Links between internet adoption and psychological well-being are small at most, despite popular assumptions about negative psychological impacts of internet technologies and platforms, according to an international study involving two million people published in the journal Clinical Psychological Science.
The study examined data from people aged 15 to 89 in 168 countries, yet found smaller and less consistent associations than would be expected, if the internet were causing widespread psychological harm, according to the Oxford Internet Institute research team.
Professor Andrew Przybylski, Oxford Internet Institute and Assistant Professor Matti Vuorre, Tilburg University and Research Associate, Oxford Internet Institute, carried out the study, which shows the last two decades have seen only small and inconsistent changes in global well-being and mental health.
Professor Przybylski says, “We looked very hard for a ‘smoking gun’ linking technology and well-being and we didn’t find it.”
Professor Vuorre notes, “We studied the most extensive data on well-being and internet adoption ever considered, both over time and population demographics. Although we couldn’t address causal effects of internet use, our descriptive results indicated small and inconsistent associations.”
Results filtered by age group and gender did not reveal any specific demographic patterns among internet users, including women and young girls. In fact, for the average country, life satisfaction had increased more for females over the period.
According to Professor Przybylski, “We meticulously tested whether there is anything special in terms of age or gender, but there is no evidence to support popular ideas that certain groups are more at risk.”
The team maintains, “We put our findings under a more extreme test to see if there are matters which we have missed and we did find increased mobile broadband adoption predicted greater life satisfaction, but this association was too small to be of practical significance.”
But, the team insists, technology companies need to provide more data, if there is to be conclusive evidence of the impacts of internet use. The research says, Research on the effects of internet technologies is stalled because the data most urgently needed are collected and held behind closed doors by technology companies and online platforms.
“It is crucial to study, in more detail and with more transparency from all stakeholders, data on individual adoption of and engagement with Internet-based technologies. These data exist and are continuously analysed by global technology firms for marketing and product improvement but unfortunately are not accessible for independent research.
In today’s study, the researchers contrast two different studies of data on well-being and mental health against the countries’ per capita internet users and mobile broadband subscriptions and use, to see if internet adoption predicts psychological well-being. In the second study they use data on rates of anxiety, depression and self-harm from 2000–2019 in some 200 countries and analyse their associations with internet adoption.
Wellbeing was assessed using data from face to face and phone surveys by local interviewers in the respondents’ native languages. Mental health was assessed using statistical estimates of depressive disorders, anxiety disorders and self-harm in some 200 countries from 2000 to 2019, as estimated by aggregated health data from WHO member states.
Cross-sectional diagram of the NexGen 7T scanner, showing the new Impulse head-only gradient coil (green) and receiver-transmit coil (white) resting on a movable bed (brown) and connected to an electronic interface (blue) containing nearly a thousand wires (blue) that extend out of the magnet. Credit: Bernhard Gruber, MGH Harvard
An intense international effort to improve the resolution of magnetic resonance imaging (MRI) for studying the human brain has culminated in an ultra-high resolution 7 Tesla scanner that records up to 10 times more detail than current 7T scanners and over 50 times more detail than current 3T scanners, the mainstay of most hospitals.
This next generation or NexGen 7T functional MRI (fMRI) scanner can resolve features 0.4mm across, compared to the 2–3mm typical of today’s standard 3T fMRIs. It is described in a paper published in Nature Methods.
“The NexGen 7T scanner is a new tool that allows us to look at the brain circuitry underlying different diseases of the brain with higher spatial resolution in fMRI, diffusion and structural imaging, and therefore to perform human neuroscience research at higher granularity,” said David Feinberg, the director of the project to build the scanner. “The ultra-high resolution scanner will allow research on underlying changes in brain circuitry in a multitude of brain disorders, including degenerative diseases, schizophrenia and developmental disorders, including autism spectrum disorder.”
The improved resolution will help neuroscientists probe the neuronal circuits in different regions of the brain’s neocortex and allow researchers to track signals propagating from one area of the cortex, and perhaps discover underlying causes of developmental disorders. This could lead to better ways of diagnosing brain disorders, perhaps by identifying new biomarkers that would allow diagnosis of mental disorders earlier or, more specifically, in order to choose the best therapy.
