Author: ModernMedia

First-of-its-kind Technology Helps Man with ALS ‘Speak’ in Real Time

An investigational brain-computer interface (BCI) allows the study participant to communicate through a computer. Credit: UC Davis

Researchers at the University of California, Davis, have developed an investigational brain-computer interface that holds promise for restoring the ability to hold real-time conversations to people who have lost the ability to speak due to neurological conditions.

In a new study published in the scientific journal Nature, the researchers demonstrate how this new technology can instantaneously translate brain activity into voice as a person tries to speak – effectively creating a digital vocal tract with no detectable delay.

The system allowed the study participant, who has amyotrophic lateral sclerosis (ALS), to “speak” through a computer with his family in real time, change his intonation and “sing” simple melodies.

“Translating neural activity into text, which is how our previous speech brain-computer interface works, is akin to text messaging. It’s a big improvement compared to standard assistive technologies, but it still leads to delayed conversation. By comparison, this new real-time voice synthesis is more like a voice call,” said Sergey Stavisky, senior author of the paper and an assistant professor in the UC Davis Department of Neurological Surgery. Stavisky co-directs the UC Davis Neuroprosthetics Lab.

“With instantaneous voice synthesis, neuroprosthesis users will be able to be more included in a conversation. For example, they can interrupt, and people are less likely to interrupt them accidentally,” Stavisky said.

Decoding brain signals at heart of new technology

The man is enrolled in the BrainGate2 clinical trial at UC Davis Health. His ability to communicate through a computer has been made possible with an investigational brain-computer interface (BCI). It consists of four microelectrode arrays surgically implanted into the region of the brain responsible for producing speech.

These devices record the activity of neurons in the brain and send it to computers that interpret the signals to reconstruct voice.

“The main barrier to synthesising voice in real-time was not knowing exactly when and how the person with speech loss is trying to speak,” said Maitreyee Wairagkar, first author of the study and project scientist in the Neuroprosthetics Lab at UC Davis. “Our algorithms map neural activity to intended sounds at each moment of time. This makes it possible to synthesise nuances in speech and give the participant control over the cadence of his BCI-voice.”

Instantaneous, expressive speech with BCI shows promise

The brain-computer interface was able to translate the study participant’s neural signals into audible speech played through a speaker very quickly – one-fortieth of a second. This short delay is similar to the delay a person experiences when they speak and hear the sound of their own voice.

The technology also allowed the participant to say new words (words not already known to the system) and to make interjections. He was able to modulate the intonation of his generated computer voice to ask a question or emphasize specific words in a sentence.

The participant also took steps toward varying pitch by singing simple, short melodies.

His BCI-synthesized voice was often intelligible: Listeners could understand almost 60% of the synthesized words correctly (as opposed to 4% when he was not using the BCI).

Real-time speech helped by algorithms

The process of instantaneously translating brain activity into synthesized speech is helped by advanced artificial intelligence algorithms.

The algorithms for the new system were trained with data collected while the participant was asked to try to speak sentences shown to him on a computer screen. This gave the researchers information about what he was trying to say.

The electrodes measured the firing patterns of hundreds of neurons. The researchers aligned those patterns with the speech sounds the participant was trying to produce at that moment in time. This helped the algorithm learn to accurately reconstruct the participant’s voice from just his neural signals.

Clinical trial offers hope

“Our voice is part of what makes us who we are. Losing the ability to speak is devastating for people living with neurological conditions,” said David Brandman, co-director of the UC Davis Neuroprosthetics Lab and the neurosurgeon who performed the participant’s implant.

“The results of this research provide hope for people who want to talk but can’t. We showed how a paralyzed man was empowered to speak with a synthesized version of his voice. This kind of technology could be transformative for people living with paralysis.”

Brandman is an assistant professor in the Department of Neurological Surgery and is the site-responsible principal investigator of the BrainGate2 clinical trial.

Limitations

The researchers note that although the findings are promising, brain-to-voice neuroprostheses remain in an early phase. A key limitation is that the research was performed with a single participant with ALS. It will be crucial to replicate these results with more participants, including those who have speech loss from other causes, such as stroke.

Surprising Shifts in Who’s Getting What in South African Cosmetic Surgery

Professor Chrysis Sofianos

Twenty years ago, cosmetic surgery was still a subject of taboo, whispered about behind closed doors. Today, that silence has been replaced by honest conversations about beauty, confidence, ageing, empowerment, and personal choice, as South Africans openly embrace a wide range of aesthetic enhancements. And what South Africans are choosing might surprise you.

Leading plastic and reconstructive surgeon Professor Chrysis Sofianos shares insights from his own practice, revealing how cosmetic surgery trends are evolving across age and race – and what that means for the future of beauty.

