Categories : UncategorizedTags : Leave a comment

UP Professor Pioneers Novel Approach to Advance Precision Treatment for Aggressive Breast Cancer

On By ModernMedia
UP Vice-Principal: Research, Innovation and Postgraduate Education Prof Sunil Maharaj, OMT chair Rebecca Oppenheimer, Prof Mike Sathekge, head of the Department of Nuclear Medicine at UP and Steve Biko Academic Hospital, as well as President and CEO of NuMeRI, UP Vice-Chancellor and Principal Prof Francis Petersen and OMT CEO Tracey Webster.

Breast cancer is the leading type of cancer among women in South Africa, and globally. Too often it is discovered too late – but a new approach promises a radical change in survivability for patients.

The solution, called theranostics, stems from the field of nuclear medicine. It holds the potential to turn the tide against breast cancer and, like the fight against HIV/Aids, change it from an outright killer to a manageable disease.

Behind this initiative is world-renowned nuclear medicine specialist Professor Mike Sathekge, head of the Department of Nuclear Medicine at the University of Pretoria and Steve Biko Academic Hospital, and president and CEO of the South African Nuclear Medicine Research Infrastructure (NuMeRI), a globally leading, not-for-profit imaging facility situated at the hospital.

He has been presented the 2025 Harry Oppenheimer Fellowship Award, a R3-million grant from the Oppenheimer Memorial Trust (OMT) to complete his research and develop a way to make it widely available.

“Theranostics, brings diagnosis and treatment together, is a combination of early diagnosis with treatment that is personalised and precise down to mere cells, which allows us to exactly detect and assess tumours, devise specific treatment regimens and assessment of treatment response over time,” says Sathekge.

“The earlier the breast cancer is detected, the more accurately it is assessed and the more precise the treatment, the exponentially better the patient’s prognosis.”

In South Africa, however, this is too often not the outcome. A comprehensive study into the availability of breast cancer services in the public healthcare sector, published recently in the South African Medical Journal, found that 67% of patients had late-stage breast cancer at diagnosis. In other words, their cancer had metastasised and spread to other parts of their bodies, and their prognosis was poor.

The study also noted that South Africa is expected to face a substantial rise in cancer cases over coming decades, driven by population growth, ageing and changing disease patterns. Sathekge’s Harry Oppenheimer Fellowship Award nomination was one of 80 received by OMT, covering a wide range of academic fields. Finalists shortlisted included proposals on a system for measuring the environment, air and our health; frost exposure in tropical Africa; a model for testing modified gravity; conversion of CO2 into useful products (such as fertilisers); and tissue T-cell response profiling of tuberculosis. “There were so many excellent applicants for this year’s award, touching on vital issues impacting the world we live in, and worthy of further research and development,” says OMT chairperson Rebecca Oppenheimer.

“This made our selection panel’s final decision all the more challenging, but I believe we have made an exciting choice that will have far-reaching, positive ramifications for South Africa’s public healthcare system and the people who use it.

“In developing a technology that makes diagnosing and treating cancers more effective, affordable and available, Prof Sathekge and his colleagues hold in their hands the potential for a quantum leap forward in improving South African patients’ health outcomes and human dignity, as well as for beating breast cancer globally. OMT is proud to support his endeavours.”

Sathekge’s solution is, essentially, one whose time has finally come. First conceived around 15 years ago, it capitalises on a protein called trophoblast cell-surface antigen 2, or Trop2. This molecule, found in high levels in breast cancers (and others, including cervical, pancreatic and lung cancers), helps the cancer multiply and makes it stubborn to treat.

Although Trop2 is already recognised as an important target in several cancers, there is still no widely established, clinically scalable way to show exactly where Trop2 is present across a patient’s entire cancer burden.

The answer may lie in nanobodies: tiny, engineered antibody fragments that are designed to bind specifically to Trop2. Their small size allows them to reach tumours rapidly and clear from the bloodstream faster than conventional antibodies, making them particularly attractive for same-day PET imaging.

Through a long-standing collaboration with Prof Frederik Cleeren, assistant professor in the Laboratory for Radiopharmaceutical Research, in the Department of Pharmaceutical and Pharmacological Sciences, and his team at KU Leuven in Belgium and the Joint Research Centre (JRC) in Karlsruhe, who bring expertise in nanobody engineering and radiolabelling, Sathekge’s team is combining these strengths with South Africa’s capabilities in molecular imaging, actinium-225 radiopharmaceutical development and targeted radionuclide therapy.

