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New Brain Stimulation Technique Improves Short Term Social Skills in Children with Autism

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Accelerated continuous theta burst stimulation (a-cTBS) may be a “viable and scalable therapeutic option” say researchers 

Photo by Emily Wade on Unsplash

A new non-invasive brain stimulation technique known as accelerated continuous theta burst stimulation (a-cTBS) improves social communication at one month follow up and has a favourable safety profile in children with autism, finds a trial from China published by The BMJ today.

The researchers say the findings suggest that a-cTBS may be “a viable and scalable therapeutic option for children with autism spectrum disorder.”

Preliminary results from a recent pilot study suggest that a-cTBS is safe and effective for enhancing social communication in children with autism. A key advantage of a-cTBS is its shorter sessions compared with conventional brain stimulation, making it more suitable for children.

To build on this work, the researchers investigated the effectiveness and safety of a five day a-cTBS protocol in improving social communication among children with autism, including younger children and those with intellectual disability.

The trial involved 200 children (167 boys and 33 girls) aged 4-10 years with autism recruited from three academic hospitals in China from July 2023 to October 2024, half of whom also had intellectual disability.

The children were randomised to receive either active a-cTBS (intervention) or sham (control) treatment for five consecutive days (10 sessions each day). The stimulation targeted the brain’s left primary motor cortex, which is linked to movement, language, and social cognition.

The researchers used the Social Responsiveness Scale (SRS-2) to measure changes in social communication impairment from baseline to post-intervention and from baseline to one month follow-up. Language improvements were also assessed using three recognised measures.

A total of 193 participants completed the full five day intervention course. Compared with the sham group, the a-cTBS group showed significantly greater improvements in social communication from baseline to post-intervention and from baseline to one month follow-up, with mean difference impairment score reductions of -6.25 and -6.17, respectively.

The a-cTBS group also showed greater improvements in language abilities. This finding was supported by a small effect size (Cohen’s d) ranging from 0.12 to 0.47, representing the difference between the two group means.

Adverse events were more frequent in the a-cTBS group than in the sham group (54.5% v 29.3%), with restlessness and scalp discomfort being the most common. All adverse events were mild to moderate and resolved spontaneously.

The researchers acknowledge some limitations with the SRS-2 measure and potential bias from greater treatment expectancy in the intervention group. The trial also had a short one-month follow-up and more than 80% of participants were boys.

However, they point out that the inclusion of young children and those with intellectual disability supports the protocol’s broad applicability, and consistent effects across sensitivity analyses provides greater confidence in their conclusions.

As such, they say their results suggest that a-cTBS may be “a feasible, effective, and scalable therapeutic option for children with autism spectrum disorder, including those with intellectual disability” and their protocol “represents a major advancement towards equitable autism care worldwide.”

In a linked editorial, researchers in Hong Kong agree that the findings show promise, but advocate for cautious optimism.

They note that while “a-cTBS should not replace psychosocial support or educational adaptation,” it “may become an important component of a multimodal pathway for children with autism with significant social communication difficulties,” provided it is “further replicated and integrated thoughtfully with behavioural care.”

Source: The BMJ Group

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Common Genetic Marker May Guide New Treatment for Acute Leukaemia

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SAG Leukaemia. Credit: Scientific Animations CC0

A genetic alteration that is already routinely analysed in patients with acute myeloid leukaemia can be used to identify patients who respond to a new targeted therapy, according to a study published in the journal Discover Oncology.

Acute myeloid leukaemia (AML) is an aggressive blood cancer in which treatment outcomes vary widely between patients. In the new study, the researchers have identified a way to better select which patients may benefit from a drug that blocks the enzyme DCPS.

Some patients respond better to the treatment

The researchers show that AML patient samples with low levels of the protein FHIT are sensitive to DCPS inhibition. The proportion of patients with low FHIT levels varies between 5 and 24%, with the highest proportion seen in children. In the related blood disorder myelodysplastic syndrome (MDS), around 36% of patients showed silencing of the FHIT gene.

The key finding is that patients with a mutation in the IDH2 gene often have low FHIT levels and respond better to DCPS-targeted treatment. Since IDH2 is already part of routine diagnostic testing at AML diagnosis, the marker can be used without introducing any additional tests.

“Many promising cancer drugs fail in clinical trials because they are tested in very broad patient groups,” says Francesca Grassi, doctoral student at the Department of Medicine, Huddinge and first author of the study. 