“Normally, MRI is not fast enough at all to see the direction of the information being passed from one area of the brain to another,” Feinberg said. “The scanner’s higher spatial resolution can identify activity at different depths in the brain’s cortex to indirectly reveal brain circuitry by differentiating activity in different cell layers of the cortex.”
This is possible because neuroscientists have found in vision brain areas that the superficial and deepest cortex layers incorporate ‘top-down’ circuits, that is, they receive information from higher cortical brain areas, whereas the middle cortex involves ‘bottom-up’ circuitry, receiving sensory input. Pinpointing the fMRI activity to a specific depth in the cortex lets neuroscientists track the flow of information throughout the brain and cortex.
With the higher spatial resolution, neuroscientists will be able to home in on the activity of something on the order of 850 individual neurons within a single voxel – a 3D pixel – instead of the 600 000 recorded with standard hospital MRIs, said Silvia Bunge, a UC Berkeley professor of psychology who is one of the first to use the NexGen 7T to conduct research on a human brain.
“We were able to look at the layer profile of the prefrontal cortex, and it’s beautiful,” said Bunge, who studies abstract reasoning. “It’s so exciting to have this state-of-the-art, world-class machine.”
For William Jagust, a UC Berkeley professor of public health who studies the brain changes associated with Alzheimer’s disease, the improved resolution could finally help connect the dots between observed changes due to Alzheimer’s that occur in the brain – abnormal clumps of protein called beta amyloid and tau – and changes in memory.
“We know that part of the memory system in the brain degenerates as we get older, but we know little about the actual changes to the memory system – we can only go so far because of the resolution of our current MRI systems,” said Jagust. “With this new scanner, we think we’re going to be able to take apart a lot more carefully exactly where things have gone wrong. This could help with diagnosis or predicting outcomes in normal people.”
Jack Gallant, a UC Berkeley professor of psychology, hopes the scanner will help neuroscientists discover how functional changes in the brain lead to developmental and mental disorders such as dyslexia, autism and schizophrenia, or that result from neurological disorders, such as dementia and stroke.
“Mental disorders have an enormous impact on individuals, families and society. Together they represent about 10% of the US GDP. Mental disorders are fundamentally disorders of brain function, but functional measures are not used currently to diagnose most brain disorders or to look to see if a treatment’s working. Instead, these disorders are diagnosed behaviourally. This is a weak approach, because there are a lot of different mental brain states that can lead to exactly the same behaviour,” Gallant said. “What we need is more powerful MRI machines like this so that we can map, at high resolution, how information is represented in the brain. To me this is the big potential clinical benefit of ultra-high resolution MRI.”
Funding initiatives lead to ‘quantum leap’
The breakthrough came about through $22 million of funding from various government and private sector sources.
Incorporating newly developed hardware technology from those groups, Siemens collaborated with Feinberg’s team to rebuild a conventional 7 Tesla MRI scanner delivered to UC Berkeley in 2000 to improve the spatial resolution in pictures captured during brain scans.
“There’s been a large increase throughout the world of sites that use 7T MRI scanners, but they were mostly for development and were difficult to use,” said Nicolas Boulant, a physicist visiting from the NeuroSpin project at the University of Paris in Saclay, where he leads the team that operates the world’s only 11.7 Tesla MRI scanner, the strongest magnetic field employed to date. “David’s team really put together many ingredients to make a quantum leap at 7 Tesla, to go beyond what was achievable before and gain performance.”
Boulant hopes to adapt some of the new ingredients in the NexGen 7T – in particular, redesigned gradient coils – to eventually achieve even better resolution with the 11.7 Tesla MRI scanner. The gradient coils generate a rising magnetic field across the brain so that each part of the brain sees a different field strength, which helps to precisely map brain activity.
“The higher the magnetic field, the more difficult it is to really grab the potential promised by these higher-field MRI scanners to see finer details in the human brain,” he said. “You need all this peripheral equipment, which needs to be on steroids to meet those promises. The NexGen 7T is really a game-changer when you want to do neuro MRI.”
To reach higher spatial resolution, the NexGen 7T scanner had to be designed with a greatly improved gradient coil and with larger receiver array coils – which pick up the brain signals – using from 64 to 128 channels to achieve a higher signal-to-noise ratio (SNR) in the cortex and faster data acquisition. All these improvements were combined with a higher signal from the ultra-high field 7T magnet to achieve cumulative gains in the scanner performance.
