covered an initial cohort of 453 patients from NewYork-Presbyterian/Weill Cornell Medical Center, plus 316 patients in two independent validation cohorts, 239 from Houston Methodist DeBakey Heart and Vascular Center and 77 from Duke University Medical Center. All patients had at least a moderate degree of tricuspid regurgitation.

The researchers showed firstly that eRVEF is a useful measure in its own right. In all cohorts, patients with impaired eRVEF, defined as less than 25% of right ventricle-filled volume, had strikingly greater risks of adverse outcomes during several years of follow-up, including worse tricuspid regurgitation and mortality, compared with patients who didn’t meet the impaired-eRVEF threshold.

The team also compared eRVEF with RVEF, showing that adding eRVEF to a prediction model that already included RVEF significantly improved mortality prediction, whereas adding RVEF to a model that already included eRVEF did not.

The results suggest that in the context of at least moderate tricuspid regurgitation, eRVEF is better than RVEF for assessing right-side heart function.

The team now hopes to show with forward-looking studies that using eRVEF to select patients for tricuspid valve treatments can improve outcomes.

“We are also interested in understanding how useful eRVEF may be as a marker of treatment response and whether it can serve as a meaningful endpoint for assessing the success of therapeutic interventions,” Dr. Zhang said.

Source: Weill Cornell Medicine

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Four Minutes of Daily Resistance Training Can Quadruple Fitness in Older Adults

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Photo by Mikhail Nilov

By Marina Naumova

Just four minutes of daily strengthening exercise dramatically increases key factors in quality of life for ageing adults, according to a new study led by researchers at Penn State College of Medicine. Results published in PLOS One showed that strength – which impacts fall risk, longevity, independent living and more – significantly improved for adults aged 65 and older in as little as 12 weeks.

Mobility, or physical fitness, is a critical indicator of quality of life for adults ages 65 and above, allowing for completion of daily tasks and movement. Unintentional injuries such as tripping or falling are among the top leading causes of death among adults ages 65 and over, according to the Centers for Disease Control and Prevention. A lack of physical fitness in aging persists because people believe that they can only reap the benefits of exercise with more extensive resistance training workouts – but that’s not the case, according to lead author Christopher Sciamanna, professor of medicine and of public health at Penn State College of Medicine. He said a short four-minute workout is enough to improve upon several factors of critical mobility indicators.

“The human body is designed to improve very quickly,” Sciamanna said. “And just a few repetitions of an exercise performed regularly can lead to huge improvements. Exercise is about forward thinking – think about what you want to be able to do and train for it.”

While resistance training can greatly increase strength in just a few months, less than one in five older adults exercise for the recommended two days per week of muscle-strengthening activity, partially due to routine length, pain and other limitations.

“Exercise is actually really complicated, because you have to decide how many repetitions, how far, how many sets, how much rest and how many times per week,” said co-author Smita Dandekar, associate professor of paediatrics at Penn State College of Medicine. “It’s hard work, so there’s huge problems with people wanting to do exercise. If we can make it short, we’re part way there.”

Previously, the team had conducted a study called FAST (Functional Activity Strength Training)-1, a smaller-scale experiment where 24 older adults performed 30 seconds of push-ups and squats daily, resulting in improved squat performance over six months. Other studies have also shown that a few sets of exercise per week can lead to nearly the same improvements as longer-length routines. Building off of those findings, Sciamanna’s team decided to test the efficacy of a shorter routine.

In the current study, researchers from Penn Statue tested the effects of a program, called FAST-2, to see if it improved mobility and physical capability in adults older than 65. A total of 97 participants with an average age of 74 years old were randomly assigned to receive either the exercise regimen treatment or no intervention. Prior to the study, participants reported performing an average of about 18 minutes of total exercise each week, which is much lower than the recommended amount of at least 150 minutes’ moderate or 75 minutes’ vigorous exercise for adults, Sciamanna explained.

The FAST-2 program included four exercises: push-ups, chair stands, two-arm rows and stair stepping. Participants performed each movement for 30 seconds followed by a 30-second rest. Participants received four elastic resistance bands and a stepper with an adjustable height. Written explanations and modifications were provided for the exercises, such as performing pushups with hands on a countertop or wall, or chair stands with hands on the knees.

As participants improved, they were encouraged to progress to higher levels of difficulty, like performing the original version of the exercise if they were doing a modified version or increasing step height on the stepper. To measure participants’ progress, the researchers assessed the participants’ ability and speed at standing up and ability to stand on one leg at the beginning, middle and end of the study.