“By using a biomarker that is already available in healthcare, patient selection can be made both simpler and more precise,” says Francesca Grassi.

May lead to more targeted cancer treatment

The researchers tested 24 primary AML samples with the compound RG3039, which inhibits DCPS, and also analysed publicly available patient data to explore the link between FHIT levels and different genetic alterations.

“The IDH2 mutation captures the information we need to identify the right patients, without additional analyses. This could facilitate the planning of future clinical trials, particularly for patient groups with limited treatment options,” says Francesca Grassi.

The next step is to validate the findings in larger patient cohorts and to gain a deeper understanding of the biological link between IDH2 mutations and FHIT expression. In the longer term, the researchers hope that the results will support the design of a clinical trial of DCPS-targeted therapy in AML.

Source: Karolinska Institutet

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One of the World’s Most Common Knee Surgeries not Helpful – May Even Be Harmful

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Partial meniscectomy does not improve patient symptoms or function, reveals a 10-year follow-up of the FIDELITY, a placebo-surgery controlled trial

Photo by Towfiqu barbhuiya

Trimming a degenerated meniscus, or partial meniscectomy, is one the most common orthopaedic surgeries in the world. Even though the number of procedures in Finland has decreased significantly in recent years, the surgery continues to be performed widely internationally.

A 10-year follow-up study has revealed that, compared to sham surgery, partial meniscectomy did not improve patients’ symptoms or function. On the contrary, the 10-year follow-up of patients who had undergone partial meniscectomy found them to have more symptoms, more reduced function, increased progression of osteoarthritis and a higher probability of subsequent knee surgery when compared to sham surgery. 

The Finnish Degenerative Meniscal Lesion Study (FIDELITY) study is unique both with regard to its research design, ie, the sham surgery control group, and its 10-year patient follow-up. In the study, patients with degenerative meniscal tears were randomised to undergo a partial meniscectomy or sham surgery.

Teppo Järvinen, Professor at the University of Helsinki and the principal investigator of the FIDELITY emphasises the broader significance of the results: “Our findings suggest that this may be an example of what is known as a medical reversal, where broadly used therapy proves ineffective or even harmful.”

“The surgery is based on the assumption that pain in the inside of the knee is caused by a medial meniscus tear, which can be treated surgically. Such reasoning – assumption based on biological credibility – is still very common in medicine but in this case, the assumption does not withstand critical examination. Based on current understanding, pain in various joints, such as the knee joint in this case, is related to degeneration brought about by aging,” says Raine Sihvonen, Specialist in Orthopaedics and Traumatology and the other principal investigator of the FIDELITY study. 

Concerns about the adverse effects of surgery

The registry and other observational data published in recent years have elicited concern about the potential harm caused by partial meniscectomy.  Based on this data, the risk of arthroplasty, or joint replacement surgery, as well as a potentially higher risk of complications following the surgery has been associated with partial meniscectomy. However, the evidence provided by observational studies is inherently indirect and cannot be used to demonstrate a causal effect.

“Several randomised studies have already demonstrated that partial meniscectomy has not improved patients’ symptoms or function in the short (1–2 years) or medium (5 years) term. Regardless, the procedure has remained widely used in many countries,” says Doctoral Researcher and Specialist in Orthopaedics and Traumatology, Dr Roope Kalske.

“For nearly a decade, many independent, non-orthopaedic organisations providing clinical guidelines have recommended that the procedure should be discontinued. Still, for example, the American Academy of Orthopaedic Surgeons (AAOS) and the British Association for Surgery of the Knee (BASK) have continued to endorse the surgery.

This effectively illustrates how difficult it is to give up inefficient therapies,” Järvinen sums up.

“The study conducted in five hospitals is an example of smooth multicentre collaboration, as well as the commitment of research patients to an interesting project. Of the original 146 participants, more than 90% took part in the final stage of the study,” says the research manager Pirjo Toivonen. 

Source: University of Helsinki

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Kidney Disease is Growing in Africa: Big New Study Casts Light on Genetic Risk Factors

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Chronic kidney disease (CKD). Credit: Scientific Animations CC4.0

Segun Fatumo, Queen Mary University of London

Every minute your kidneys are hard at work, filtering around 200 litres of blood, removing waste, balancing salts and fluids, and regulating blood pressure. This happens without any conscious effort on your part.