Together, the collaborators are developing a Trop2-targeted theranostic approach that links diagnosis with treatment. The first step uses a tiny targeting protein, known as a nanobody, designed to bind specifically to Trop2 on cancer cells. This nanobody is labelled with fluorine-18, a short-lived radioactive tracer that allows doctors to visualise Trop2-positive tumours on a PET/CT scan.PET/CT is an advanced imaging method that uses a small amount of radioactive tracer to show biological activity inside the body. In this case, it could help clinicians map Trop2 expression across a patient’s full cancer burden, including disease that may not be accessible for repeated biopsy. It may also allow doctors to monitor changes in the target and treatment response over time.

Where imaging confirms sufficient Trop2 expression, the same targeting strategy can be developed for treatment using actinium-225, a powerful alpha-emitting isotope. Actinium-225 can deliver highly localised radiation over a very short distance, with the aim of concentrating treatment in Trop2-positive cancer cells while limiting radiation exposure to surrounding healthy tissue.

The ambition is to move beyond treating patients based on limited information from a single biopsy, towards a more personalised approach: seeing the target throughout the body, selecting patients more accurately, and laying the foundation for future Trop2-targeted alpha therapy.

Sathekge’s work puts South Africa at the forefront of worldwide research into effective responses to breast cancer, says the University of Pretoria’s Vice-Chancellor and Principal, Prof Francis Petersen.

“South Africa urgently needs better ways to detect, understand and treat aggressive breast cancer. Too many patients still present late, when the disease is more difficult to manage and treatment options are limited.

“Prof Sathekge’s work at NuMeRI brings together advanced imaging, radiopharmaceutical science and targeted treatment in a way that could help doctors make more informed, patient-specific decisions. The research aims to improve how cancer is identified, how treatment is selected and how response is monitored over time.

“It also demonstrates the depth of scientific talent, innovation and academic rigour in South Africa. Through work of this calibre, African researchers are not only responding to local health challenges, but helping to shape the global future of cancer care. We look forward to seeing this research strengthen South African capacity and contribute to better outcomes for patients here and internationally,” says Petersen.

For Sathekge, the most exciting element of his work is how it centres on the patient, giving them dignity and the opportunity to live long and fulfilling lives.

Provided by The University of Pretoria

Categories : IT in HealthcareTags : Leave a comment

Incorrect AI Advice is a Blind Spot – Even for Doctors

On By ModernMedia

 New study highlights potential challenges for using automated tools in healthcare

Photo by Accuray on Unsplash

In experiments in which physicians made decisions about treating hypothetical patients, the physicians tended to trust incorrect advice presented as being generated by artificial intelligence (AI), even after given the opportunity to notice that patient recovery data contradicted the recommendations. Aranzazu Vinas of the University of the Basque Country, Spain, and colleagues present these findings in the open-access journal PLOS Digital Health. 

AI systems can help physicians categorise patients according to their different care needs, such as whether a patient is more or less likely to benefit from a certain treatment. Since these systems are not perfect, they are meant to be used as suggestions, with potential errors caught and corrected by physicians.

 Prior research has shown that, in general, people struggle to notice and correct mistakes made by AI. To explore how this challenge may extend to physicians, Vinas and colleagues analysed data from 223 physicians who anonymously participated in online experiments.

 The physicians were asked to imagine they had the option to treat patients for a rare disease using a not-yet-proven treatment still under development. They were told that an AI system had identified which patients were more or less likely to benefit from the treatment. The physicians then chose which patients to treat, and after being presented with data on patient recovery, rated their perceptions of how reliable the AI was.

 Crucially, the actual effectiveness of the hypothetical treatment did not align with the AI recommendations. In one experiment, the treatment was equally moderately effective for all patients, and in a second experiment, it was equally ineffective for all.

 However, in both experiments, the physicians tended to rate the AI system as reliable and apparently did not use the patient recovery data to conclude that the AI recommendations were incorrect. In the second experiment, the physicians did not realise that the treatment was entirely ineffective.

These findings highlight potential challenges for incorporating AI-based classification into healthcare. Future research could build on this study, such as by developing and testing strategies and protocols that could increase human critical thinking and detection of AI errors, in order to maximize the benefits of the human-AI collaboration while minimising potential errors.”

Lead author Aranzazu Vinas notes: ” In both experiments, physicians mostly trusted the AI’s classifications and had trouble learning from the feedback. Furthermore, in the second experiment, professionals did not notice that the treatment was completely ineffective.”

 Co-author Helena Matute adds, “People tend to say that there is always a human controlling the algorithm, but our experiments show that doctors (as well as anyone else) have problems in learning from the available evidence when it contradicts the suggestions of an algorithm.”

Co-author Fernando Blanco summarizes: “It is important to investigate the errors that humans (including doctors) make when working with algorithms, in order to learn how to minimize the problems that arise from them.”

Press Preview: https://plos.io/4wjPxSs

In your coverage please use this URL to provide access to the freely available article in PLOS Digital Health: https://plos.io/4blGKHA

Contact: Aranzazu Vinas, aranzazu.vinas@ehu.eus

Image Caption: Doctors working on an AI-support system

Image Credit: Photo by Accuray on Unsplash. Free to share under the Unsplash license.