“Cosmetic surgery is no longer about fitting a single mould, but about choosing how we, as individuals, want to age, restore, or refine. Today’s patients are more informed, intentional, and unapologetic about their tastes, and wanting to feel good in their own skin,” he says.

Aesthetic choices by age

Gone are the days where cosmetic procedures were the exclusive domain of patients of a certain age. According to Professor Sofianos, the modern approach views aesthetics as a journey, although age still plays a major role in shaping the types of treatments individuals may seek:

  • 20s: Patients in their twenties are often navigating early self-image issues, driven by social media influences. The most requested procedures include breast augmentations, lip fillers, and occasional rhinoplasties to address long-held insecurities.
  • 30s: Often post-pregnancy or in the midst of career and family life, this group leans toward tummy tucks, mommy makeovers, and the start of anti-ageing injections, cosmetic fillers, and preventative treatments. Restoration without exaggeration is usually the goal.
  • 40s: This is the decade of refinement. Liposuction, eyelid lifts, and more assertive facial rejuvenation procedures become common, as patients seek to stay ahead of midlife volume loss and skin laxity.
  • 50s and beyond: For those who want long-term, natural results, the deep plane facelift, neck lifts, and biostimulators become top of mind. “Our approach is structural, not superficial,” he notes. “It’s about restoring facial harmony without compromising identity.”

“What fascinates me is how differently my patients may define beauty. A 22-year-old influencer and a 55-year-old executive might sit in the same waiting room, but their goals couldn’t be more different. We’re not selling a standard look – we’re facilitating personal choices, and sometimes, those choices may even challenge conventional aesthetic norms.”

Understanding patient preferences: A cultural lens

Perhaps the most significant change is how different communities and racial groups are approaching enhancement in South Africa, reflecting new trends in beauty ideals. For example, African women are increasingly choosing breast reductions, prioritising comfort and opting for a different aesthetic from more traditional beauty standards which often favour a fuller figure or more pronounced curves.

Indian patients are leading the way in tummy tucks and body contouring, while Caucasian patients tend to focus on breast augmentations and high-definition liposuction, particularly around the waistline and abdomen, to refine their silhouette and definition.

“What’s beautiful about this shift is how it reflects our diversity. We’re not seeing patients trying to look like someone else – they’re choosing procedures that enhance their natural features and fit their lifestyles,” says Sofianos. “Critically, there is no one-size-fits-all in aesthetic medicine. The more we understand the nuances of each patient’s background and goals, the better we can serve them.”

Why winter is the most strategic time for surgery

No matter your personal objectives, an insider tip could make a huge difference in your surgical recovery: while people mistakenly tend to plan procedures for December – unaware that most surgeons do not operate after November due to holiday closures and the necessity of post-operative care – smart patients are booking for winter.

Cooler temperatures help to reduce swelling, promote easier healing, and generally mean less downtime. Patients also benefit from increased coverage beneath bulkier clothing, allowing them to recover more discreetly while still going about their daily lives. With fewer social commitments and sunnier distractions, winter becomes the ideal window for surgical recovery.

“If you want to look and feel your best by summer, now is the time to plan,” he advises. “Winter is a strategic opportunity for recovery.”

As aesthetic surgery continues to evolve in South Africa, Professor Sofianos believes that education, access, and authenticity are key pillars moving forward.

“My role is to guide patients through their options, help them make informed choices, and deliver results that are both technically excellent and emotionally empowering. The most rewarding part of my practice isn’t about creating one particular look, but about helping people become more confident versions of themselves. Whether that means a subtle enhancement or a more significant change, the choice is truly personal.”

Long-Term Atopic Dermatitis Treatment Benefits Patients with Delayed Response

Atopic dermatitis in a young patient. Source: NIH

New research from the Icahn School of Medicine at Mount Sinai reveals that patients with moderate-to-severe atopic dermatitis (eczema) who did not initially respond to biologic treatment may still achieve significant clinical improvements with continued therapy.  

The findings, published in the latest issue of Journal of the American Academy of Dermatology (JAAD), highlight the efficacy of extended lebrikizumab treatment up to 52 weeks and pave the way for more personalised, patient-centred approaches to managing this chronic skin condition. 

Lebrikizumab is designed to treat moderate-to-severe eczema by targeting a key source of inflammation in the body. It works by blocking interleukin-13 (IL-13), a protein that plays a central role in the itching, redness, and skin damage seen in atopic dermatitis. 

“This is a significant breakthrough because it shows that people who do not respond to lebrikizumab treatment right away should not give up,” says lead author Professor Emma Guttman-Yassky, MD, PhD, at Mount Sinai. “Initial non-response at 16 weeks does not mean treatment failure. By sticking with treatment longer (52 weeks), most patients saw their eczema improve significantly.” 

