Year: 2025

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What are the Best Methods to Treat Rotator-cuff Tears?

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Photo by Kampus Production

Rotator-cuff disorders are the most common cause of shoulder symptoms. Tears of the rotator cuff can result from a substantial traumatic injury or can occur slowly over time. Most degenerative tears occur in the dominant arm of adults over the age of 40, and their prevalence increases with as you age. There are a variety of treatments.

In a recent publication in the New England Journal of Medicine, University of Michigan Health professor and chair of Physical Medicine and Rehabilitation, Nitin Jain, MD, MSPH, talks through the different treatments available for rotator-cuff tears to help bring together a better understanding of how to treat the issue for patients and providers.

Nonoperative treatment, such physical therapy, is the typical approach to treating rotator-cuff tears. However, surgery is considered in certain patients whose rotator-cuff tears don’t resolve with nonoperative treatments. Topical treatments also exist, such as glyceryl trinitrate (nitro-glycerine) gel which appears to have the greatest success.

Symptoms of rotator-cuff tears

“Patients with nontraumatic or degenerative rotator-cuff tears typically experience an onset of shoulder pain that seems to have no cause,” said Jain. 

“However, it is not uncommon for tears to be asymptomatic and become slowly painful over time, or even cause no pain at all.”

Jain says there are some activities that make the injury more painful as the tear worsens. This can include sleeping on your shoulder, overhead activities and/or lifting items above your shoulder level.

“Rotator-cuff tears may also grow over time, but there’s a lack of correlation between patient symptoms and the size and thickness of the tear,” explained Jain.

Your active range of motion and arm strength are usually affected by the tear, which gets assessed by using certain protocols when providers are searching for a diagnosis.

Rehabilitation and physical therapy for rotator-cuff tears 

This is the most common form of treatment for rotator-cuff tears, says Jain: “It is recommended that as the first line of specialist referral, patients seek care from a physical medicine and rehabilitation doctor (physiatrist) or sports medicine doctor.

“Rehabilitation and physical therapy routines address areas such as periscapular muscle weakness, correcting scapular posture and improve rotator cuff muscle strength and endurance.”

In observational studies, more than 80% of patients who received supervised physical therapy reported reduced pain and improved function between 6 months to a year. However, the trial populations consisted of patients with various types of rotator-cuff injuries and had no requirement for advanced imaging to confirm their diagnosis.

“One of the biggest factors in a successful rehabilitation was trust from patients that their physical therapy routine would improve their rotator-cuff condition,” said Jain. “The more patients leaned into the physical therapy routine, the better their outcomes were.”

Other nonpharmacologic therapies for rotator-cuff tears

Evidence suggests that psychosocial distress and depression are associated with shoulder pain and reduced function in patients with rotator-cuff tears.

“Despite this, though, there isn’t much data supporting psychosocial interventions in the treatment of rotator-cuff disorders, even though they show benefit in the treatment of other musculoskeletal disorders such as lower back pain,” said Jain.

In addition to the lack of data for psychological interventions for rotator-cuff repairs, there’s also a lack of high quality trials supporting the use of manual therapy, massage therapy, acupuncture, therapeutic ultrasonography, transcutaneous electrical nerve stimulation, shock-wave therapy or pulsed-electromagnetic-field therapy.

Topical and oral medications and injections for rotator-cuff tears

There isn’t a lot of evidence supporting the use of topical medications in treating rotator-cuff disorders. The topical treatment with the best outcomes so far has been glyceryl trinitrate.

In a small, randomised trial it showed short term benefits in the treatment of rotator-cuff disorders, but it also found there was a considerably high bias towards this treatment from participants in the study.

Topical nonsteroidal anti-inflammatory drugs such as diclofenac and ketoprofen have also been effective in providing pain relief in chronic musculoskeletal pain and tendinitis and have a better safety profile than oral, nonsteroidal anti-inflammatory drugs.

“But high quality evidence supporting their use in rotator-cuff disorders is still lacking,” explained Jain.

For oral medications, randomised research trials have shown that oral nonsteroidal anti-inflammatory drugs (NSAIDs) reduced pain, although modestly, in patients with rotator-cuff disorders. 