The extremely powerful gradient coil is the first to be made with three layers of wire windings. Designed by Peter Dietz at Siemens in Erlangen, Germany, the “Impulse” gradient has 10 times the performance of gradient systems in current 7T scanners. Mathias Davids, then a physics graduate student at Heidelberg University in Mannheim, Germany, and a member of Feinberg’s team, collaborated with Dietz in performing physiologic modelling to allow a faster gradient slew rate – a measure of how quickly the magnetic field changes across the brain – while remaining under the neuronal stimulation thresholds of the human body.
“It’s designed so that the gradient pulses can be turned on and off much quicker – in microseconds – to record the signals much quicker, and also so the much higher amplitude gradients can be utilised without stimulating the peripheral nerves in the body or stimulating the heart, which are physiologic limitations,” Feinberg said.
A second key development in the scanner, Feinberg said, is the 128-channel receiver system that replaces the standard 32 channels. The large receiver coil arrays built by Shajan Gunamony of MR CoilTech in Glasgow, UK, gave a higher signal-to-noise ratio in the cerebral cortex and also provided higher parallel imaging acceleration for faster data acquisition to encode large image matrices for ultra high resolution fMRI and structural MRI.
To take advantage of the new hardware technology, Suhyung Park, Rüdiger Stirnberg, Renzo Huber, Xiaozhi Cao and Feinberg designed new pulse sequences of precisely timed gradient pulses to rapidly achieve ultra high resolution. The smaller voxels, measured in units of cubic millimetres and less than 0.1 microlitre, provide a 3D image resolution that is 10 times higher than that of previous 7T fMRIs and 125 times higher than the typical hospital 3T MRI scanners used for medical diagnosis.
Voxel-perfect resolution
The most common MRI scanners employ superconducting magnets that produce a steady magnetic field of 3 Tesla – 90 000 times stronger than Earth’s magnetic field and 3000 times stronger than a fridge magnet.
“A 3T fMRI scanner can resolve spatial details with a resolution of about 2 to 3mm. The cortical circuits that underpin thought and behaviour are about 0.5mm across, so standard research scanners cannot resolve these important structures,” Gallant said.
In contrast, fMRI focuses on blood flow in arteries and veins and can vividly distinguish oxygenated haemoglobin funnelling into working areas of the brain from deoxygenated haemoglobin in less active areas. This allows neuroscientists to determine which areas of the brain are engaged during a specific task.
But again, the 3mm resolution of a 3T fMRI can distinguish only large veins, not the small ones that could indicate activity within microcircuits.
The NexGen 7T will allow neuroscientists to pinpoint activity within the thin cortical layers in the grey matter, as well as within the narrow column circuits that are organised perpendicular to the layers. These columns are of special interest to Gallant, who studies how the world we see is represented in the visual cortex. He has actually been able to reconstruct what a person is seeing based solely on recordings from the brain’s visual cortex.
“The machine that David has built, in theory, should get down to 500 microns, or something like that, which is way better than anything else – we’re very near the scale you would want if you’re getting signals from a single column, for example,” Gallant said. “It’s fantastic. The whole thing about MRI is how big is the little volumetric unit, the voxel […] that’s the only thing that matters.”
For the moment, NexGen 7T brain scanners must be custom-built from regular 7T scanners but should be a lot cheaper than the $22 million required to build the first one.
Feinberg said that UC Berkeley’s NexGen 7T scanner technology will be disseminated by Siemens and MR CoilTech Ltd.
“My view is that we may never be able to understand the human brain on the cellular synaptic circuitry level, where there are more connections than there are stars in the universe,” Feinberg said. ” But we are now able to see signal patterns of brain circuits and begin to tease apart feedback and feed forward circuitry in different depths of the cerebral cortex. And in that sense, we will soon be able to understand the human brain organisation better, which will give us a new view into disease processes and ultimately allow us to test new therapies. We are seeking a better understanding and view of brain function that we can reliably test and reproducibly use noninvasively.”
In a large, international clinical trial, people with obesity or overweight but not diabetes taking semaglutide for more than three years had a 20% lower risk of cardiovascular disease outcomes and lost an average of 9.4% of their body weight.