The tests mimic the movements required in everyday activities, making them useful predictors of potential risks and future need for care, the researchers said.

The authors found that this exercise regimen, which included only 60 seconds of lower body resistance training, was enough to give significant improvements in functional performance: 4.2 more repetitions in a 30 second chair stand, 3.6 more seconds in one-legged stand time and a decrease of 2.3 seconds in sit-to-stand time. These changes point to related improvements in daily life fitness, such as standing up from a chair, climbing stairs and walking, Sciamanna explained.

“These indicators predict your future ability to go into a nursing home, your future likelihood of falling and of developing difficulty walking,” Sciamanna said. “They give you a sense of whether or not you’re going to be able to be active in the future.”

One of the additional benefits of a shorter program like FAST-2, Sciamanna explained, is a higher chance that people will stick to the routine. Participants completed the exercise on 81% of days during the study period, demonstrating that the program can fit into days even with time constraints or other concerns that may keep people from continuing an exercise program, even though it could lead to improvements in everyday life.

The findings are a promising indication that resistance training regimens do not have to be long to make a big difference in strength, mobility and quality of life, Sciamanna explained.

“Exercise is the key to freedom,” he said. “Freedom is the ability to be able to do what you want to do, and I would say that if you can’t do what you want to do, you’re not free. I approach exercise by thinking of what I want to be able to do in 20 years, and then I train to do that.”

Source: Pennsylvania State University

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Study Finds RSV Vaccination During Pregnancy Cuts Infant Hospitalisations by Nearly 70%

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Source: Pixabay CC0

A study led by researchers at the University of Pittsburgh and UPMC published in JAMA Network Open, a peer-reviewed journal of the American Medical Association, found that vaccination against respiratory syncytial virus (RSV) during pregnancy reduced the risk of hospitalisation in young infants by nearly 70%.

This study provides early real-world evidence from US clinical care, showing that administering one dose of the maternal RSV vaccine (RSVpreF vaccine) reduces hospitalisation related to RSV in young infants. The results are consistent with findings from RSVpreF vaccine clinical trials. The RSVpreF vaccine was approved by the US Food and Drug Administration in 2023.

Among infants younger than 3 months, maternal vaccination was associated with approximately 68% effectiveness against hospitalisation for respiratory illness caused by RSV, and 69% effectiveness against more severe lung infections also caused by the virus.

“We designed this study to focus on what matters most to families: whether their baby might end up in the hospital,” said lead author of the study, Anne-Marie Rick, MD, PhD, assistant professor of paediatrics and clinical and translational science at Pitt School of Medicine and a physician at UPMC Children’s Hospital of Pittsburgh and UPMC Magee-Womens Hospital. “The findings show a significant impact for families and for the health system, and it highlights how effective this intervention can be during the most vulnerable months of life.”

RSV is the leading cause of hospitalisation among infants in the United States. According to the Centers for Disease Control and Prevention (CDC), about 2 to 3 out of every 100 babies younger than 3 months are hospitalised each year due to RSV, with severe cases sometimes requiring oxygen support or mechanical ventilation. Until the RSVpreF vaccine’s approval, there was no reliable way to protect healthy newborns from RSV starting at birth.

The study analysed health records from infants 90 days old or younger who were hospitalised for respiratory illness in Western Pennsylvania during the 2023–2024 and 2024–2025 RSV seasons. Researchers focused on infants who were tested for RSV and compared outcomes between those whose mothers received the vaccine during pregnancy and those whose mothers did not. Infants who received monoclonal antibody protection – a separate RSV prevention option administered after birth – were excluded.

The results are part of an ongoing four-year study to evaluate the effectiveness of maternal RSV vaccination across multiple seasons. Researchers will continue to follow patients during the 2025–2026 and 2026–2027 RSV seasons, expanding the analysis to include infants up to 180 days old and assessing how long protection lasts.

“We’re continuing to follow patients to understand how well this protection holds over time and across different groups,” said Rick. “These kinds of real-world data are critical for helping families, clinicians, and policymakers make informed decisions about how best to protect infants.”

Source: University of Pittsburgh

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Why Midnight Eating Can Be a Gut Punch

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Study finds that intestinal circadian clocks become misaligned by off-schedule eating, causing gastrointestinal issues

A microscopic image shows enteric neurons (orange) and macrophages (green) in the muscularis externa of a mouse small intestine. Muscularis macrophages were among the intestinal cell types that glowed green when a key circadian clock gene called Per2 was active during UT Southwestern investigators’ research.