But when your kidneys begin to fail, the consequences are devastating, including fatigue, fluid buildup and heart complications. Some people eventually need dialysis or a transplant to stay alive.

Kidney disease is one of the fastest-growing causes of death across the world. Around 850 million people are living with some form of it, more than the combined number of people affected by diabetes and cancer. Chronic kidney disease – when your kidneys slowly lose the ability to do their job – causes approximately 1.5 million deaths each year globally and that toll is rising.

But kidney disease develops silently, with few symptoms until it is already severe.

And the burden is not shared equally. People of African ancestry are four times more likely to develop the most severe form of kidney failure than people of European ancestry. In sub-Saharan Africa, rates of high blood pressure and type 2 diabetes are rising too. Both are leading drivers of kidney damage. Around 30% of adults in sub-Saharan Africa have high blood pressure, and 25 million (one in 20 adults) have diabetes) – mostly undiagnosed and untreated.

Sub-Saharan Africa has lower numbers of kidney specialists, dialysis facilities and transplant services per capita than the rest of the world. Africa as a whole has fewer than one nephrologist per million people. In some African countries there are no kidney specialists at all. The global median is around 10 per million. In high-income countries the figure reaches 23 per million. For most Africans who reach kidney failure, there is simply no treatment available.

Identifying who is at risk before their kidneys fail is therefore vital.

Our recently published research fills a big gap here. We are members of the KidneyGenAfrica consortium, a pan-African partnership that aims to deliver research and training excellence in genomics of kidney disease.

We found new genetic variants that point to kidney disease risk in African populations. And we uncovered differences between the genetic risks faced by people living in Africa, on one hand, and people of African descent living in the North America and Europe, on the other.

This shows how important it is for medicine to be based on relevant research.

Understanding kidney disease

Kidney disease does not appear suddenly. It often develops gradually, shaped by a combination of factors. Some people carry genetic variants, small differences in their DNA, that make their kidneys more susceptible to damage.

Others face environmental risks such as high-salt diets, uncontrolled high blood pressure or diabetes infections. The use of herbal medicines, contaminated water and environmental toxins are risks too.

In most cases, it is the combinations of these factors that determine who gets sick and how quickly. But until recently, African populations had barely featured in the scientific conversation about this. Africa, home to the most genetically diverse human populations on Earth, have been represented in only a small fraction of the world’s genomic research.

That is beginning to change.

Large genetic study of Africans

We analysed genomic data from about 26,000 individuals across eastern, western and southern Africa, and around 81,000 individuals of African ancestry living elsewhere. It’s the largest genetic study of kidney function in continental Africans ever conducted.

Our study sheds new light on the genetics of chronic kidney disease across diverse African populations. It will also support future work aimed at improving prevention, diagnosis and treatment of kidney disease among these populations and worldwide.

The team used a method called a genome-wide association study, which scans the entire human genetic code to find variants linked to a particular trait or disease. Here, the trait of interest was estimated glomerular filtration rate, a standard blood test result that measures how efficiently the kidneys are filtering waste. A lower score signals poorer kidney function and higher risk of disease.

Analysing continental African populations alone, the study identified four relevant locations on genes, including two that hadn’t been reported before.

Adding African-ancestry populations across the diaspora, the number rose to 19 locations, three of them new. Four of these genetic locations were pinpointed with high precision. This means the team was able to identify the specific genetic variant most likely driving the effect, rather than simply flagging a region of the genome where something relevant was happening.

Each newly discovered location is now a potential target for future drugs or diagnostic tools.

The study also examined polygenic scores, which are tools that estimate a person’s overall risk of developing a disease. A key finding here was that scores built using data from genetically similar African populations performed better than scores derived from larger but genetically distant datasets.

This matters enormously for medicine in Africa: the science only works if the reference data matches the population it is meant to serve.

A gene that behaves differently on either side of the Atlantic

An important finding from the study concerns a gene called APOL1. Two variants of the APOL1 gene, known as G1 and G2, increase the risk of several serious forms of kidney disease in African Americans. It was widely assumed that the same risk would apply equally to people living on the African continent.

However, the data suggests otherwise. In continental Africa, these high-risk APOL1 variants occur at lower frequencies (and vary across regions of Africa). Their association with reduced kidney function is markedly weaker than in the African diaspora.

The same gene appears to behave differently depending on where a person lives and what population they descend from.

The finding matters for drug development. Clinical trials for kidney disease treatments must include people living in Africa and not just people of African descent living elsewhere.