Semaglutide, a GLP-1 medication primarily prescribed for people with Type 2 diabetes, is also FDA-approved for weight loss in people with obesity.
These results were shared in a late-breaking science presentation at the American Heart Association’s Scientific Sessions 2023 and the full manuscript was also published in The New England Journal of Medicine.
“This news is very encouraging for people with overweight or obesity because no treatment specifically directed at the management of obesity and overweight in people without Type 1 or Type 2 diabetes has been tested in a randomised trial and been shown to influence cardiovascular outcomes,” said lead study author A. Michael Lincoff, MD.
While prior research has confirmed the benefits of semaglutide in managing blood sugar, decreasing cardiovascular disease events and reducing weight in people with Type 2 diabetes, this study specifically investigated the potential impact of semaglutide on cardiovascular disease in people with overweight or obesity and cardiovascular disease who did not have either Type 1 or Type 2 diabetes.
In this randomised, controlled, double-blind trial, participants were assigned to take either 2.4mg of semaglutide (the FDA-approved semaglutide dose for weight management) or a placebo once a week, which is higher than the FDA-approved semaglutide dose limit for Type 2 diabetes of 2.0mg/week. Each person in the study used a ‘pen’ to inject the medicine or placebo into a skin fold in their stomach, thigh or upper arm each week on the same day, and the dose started at 0.24mg and gradually increased every four weeks up to 2.4mg, and mean follow-up for all participants was 40 months.
In addition to taking either semaglutide or placebo for the trial, all participants also received standard of care treatment for cardiovascular disease, such as cholesterol modifying medications, antiplatelet therapies, beta blockers or other treatments. The authors note that heart disease diagnoses varied among the participants, therefore, treatment was adjusted to meet each individual’s diagnosis and needs, as well as the treatment guidelines in their country of residence.
The study, which ran from October 2018 through June 2023, indicated the following:
There was a 20% reduction in the risk of heart attacks, strokes or death due to cardiovascular disease in the participants who took semaglutide, compared to the participants in the placebo group.
In the semaglutide group, the participants’ body weight was reduced, on average, by 9.4% compared to a reduction of 0.9% among the adults in the placebo group.
There were no new safety concerns found in the study, which researchers note is encouraging since the SELECT trial is the largest and longest (4.5 years) trial of semaglutide in adults without Type 1 or Type 2 diabetes.
The number of serious adverse events was lower in the semaglutide group. Previous studies of medications of the GLP-1 receptor agonist class have shown an association with gallbladder disorders, and in SELECT, there was a slightly higher rate of gallbladder disorders in the semaglutide vs placebo group (2.8% vs 2.3%, respectively).
Semaglutide was stopped more frequently than placebo for gastrointestinal intolerance, a known side effect of this class of medications; however, there was no higher rate of serious gastrointestinal events.
The researchers noted that this medication did not lead to an increased rate of pancreatitis, which has been a concern with prior medications of this type.
Of note, other weight-loss medications that are not GLP-1 receptor agonists have been associated with increased risks of psychiatric disorders or cancer; these risks were not elevated with semaglutide in the SELECT trial.
“It’s been estimated that within about ten years, over half of the world’s population will have overweight or obesity,” said Dr Lincoff. “And while GLP-1 medications are frequently prescribed for patients with vascular disease and Type 2 diabetes, there is a significant number of people who do not have Type 1 or Type 2 diabetes but do have vascular disease and overweight or obesity for whom these medications are often not available due to access to care issues, insurance coverage or other factors. This population may now potentially benefit from semaglutide, and importantly, our results indicate the magnitude of cardiovascular risk reduction with semaglutide among people without Type 1 or Type 2 diabetes is the same as what we have seen in people with Type 2 diabetes. Our findings expand the opportunity to treat patients who have overweight or obesity and existing heart disease without Type 1 or Type 2 diabetes, and we have a chance to significantly reduce their risk of a secondary cardiovascular event including death.”
Among the study limitations were including adults with prior cardiovascular disease, thereby not investigating primary prevention of cardiovascular disease (people with no history of a heart attack, stroke and/or peripheral artery disease). In addition, 28% of the study participants were female, which is not proportionate to the number of women with cardiovascular disease and overweight or obesity in the general population.