“Opioid drugs are generally not recommended due to risks associated with their use and lack of evidence of superiority to nonopioid therapy in a variety of musculoskeletal conditions,” said Jain.

Jain says acetaminophen hasn’t been studied specifically in rotator-cuff disorders, but what has been studied has shown little or no benefit regarding pain or function.

“Rigorous evidence is lacking to inform the use of pain-modulating drugs such as gabapentin, duloxetine, and pregabalin, specifically regarding the nonoperative treatment of rotator-cuff disorders,” said Jain.

Injection of a glucocorticoid, together with a local anaesthetic, has been reported to provide symptomatic pain relief in patients with rotator-cuff disorders.

Small trials have shown short term benefit, about four weeks long, of pain relief through using this method. The injections are performed in the subacromial space of the rotator-cuff for those with subacromial impingement syndrome. Some centres use ultrasound guidance to administer this treatment, which can reduce the risk of an inadvertent injection into the tendon.

Surgical interventions for rotator-cuff injuries

“Surgical interventions are not the initial recommendation when it comes to rotator-cuff repairs. However, they may be considered in some patients whose condition does not improve with conservative treatment,” said Jain.

Observational data supports that surgery is associated with better function and reduced pain in patients who are under 65 years of age and have smaller tears.

Surgical repairs are mostly performed arthroscopically, involving the repair of the torn tendon and resecuring it to the humerus to allow for tendon-to-bone healing as well as a low incidence of complications, explains Jain.

The hypothesis that surgical intervention can reduce the progression of muscle degradation has led some experts to recommend early surgical intervention, but data is still lacking on outcomes of early surgery compared to surgery later.

Source: Michigan Medicine – University of Michigan

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Could the Contraceptive Pill Reduce the Risk of Ovarian Cancer?

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Photo by Reproductive Health Supplies Coalition on Unsplash

It’s a little pill with big responsibilities. But despite its primary role to prevent pregnancy, the contraceptive pill (or ‘the Pill’) could also help reduce the risk of ovarian cancer, according to new research from the University of South Australia.

Screening for risk factors of ovarian cancer using artificial intelligence, UniSA researchers found that the oral contraceptive pill reduced the risk of ovarian cancer by 26% among women who had ever used the Pill, and by 43% for women who had used the Pill after the age of 45.

The study, published in the International Journal of Gynecologic Cancer, also identified some biomarkers associated with ovarian cancer risk, including several characteristics of red blood cells and certain liver enzymes in the blood, with lower body weight and shorter stature associating with a lower risk of ovarian cancer.

Researchers also found that women who had given birth to two or more children had a 39% reduced risk of developing ovarian cancer compared to those who had not had children.

UniSA researcher Dr Amanda Lumsden says understanding risks and preventative factors for ovarian cancer is key for improved treatment and outcomes.

“Ovarian cancer is notoriously diagnosed at a late stage, with about 70% of cases only identified when they are significantly advanced,” Dr Lumsden says.

“Late detection contributes to a survival rate of less than 30% over five years, in comparison to more than 90% for ovarian cancers that are caught early. That’s why it’s so important to identify risk factors.

“In this research, we found that women who had used the oral contraceptive pill had a lower risk of ovarian cancer. And those who had last used the Pill in their mid-40s, had an even lower level of risk.

“This poses the question as to whether interventions that reduce the number of ovulations could be used as a potential target for prevention strategies for ovarian cancer.”

Supported by the MRFF, the study used artificial intelligence to assess the data of 221 732 females (aged 37-73 at baseline) in the UK Biobank.

Machine learning specialist, UniSA’s Dr Iqbal Madakkatel, says the study shows how AI can help to identify risk factors that may otherwise have gone undetected.

“We included information from almost 3000 diverse characteristics related to health, medication use, diet and lifestyle, physical measures, metabolic, and hormonal factors, each measured at the start of the study,” Dr Madakkatel says.