High-Resolution Image Link: https://unsplash.com/photos/a-few-men-looking-at-a-computer-screen-S34fEzWT6eE

Categories : Lab Tests and ImagingTags : Leave a comment

Get the Lead out: Lighter X-ray Aprons for Radiology

On By ModernMedia

Researchers develop a flexible polymer shield that provides radiation protection without the health and ergonomic risks associated with lead

Researchers show flexible polymer material
Professor Tizazu Mekonnen (left) and PhD student Aklilu G. Messele holding the flexible polymer material developed to replace the lead in heavy X-ray aprons (University of Waterloo/Nicola Kelly). Credit: University of Waterloo/Nicola Kelly

A light, flexible polymer material developed at the University of Waterloo could replace the lead in heavy X-ray aprons, providing the same protection from harmful radiation while reducing their weight by almost 90%.

“For patients who only get X-rays once in a while, heavy lead aprons might be okay, but technicians who wear them every day often develop back and neck pain,” said Dr Tizazu Mekonnen, a chemical engineering professor at Waterloo. “Some of them have to retire early as a result.”

Most aprons used for long periods of time also shed lead dust that can be inhaled or ingested by workers. Lead affects many areas of the body, including the cardiovascular and neurological systems and no amount of exposure is considered safe by the World Health Organization.

“Our research shows that radiation shielding does not have to rely on toxic, heavy materials such as lead,” Mekonnen said. “By engineering the size, shape, arrangement and distribution of nanoparticles within flexible polymers, we can achieve excellent X-ray protection while dramatically reducing weight. This opens the door to safer, more comfortable shielding materials for health-care workers and others who are routinely exposed to radiation.”

Researchers experimented with several alternatives to lead – including bismuth, gadolinium, barium and other heavy metals – before focusing on tungsten, which is well-suited to blocking X-rays because of its high density at the atomic level.

After first processing tungsten into tiny nanoparticles, they mixed them into a soft, silicone-based plastic to form nanocomposite sheets.

To prevent the nanoparticles from making the new material too stiff, they arranged them in layers called gradients. They also determined rod-shaped nanoparticles work best to block X-rays, a necessary tool in medicine, industrial inspection, security screening and military applications.

Tests and modelling with the flexible, lightweight polymer material for X-ray aprons were conducted at Grand River Hospital in Kitchener with Dr. Ernest Osei. 

PhD student Aklilu G. Messele, who co-authored a paper on the research, is now exploring its use for other types of radiation, including gamma ray emissions in the nuclear energy sector and to block electromagnetic waves from devices such as cellphones and Wi-Fi.

“We carry cellphones every day,” said Mekonnen, a Canada Research Chair in Sustainable Multiphase Polymers. “The impact on our bodies is unknown. What if we can design a cover that protects from the radiation emitted by our phones?”

The study, Tailoring X-ray attenuation in tungsten-based nanocomposites via particle morphology, multilayering, and concentration gradients, was recently published in the journal Materials Today Physics.

Source: EurekAlert!

Categories : Metabolic DisordersTags : Leave a comment

Most Obesity Drugs Do Not Improve Quality of Life or Heart Health

On By ModernMedia

Treatment decisions should be individualised, balancing expected benefits, harms, treatment burden, costs, availability, and patient preferences, say researchers

By HualinXMN – Own work, CC BY-SA 4.0

Despite substantial weight loss, most obesity drugs such as Wegovy and Mounjaro do not meaningfully improve quality of life and few show cardiovascular benefits at one year, finds an analysis of the latest evidence published by The BMJ today.

More weight loss is also generally accompanied by greater harms including stomach and bowel symptoms, fatigue, and loss of lean (muscle) mass – and improvements are not sustained after stopping treatment.

Several drugs for adults with overweight or obesity produce substantial weight loss, but most have not been compared directly in head-to-head trials, leaving uncertainty about the broader balance of benefits and harms.

To address this, researchers searched scientific databases for randomised controlled trials comparing one or more drugs with lifestyle changes, placebo, or another drug.

They found 262 eligible trials involving 99,791 participants (average age 49; 63% female; average BMI 35) that evaluated 19 currently available and emerging obesity drugs with follow-up from 12 to 172 weeks.

Benefits included changes in body weight, fat mass, and quality of life, while potential harms included changes in lean mass, gastrointestinal adverse events, gallbladder related disorders and fatigue.

The trials were of varying quality, but the researchers were able to assess the certainty of evidence using the recognised GRADE system.

Compared with lifestyle changes alone, the largest weight loss after one year was with tirzepatide (14.9%) and CagriSema (14.8%), followed by oral semaglutide (10.9%), orforglipron (9.9%), subcutaneous semaglutide (9.8%), and phentermine-topiramate (8.1%).