Additional analyses will include identifying the mediators of the cardiovascular benefit to determine to what extent the results were driven by reduction of metabolically unhealthy body fat, positive impacts on inflammation or blood sugar, direct effects of the medication itself on plaque build-up in the arteries, or a combination of one or more variables.
Researchers may potentially have found a preventive solution for neurodegenerative disorders in the most unlikely of sources: used coffee grounds. The researchers found caffeic-acid based Carbon Quantum Dots (CACQDs) have the potential to protect brain cells from the damage caused by several neurodegenerative diseases – if the condition is triggered by factors such as obesity, age and exposure to pesticides and other toxic environmental chemicals.
Carbon Quantum Dots are essentially simple nanoparticles made of carbon that have found a growing number of applications, including bioimaging thanks to its fluorescent properties and as photochemical catalysts. Their active surfaces can be doped with different elements for desired effects, are biocompatible and can be produced simply from a range of organic substances such as lemon juice and used tea leaves.
The University of Texas at El Paso team behind the study was led by Jyotish Kumar, a doctoral student in the Department of Chemistry and Biochemistry, and overseen by Mahesh Narayan, PhD, a professor and Fellow of the Royal Society of Chemistry in the same department. Their work is described in the journal Environmental Research.
“Caffeic-acid based Carbon Quantum Dots have the potential to be transformative in the treatment of neurodegenerative disorders,” Kumar said.
“This is because none of the current treatments resolve the diseases; they only help manage the symptoms. Our aim is to find a cure by addressing the atomic and molecular underpinnings that drive these conditions.”
Neurodegenerative diseases, when they are in their early stages and are caused by lifestyle or environmental factors, share several traits.
These include elevated levels of free radicals in the brain, and the aggregation of fragments of amyloid-forming proteins that can lead to plaques or fibrils in the brain.
Kumar and his colleagues found that CACQDs were neuroprotective across test tube experiments, cell lines and other models of Parkinson’s disease when the disorder was caused by a pesticide called paraquat.
The CACQDs, the team observed, were able to remove free radicals or prevent them from causing damage and inhibited the aggregation of amyloid protein fragments without causing any significant side effects.
The team hypothesises that in humans, in the very early stage of a condition such as Alzheimer’s or Parkinson’s, a treatment based on CACQDs can be effective in preventing full-on disease.
“It is critical to address these disorders before they reach the clinical stage,” Narayan said.
“At that point, it is likely too late. Any current treatments that can address advanced symptoms of neurodegenerative disease are simply beyond the means of most people. Our aim is to come up with a solution that can prevent most cases of these conditions at a cost that is manageable for as many patients as possible.”
Caffeic acid belongs to a family of compounds called polyphenols, which are plant-based compounds known for their antioxidant, or free radical-scavenging properties. Caffeic acid is unique because it can penetrate the blood-brain barrier and is thus able to exert its effects upon the cells inside the brain, Narayan said.
In the simple one-step ‘green chemistry’ method, the team ‘cooked’ caffeic acid at 230°C for two hours to reorient the caffeic acid’s carbon structure and form CACQDs. The CACQDs were then extracted according to a molecular weight cutoff of 1kDa.
The sheer abundance of coffee grounds is what makes the process both economical and sustainable, Narayan said.
New research that had participants compare the taste perception of less processed foods with ultra-processed foods (UPFs), found that UPFs were no more pleasant tasting than less processed foods. The University of Bristol-led findings, published in the journal Appetite, support the theory that humans are programmed to learn to like foods with more equal amounts of carbohydrate and fat. Carbohydrate (including sugars) and fat provide most of the calories in human diets.
The study wanted to test the common but largely untested assumptions that food energy density (calories per gram), level of processing, and carbohydrate-to-fat ratio are key factors influencing food liking and desirability.
In the experiment, involving 224 adult volunteers, participants were presented with colour images of between 24 and 32 familiar foods, varying in energy density, level of processing (including UPFs), and carbohydrate-to-fat ratio. There were 52 different foods in total, including avocado, grapes, cashew nuts, king prawns, olives, blueberry muffin, crispbread, pepperoni sausage, and ice cream.