What must happen now

Several things must follow from this research if it is to benefit people’s health:

  • African health systems must invest in early kidney disease detection. Simple, affordable blood and urine tests can identify kidney damage when lifestyle changes and medication can still make a difference. Genetic risk tools can help identify who needs screening most urgently.
  • Pharmaceutical companies must include continental African populations in their clinical trials.
  • The global research community must continue investing in African genomic infrastructure – research cohorts and large groups of consenting participants whose genetic and health data are collected and stored for analysis.

This research is evidence that African scientists, working with African communities, can generate knowledge that shifts the global picture. The world’s understanding of one of its most urgent health challenges will be sharper for it.

Segun Fatumo, Professor and Chair of Genomic Diversity, Queen Mary University of London

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

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South Africa’s Weight-loss Revolution is Testing Medical Discipline

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Photo by I Yunmai on Unsplash

One in every two South African adults is considered overweight or obese. It is not surprising, then, that potentially lifesaving prescription-based metabolic medicines are surging in popularity. The challenge: demand is rising faster than the clinical structure needed to support it, leaving many patients unsure what responsible, medically supervised care should look like.

It is a concern Dr Gerhard Vosloo, a prominent sports, exercise, and lifestyle physician, says he is encountering more frequently in clinical practice. “Expectations are becoming unreasonably high, while few understanding the level of medical oversight required to manage these therapies responsibly. It’s just not as simple as prescribing an aggressive regime and standing back.”

To address issues in today’s weight management sector, Dr Vosloo established Dr GL Vosloo Medical Practice, managed by BioWell, as a formal online medical practice built around sound clinical judgment, structured care, and meaningful patient oversight. He says, “We’re building a model – one that could serve as a stable structure for the wider industry, where sound medical judgment is consistently prioritised over the public’s growing appetite for weight loss drugs.”

The danger of normalising prescription therapy

Dr Vosloo cautions that the rapid rise of these medicines in the mainstream is oversimplifying a highly complex subject and making pharmaceutical use seem routine, when it should remain a final option after disciplined nutrition- and exercise-led approaches have been fully explored.

“Misinformation spreads like wildfire online. People are starting to view prescribed medicines as a routine diet option, when they should be a last resort. Pharmaceuticals are powerful tools for people who struggle to lose weight, but they should be introduced only when medically appropriate, and only after nutrition, exercise, and appropriate supplementation have been fully explored.”

He maintains that prescribed medicines should form part of a structured metabolic management programme that, when used correctly, will reduce cardiometabolic risk, improve insulin sensitivity, regulate appetite, and support meaningful body composition change. The goal is to improve metabolic health under disciplined supervision, and when treatment is not medically necessary, doctors must refuse to prescribe.

“Clinical eligibility must be determined by medical rationale,” he says. “A patient’s preference for medication, emotional pressure to start treatment, or the ability to pay cannot override clinical judgement. Where medical need is absent, a BioWell doctor will decline to prescribe and direct the patient to a non-pharmaceutical, doctor-supported metabolic management pathway.”

Dosing with discipline

Beyond unnecessary prescribing practices, Dr Vosloo stresses that the industry is undermined by over lenient dosing habits. As practiced on the BioWell platform, dosing decisions should instead follow a conservative model guided by clinical responses and tolerability rather than speed of weight loss. The objective is to protect overall health while supporting steady progress that the body can sustain.

“An unfortunate consequence of aggressive dosing is the loss of muscle mass. It’s easier for the body to draw from muscle than it is to mobilise fat, particularly when calories and protein are low – a hallmark of aggressive dosing protocols. The nutritional and training commitment needed to offset muscle loss under more radical regimens are difficult to manage for most people. It’s far safer and more sustainable to take low doses over a longer period.”

“BioWell doctors are more measured in our approach. Conservative dosing and escalation protocols help keep muscle loss to a minimum, while structured nutrition and exercise support plans strengthen the muscular system. This also reduces the risk of nutritional deficiency and limits the physiological stress that often accompanies poorly managed treatments.”

The end goal, Dr Vosloo explains, is to safely and gradually bring South Africa’s obesity crisis under control without creating any additional harm. “Prescription-based metabolic medicine is an undeniably powerful tool in the fight against obesity – one we cannot afford to lose. It’s a lifeline for people battling weight-related illness, but it’s also become a dangerous crutch for those willing to gamble with their health just to lose a few kilograms quickly. If we want to change the health trajectory of millions, we need to rein in aggressive dosing practices and establish a common-sense structure across the sector.”