Researchers analysed data from two international clinical trials. At 16 weeks, 38.1% of lebrikizumab-treated patients failed to meet strict trial criteria for response. However, 58.1% had already achieved at least a 50% improvement in their Eczema Area and Severity Index (EASI) scores. By 52 weeks, 75.5% had reached a 75% improvement (EASI 75), 44.2% had achieved a 90% improvement (EASI 90), and 66.4% reported a significant reduction in itching. 

“This research supports a more personalised approach to care,” Dr. Guttman-Yassky says. “It offers new hope for patients with difficult-to-treat eczema and may help guide treatment decisions in clinical practice.” 

Source: Mount Sinai Hospital

Space-age Lessons Could Protect Childhood Cancer Survivors’ Bone Health

Corresponding author Kiri Ness, PT, PhD, FAPTA, St. Jude Department of Epidemiology and Cancer Control, working with a patient.

Space has inspired and delighted people for centuries. The much-anticipated advent of crewed spaceflight taught invaluable lessons, even for the most unexpected groups back on terra firma. In the 1960s, astronauts returned from microgravity with decreased bone density. This decrease revealed that bones must undergo constant stress to grow and maintain themselves.

Survivors of childhood cancer, while seemingly unrelated to astronauts in the weightlessness of space, are one group unexpectedly impacted by this revelation. These two distinct groups share a connection in the loss of bone density occurring during a significant life event. Children receiving cancer treatment are often sedentary due to their therapy. Their listlessness mimics microgravity’s effect on astronauts, while the treatment itself may also negatively impact their bone health.

Recent research spearheaded by first author Chelsea Goodenough, PhD, St. Jude Department of Epidemiology and Cancer Control, characterised bone mineral density loss in survivors of childhood cancer. Published in JAMA Network Open, her study looked at survivors five or more years after treatment using the St. Jude Lifetime Cohort Study (St. Jude LIFE). She found that survivors were more likely than age-matched peers to experience low bone mineral density. Low bone mineral density predicted a higher chance of lacking independence, including being unemployed or requiring a personal care attendant, highlighting the need to find ways to intervene to protect and promote survivors’ bone health.

“Glucocorticoids given during cancer therapy can act as a giant hammer to bone mineral density,” said corresponding author Kiri Ness, PT, PhD, FAPTA, St. Jude Department of Epidemiology and Cancer Control. “We found that this loss could have long-term consequences for survivors. We saw 30-year-olds that functionally looked like they were in their 70s and 80s, showing the need for early interventions after treatment.”  

Modifiable factors influence survivors’ bone mineral density

“The unique aspect of this study is that we calculated the extent to which different factors contributed to loss of bone density,” Ness said. “That gives us a starting place to design interventions.”

Bone loss decades after treatment could be related to therapy, something investigators can’t change after the fact, but potentially modifiable factors could also be contributing. The St. Jude researchers wanted to see if they could identify any modifiable factors that could point to protective interventions for further investigation.

“We found that about 33% of bone density loss was due to cranial radiation for those who received it,” Ness explained. “But about 25% of the deficit was related to hormone deficiencies, such as hypogonadism.” Hypogonadism is a common consequence of childhood cancer therapy. During treatment, the patient receives hormone-disrupting chemicals, sometimes resulting in an extended deficiency of testosterone or oestrogen and human growth hormone. These three hormones are known to have significant impacts on bone health. Since hormone replacement therapies already exist, the study has identified an area for potential pharmaceutical intervention to address hypogonadism to improve bone density among survivors of childhood cancer. 

Lifestyle changes can impact bone health

“Compared to hypogonadism, smoking and sedentary behaviour were responsible for a smaller but still significant decrease in bone density,” Ness said. “But we already have interventions for both; we just need to test them for their effect on bone mineral density.”

Sedentary behaviour is a common experience during treatment. “Understandably, kids don’t feel good during cancer therapy,” Ness explained. “So, they lay in bed.” Lying in bed acts like microgravity: The kids don’t put stress on their bones, resulting in bone loss. However, survivors can prevent this with physical activity. Exercise has already been shown to help protect cardiovascular health among survivors, so the research provides another potential motivation for exercise.

Ness, whose research focuses on lifestyle interventions to support survivors of childhood cancer, already promotes the positives of physical activity. Her insistence, bolstered by this study, has gained her a reputation among patients. “The kids on the floor call me the ‘exercise lady,’” Ness proudly acknowledged. “When they see me, they say, ‘Here she comes, the exercise lady is here.’”

Physical activity to improve bone health could be as simple as jumping or as elaborate as a dedicated heavy weight-lifting programme. The increased activity will likely promote bone maintenance and, hopefully, growth, a parallel to the exercise programme astronauts undergo upon returning from space to re-establish their bone mass.