Eating when the body is normally asleep appears to desynchronise the circadian clocks of different cell types in the intestines, a UT Southwestern Medical Center study suggests. The findings, published in PNAS, could help explain why shift work, jet lag, and other environmental stressors that affect circadian rhythms are associated with irritable bowel syndrome, inflammatory bowel disease, constipation, and other gastrointestinal disorders.

“Understanding how intestinal circadian clocks become misaligned may ultimately guide strategies involving meal timing, circadian-based therapies, or dietary interventions to improve gastrointestinal and metabolic health,” said Yuuki Obata, PhD, Assistant Professor of Immunology and Neuroscience at UT Southwestern. Dr Obata co-led the study with Shin Yamazaki, PhD, Professor of Neuroscience.

Research in the 1990s and 2000s showed that a region of the brain known as the suprachiasmatic nucleus (SCN) acts as a master timekeeper for the body, setting various cellular processes to occur rhythmically on a 24-hour period based on cycles of light and darkness. However, in 2000, Dr Yamazaki and his colleagues showed that cells throughout the body have their own autonomous circadian clocks that are influenced both by signals from the SCN and environmental cues.

In line with this idea, research has shown that the intestines have their own rhythms that can be influenced by a variety of factors, such as timing of meals. These findings were made using whole intestinal tissue, Dr Obata explained, but the intestines contain a variety of cell types – including muscle, nerve, and immune cells. It’s been unclear whether each of these populations has its own circadian clock and if they run on the same schedule.

To find out, Drs Obata and Yamazaki monitored novel mice with set 12-hour cycles of light and dark. They were engineered by Joseph Takahashi, PhD, Chair and Professor of Neuroscience at UT Southwestern, and his colleagues in the Takahashi Lab. Five intestinal cell types – enteric neurons, enteric glial cells, interstitial cells of Cajal (ICCs), smooth muscle cells, and muscularis macrophages – glowed green when a key circadian clock gene called Per2 was active. Although food was available at all times, the mice ate about 80% of their meals at night due to their nocturnal nature.

After about a week in this environment, the researchers observed intestinal cells glowing green at approximately the same times, suggesting the different cell populations had their own autonomous circadian clocks that cycled in sync. But when the researchers made food available only for four hours in the daytime – forcing the mice to eat at abnormal times – Per2 activity shifted to match this new rhythm in every cell population except for the ICCs. These cells resisted changes to their circadian clock, staying out of sync with the other cell types for weeks.

Such asynchrony may also occur in people who eat outside the body’s usual circadian rhythms, such as night shift workers or those who fly to different time zones. Because ICCs play a key role in intestinal motility, their resistance to adapt to a changed circadian clock could affect digestive and metabolic function.

Finding a way to synchronise the different intestinal cell populations through diet, probiotics, or drugs could eventually help ease the gastrointestinal problems associated with altered circadian timing, the researchers said.

Source: UT Southwestern Medical Center

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Tiny Wearable Auscultation Sensor Aims to be a Doctor’s Stethoscope for Every Home

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The AusculPatch is a tiny wearable sensor that weighs just 3.2 grams.

Australian researchers have developed a lightweight wearable sensor that could continuously check on people with heart and breathing problems, potentially reducing hospital visits and allowing doctors to detect problems earlier. 

The flexible sensor patch, which attaches to the chest or over peripheral arteries using medical adhesive tape, is designed to continuously capture subtle vibrations produced by the heart, lungs and, blood flow, and pulse waves. 

Researchers hope the technology could eventually help people with chronic heart and respiratory conditions track their health remotely and alert clinicians when something may be wrong before symptoms become severe.

The proof-of-concept work, led by researchers from UNSW in collaboration with clinicians and biomedical engineers, has been published in Nature Communications. 

Lead researcher and corresponding author of the paper, Scientia Associate Professor Hoang-Phuong Phan, says the goal is to create a wearable device which patients can use themselves – as a home alternative to the traditional doctor’s stethoscope.

“What we have developed is a tiny wearable device that can attach onto the human chest and hear heart sound and respiration,” A/Prof. Phan says.

“Technically, it aims to replace the stethoscope, which is normally used in clinic centres to assess cardiovascular or respiration disease.”

Addressing a growing healthcare challenge

Heart disease and chronic respiratory illnesses remain among the leading causes of death worldwide, but many patients only receive brief assessments during occasional medical appointments. A/Prof. Phan says this can create major challenges for people living in regional and remote areas, or patients reluctant to repeatedly visit hospitals and clinics.