Source: University of South Australia

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Review of Research Finds No Link between Sickle Cell Trait and Sudden Death

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Expert panel’s findings refute attribution of sudden death to sickle cell trait

Photo by National Cancer Institute on Unsplash

A systematic literature review found no evidence to support that physical exertion without rhabdomyolysis (muscle breakdown) or heat injury can cause sudden death for individuals with sickle cell trait (SCT), nor is there any high-level evidence that SCT causes acute pain crises. These results were published in the American Society of Hematology’s flagship journal, Blood, and informed the Society’s updated position statement on SCT.

“SCT has long been misunderstood, fuelling widespread misinformation and medically inaccurate claims that it can lead to sudden death. This misconception has been especially prominent in cases of Black men with SCT,” said Belinda Avalos, MD, ASH president. “In light of the pervasive, widely publicized, and harmful nature of this myth, the Society aims to further promote accurate information to protect and empower affected communities.”

Individuals with SCT have one copy of the gene associated with sickle cell disease (SCD). SCD is a blood disorder characterised by misshapen blood cells that can cause blockages, leading to infections and episodes of severe pain, often referred to as acute pain crises. Unlike SCD, SCT – which affects over 100 million people worldwide, including 8 to 10% of Black Americans – is not a disease. Individuals with SCT do not go on to develop SCD and generally do not experience any related health complications.  

“To date, this is the most authoritative and definitive systematic review on this subject,” said study author Michael R. DeBaun, MD, MPH, professor of pediatrics and medicine at Vanderbilt University School of Medicine and founder and director of the Vanderbilt-Meharry Sickle Cell Disease Center of Excellence. “This review shows that any primary, secondary, or tertiary cause of death attributable to SCT is not a diagnosis substantiated by the medical evidence.”

ASH convened an expert panel of hematologists and forensic pathologists to systematically review all existing available research to answer two primary questions: 1) Do uncomplicated acute pain crises occur in people with SCT? and 2) Can physical activity above baseline result in sudden death among those individuals?

The experts conducted a multi-database search for English-language studies on SCT and pain crises or mortality, identifying 1474 such citations. Only seven of those studies reported original data, included laboratory testing for SCT in individuals, and addressed the two primary research questions.

Of these studies, none assessed acute pain crises in individuals with SCT compared to those with SCD and only one described death in individuals reported to have SCT. This study of active-duty U.S. soldiers found only that SCT was associated with a higher risk of heat-related-exertional rhabdomyolysis, or muscle breakdown, but not a higher risk of death from any cause. After the implementation of precautions to prevent heat and environmental-related injury in military personnel, the race-adjusted risk of death was no different in individuals with SCT compared to individuals without SCT.

“In the absence of two medical conditions that we are all at risk for, exertional rhabdomyolysis or crush injuries leading to rhabdomyolysis, individuals with SCT are not susceptible to sudden death. Even under these extreme environmental conditions, unexplained sudden death cannot be attributed to SCT,” said Dr. DeBaun. Taken together, these findings demonstrate that “in individuals with SCT, the likelihood of SCT alone or pain crises being the root cause of sudden death is medically impossible,” he added.

While conducting this systematic review, the experts found several studies in which the presence of sickled blood cells at autopsy was cited as evidence of death by acute pain crisis in individuals with SCT. However, the experts did not find any studies that had human data to support this hypothesis, nor any clinical descriptions sufficient to make a diagnosis of an acute pain crisis immediately preceding death.

“Medicine, even in the post-mortem setting, is science,” said corresponding study author Lachelle D. Weeks, MD, PhD, assistant professor of medicine at Harvard Medical School and physician-scientist in the division of population sciences at Dana-Farber Cancer Institute. “Our diagnoses have to make sense and be backed by medical evidence. Given the findings of this study, we owe it to individuals with SCT to ensure that post-mortem examinations check for evidence of rhabdomyolysis and other medical or traumatic causes of death.”

The review had some limitations, most notably a lack of high quality, peer-reviewed direct evidence. To help mitigate this challenge, panel members were encouraged to consider indirect evidence when reviewing abstracts and judged evidence certainty following the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) framework. However, given this paucity of data, the experts hope this review prompts additional SCT research.

Following the results of this study, ASH revised its position statement on SCT, which states that listing “sickle cell crisis” or “sickle cell trait” as a cause of death on an autopsy report for an individual with sickle cell trait is medically inaccurate and without medical evidence of causation. To read the updated statement and learn more about ASH’s advocacy efforts in this area, visit https://hematology.org/advocacy.