While exercise is one way in which survivors can improve their bone health, the study also suggested that those who develop a smoking habit may have one more reason to quit. Survivors who smoked were more likely to have a moderate or severe bone mineral density deficit, along with a host of other problems.

“Smoking is just a bad idea for survivors,” Ness said. “Smoking causes a lot of ill effects, not just bone loss. So, we need to encourage young cancer survivors never to start and give cessation interventions to those that have.” Over 20% of survivors in the study currently smoked, indicating a significant opportunity for intervention.

Better understanding means more chances to help

By attributing the sources of bone mineral density loss, the St. Jude scientists have created a roadmap for exploring potential interventions. The ultimate goal is to give survivors of childhood cancer as much independence as possible to take control of their futures.

“I want survivors to know that if they have low bone mineral density, it’s not an insurmountable problem,” Ness said. “You can be proactive – by being physically active, avoiding smoking and making sure your physician understands your chronic health condition. That’s how you give yourself the best chance of having an independent life as an adult, chasing your dreams.” 

Maybe, one day, they could even become an astronaut.

Written by Alex Generous, PhD.

Source: St. Jude Children’s Research Hospital

Dapagliflozin Shows Benefits for Patients with MASH

Results support the potential for dapagliflozin to benefit these patients

Human liver. Credit: NIH

The sodium glucose cotransporter 2 (SGLT-2) inhibitor drug dapagliflozin, widely used to treat type 2 diabetes, also shows improvements for patients with progressive liver disease, according to results of a clinical trial in China published by The BMJ.

The results show that treatment with dapagliflozin improved metabolic dysfunction-associated steatohepatitis (MASH) – a condition where excess fat accumulates in the liver, leading to inflammation – and liver fibrosis compared with placebo.

MASH affects more than 5% of adults, more than 30% of individuals with diabetes or obesity, and can progress to cirrhosis in up to 25% of individuals.

Several studies have reported that SGLT-2 inhibitors can improve liver fat content, liver enzymes, and liver stiffness, but no trial has been carried out among patients with MASH.

To address this, researchers enrolled 154 adults (average age 35; 85% men) diagnosed with MASH after a liver biopsy at six medical centres in China from November 2018 to March 2023.

Almost half (45%) had type 2 diabetes, and almost all had liver fibrosis (33% stage 1, 45% stage 2, 19% stage 3).

After an initial screening biopsy, participants were randomly assigned to receive 10 mg of dapagliflozin or matching placebo once daily for 48 weeks and attended health education sessions twice a year.

Various factors including body weight, blood pressure, blood glucose, liver enzymes, physical activity, diet, insulin, and lipids were also assessed at enrollment and throughout the trial.

MASH improvement was defined as a decrease of at least 2 points in non-alcoholic fatty liver disease activity score (NAS) or a NAS of 3 points or less.

After an end of study biopsy at week 48, 53% (41 of 78) participants in the dapagliflozin group showed improvement in MASH without worsening of fibrosis (defined as no increase in fibrosis stage) compared with 30% (23 of 76) in the placebo group.

Resolution of MASH without worsening of fibrosis occurred in 23% (18 of 78) participants in the dapagliflozin group compared with 8% (6 of 76) in the placebo group.

Fibrosis improvement without worsening of MASH was also reported in 45% (35 of 78) participants in the dapagliflozin group compared with 20% (15 of 76) in the placebo group.

The percentage of participants who discontinued treatment because of adverse events was 1% (1 of 78) in the dapagliflozin group and 3% (2 of 76) in the placebo group.

The researchers acknowledge that the trial was conducted in a Chinese population, which limits its broader generalisability, and that female and older patients were under-represented. But they point out that results were consistent after further analyses, suggesting they are robust.

As such, they conclude: “Our findings indicate that dapagliflozin may affect key aspects of MASH by improving both steatohepatitis and fibrosis.” Large scale and long term trials are needed to further confirm these effects, they add.

The coming years are expected to be particularly exciting in the field of pharmacological treatment for MASH, say researchers from Argentina in a linked editorial.

As more drugs become available, therapeutic decisions will likely become increasingly tailored to individual patient profiles, they write. “Ideally, such treatments should provide cardiovascular benefit, have an established safety profile, and be accessible to broad and diverse patient populations,” they conclude.

Source: BMJ Group

New Weight Loss Drug Targets Four Hormone Receptors

Photo by I Yunmai on Unsplash

In the US, drugs like semaglutide are used by over 15 million adults in the U.S., or 4.5% of the population for diabetes and also weight loss. Despite their effectiveness, they have drawbacks. Their effect may not last after discontinuing use, and side effects including osteoporosis and muscle loss have raised concerns about long-term harms. They also induce nausea, which can make it difficult to stay the course of treatment.