“Normally, when patients are assessed by a doctor, they have to go to a clinic centre, and it’s not very convenient for those who live in remote areas,” he says. “Sometimes people are hesitant to go to hospital, so they wait until symptoms are clearly developed.”

By the time symptoms become serious enough to seek medical care, diseases may already have significantly worsened.

“At that stage, the disease may already have worsened, leaving poorer outcomes for patients even when treated,” says Dr Anthony Sunjaya, a medical doctor and Program Lead for Chronic Respiratory Disease at UNSW’s School of Population Health, who co-authored in this work.  “When they go to a clinic, patients often only have a 15-minute window for assessment. The danger is that the abnormalities experienced will not be fully recognised during that short period of time they are being seen.” 

How the patch works

The device, known as ‘AusculPatch’, is smaller and lighter than many existing wearable monitoring systems, weighing only 3.2 grams and measuring roughly 20x47x3 millimetres. At the centre of the patch is an ultra-thin silicon sensing element that detects tiny mechanical vibrations travelling through the skin from the heart, lungs and blood vessels.

“The heart sound propagates through the body fluid and tissue generates an acoustic pressure that vibrates the sensing element,” Tran Bach Dang, the first author and a PhD candidate from the School of Mechanical and Manufacturing Engineering says. “What the patch is doing is picking up that vibration.”

The new sensor can detect extremely low-frequency vibrations that are difficult to capture with current wearable technology. The device can detect a remarkably broad range of physiological signals, including breathing patterns, pulse waves, heart sounds and blood flow vibrations.

In tests, the AusculPatch was able to continously monitor a range of physiological markers while the wearer was undertaking regular daily tasks. Importantly, researchers say the patch was designed to minimise interference from surrounding environmental noise — a major challenge for wearable acoustic sensors.

“The sensor element is designed to shield the sound coming from one direction, typically from the human body,” Dang says. “In that way, it is less susceptible to ambient sound.”

Although tested on only a small number of healthy participants, the research paper showed the device could continue capturing clear heart sounds even in noisy environments, including during conversation and under simulated background noise conditions. 

Beyond smartwatches and fitness trackers

While consumer devices such as smartwatches and sleep trackers can already monitor heart rate and blood oxygen levels, the research team says AusculPatch captures more direct mechanical information about how the heart and lungs are functioning.

The researchers believe the technology could eventually have applications ranging from chronic disease management to sleep monitoring and general wellbeing.

The paper also highlights potential use in monitoring blood pressure, pulse waves and subtle heart valve abnormalities that are difficult to continuously track outside hospital settings. 

In laboratory and early human testing, the device showed strong agreement with clinical tools including electrocardiograms (ECGs), ultrasound scans, blood pressure monitors and digital stethoscopes. 

Researchers were also able to continuously record cardiorespiratory data over extended periods while participants walked, worked, ate meals and climbed stairs. 

AI-powered monitoring

One of the most promising aspects of the technology is the possibility of combining continuous monitoring with artificial intelligence.

Because the patch collects large amounts of physiological data over time, researchers hope machine learning systems could eventually identify patterns linked to worsening disease or emerging health problems.

“We can potentially apply machine learning to identify abnormal signal and warn the patients, and also notify their doctor,” Dr. Chi Cong Nguyen, an Associate Lecturer and a corresponding author of the paper says.

“The goal is to create a system that can automatically flag concerning changes before patients experience severe symptoms.”

Potential future applications

Beyond cardiorespiratory monitoring, the researchers also demonstrated that the patch could detect vocal cord vibrations from the throat. In proof-of-concept experiments, the team used machine learning to recognise spoken words and wirelessly control a robotic arm. While those experiments are still early-stage, the researchers say the technology could eventually support people with speech disorders or physical disabilities.

Although the technology is still in the research and testing phase, larger clinical studies are already being planned.

The team, which also includes Associate Professor Thanh Nho Do, Scientia Professor Nigel Lovell, and Professor Tracie Barber, as well as external partners, hopes to begin testing the device on around 200 patients this year.

That group is expected to include people with heart valve disease or implanted heart assist devices. Researchers then hope to scale up studies to around 1000 patients over the following years to further develop AI-assisted diagnostic tools. Regulatory approval for a medical-grade device would still take time, with A/Prof. Phan estimating a timeline of around four to five years before possible clinical deployment. However, consumer-focused wellness versions of the technology could potentially become available sooner.

Source: University of New South Wales