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HEPA Air Purifiers May Boost Brain Power in Adults Over 40 – New Research

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Photo by Mari Lezhava on Unsplash

Nicholas Pellegrino, University of Connecticut; Doug Brugge, University of Connecticut, and Misha Eliasziw, Tufts University

Using an in-home HEPA purifier for one month spurs a small but significant improvement in brain function in adults age 40 and older. That’s the result of a new study we co-authored in the journal Scientific Reports.

HEPA purifiers – HEPA stands for high efficiency particulate air – remove particulate matter from the air. Exposure to particulate matter has been connected to respiratory and cardiovascular illnesses as well as neurological diseases such as Alzheimer’s and Parkinson’s. Environmental health researchers increasingly recommend that people use HEPA air purifiers in their homes to lower their exposure to particulate matter, but few studies have examined whether using them boosts mental function.

We analysed data from a study of 119 people ages 30 to 74 living in Somerville, Massachusetts. Somerville sits along Interstate 93 and Route 28, two major highways, resulting in relatively high levels of traffic-related air pollution. This makes it an especially good location for testing the health effects of air purifiers.

We randomly assigned participants to one of two groups. One used a HEPA air purifier for one month and then a sham air purifier – which looked and acted like the real thing but did not contain the air-cleaning filter – for one month, with a monthlong break in between. The second group used the real and sham purifiers in reverse order.

After each month, participants took a test that measured different aspects of their mental capacity. The test probed people’s visual memory and motor speed skills by measuring how quickly they could draw lines between sequential numbers, and it tested executive function and mental flexibility by asking them to draw lines between alternating sequential numbers and letters.

We found that participants 40 years and older – about 42% of our sample – on average completed the section testing for mental flexibility and executive function 12% faster after using the HEPA purifier than after using the sham purifier. That was true even when we accounted for factors like differences in the amount of time participants spent indoors, with either filter, as well as how stressful they found the test.

This improvement may seem small, but it is similar to the cognitive benefits that people experience from increasing their daily exercise. While you may not experience a sudden increase in clarity from a 12% boost, preventing cognitive decline is vital for long-term well-being. Even small decreases in cognitive functioning may be associated with a higher risk of death.

Studies increasingly show that air pollution can be detrimental to brain health.

Why it matters

Air pollution can negatively affect mental function after just a few hours of exposure. Studies show that air purifiers are effective at reducing particulates, but it’s unclear whether these reductions can prevent cognitive harm from ongoing pollution sources like traffic. Research has been especially lacking in people living near major sources of air pollution, such as highways.

People living near highways or major roadways are exposed to more air pollution and also experience higher rates of air pollution-related diseases. These risks aren’t encountered by all Americans equally: People of color and low-income people are more likely to live near highways or areas with heavy traffic.

Our study shows that HEPA air purifiers may offer meaningful health benefits under these circumstances.

What still isn’t known

Research shows that air pollution begins to affect cognitive function especially strongly around age 40. These effects may become increasingly prominent as people age.

HEPA air purifiers may therefore be especially beneficial for older adults. Our study did not explore this possibility, as fewer than 10 of our 119 participants were over the age of 60.

Also, our participants only used a HEPA air purifier for one month. It’s possible that longer durations of air purification may sustain or even increase the improvement in cognitive function we observed in our study.

Finally, it is unclear exactly how air purifiers improve cognition. Some studies suggest that exposure to particulate matter reduces the amount of the brain’s white matter, which helps brain cells conduct electrical signals and maintains connections between brain regions. The brain regions most harmed by air pollution are the ones that control mental flexibility and executive function, the same domains in which we saw improvements in our study.

We plan to study whether reducing particulate matter by using air purifiers is indeed protecting the brain’s white matter, and whether it could reverse some cognitive decline. We will explore that possibility by studying how levels of molecules called metabolites, which cells produce as they do their jobs, change in response to breathing polluted air and air cleaned by a HEPA filter.

The Research Brief is a short take on interesting academic work.