Emerging drugs – including retatrutide, ecnoglutide, and mazdutide – showed large effects on weight loss but are supported by low or very low certainty evidence.

Greater weight loss was consistently accompanied by higher rates of side effects and treatment discontinuation, which the authors say indicates a clear benefit-harm trade-off.

Tirzepatide reduced fat mass the most (by 25.7%) but also lean mass the most (8.3%). Subcutaneous semaglutide was the only drug associated with a reduced risk of death from any cause (19%), heart attack (28%), and heart failure (57%). Tirzepatide also reduced heart failure risk by 51%.

No drug convincingly reduced kidney failure or showed clinically important improvements in quality of life.

The authors acknowledge that most trials had relatively short follow-up, limiting conclusions about long term safety, quality of life, and effects on heart and kidney health. In addition, evidence for several newer drugs was sparse and of low certainty, and trial populations may not fully represent real world patients.

However, they say this review provides a comprehensive and up-to-date comparison of currently available and emerging obesity drugs across a broad set of outcomes important to patients, clinicians, and policymakers.

They conclude: “Treatment decisions for obesity should be individualised, balancing expected benefits, harms, treatment burden, costs, availability, and patient preferences.”

This study represents an important step in providing comparative information to inform patient-clinician discussions about obesity drugs in this rapidly evolving landscape of treatment options, say researchers in a linked editorial.

And they suggest future studies that incorporate individual characteristics, as well as long term outcomes, such as mortality, should provide additional data to inform individualised decision making.

Source: The BMJ Group

Categories : Ageing Diet and NutritionTags : Leave a comment

Are Meat Eaters Really More Likely to Live to 100 than Non‑meat Eaters, as a Recent Study Suggests?

On By ModernMedia
Photo by Jose Ignacio Pompe on Unsplash

Chloe Casey, Bournemouth University

People who don’t eat meat may be less likely than meat eaters to reach the age of 100, according to a recent study. But before you reconsider your plant-based diet, there’s more to these findings than meets the eye.

The research tracked over 5,000 Chinese adults aged 80 and older who participated in the Chinese Longitudinal Healthy Longevity Survey, a nationally representative study that began in 1998. By 2018, those following diets that don’t contain meat were less likely to become centenarians compared with meat eaters.

On the surface, this appears to contradict decades of research showing that plant-based diets are good for your health. Vegetarian diets, for example, have been consistently linked to lower risks of heart disease and stroke, type 2 diabetes and obesity. These benefits come partly from higher fibre intake and lower saturated fat consumption.

So what’s going on? Before drawing any firm conclusions, there are several important factors to consider.

Your body’s needs change as you age

This study focused on adults aged 80 and older, whose nutritional needs differ markedly from those of younger people. As we age, physiological changes alter both how much we eat and what nutrients we need. Energy expenditure drops, while muscle mass, bone density and appetite often decline. These shifts increase the risk of malnutrition and frailty.

Most evidence for the health benefits of diets that exclude meat comes from studies of younger adults rather than frail older populations. Some research suggests older non-meat eaters face a higher risk of fractures due to lower calcium and protein intake.

In later life, nutritional priorities shift. Rather than focusing on preventing long-term diseases, the goal becomes maintaining muscle mass, preventing weight loss and ensuring every mouthful delivers plenty of nutrients.

The study’s findings may, therefore, reflect the nutritional challenges of advanced age, rather than any inherent problems with plant-based diets. Crucially, this doesn’t diminish the well-established health benefits of these diets for younger and healthier adults.

Maintaining muscle mass in older age is important, and that requires protein. Photo by Barbara Olsen on Pexels

Here’s a crucial detail: the lower likelihood of reaching 100 among non-meat eaters was only observed in underweight participants. No such association was found in older adults of healthy weight.

Being underweight in older age is already strongly linked with increased risks of frailty and death. Body weight therefore appears to be a key factor in explaining these findings.

It’s also worth remembering that this was an observational study, meaning it shows associations rather than cause and effect. Just because two things occur together doesn’t mean one causes the other.

The findings also align with the so-called “obesity paradox” in ageing, where a slightly higher body weight is often linked to better survival in later life.

Notably, the reduced likelihood of reaching 100 observed among non-meat eaters was not evident in those who included fish, dairy or eggs in their diets. These foods provide nutrients that are essential for maintaining muscle and bone health, including high-quality protein, vitamin B12, calcium and vitamin D.

Older adults following these diets were just as likely to live to 100 as meat eaters. The researchers suggested that including modest amounts of animal-source foods may help prevent undernutrition and loss of lean muscle mass in very old age, compared with strictly plant-based diets.