Source: American Society of Hematology

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Why Antibiotics can Fail Even against Non-resistant Bacteria

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Drug-resistant Salmonella. Credit: CDC

Antibiotics are indispensable for treating bacterial infections. But why are they sometimes ineffective, even when the bacteria are not resistant? In their latest study published in the journal Nature, researchers from the University of Basel challenge the conventional view that a small subset of particularly resilient bacteria are responsible for the failure of antibiotic therapies.

In certain infectious diseases caused by bacteria, antibiotics are less effective than expected. One example is infections caused by Salmonella bacteria, which can lead to illnesses such as typhoid fever. For many years, researchers believed that a small subset of dormant bacteria are the main problem in fighting infections. These so-called persisters can survive antibiotic treatment and cause relapses later. Researchers worldwide have been working on new therapies aimed at targeting and eliminating these “sleeping” bacteria.

In a new study, Professor Dirk Bumann’s team from the Biozentrum of the University of Basel challenges the prevailing concept that persisters are the cause of antibiotic ineffectiveness. “Contrary to widespread belief, antibiotic failure is not caused by a small subset of persisters. In fact, the majority of Salmonella in infected tissues are difficult to kill,” explains Bumann. “We have been able to demonstrate that standard laboratory tests of antimicrobial clearance produce misleading results, giving a false impression of a small group of particularly resilient persisters.”

Nutrient starvation increases Salmonella resilience

The researchers investigated antimicrobial clearance in both Salmonella-infected mice and tissue-mimicking laboratory models. The body’s defense mechanisms against bacteria often include reducing the availability of nutrients. The researchers have now revealed that in fact, this nutrient starvation is the main reason for Salmonella bacteria surviving treatments with antibiotics. The researchers assume that the same applies to other bacterial pathogens.

“Under nutrient-scarce conditions, bacteria grow very slowly,” says Bumann. “This may seem good at first, but is actually a problem because most antibiotics only gradually kill slowly growing bacteria.” As a result, the drugs are much less effective, and relapses can occur even after prolonged therapy.

Real-time analyses reveal misconception

The scientists used an innovative method to monitor antibiotic action in single bacteria in real time. “We demonstrated that nearly the entire Salmonella population survives antibiotic treatment for extended periods, not just a small subset of hyper-resilient persisters,” says first author Dr Joseph Fanous.

A major issue with the standard methods used worldwide for decades is their indirect and delayed measurement of bacterial survival, leading to distorted results. “Traditional tests underestimate the number of surviving bacteria,” explains Fanous. “And they falsely suggest the presence of hyper-resilient subsets of persisters that do not actually exist.” This misinterpretation has influenced research for many years.

Novel tools for antibiotics research

These findings could fundamentally change antibiotics research. “Our work underlines the importance of studying bacterial behaviour and antibiotic effects live and under physiologically relevant conditions,” emphasises Bumann. “In a few years, modern methods like real-time single-cell analysis will hopefully become standard.” Shifting the focus from persisters to the impact of nutrient starvation is an important step toward more effective therapies against difficult-to-treat infections.

The project is part of the National Center of Competence in Research (NCCR) “AntiResist”. The research consortium aims to develop innovative strategies to combat bacterial infections. Dirk Bumann is one of the directors of the NCCR “AntiResist”.

Source: University of Basel

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Could the Key to IBS Treatment Lie in the Brain?

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Irritable bowel syndrome. Credit: Scientific Animations CC4.0

Although irritable bowel syndrome (IBS) affects about a tenth of the global population, the underlying causes and mechanisms of IBS remain unclear and thus treatments focus on symptom management. At Tokyo University of Science (TUS), Japan, Professor Akiyoshi Saitoh and his research group have spent the past decade exploring this topic. This study, published in the British Journal of Pharmacology, discovered that a class of drugs called opioid delta-receptor (DOP) agonists may help alleviate IBS symptoms by targeting the central nervous system rather than acting directly on the intestine.