Now Tufts researchers led by Professor Krishna Kumar, have designed a new, next-generation compound with hopes that it could be more effective with fewer side effects, which they report in a paper in the Journal of the American Chemical Society

While weight loss drugs currently on the market and in development target one, two, or even three hormone receptors related to glucose metabolism and the desire to eat, the Tufts team has identified a fourth target that could potentially further enhance the control strategy.

“Obesity is linked to over 180 different disease conditions, including cancer, cardiovascular disease, osteoarthritis, liver disease, and type 2 diabetes, and affects over 650 million people worldwide,” said Kumar. “What drives us is the idea that we can design a single drug to treat obesity and simultaneously mitigate the risk of developing a long list of health problems plaguing society.”

How the Drugs Work

After a meal, the hormone glucagon-like peptide 1 (GLP-1) is released to help stimulate the production of insulin and the uptake of glucose in muscle and other tissues. With the cells now loaded with fuel, the level of glucose in the blood returns to normal. Semaglutide uses GLP-1 with slight modifications to increase its availability in the bloodstream. Its success in controlling blood glucose has prompted the American Diabetes Association to recommend it and other GLP-1-based drugs as the new first line injectable treatments for diabetes, ahead of insulin.

But GLP-1 also acts directly on the brain, prompting satiety after a meal, and it slows down the rate at which stomach contents are emptied into the intestines, evening out the release of nutrients and glucose into the bloodstream. That’s why it has also become extremely popular as a weight loss treatment.

It’s still not a perfect drug strategy for weight loss, though. “The biggest problem with GLP-1 drugs is that they have to be injected once a week, and they can induce a very strong feeling of nausea,” said Kumar. “As much as 40% of people using these drugs give up after the first month.”

A second hormone released after eating is glucose-dependent insulinotropic peptide (GIP). It also makes us feel full after a meal. GIP looks a lot like GLP-1, so rather than administer two drugs, researchers created one peptide that incorporates structural elements of both – what’s called in drug development a chimera. That drug, tirzepatide, has the added benefit of significantly reducing nausea. As a more tolerable treatment, it may overtake semaglutide in the weight loss market. 

“And then there is a third hormone, glucagon,” said Kumar. “Paradoxically, it actually increases blood glucose, but at the same time increases the expenditure of energy in cells of the body, raises body temperature, and suppresses appetite.” By adding glucagon to the mix, GLP-1 and GIP end up neutralizing its glucose-enhancing effect, leaving the remaining functionalities of all three hormones working together to enhance weight loss.

Glucagon is also similar in structure to GLP-1 and GIP, so drug developers created a single chimera peptide that incorporates elements of all three hormones, which can be recognised by their three separate receptors. That drug, called retatrudide, is currently in clinical trials that indicate even greater achievable weight loss (up to 24%) compared to the original GLP-1 drugs (6-15%).

Going for the Weight Loss Gold Standard with a Fourth Target

“The goal that people are trying to shoot for is bariatric surgery,” said Kumar. That’s a surgical procedure significantly reducing the size of the stomach, which can achieve long-lasting weight loss up to 30%. “For individuals with persistent obesity and potential deadly associated conditions, it becomes a necessary but invasive treatment.” 

Current injectable weight loss drugs still fall short of that gold standard, so the Tufts chemists are focused on a drug redesign that could match the 30% weight loss outcome. 

“There is one more hormone we wanted to bring in to complete a weight control quartet,” said Tristan Dinsmore, a graduate student in the Kumar lab and the lead author of the study. “It’s called peptide YY (PYY). This molecule is also secreted by the gut after we eat a meal, and its job is to reduce appetite and slow the process of emptying food from the stomach, but via different mechanisms than either GLP-1 or GIP. It may also be involved in directly ‘burning off’ fat.”

PYY is from a separate and structurally unrelated class of hormones than the first three, so blending its structure into a chimeric peptide that also mimics GLP-1, GIP, and glucagon was not easy. Instead, the Tufts team was able to join two peptide segments end-to-end, creating a new ‘tetra-functional’ clinical candidate.

“One of the limitations of the current drugs is that individual variation, possibly including how people express target receptors or respond to their corresponding hormones, can lead to lesser than desired weight loss outcomes in many patients,” said Martin Beinborn, visiting scholar in the Department of Chemistry. “By hitting four different hormone receptors at the same time, we hope to improve the chances of averaging out such variation toward the goal of achieving greater and more consistent overall effectiveness.”

“A second issue is that patients tend to regain weight after discontinuing currently available GLP-1 related drugs,” said Beinborn, who notes that lifestyle changes should ideally be a complement to medication treatment. This two-pronged approach will not only support reaching and keeping one’s target weight, but may also help preserve bone and muscle mass.