Nicholas Pellegrino, Research Associate in Public Health Sciences, University of Connecticut; Doug Brugge, Professor of Public Health Science and Community Medicine, University of Connecticut, and Misha Eliasziw, Associate Professor of Biostatistics, Public Health and Community Medicine, Tufts University

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

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Alzheimer’s Risk Gene APOE4 Silently Undermines Bone Quality in Women

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Buck Institute researchers discover a surprising connection between a major risk factor for Alzheimer’s

Photo by Karolina Grabowska on Pexels

Scientists at the Buck Institute for Research on Aging, along with collaborators at UC San Francisco, have discovered that APOE4, the most common genetic risk factor for Alzheimer’s disease, causes bone quality deficits specifically in female mice, through a mechanism that is invisible to standard imaging and can emerge as early as midlife.

The findings, published in Advanced Science, reveal an unexpected biological link between Alzheimer’s risk and skeletal health, and identify a new molecular pathway that could one day inform earlier diagnosis of cognitive decline or guide treatment for bone quality loss in women who carry the APOE4 gene.

“What makes this finding so striking is that bone quality is being compromised at a molecular level that a standard bone scan simply will not catch,” says Buck professor Birgit Schilling, PhD, a senior author of the study. “APOE4 is quietly disrupting the very cells responsible for keeping bone strong, and it is doing this specifically in females, which mirrors what we see with Alzheimer’s disease risk.”

Physicians have long observed that people with Alzheimer’s disease suffer bone fractures at higher rates, and that a diagnosis of osteoporosis in women is actually the earliest known predictor for Alzheimer’s. But the underlying mechanism connecting brain and bone health has remained elusive.

To investigate this connection, researchers, led by research scientist and co-first author of the paper Charles Schurman, PhD, first performed a proteomic analysis of aged mouse bone, a comprehensive survey of all the proteins present in the tissue. “The team discovered that bone, and particularly osteocytes, the long-lived cells embedded within it, is unusually rich in proteins associated with neurological disease, including apolipoprotein E [APOE] and amyloid precursor protein,” says Schurman. “Notably, APOE expression in osteocytes was twice as high in aged female mice as in young or male mice.”

The team then turned to a humanised mouse model carrying either APOE2 (associated with reduced Alzheimer’s risk), APOE3 (considered neutral), or APOE4 (the risk variant), and analysed bone and hippocampal tissue from the same animals. APOE4 produced strong, sex-specific effects on both the bone transcriptome and proteome; researchers found the protein-level disruption in bone was actually more pronounced than the corresponding changes in the hippocampus.

Despite the protein level disruption, cortical bone structure appeared normal under imaging. Researchers found that bone quality deficits arose not from changes in bone shape or density, but from APOE4’s suppression of perilacunar/canalicular remodelling, the process by which osteocytes actively maintain the microscopic channels that keep bone mechanically resilient. When this maintenance breaks down, bone quality deteriorates even when it looks intact.

“These results suggest that osteocytes could serve as early biological sentinels for age-related cognitive decline in women carrying APOE4,” says professor Lisa Ellerby, PhD, also a senior author of the paper. The Ellerby lab studies genetic risk factors for Alzheimer’s.  “We think that targeting osteocyte function may open a new front in preserving bone quality in this population.”

Researchers say there is a larger takeaway from this research that links brain and bone science.  “While we think this work is relevant for human patients with Alzheimer’s disease or with osteoporosis, this study also highlights the need for researchers to consider the human body as an entire system without isolating organs and diseases from each other,” says Ellerby.

Source: Buck Institute for Research on Aging

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Searching for the Weak Spots in C. Diff’s Defences

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New studies reveal how Clostridioides difficile behaves inside the body

Clostridioides difficile. Credit: CDC

Bacterial infections caused by Clostridioides difficile are a serious and persistent problem for patients and hospitals alike. The bacterium can cause severe diarrhoea, life-threatening inflammation of the colon, and recurring illness that dramatically reduces quality of life – especially for older adults, who face the highest risk of complications and death.  

C. diff remains difficult to control for a combination of factors. The bacterium survives many disinfectants, allowing it to easily spread in health care settings, where it is the most common cause of infectious diarrhoea. After entering the body through the mouth, the bacterium travels to the colon, where it colonises and starts releasing toxins that damage tissues. About one in nine patients treated for C. diff will develop another infection within weeks or months, often unpredictably, with the risk of a repeat infection increasing from there. And some strains of the bacterium have become resistant to the first-line antibiotics used to treat it.

Researchers at Tufts University School of Medicine are tackling these challenges by studying C. diff at multiple levels, from how individual bacterial cells behave inside the gut to the molecular switches that help them survive and spread. Together, these approaches are revealing hidden vulnerabilities that could lead to better ways to prevent new or recurrent infections, predict severe disease, or stop the bacterium before it causes harm. 