What this means for healthy ageing

Rather than focusing on whether one diet is universally better than another, the key message is that nutrition should be tailored to your stage of life. Energy needs decline with age (due to decreased resting energy expenditure), but some nutrient requirements increase.

Older adults still require adequate protein, vitamin B12, calcium and vitamin D – especially to preserve muscle mass and prevent frailty. In older adulthood, preventing malnutrition and weight loss often becomes more important than long-term chronic disease prevention.

Plant-based diets can still be healthy choices, but they may require careful planning and, in some cases, supplementation to ensure nutritional adequacy, particularly in later life.

The bottom line is that our nutritional needs at 90 may look very different from those at 50, and dietary advice should reflect these changes across the lifespan. What works for you now might need adjusting as you age – and that’s perfectly normal.

Chloe Casey, Lecturer in Nutrition and Behaviour, Bournemouth University

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

Categories : Neurodegenerative DiseasesTags : Leave a comment

Researchers Affirm Long-held Belief that Viruses Can Trigger Parkinson’s Disease

On By ModernMedia

A new study shows that a common virus can induce Parkinson’s-like brain damage and movement problems

Source: CC0

Scientists usually use animal models when studying Parkinson’s disease because these models mimic the disease well. They are limited, however, because they require either gene modifications or the injection of toxicants, which may not accurately represent how the disease occurs in humans.

But now, researchers at Texas A&M University have developed a model that uses a nontoxic way to generate the symptoms of Parkinson’s: infection with a virus called Theiler’s murine encephalomyelitis virus (TMEV), a natural pathogen in mice.

Their study is a game changer because it proves that a simple viral infection can trigger the exact brain damage and physical disabilities in animal models that are seen in people with Parkinson’s disease – and it sets the stage for additional studies.

“The toxic-exposure models are useful for studying Parkinson’s, but not all people who are exposed to chemicals go on to develop Parkinson’s, so these models cannot show all the ways a disease as complex as Parkinson’s actually begins or develops over time in people,” said Candice Brinkmeyer-Langford, a neurogenerative disease expert with the Texas A&M University School of Public Health at Texas A&M Health.

Parkinson’s affects more than 10 million people worldwide, making it second only to dementia among brain disorders. It destroys the cells that produce dopamine, a chemical essential for smooth body movement, leading to problems with balance and walking, tremors in the hands or fingers and overall stiffness, as well as mental or emotional distress.

Its origins are unknown, but for decades, experts have believed that the disease could be triggered by the brain inflammation caused by viruses – even those contracted decades earlier – as well as by a combination of a person’s genetics and environmental factors. This idea recently was affirmed by Brinkmeyer-Langford and others at Texas A&M in the case of another devastating motor neuron disease, amyotrophic lateral sclerosis (ALS).

“Viruses are known to cause entirely different diseases based on a person’s genetics,” she said. “For example, the Epstein-Barr virus causes mononucleosis, but may also contribute to cancer or multiple sclerosis, and SARS-CoV-2 can attack the heart and brain as well as the lungs.”

For this pilot study to test the validity of TMEV in studying Parkinson’s, the researchers conducted experiments to measure the following:

  • Brain cell infection and damage. One week after infection, the researchers confirmed that the virus had infected the dopamine-producing brain cells. At one month after infection, the dopamine-producing cells were destroyed in the site of viral infection. Dopamine-induced behaviours were compared between 13 infected animal models and 14 healthy control animal models after administering a dopamine-mimicking drug which produced a distinct movement pattern confirming dopamine neuron loss. This test confirmed that the virus caused a significant loss of these crucial dopamine brain cells over time.
  • Speed and coordination. They compared 13 infected animal models against 14 healthy control animal models to track and measure their motor skills with a standard assessment called the pole test to determine if losing dopamine-producing cells causes the physical movement problems typically seen in Parkinson’s patients. Animal models infected with TMEV had slower times to complete the test compared to the healthy control models, and this still was the case at week 20, when the study ended.
  • Gait abnormalities. They used a specialised treadmill, which evaluated over 100 factors involved in walking, motor function and balance, to analyse how quickly and efficiently the animal models walked. The test confirmed that the virus caused physical weakness following the loss of dopamine producing cells due to viral infection, proving that the virus damaged the brain in a similar way as seen in Parkinson’s patients.

Now that this innovative model has been proven, Brinkmeyer-Langford said future studies will include testing the TMEV model directly against standard, older animal models used in Parkinson’s research, looking for early warning signs and biological markers for Parkinson’s and analyzing how the body’s immune response to a virus changes the brain.

“The clock is ticking, since the rapidly aging global population means the number of people with Parkinson’s is expected to jump significantly,” she said.