Participants were then asked to rate the foods for taste pleasantness (liking), desire to eat, sweetness, and saltiness while imagining tasting them. The validity of this method was confirmed by, for example, finding a strong relationship between sweetness ratings and food sugar content.
Results from the study showed that, on average, UPFs were no more liked or desired than processed or unprocessed foods. But foods that combined more equal amounts (in calories) of carbohydrate and fat were more liked and desired than foods equivalent in calories but mostly from either carbohydrate or fat. This is known, from previous research, as the ‘combo’ effect.
Further results revealed that foods with higher amounts of dietary fibre were less liked and desired, and foods tasting more intense (mainly related to the level of sweetness and saltiness), were more liked and desired.
Lead author Professor Peter Rogers found the results for UPFs surprising. He said: “Our results challenge the assumption that ultra-processed foods are ‘hyperpalatable’, and it seems odd that this has not been directly tested before.
“However, whilst ultra-processing didn’t reliably predict liking (palatability) in our study, food carbohydrate-to-fat ratio, food fibre content, and taste intensity did – actually, together, these three characteristics accounted for more than half of the variability in liking across the foods we tested.
“The results for sweetness and saltiness, are consistent with our innate liking for sweetness and saltiness. And the results for carbohydrate-to-fat ratio and fibre might be related to another important characteristic that determines food liking.
“Our suggestion is that humans are programmed to learn to like foods with more equal amounts of carbohydrate and fat, and lower amounts of fibre, because those foods are less filling per calorie. In other words, we value calories over fullness.
“In turn, this trait helps us to maximise calorie intake and build up fat reserves when food is abundant – which is adaptive in circumstances when food supplies are uncertain or fluctuate seasonally, but not when food is continuously available in excess of our immediate needs.”
The researchers at the Nutrition and Behaviour Group are currently testing the calories versus fullness idea in further studies of food liking and meal preferences, including across different countries and cuisines.
Trans-vaccenic acid (TVA), a long-chain fatty acid found in meat and dairy products from grazing animals such as cows and sheep, improves the ability of CD8+ T cells to infiltrate tumours and kill cancer cells, according to a new study by researchers from the University of Chicago.
The research, published in Nature, also shows that cancer patients with higher levels of TVA circulating in the blood responded better to immunotherapy, suggesting potential as a nutritional complement to conventional cancer therapy. Although trans fatty acids that are industrially produced are known to be harmful to health, natural ones such as TVA are linked to health benefits. But the researchers don’t envision prescribing diets packed with red meat and cheese – rather, TVA would be a supplement.
“There are many studies trying to decipher the link between diet and human health, and it’s very difficult to understand the underlying mechanisms because of the wide variety of foods people eat. But if we focus on just the nutrients and metabolites derived from food, we begin to see how they influence physiology and pathology,” said Jing Chen, PhD, professor of medicine at UChicago and one of the senior authors. “By focusing on nutrients that can activate T cell responses, we found one that actually enhances anti-tumour immunity by activating an important immune pathway.”
Searching for nutrients that activate immune cells
Chen’s lab focuses on understanding how metabolites, nutrients and other molecules circulating in the blood influence the development of cancer and response to cancer treatments. For the new study, they started with a database of around 700 known metabolites that come from food and assembled a ‘blood nutrient’ compound library consisting of 235 bioactive molecules derived from nutrients. They screened the compounds in this new library for their ability to influence anti-tumour immunity by activating CD8+ T cells, which are critical for killing cancerous or virally infected cells.
After the scientists evaluated the top six candidates in both human and mouse cells, they saw that TVA performed the best. TVA is the most abundant trans fatty acid present in human milk, but the body cannot produce it on its own. Only about 20% of TVA is broken down into other byproducts, leaving 80% circulating in the blood. “That means there must be something else it does, so we started working on it more,” Chen said.
Feeding mice a diet enriched with TVA significantly reduced the tumour growth potential of melanoma and colon cancer cells compared to mice fed a control diet. The TVA diet also enhanced the ability of CD8+ T cells to infiltrate tumours.