“Recent studies indicate that weight rebound after drug discontinuation is delayed with the newer, more effective GLP-1 mimetics,” he said. “Extending from this observation, one may speculate that multi-chimeras along the lines of the one we discovered could get us closer to the bariatric surgery standard of lasting weight loss.”

Source: Tufts University

Can Early Exposure to Dogs Lessen Genetic Susceptibility to Eczema?

Photo by Pauline Loroy on Unsplash

New research published in Allergy indicates that certain environmental exposures may affect a child’s risk of developing atopic eczema, a condition characterised by dry, itchy, and inflamed skin. In other words, although some people may be genetically predisposed to eczema, certain environmental factors may increase or decrease that risk.

For the study, investigators analysed data from 16 European studies to test for interactions between the 24 most significant eczema-associated genetic variants and 18 early-life environmental factors. They applied their findings to an additional 10 studies and used lab modelling tests to assess their results.

The first analysis (including 25 339 individuals) showed suggestive evidence for interaction between 7 environmental factors (antibiotic use, cat ownership, dog ownership, breastfeeding, elder sibling, smoking, and washing practices) and at least one established genetic variant for eczema, with 14 interactions in total.

In the additional analysis (254 532 individuals), dog exposure interacted with a particular genetic risk variant on chromosome 5, near the gene that codes for the interleukin-7 receptor, a protein involved in immune cell function. Lab modelling tests showed that this variant affects expression of interleukin-7 receptor in human skin cells and that dog exposure modifies the genetic effect of this variant on the development of eczema, essentially providing a protective effect by suppressing skin inflammation.

Additional studies are needed to explore these lab findings and the other potential interactions identified in the first analysis.

“Our research aims to answer some of the most difficult questions that I am asked in clinic: ‘Why does my child have eczema?’ and ‘What can I do to help protect my baby?’ We know that genetic make-up affects a child’s risk of developing eczema and previous studies have shown that owning a pet dog may be protective, but this is the first study to show how this may occur at a molecular level,” said corresponding author Sara J. Brown, MD, PhD, FRCPE, of the University of Edinburgh. “More work is needed, but our findings mean we have a chance to intervene in the rise of allergic disease, to protect future generations.”

Source: Wiley

Newly Discovered Cancer Cell Energy Pathway Blocked with Compound in Ginger

Photo by TUMERI on Unsplash

Looking to nature for answers to complex questions can reveal new and unprecedented results that can even affect cells on molecular levels. For instance, human cells oxidise glucose to produce ATP (adenosine triphosphate), an energy source necessary for life.

Cancer cells produce ATP through glycolysis, which does not utilise oxygen even under conditions where oxygen is present, and convert glucose into pyruvic acid and lactic acid. This method of producing ATP, known as the Warburg effect, is considered inefficient, thus raising questions as to why cancer cells choose this energy pathway to fuel their proliferation and survival.

In search for this energy catalyst, Associate Professor Akiko Kojima-Yuasa’s team at Osaka Metropolitan University’s Graduate School of Human Life and Ecology analysed the cinnamic acid ester ethyl p-methoxycinnamate, a main component of kencur ginger, and its mechanism of action. In previous research, the team discovered that ethyl p-methoxycinnamate has inhibitory effects on cancer cells. Furthering their study, the acid ester was administered to Ehrlich ascites tumour cells to assess which component of the cancer cells’ energy pathway was being affected.

Results revealed that the acid ester inhibits ATP production by disrupting de novo fatty acid synthesis and lipid metabolism, rather than through glycolysis as commonly theorised. Further, the researchers discovered acid ester-induced inhibition triggered increased glycolysis, which acted as a possible survival mechanism in the cells. This adaptability was theorised to be attributed to ethyl p-methoxycinnamate’s inability to induce cell death.

“These findings not only provide new insights that supplement and expand the theory of the Warburg effect, which can be considered the starting point of cancer metabolism research, but are also expected to lead to the discovery of new therapeutic targets and the development of new treatment methods,” stated Professor Kojima-Yuasa.

Source: Osaka Metropolitan University

Rates of Obesity Are Soaring Worldwide: Have We Been Misunderstanding the Problem?

Photo by Andres Ayrton on Pexels

By Jesse Copelyn

Authors of a recent Lancet report argue that obesity should not just be seen as a risk factor for other diseases – but in some cases, should be seen as a disease itself. The position could change how we treat obesity globally. In the first of this two-part Spotlight series, we break down the debate around the issue, and its implications for health policy.    