By Ann Kellett

Source: Texas A&M University

Categories : NeurologyTags : Leave a comment

A Sleepless Night Increases Synaptic Connections

On By ModernMedia

An increase in a marker for connections was associated with deeper sleep during later naps

Photo by Andrea Piacquadio

A night without sleep produced increased markers of connections between brain cells, showing that sleep in humans may be important for restoring cellular balance in the brain, according to a study published June 23rd in the open access journal PLOS Biology by David Elmenhorst from the Forschungszentrum Jülich Institute of Neuroscience and Medicine in North Rhine-Westphalia, Germany, and colleagues.

Scientists have long wondered why exactly humans and other animals need to sleep. One potential mechanism is that sleep is required to restore synaptic connections and homeostasis in the brain. Synapses – the connections between brain cells – become stronger during wakefulness. This increases the amount of energy the brain needs and leads to buildup of proteins in the brain. Sleep is thought to reset these levels, reducing synaptic connections and restoring homeostasis, but evidence has thus far been limited to animal models. To determine whether the synaptic homeostasis hypothesis is supported in humans, the authors of this study used positron emission tomography (PET) to look for markers of synaptic vesicle glycoprotein 2A (SV2A), a marker of brain synapses in 40 participants, half of whom had gone one night without sleep.

The authors found that after 28 hours of continuous wakefulness, the sleep deprivation group had higher measures of SV2A in several brain regions, including the hippocampus (an area important for memory), and the thalamus, an important information relay in the brain. When the sleep-deprived participants were allowed a two-hour nap, higher levels of SV2A were associated with more slow wave activity during sleep, a marker of deep sleep and sleep pressure. While SV2A is only a proxy for brain cell connections and the elevations were relatively small, the results support the synaptic homeostasis model of sleep, and suggest a biological connection between the need for sleep and the buildup of cell connections. 

The authors add, “During sleep deprivation, the brain remains awake longer and continues to process stimuli and information. Our study shows that after approximately 28.5 hours of wakefulness, a marker for synaptic density increases in several brain regions. This suggests that sleep deprivation not only causes fatigue but is also accompanied by measurable changes in neural connections.”

Provided by PLOS

Categories : Respiratory DiseasesTags : Leave a comment

Higher Vitamin A Levels Linked to Better Lung Function in Asthmatic Kids and Adults

On By ModernMedia

Vitamin D shows similar benefits in adults with asthma, including slower biological ageing

Photo by cottonbro studio from Pexels

Higher levels of circulating vitamin A are linked to better lung function in children and adults with asthma, while vitamin D shows similar benefits in adults, including slower biological ageing, finds the first study of its kind, published online in the respiratory journal Thorax.

Poor lung function is a key predictor of death, irrespective of whether or not a person has lung disease. And making sure that the lungs keep working well is essential for staving off long term respiratory conditions, explain the researchers.

Previously published research suggests that vitamins A and D both protect against and worsen asthma, as well as influencing lung development, depending on the dose and context, they add.

To clarify the role of these vitamins, the researchers drew on two groups of participants with asthma: 1165 children in the GACRS (Genetic Epidemiology of Asthma in Costa Rica Study); and 1041 adults in the ODOLLFA (Omic Determinants of Longitudinal Lung Function in Asthma).

Small molecules that fine-tune the activity of genes (serum microRNAs or miRNAs for short) and those that mark genes as either active or inactive (DNA methylation), plus levels of vitamins A and D, were measured in all the participants.

Lung capacity/health was assessed through measures of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and the FEV:FVC ratio.

In adults, further analysis assessed whether methylation status and miRNAs influenced the association between the vitamins and lung function or epigenetic ageing – the response of genes to external biological and environmental factors which then promotes cellular ageing.

The findings showed that children and adults with asthma and higher vitamin A levels had better lung function (FEV1 and FVC) than those with lower levels.

And among adults with asthma, those with higher vitamin D levels of at least 30 ng/ml had better lung function than those with lower levels. They also had less evidence of epigenetic ageing, suggesting that vitamin D may help slow biological ageing, particularly in people with asthma, say the researchers.

“These findings emphasise the value of adequate vitamin D, not only for lung health but also in slowing age-related processes,” they write.

In people with asthma, vitamin D deficiency is more common and is associated with more severe disease, worse asthma control, higher inhaled steroid need and more frequent  sudden worsening of asthma symptoms, they explain.

The researchers identified MiRNAs that regulate 248 genes commonly associated with vitamins A and D in both age groups, which, further analysis suggests, are involved in controlling inflammation and lung function.

This secondary analysis also revealed that changes in the expression of specific miRNAs strongly influence the effects of vitamins A and vitamin D on lung function and epigenetic ageing.

“To our knowledge, this is the first study to integrate vitamin A and D levels with lung function and epigenetic markers – miRNA expression and DNA methylation – in both children and adults with asthma,” write the researchers.

Lung function was inversely correlated with all age acceleration measures, reinforcing the link between respiratory health and ageing,” they add.