One of the main motivations for this study was the growing evidence linking IBS closely to psychological stress. Saitoh’s group aimed to address this potential root cause by focusing on finding a novel animal model for this condition. In a 2022 study, they developed a mice model repeatedly exposed to psychological stress – using a method called chronic vicarious social defeat stress (cVSDS) – which developed symptoms similar to a type of IBS called IBS-D. These symptoms included overly active intestines and heightened sensitivity to abdominal pain, even though their organs showed no physical damage. The cVSDS animal model involved having the subject mouse repeatedly witness a territorial, aggressive mouse defeating a cage mate, inducing indirect chronic stress.

Using the cVSDS model, the researchers sought to determine whether DOP in the brain, which is closely linked to pain and mood regulation, could serve as promising drug targets for treating stress-induced IBS. To achieve this, they performed a series of detailed experiments to observe the effects of DOP agonists on IBS symptoms and chemical signaling in the brain. Some experiments involved measuring the speed of a charcoal meal through the intestine to assess gastrointestinal motility and evaluate the impact of stress or treatments on bowel movement speed, along with directly measuring neurotransmitter concentrations using in vivo brain microdialysis. This revealed that re-exposure to VSDS increased glutamate levels in the insular cortex, but these elevated levels were normalised with DOP agonists.

According to the results, the administration of DOP agonists helped relieve abdominal pain and regulated bowel movements in cVSDS mice. Interestingly, applying the DOP agonists directly to a specific brain region called the insular cortex had similar effects on IBS symptoms as systemic treatment. “Our findings demonstrated that DOP agonists acted directly on the central nervous system to improve diarrhoea-predominant IBS symptoms in mice, and suggest that the mechanism of action involves the regulation of glutamate neurotransmission in the insular cortex,” highlights Saitoh.

Taken together, the continued research by Saitoh’s group on this topic could pave the way for effective treatments for IBS. “DOP agonists could represent a groundbreaking new IBS treatment that not only improves IBS-like symptoms but also provides anti-stress and emotional regulation effects. In the future, we would like to conduct clinical developments with the goal of expanding the indication of DOP agonists for IBS, in addition to depression,” remarks Saitoh.

Compared to currently available IBS treatments, such as laxatives, antidiarrhoeals, analgesics, and antispasmodics, targeting the underlying stress with DOP agonists may offer a more definitive solution with minimal adverse effects. Further clarification of the roles of stress and brain chemistry in the development of IBS will be essential in achieving this much-needed medical breakthrough. With promising prospects, future studies will translate Saitoh’s group’s findings to humans, bringing great relief to those affected by IBS.

Source: Tokyo University of Science

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Slow Traffic Pushes Commuters to Choose Fast Food

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Photo by Why Kei on Unsplash

Ever notice how much more tempting it is to pick up fast food for dinner after being stuck in traffic? It’s not just you. New research shows that traffic delays significantly increase visits to fast food restaurants, leading to unhealthier eating.

“In our analysis focusing on Los Angeles County, unexpected traffic delays beyond the usual congestion led to a 1% increase in fast food visits. That might not sound like a lot, but it’s equivalent to 1.2 million more fast food visits per year in LA County alone. We describe our results as being modest but meaningful in terms of potential for changing unhealthy food choices,” said study author Becca Taylor, assistant professor at the University of Illinois Urbana-Champaign.

Taylor and her co-authors had access to more than two years’ of daily highway traffic patterns in Los Angeles, along with data showing how many cell phone users entered fast-food restaurants in the same time period.

With these data, the team created a computational model showing a causal link between unexpected traffic slow-downs and fast food visits. This pattern held at various time scales, including 24-hour cycles and by the hour throughout a given day. When analysed by the day, traffic delays of just 30 seconds per mile were enough to spike fast-food visits by 1%.

“It might not be intuitive to imagine what a 30-second delay per mile feels like,” Taylor said. “I think of it as the difference between 10a.m. traffic and 5p.m. traffic.”

When the researchers broke the day into hour-long segments, they found a significantly greater number of fast food visits when traffic delays hit during the evening rush hour. At the same time, grocery store visits declined slightly.

“If there’s traffic between 5 and 7p.m., which happens to be right around the evening meal time, we see an increase in fast food visits,” Taylor said.