In 1990, just 2% of all young people around the world aged 5 to 24 were living with obesity. By 2021, this figure had more than tripled to over 6%. This is according to a recent study, which relied on Body Mass Index (BMI) data from 180 countries and territories around the world. It estimates that the rise in obesity among children and young people will only continue in the coming decades.

South Africa certainly isn’t immune to the crisis. A survey conducted in 2021/2022 found that 16% of all children aged 6 to 18 were “severely overweight”. Meanwhile, World Health Organization (WHO) data suggests that about 30% of all adults in South Africa are living with obesity, meaning a BMI of over 30, which is almost double the global level.

BMI, which simply looks at a person’s weight in relation to their height, is a crude measure of obesity. For instance, a person may have a high BMI simply because they have a lot of muscle rather than fat. But while it is agreed that BMI is a flawed indicator at the individual level, many experts recommend using it as a rough proxy for “health risk at a population level”.

For instance, a study which collected data on nearly three million people found that those who had very high BMI levels were, on average, more likely to die at an early age. The study also found that this was true of people with very low BMI levels (those who were underweight). In this context, the above figures paint a concerning picture.

Given the rising rates, experts argue that we need health systems to be able to track and respond to obesity urgently. But, according to a Lancet Commission published in January, health systems around the world may struggle to do this, because of a failure to accurately conceptualise and measure what obesity actually is.

The Lancet commission was developed by 58 experts from different medical specialties and though it has been the subject of debate, it has since been widely endorsed as a new way to understand obesity. Spotlight takes a look at what it concluded.

Delaying treatment for no reason

Obesity is often regarded as a risk factor for other diseases, for instance, type 2 diabetes. But according to the commission, there are certain cases in which obesity is not just a risk factor, but a disease itself – one that should be immediately treated.

One of the reasons for this is that obesity not only contributes to the emergence of other conditions but sometimes leads to clinical symptoms directly. For example, the cartilage that protects the joints in a person’s knees can sometimes become eroded when adults carry too much weight. In this case, a person could suffer from joint pain, stiffness and reduced mobility where obesity is clearly the cause.

Take another example. If fat deposits build up in the abdomen, this may limit how much the lungs can expand, causing breathlessness. Similarly, a build-up of fat around the neck can narrow a person’s upper airways, which can cause sleep apnoea.

Thus, obesity is not simply something which increases the risk of developing a separate disease in the future – but something which can directly (and presently) affect the functioning of organs.

More broadly, the commission argues that by hindering a person’s “mobility, balance and range of motion” obesity can in certain cases “restrict routine activities of daily living”. In these instances, obesity is a disease by definition, according to the commission. This is given that it defines disease as a “harmful deviation from the normal structural or functional state of an organism, associated with specific signs and symptoms and limitations of daily activities”.

But why does this conceptual debate matter?

Because at present, people often have to wait for other diseases to crop up before insurers or public health systems cover them for weight loss drugs or bariatric surgery – a procedure to help with weight loss and improve obesity-related health conditions. And when they do cover these services, it is often only after severe delay. Because obesity is only considered to be a risk factor, it isn’t typically treated with the same urgency as life-threatening diseases, according to the authors of the commission.

Professor Frances Rubino, the lead author of the commission, details how this problem manifests in the healthcare system.

“I’ve been doing bariatric surgery for 25 years in four different countries; in America, Italy, France and the UK,” he tells Spotlight, “In all of those countries, to meet the criteria for surgery people very often have to undergo six to 12 months of weight monitoring before their surgery is covered. So systematically you delay treatment”.

He continues: “Someone who has clinical obesity and has heart failure as a result of it is waiting for a year for what reason? That condition will only worsen and if the patient is still alive, the treatment [is] going to cost the same amount to the payer but it’s going to be less effective.”

Can’t people just diet?

One of the reasons that some academics have historically been reluctant to classify obesity as a disease is because of a fear that this may reduce people’s agency – instead of taking proactive steps to diet and exercise, people with obesity may simply view themselves as afflicted by a disease.

The belief that people with obesity can simply diet their way out of their situation is in fact partially why Rubino’s patients were forced to wait long periods of time before receiving bariatric surgery.

Rubino explains: “In America, many private payers [i.e. medical insurance schemes] have required weight monitoring programmes, where patients do nothing else other than see a dietician for 12 months, and if they skip one appointment, they have to start all over again. I think that in some cases, this has been misguided by the idea that you want to see if obesity can be reversed by somebody going on a diet.”

This, according to him, is a “misconception”, arguing that if someone faces such severe levels of obesity that they require surgery, diet is unlikely to offer a solution.