Watching Infections Unfold, Cell by Cell

“C. diff is everywhere,” said Aimee Shen, an associate professor of molecular biology and microbiology at Tufts School of Medicine. “But infections can look very different from one patient to the next.”  

Some people carry the bacterium without ever getting sick. Others develop severe, life-disrupting illness – typically after being treated for another illness with antibiotics that wipe out beneficial gut bacteria that may have otherwise warded off an infection.  

“A bad C. diff infection is reportedly incredibly painful, like glass shards moving through your intestine,” said Shen. “And there’s some research that shows that C. diff toxins actually act on neurons in the gut.” 

To better understand why the spectrum of disease severity varies so widely, Shen, Tufts’ School of Medicine professor Carol Kumamoto, and their collaborators developed a new imaging approach that lets them track what individual C. diff cells were doing inside the body. They applied fluorescent “reporters” – microscopic glowing tags that mark gene activity – to track which genes are turned on in individual C. diff cells in tissue samples from infected mice. This allowed them to see where the bacteria hide in the gut, which cells switched on toxin genes, and how activity differed from cell to cell during infection.

Their study, recently published in Nature Communications, showed that C. diff spread throughout the entire gut, including closer to the gut’s vulnerable lining than previously thought.  

However, toxin production didn’t depend on the bacteria’s location and only some cells made toxins at any given time. Shen said this suggests that disease may be driven by a small, hard-to-detect subpopulation rather than simply how many bacteria are present.

The imaging study also revealed other unexpected findings, including that a strain of toxin-overproducing bacteria formed unusually long, filament-like shapes in the gut during the acute phase of infection. “These were not observed in later stages of an infection,” said Shen. “This suggests that bacteria producing the most destructive amounts of toxins may be particularly susceptible to certain stresses encountered during infection.”

By illuminating how infections unfold cell by cell in this way, the new imaging method may provide information that could someday help doctors predict which patients are likely to develop severe or recurrent disease. It also may help researchers develop new treatments that better target harmful subpopulations of C. diff bacteria while sparing beneficial gut microbes.

Finding a Potential Weak Spot  

One reason C. diff spreads so effectively is its ability to form tough, dormant spores that act like microscopic seeds sealed in armour. Transmitted via trace amounts of faecal matter, these spores can survive for long periods, stubbornly resisting heat and many common disinfectants, including hand sanitisers. Once ingested, C. diff spores germinate – springing back to life and thus able to spawn toxins.  

This is a pivotal moment scientists hope to block.

Shen’s lab has long studied how the bacterium recognises it has reached the right place to reawaken. Most spore-forming bacteria rely on the same standard molecular sensors, but C. diff uses a different system. Its spores respond to bile acids found in digestive fluids, along with other signals that together flip the bacterium’s switch from dormancy to active growth.

In a study recently published in PLOS Biology, Shen, Tufts’ School of Medicine professor Ekaterina Heldwein, and their collaborators identified a key part of that switch. They found that two proteins, CspC and CspA, lock together to form a signalling hub that helps spores interpret environmental cues. By mapping the structure of this protein pair and testing how it functions, the team showed the combined complex controls how sensitive spores are to germination signals.

“It’s like we’ve identified a central control panel for deciding when the spore comes back to life,” Shen says. “If we understand how that panel works, scientists someday may be able to design new drugs to keep it switched off.”

Searching for More Precise Targets

Together, the studies offer a clearer picture of both how C. diff causes disease and when it becomes dangerous.

Now, in addition to continuing their work on single-cell imaging and spore germination, Shen’s lab is working to uncover other hidden rules that govern C. diff’s behaviour. This includes how it reproduces using a division mechanism unlike those seen in other well-studied bacteria – the focus of a 2023 study published by Shen and collaborators in Nature Communications.  

“The hope is the aspects that make C. diff unique – how it spreads, reproduces, and damages tissue – will allow researchers to design ways to target it much more specifically, while keeping the rest of the gut microbiome healthy and intact,” she said.