“Drivers have to make a decision about whether to go home and cook something, stop at the grocery store first, or just get fast food.”

Considering every major city has both traffic and fast food restaurants lining highway feeder roads, it’s not a stretch to extrapolate the pattern beyond Los Angeles.

Taylor and her co-authors say the link between traffic and unhealthy food choices is just one more reason policymakers around the country and the globe should prioritize infrastructure reforms to ease congestion.

“Our results contribute to the literature suggesting time constraints are really important to the food choices people make. Any policies aimed at loosening time constraints – and traffic is essentially lost time – could help battle unhealthy eating,” Taylor said. “That could mean improvements in infrastructure to mitigate traffic congestion, expanding public transport availability, and potentially increasing work from home opportunities.”

Source: University of Illinois College of Agricultural, Consumer and Environmental Sciences

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Omega-3s can Slow Down the Aging Process – Slightly

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Photo by Ravi Patel on Unsplash

Previous clinical studies have shown that a reduced calorie intake can slow down the aging process in humans. Taking vitamin D or omega-3 fatty acids has also shown promising results in slowing biological aging in animals. However, it was unclear whether these measures would also work in humans.

The therapies previously tested in the DO-HEALTH study led by Heike Bischoff-Ferrari are also associated with a slowing of the aging process. These showed that vitamin D and omega-3 fatty acids, as well as regular physical activity, reduce the risk of infections and falls, and prevent cancer and premature frailty. “These results inspired us to measure the direct influence of these three therapies on the biological aging process in the Swiss DO-HEALTH participants,” says Bischoff-Ferrari, professor of geriatrics and geriatric medicine at the University of Zurich.

Measuring biological and chronological age

One scientific approach to making biological aging measurable is the use of epigenetic clocks. They record chemical modifications of the DNA molecule, known as methylation, and thus quantify the difference between biological and chronological aging. The DO-HEALTH study has now for the first time investigated how sensitively this molecular biological measurement method reacts to targeted treatment.

The team led by Heike Bischoff-Ferrari, in collaboration with Steve Horvath, senior researcher at Altos Labs Cambridge (UK), who developed the watches, investigated the effect of omega-3s and/or vitamin D and/or simple strength training on biological aging in 777 people over the age of 70. Eight different treatment combinations were tested during the three-year study: subjects took 2000 international units (IU) of vitamin D and/or 1 gram of omega-3 fatty acids (from algae) daily and/or performed 30 minutes of strength training at home three times a week.

Biological age slowed down

When the researchers analysed the blood samples, they found that taking omega-3 fatty acids slowed down biological aging across several epigenetic clocks by up to four months – regardless of subjects’ gender, age or body mass index. The combination of omega-3, vitamin D and strength training proved to be even more effective, according to one of the four epigenetic clocks used.

“This result extends our previous findings from the DO-HEALTH study, in which these three factors combined had the greatest impact on reducing the risk of cancer and preventing premature frailty over a three-year period, to slowing down the biological aging process,” says Bischoff-Ferrari. Each of these measures works through different mechanisms that complement each other and, when combined, result in a heightened overall effect, according to the study author.

DO-HEALTH as a validation platform

At the same time, the research team draws attention to the limitations of the study. “There is no generally accepted gold standard for measuring biological age,” Bischoff-Ferrari explains. “However, we analysed the best currently validated epigenetic clocks, which reflect the state of the art.” To further advance the clinical application of biological clocks, Bischoff-Ferrari, together with leading international researchers in the Global Health Span Extension Consortium, plans to use DO-HEALTH and other global intervention studies as a validation platform for novel biomarkers of aging.

The researchers also point out that the sample consists exclusively of Swiss participants but will extend the trial to more countries.

Source: University of Zurich

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New Discovery Nips Childhood Brain Tumour in the Bud

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Credit: National Cancer Institute

Scientists at The Hospital for Sick Children (SickKids) have discovered a way to stop tumour growth before it starts for a subtype of medulloblastoma, the most common childhood malignant brain cancer.

Brain cancer presents a unique set of challenges for researchers – by the time a person experiences symptoms, the tumours are often so complex that the fundamental mechanisms driving the tumour growth are no longer easy to identify. A research team led by Dr Peter Dirks is working to combat this challenge for sonic hedgehog (SHH) medulloblastoma.