They conclude: “Our findings emphasise that epigenetic mechanisms play a key role in mediating the effects of vitamins on lung function in individuals with asthma, pointing to potential targets for personalised nutrition and therapeutic strategies in asthma care.”

In a linked editorial, Drs Sze Man Tse and Genevieve Mailhot of the CHU Sainte-Justine Research Center, Montreal, and the University of Montreal, caution: “While these findings open a novel line of investigation linking vitamin D, biological ageing and lung health, there is a need for further studies to clarify causality.”

But they add: “By examining the underlying biological mechanisms, [the researchers have] revealed a nuanced interplay between vitamins A and D, lung function, and their epigenetic mediators.

“Their findings highlight age-dependent and age-independent mechanisms, underscoring complex interactions between vitamin levels and lung physiology.”

And they conclude: “Overall, advancing our understanding of how nutritional exposures impact gene regulation may open new avenues for managing asthma across the lifespan.”

Source: The BMJ Group

Categories : EndocrinologyTags : Leave a comment

Cortisol from Adrenal Tumours Progressively Raises Cardiovascular Risk

On By ModernMedia

Landmark international study finds persistent mild cortisol excess drives hypertension progression, challenging the standard diagnostic test.

A graphic of a human skeleton, also showing the kidneys with the adrenal glands on top, highlighted in red.
The adrenal glands produce the steroid hormone cortisol, a master regulator of metabolism, blood pressure and immune function.

A major new study, led by the University of Birmingham and published in The Lancet Diabetes & Endocrinology, has shown that cortisol levels in patients with adrenal tumours are far less stable than previously assumed.

The study also identified that those in whom cortisol remains persistently elevated carry a significantly greater risk of worsening high blood pressure and a heavier overall cardiometabolic burden.

Cortisol, often referred to as the “stress hormone”, is a steroid hormone produced by the adrenal glands that acts as a master regulator of metabolism, blood pressure, and immune function. When benign tumours form on the adrenal glands (found incidentally in 3-7% of adults) they can cause the body to produce cortisol independently of normal regulatory controls, a condition known as mild autonomous cortisol secretion (MACS). Until now, it was unclear how cortisol levels in these patients change over time, and what that means for their long-term health.

The study of over 2500 patients is the largest study of its kind to examine how cortisol patterns evolve over time in patients with benign adrenal tumours and what this means for cardiovascular outcomes.

These findings should prompt us to think more carefully about which patients need closer follow-up, and whether active treatment to reduce cortisol excess – including surgery in selected cases – could protect their long-term cardiovascular health.

Alessandro Prete, Clinical Associate Professor in Endocrinology and Diabetes

The study followed 2525 patients with benign adrenal tumours for an average of nearly 7 years. Each patient underwent repeated hormonal testing using the 1mg overnight dexamethasone suppression test, the standard clinical test used to assess whether the adrenal gland is overproducing cortisol autonomously. Patients were classified based on whether their cortisol levels remained normal, remained elevated (persistent MACS), or changed between categories over time.

The researchers found that cortisol secretion status changed in 22% of patients, far more frequently than previously recognised, with most changes occurring within the first three years after diagnosis. These findings challenge the assumption that a single hormonal test is sufficient to characterise a patient’s long-term cortisol profile.

Patients with persistent MACS had the greatest overall cardiovascular burden and faced a 34% higher rate of worsening high blood pressure than those with persistently normal cortisol. Over 10 years, patients with persistent MACS lost an average of 2 years of well-controlled hypertension-free time compared with those whose cortisol remained normal – a clinically meaningful difference in long-term blood pressure control.

Cardiometabolic burden refers to the combined impact of interrelated metabolic and cardiovascular risk factors (including obesity, high blood pressure, type 2 diabetes, and high cholesterol) on overall health, predisposing serious, chronic diseases such as heart failure, heart attack, and stroke.

The study identified patients with persistently abnormal cortisol levels (persistent MACS) as a clinically important, higher-risk group who may benefit from closer monitoring and more proactive management of modifiable risk factors – including blood pressure, cholesterol, weight, and smoking. The results are also consistent with recent randomised trial data, also published in The Lancet Diabetes & Endocrinology, showing that surgery to remove the adrenal tumour can improve blood pressure control in MACS.

Professor Alessandro Prete, Clinical Associate Professor of Endocrinology in the Department of Metabolism and Systems Science at the University of Birmingham, Co-lead for the National Institute for Health and Care Research (NIHR) Biomedical Research Centre: Birmingham’s Women’s Metabolic Health theme, through which the study was delivered, and corresponding author and senior investigator of the study, said: “For many years, the assumption has been that a single hormone test at adrenal tumour diagnosis tells us everything we need to know about a patient’s cortisol status.