Indeed, research has shown that it’s very rare for people with obesity to lose large amounts of weight quickly without surgery or medication. For instance, a study on over 176 000 patients in the UK found that among men with “simply obesity” or a BMI of 30-34.9, only 1 in 210 were able to achieve a “normal” weight level within a year. Among men with morbid obesity or BMI of 35 or more, the chance was less than 1 than in 1000. Chances for women were roughly twice as good as men’s – so still exceedingly small.

Thus, if someone is severely obese and their excess weight is causing life-threatening symptoms, putting them on a diet for a year is unlikely to result in the urgent changes that may be required for them to get better. In fact, Rubino argues that they may simply die of their condition in the interim.

Taking a medical approach more quickly is easier now than ever before due to the regulatory approval of GLP-1 agonists like semaglutide and tirzepatide – Spotlight previously reported on the availability of these new diabetes and weight loss medicines in South Africa. An article by WHO officials from December states that because of the approval of these medicines “[h]ealth systems across the globe now may be able to offer a treatment response integrated with lifestyle changes that opens the possibility of an end to the obesity pandemic”.

Not all people with obesity are ill

There is a more scientific argument against categorising obesity as a disease. This is that while obesity can sometimes result in the negative health symptoms discussed above (like respiratory issues or reduced mobility) it doesn’t always do this.

In fact, the commission acknowledges that some people with obesity “appear to be able to live a relatively healthy life for many years, or even a lifetime”. One of the reasons for this is that excess fat may be stored in areas that don’t surround vital organs. For instance, if fat is stored in the limbs, hips, or buttocks, then this may cause less harm than if it is stored in the stomach.

Since obesity doesn’t always cause health problems, it isn’t always a disease. In order to deal with this conceptual hurdle, the commission classifies obesity into two categories – clinical and preclinical obesity.

If a person has pre-clinical obesity, this means they have a lot of excess fat, but no obvious health problems that have emerged as a result. In this case, obesity is not classified as a disease, though it may still increase the chance of future health problems (depending on a range of factors, like family history).

For a person to have clinical obesity, they must have a lot of excess fat as well as health problems that have already been directly caused by this. It is this that the commission defines as a disease.

This classification system, according to Rubino, ensures not only that we urgently treat people living with clinical obesity, but also that we don’t overtreat people – since if a person falls into the pre-clinically obese group, then they may not need treatment.

But if we’re going to treat clinical obesity as a disease, we’ll need clear methods of diagnosing people. Since BMI is deeply flawed and provides little information about whether a person is ill at the individual level, health systems will need something else. In part 2 of this Spotlight special series, we’ll discuss the options offered by the commission, and how this all relates to the situation in South Africa.

Republished from Spotlight under a Creative Commons licence.

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Y Chromosome Loss in Immune Cells Creates Opportunity for Cancers

Scanning electron micrograph of a T cell lymphocyte. Credit: NIH / NIAID

A study initiated by a University of Arizona Comprehensive Cancer Center physician-scientist has for the first time defined how loss of the Y chromosome in male immune cells negatively affects immune system function. The findings, published in Nature, may explain why loss of Y is associated with lower cancer survival rates.

In males, each cell in the body usually contains one X and one Y chromosome. “Loss of Y” is a common, nonhereditary genetic change in men in which an immune cell in the blood loses its Y chromosome. It is often associated with aging. Loss of Y has been linked to increased mortality from carcinomas for many years, though no one knew why.

This study is the first to identify and define the relationship between loss of Y in white blood cells, immune cells and tumours, providing insights as to why men with loss of Y have increased cancer risks and poorer outcomes.

“These findings represent a big step forward in our understanding of why men with loss of Y in their blood cells have a higher mortality from cancer. It turns out it’s because these cells make the immune system infiltrating the cancer less effective,” said Dan Theodorescu, MD, PhD, director of the Cancer Center and a professor in the College of Medicine – Tucson

“We hope this provides a solid lead and framework for the nascent Y chromosome field to pursue so we can collectively better understand all the possible biological implications of this finding and how to use them to develop more effective approaches in prevention, treatment resulting in higher survival rates for patients.”

The research team discovered that loss of the Y chromosome – previously identified in malignant epithelial cells by the Theodorescu lab – also occurred in nearby noncancerous tissues, including connective tissue and immune cells.

Most notably, the team found that this chromosomal loss in helper and cytotoxic T cells, which are responsible for attacking cancer cells, was associated with a reduced ability to kill those cancerous cells. The findings suggest a mechanism by which tumours may evade immune detection and suppression.

Finally, the research team found that loss of Y in epithelial cells, combined with loss of Y in T cells, resulted in more aggressive cancers and lower survival rates in patients.

“The study has potential implications for current immunotherapies, including CAR T therapy,” Theodorescu said. “Further research is clearly needed but perhaps immunotherapies using cells from a patient’s immune system could be screened for loss of Y before being used in treatment.”

Source: University of Arizona