In a new study published in Nature Communications, the researchers identify that a protein is responsible for awakening ‘sleeping’ stem cells and driving SHH medulloblastoma tumour formation and regrowth. By blocking this protein and preventing the stem cells from waking, the study demonstrates what could be a pivotal treatment strategy for the cancer, utilising cutting-edge genomic approaches in combination with functional experiments in a preclinical model.

“Our findings offer a novel strategy to target cancer stem cells, providing hope for more effective treatments against aggressive brain tumours,” says Dirks, Senior Scientist in the Developmental, Stem Cell & Cancer Biology program and Chief of the Division of Neurosurgery.

Cancer interception in action

The research team began by examining cellular transitions that drove the development of SHH medulloblastoma tumours. They found that early in tumour development and after conventional treatments, a protein called OLIG2 would activate ‘sleeping’ stem cells, causing them to divide and grow into a tumour.

“There is order to how the cancer initiating stem cells undergo fate changes to form tumours. We can target an early transition event and intercept the entire process – essentially stopping the cancer in its earliest form,” says first author Dr Kinjal Desai, a postdoctoral researcher in the Dirks lab.

During these transitions, the researchers uncovered a key window during which tumour progression could be blocked. By combining a previously established treatment with a small molecule called CT-179, which disrupts the OLIG2 protein, the research team were able to target the residual stem cells left after treatment and prevent them from re-awakening, effectively preventing tumour relapse.

Similarly for early-stage SHH medulloblastoma, CT-179 prevented the tumour from forming and significantly increased survival rates in the preclinical model.

Together with additional preclinical models in a study published simultaneously in Nature Communications from colleagues at Children’s Healthcare of Atlanta and QIMR Berghofer Medical Research Institute in Australia, the findings showcase what could be an effective new treatment for SHH medulloblastoma, as well as other brain cancers including diffuse intrinsic pontine glioma (DIPG).

Model of proposed role of Olig2 and OLIG2 inhibition in tumour initiation and relapse; created in BioRender.com. Desai et al., Nat. Comm. 2024.

The study complements recent research from the Dirks Lab in Nature, which describes the early stages of glioblastoma development. While future research will expand these findings into clinical trials for patients, particularly among those being monitored for relapse, the Dirks lab, part of the Arthur and Sonia Labatt Brain Tumour Research Centre (BTRC), is excited for the diagnostic potential this discovery presents.

“At SickKids, we’re already genetically testing every child with cancer to inform their diagnosis and treatments – our study goes beyond genetic testing to precision biology,” says Dirks. “I am excited for a future where this ‘magic bullet’ for early treatment could be combined with diagnostic tests to potentially prevent the cancer from developing at all.”

Source: The Hospital for Sick Children

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Music Can Influence Foetal Heart Rate in the Womb

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Photo by Sergio Capuzzimati on Unsplash

Playing music has long been a way for expectant parents to connect with their children in the womb, but a group of researchers has found evidence it can calm foetal heart rates, potentially providing developmental benefits.

In the interdisciplinary journal Chaos, researchers studied the effect of classical music on a foetal heartbeat. The team used mathematical analysis tools to identify patterns in heart rate variability.

Typical measures of heart rate are an average of several beats across multiple seconds. In contrast, heart rate variability measures the time between individual beats. This measure can provide insight into the maturation of the foetal autonomic nervous system, with greater variability often indicating healthy development.

To test the effects music can have on foetal heart rate, the group of researchers recruited 36 pregnant women and played a pair of classical pieces for their foetuses. For the experiment, they chose “The Swan,” by French composer Camille Saint-Saëns, and “Arpa de Oro,” by Mexican composer Abundio Martínez.

By attaching external heart rate monitors, the researchers could measure the foetal heart rate response to both songs. And by employing nonlinear recurrence quantification analysis, they could identify changes in heart rate variability during and after the music was played.

“Overall, we discovered that exposure to music resulted in more stable and predictable foetal heart rate patterns,” said author Claudia Lerma. “We speculate that this momentary effect could stimulate the development of the foetal autonomic nervous system.”