Original written by Genevieve Rajewski

Source: Tufts University

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Age, Sex, and Cancer Type Influence Risk of Subsequent Cancers Among Survivors

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Findings may have implications for long-term cancer survivorship surveillance

Researchers assess the risk of developing a subsequent primary cancer based on demographic factors and cancer characteristics. Tara Winstead, Pexels (CC0, https://creativecommons.org/publicdomain/zero/1.0/)

Risk of developing a subsequent primary cancer varied significantly by age at initial diagnosis, sex, and type of first cancer, according to a study by Oxana Palesh and Susan Hong and colleagues at Virginia Commonwealth University, U.S., published April 28th in the open-access journal PLOS Medicine.

Advances in cancer detection and treatment have led to a growing population of cancer survivors. In the U.S., the number of cancer survivors is expected to grow by 22% over the next decade – from 18 million in 2025 to more than 22 million by 2035. Survivors remain at higher risk for developing new primary cancers distinct from their original diagnosis. This risk may be influenced by factors such as older age, exposure to radiation and/or chemotherapy and ongoing lifestyle factors like smoking, obesity and poor diet. Understanding who is at greater risk and how this risk changes over time can help to inform prevention and monitoring strategies.

Using retrospective data from more than 3 million cancer survivors in the U.S., researchers examined how demographic factors and cancer characteristics correlate with subsequent cancer risk. Several factors were associated with developing a subsequent cancer, including older age at initial diagnosis and male sex. In addition, survivors of lung, bladder, and skin melanoma were at higher risk of developing new cancer.

These findings reinforce the importance of long‑term survivorship care and risk‑based monitoring. By identifying survivor groups at heightened risk, studies like this can help to inform tailored prevention strategies, surveillance guidelines, and survivorship care planning as the cancer survivor population continues to grow.

First author Hui Cheng adds, “By examining nearly five decades of national data, we found population-level shifts in subsequent primary cancer risk, with several survivor groups experiencing rising risks. These findings can help design more tailored surveillance and prevention strategies.”

Provided by PLOS

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Beware the Salt Trap: Why South Africa’s Heart Health Depends on More Than Regulation

On By ModernMedia
Credit: Pixabay CC0

While South Africa was among the first countries to introduce mandatory salt reduction targets in processed foods, health experts warn that hypertension remains a major public health concern. The reason is increasingly clear, the problem is no longer only what is manufactured, but how people eat every day.

As World Salt and Hypertension Awareness Week (4–29 May) approaches, the focus should shift from reformulated products to daily behaviour change. High salt intake causes the body to retain excess fluid, which increases the volume of blood in the system and places greater pressure on the artery walls, directly leading to the development of hypertension.

“While the policy has successfully reduced hidden salt in many staple foods, it has not yet shifted South African taste preferences.,” says Lizeth Kruger, Clinic Executive at Dis-Chem. “We are still reaching for the shaker out of habit, and that’s where the real danger lies.”

Hypertension remains one of South Africa’s leading risk factors for heart disease and stroke, often progressing silently until complications arise. According to the Heart and Stroke Foundation South Africa, more than one in three adults lives with high blood pressure, a ‘silent killer’ that accounts for roughly half of all strokes and 40% of heart attacks in the country.

Kruger says a shift in everyday eating habits could reduce excess salt intake

1. Automatic salt shake

Many people add salt before tasting their food, even when meals have already been seasoned during cooking or processing.

2. Hidden salt in everyday staples

Stock cubes, processed meats, margarine and sauces remain significant sodium sources, especially when used frequently in daily cooking.

3. Convenience meals and takeaways

Ultra-processed foods and fast meals are often high in sodium, with a single serving sometimes approaching or exceeding the recommended daily limit.

4. A conditioned taste for salt

Long-term high-salt diets have shaped taste preferences, making fresh, whole foods seem bland and reinforcing reliance on added seasoning.

5. Unnoticed snack intake

Savoury snacks, biltong and crackers contribute meaningful sodium but are often not counted in daily intake.

Small changes, meaningful impact

Kruger says reducing salt intake is less about strict diets and more about changing repeat behaviours.

“Small, consistent adjustments can make a real difference over time,” she explains.

  • Tasting food before adding salt is a simple first step, as many meals are already seasoned. Rinsing canned foods such as beans or corn can also reduce sodium content.
  • Flavour can be enhanced using alternatives such as garlic, lemon juice, herbs and black pepper, while checking labels for lower-sodium options helps guide better choices.

A shared responsibility

“Regulation has laid the foundation, but the final step is ours,” Kruger advises. “By becoming more aware of everyday habits, we can reduce the risk of hypertension, stroke and heart disease in our homes.”