“This study shows that it is simply not the case – cortisol levels change over time in a substantial proportion of patients, and those in whom they remain persistently elevated are at a meaningfully higher risk of developing uncontrolled blood pressure.”

The study also provides important new evidence to inform the ongoing debate around whether, and how often, cortisol testing should be repeated in patients with benign adrenal tumours. Current guidelines recommend repeating the test only in specific clinical circumstances; the authors of the study are calling for prospective studies to determine whether repeated hormonal assessment contributes meaningfully to risk stratification beyond established cardiovascular risk factors. 

Source: University of Birmingham

Categories : CancerTags : Leave a comment

Uncovering Sex-specific Immune Differences in Glioblastoma

On By ModernMedia
Photo by Anna Shvets

Men and women experience many diseases very differently. Certain diseases present more commonly in one sex than in another. Some conditions like heart attacks may cause different symptoms in men and women. Some treatments work better or not at all for one sex over the other.

Cancer is no exception. There are major differences in male and female immune systems, a system critical for cancer’s growth and for successfully becoming cancer-free. For example, some immunotherapies work better in men than in women and vice versa.

Glioblastoma, the most common and fatal form of brain cancer, is more common and more deadly in men than in women. The reasons behind this difference and how the cancer’s biology differs between men and women remain largely unclear.

Now, a study has identified a cellular mechanism that differs between male and female laboratory models with glioblastoma. The study was published in the journal Nature Cancer and led by Defne Bayik, PhD, assistant professor of molecular and cellular pharmacology at the University of Miami Miller School of Medicine, and Asmita Pathak, PhD, a former postdoctoral fellow in the Bayik Lab.

“We have a growing appreciation that cancer doesn’t act the same way in men and women. There are differences in incidence rates. There are differences in treatment responses. There are differences in outcomes,” Dr Bayik said. “But we don’t really have a good, fundamental understanding of the mechanisms underlying these observational studies.”

Delving Into Immune Differences

To uncover that mechanism for glioblastoma, Dr Bayik and her colleagues focused on a certain class of immune cells in the brain known as myeloid-derived suppressor cells, or MDSCs. As their name suggests, these cells suppress other cells’ immune activity, especially that of T cells. In healthy contexts, their activity is important for regulating the immune system and keeping inflammation under control. But in the context of cancer, these cells are often recruited by tumours to suppress surrounding T cells and other immune cells, protecting cancerous cells from the rest of the immune system and allowing them to grow unchecked.

In previous work, Dr Bayik found sex-specific differences in the immune landscape of glioblastoma, with higher levels of monocytic myeloid-derived suppressor cells associated with disease in male laboratory models. Granulocytic MDSCs play a more prominent role in females. In studies of human glioblastoma tumours, she observed a similar pattern. Men tend to have more monocytic MDSCs within their tumours, Granulocytic MDSCs, or proteins associated with these cells, correlate with worse outcomes for women but not for men.

Women still constitute 40% of glioblastoma patients. By identifying these differences, we can better tailor treatments for both men and women.

Dr Defne Bayik

In the new study, Dr Bayik and her colleagues wanted to understand what drives this difference. How do granulocytic MDSCs act to promote cancer growth in female but not male laboratory models? In Dr Bayik’s previous study, she’d found several drug candidates that are predicted to act on granulocytic MDSCs. A few of these candidate drugs target proteins related to GABA, a brain signaling molecule also known as a neurotransmitter.

By exposing different populations of MDSCs to GABA in the lab, the scientists found that the neurotransmitter specifically affects cellular metabolism only in female granulocytic MDSCs. The process is unaffected in male MDSCs. They also found that this reprogramming of the cells’ metabolism by GABA made the granulocytic MDSCs more immunosuppressive. Finally, they found that blocking the GABA receptor in female laboratory models with glioblastoma improved their outcome. This had no effect on male laboratory models with the cancer.

Potential for treatment personalised by sex

Dr Bayik and her colleagues found that many of their lab findings held up in human samples donated by patients with glioblastoma. Tumour biopsies from women had higher levels of GABA and the GABA receptor in granulocytic MDSCs than did those from men. They also found that GABA reprograms granulocytic MDSC metabolism in women as it does in lab models.

These findings point to the potential for a sex-specific treatment for glioblastoma, Dr. Bayik said. She’s currently working to understand the basis for the difference in cellular metabolism in these immune cells between male and female laboratory models. Further uncovering the mechanism of this sex difference will help her and other scientists find new potential drug targets for the disease. MDSCs are involved in many other types of cance. Drugs that target these cells could have broader applications than just glioblastoma.

“Glioblastoma may be more common in men, but women still constitute 40% of patients,” said Dr Bayik. “By identifying these differences, we can better tailor treatments for both men and women.”

By Rachel Tompa, PhD

Source: University of Miami