In addition to the overall effects of playing music, the researchers looked at the differences between the two classical pieces. While both were effective, they found that the Mexican guitar melody had a stronger effect.

“When contrasting ‘The Swan’ with ‘Arpa de Oro,’ we did notice some significant differences,” said author Eric Alonso Abarca-Castro. “In particular, the second piece appeared to have a stronger impact on some measures, indicating that it produced heart rate patterns that were more predictable and regular. Factors like rhythmic characteristics, melodic structure, or cultural familiarity may be linked to this differentiation.”

For expectant parents at home, the researchers suggest that classical music could help promote fetal development.

“Our results suggest that these changes in foetal heart rate dynamics occur instantly in short-term fluctuations, so parents might want to consider exposing their foetuses to quiet music,” said Abarca-Castro. “Parents who play soothing music may stimulate and benefit the foetal autonomic system.”

The authors plan to continue to explore this effect, looking at different genres and types of music to further their understanding.

“To ascertain whether rhythmic or cultural variations elicit distinct foetal cardiac responses, we intend to increase the size of our sample and expand our investigation to include a variety of musical styles beyond classical pieces,” said author José Javier Reyes-Lagos.

Source: American Institute of Physics

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All in the Eyes: High Resolution Retinal Maps Aid Disease Diagnoses

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Photoreceptor cells in the retina. Credit: Scientific Animations

Researchers have conducted one of the largest eye studies in the world to reveal new insights into retinal thickness, highlighting its potential in the early detection of diseases like type 2 diabetes, dementia and multiple sclerosis.

The WEHI-led study, using cutting-edge artificial intelligence technology to analyse over 50 000 eyes from the UK Biobank, producing maps of the retina in unprecedented detail to better understand how retinal differences link to various diseases.

The findings, published in Nature Communications, open up new possibilities for using routine eyecare imaging as a tool to screen for and manage diseases, much like mammograms have for breast cancer.

Unlocking a window into the brain

The retina is part of the central nervous system, which also comprises the brain and spinal cord. Many diseases are linked to degeneration or disruption of this critical system, including neurodegenerative conditions such as dementia and metabolic disorders like diabetes.

Globally, neurological conditions alone are one of the leading causes of disability and illness, with over 3 billion people, or 43% of the world’s population living with a brain related condition.

Lead researcher, WEHI’s Dr Vicki Jackson, said the findings broaden the horizons for using retinal imaging as a doorway into the central nervous system, to help manage disease.

“We’ve shown that retinal imaging can act as a window to the brain, by detecting associations with neurological disorders like multiple sclerosis and many other conditions,” said Dr Jackson, a statistician and gene expert.

“Our maps’ fine-scale measurements reveal critical new details about connections between retinal thinning and a range of common conditions.”

The study also identified new genetic factors that influence retinal thickness, which are likely to play a role in the growth and development of a person’s retina.

“This research underscores the potential for retinal thickness to act as a diagnostic biomarker to aid in detecting and tracking the progression of numerous diseases. We can now pinpoint specific locations of the retina which show key changes in some diseases.”

The international research team, led by WEHI, applied AI methods to big population data of retinal imaging and compared information about each person’s genetics and health to reveal unprecedented links to disease.

The results created 50 000 maps with measurements at over 29 000 locations across the retina, identifying retinal thinning relating to 294 genes that play an important role in disease.

AI fast-tracking the diagnostic future

Study lead and bioinformatician, Professor Melanie Bahlo AM, said past studies had indicated correlations between retinal thickness and disease, but her team’s AI-powered discoveries shed deeper light on the complex spatial anatomy of the retina and its role in disease.

“Technologies like AI fuel discovery, and when fused with brilliant minds, there is an extraordinary ability to transform big population data into far-reaching insights,” Prof Bahlo, a lab head at WEHI, said.

“There has never been a time in history where this powerful combination — technology, big data and brilliant minds — has come together to advance human health.”

The research reinforces the growing field of oculomics (using the eye to diagnose health conditions) as an emerging, powerful and non-invasive approach for predicting and diagnosing diseases.

Source: Walter and Eliza Hall Institute