The team also performed a series of molecular and genetic analyses to understand how TVA was affecting the T cells. These included a new technique for monitoring transcription of single-stranded DNA called kethoxal-assisted single-stranded DNA sequencing, or KAS-seq, developed by Chuan He, PhD, professor of chemistry at UChicago and another senior author of the study. These additional assays, done by both the Chen and He labs, showed that TVA inactivates a receptor on the cell surface called GPR43 which is usually activated by short-chain fatty acids often produced by gut microbiota. TVA overpowers these short-chain fatty acids and activates a cellular signaling process known as the CREB pathway, which is involved in a variety of functions including cellular growth, survival, and differentiation. The team also showed that mouse models where the GPR43 receptor was exclusively removed from CD8+ T cells also lacked their improved tumour fighting ability.
Finally, working with other researchers, the team analysed blood samples taken from patients undergoing CAR-T cell immunotherapy treatment for lymphoma. They saw that patients with higher levels of TVA tended to respond to treatment better than those with lower levels. They also tested leukaemia cell lines and saw that TVA enhanced the ability of an immunotherapy drug to kill leukaemia cells.
TVA as a supplement
The study suggests that TVA could be used as a dietary supplement to help various T cell-based cancer treatments, although Chen points out that it is important to determine the optimised amount of the nutrient itself, not the food source. There is a growing body of evidence about the detrimental health effects of consuming too much red meat and dairy, so this study shouldn’t be taken as an excuse to eat more cheeseburgers and pizza; rather, it indicates that nutrient supplements such as TVA could be used to promote T cell activity. Chen thinks there may be other nutrients that can do the same.
“There is early data showing that other fatty acids from plants signal through a similar receptor, so we believe there is a high possibility that nutrients from plants can do the same thing by activating the CREB pathway as well,” he said.
‘The new research also highlights the promise of this ‘metabolomic’ approach to understanding how the building blocks of diet affect our health. Chen said his team hopes to build a comprehensive library of nutrients circulating in the blood to understand their impact on immunity and other biological processes like aging.
“After millions of years of evolution, there are only a couple hundred metabolites derived from food that end up circulating in the blood, so that means they could have some importance in our biology,” Chen said. “To see that a single nutrient like TVA has a very targeted mechanism on a targeted immune cell type, with a very profound physiological response at the whole organism level — I find that really amazing and intriguing.”
Reducing the dose of a widely used COVID booster vaccine produces a similar immune response in adults to a full-dose with fewer side effects, according to a new study published in The Lancet Regional Health – Western Pacific. The research found that a half dose of a Pfizer COVID booster vaccine elicited a non-inferior immune response to a full dose in Mongolian adults who previously had AstraZeneca or Sinopharm COVID shots. But it found half-dose boosting may be less effective in adults primed with the Sputnik V COVID vaccine.
The research, led by Murdoch Children’s Research Institute (MCRI) and the National Centre for Communicable Diseases in Mongolia, is part of an international clinical trial investigating the different COVID booster shot approaches to help guide future vaccination strategies.
The first batch of findings, and involving 601 participants over 18 years old from Mongolia, reports on the initial responses seen 28-days after vaccination. The study is the first of its kind to assess and compare COVID-19 vaccines widely used in low- and middle-income countries.
MCRI Professor Kim Mulholland, who also sits on the WHO SAGE committee, said the study found that fractional doses elicited an immune response that was non-inferior to a full dose with fewer side effects and was less costly.
“Fractional dosing may improve COVID booster acceptability and uptake and reduce the per-dose cost of COVID-19 booster programs,” he said. “Policymakers and immunisation advisory committees can draw upon this data to make flexible boosting schedules decisions.”
The study found that participants receiving a half dose reported fewer local reactions than those receiving full doses (60% versus 72%) including less pain and tenderness. They also reported fewer systemic reactions (25% vs 32%) including less fevers, vomiting, diarrhoea and headaches.
The cohort will be followed up at six and 12 months with the data to answer key questions on other aspects of the immune response including the rate of waning and breakthrough infections.
The burden of heat-related mortality during the summer of 2022 in Europe may have exceeded 70 000 deaths according to a study led by the Barcelona Institute for Global Health (ISGlobal). The authors of the study, published in The Lancet Regional Health – Europe, revised upwards initial estimates of the mortality associated with record temperatures in 2022 on the European continent.
In an earlier study, the same team used epidemiological models applied to weekly temperature and mortality data in 823 regions in 35 European countries and estimated the number of heat-related premature deaths in 2022 to be 62 862. In that study, the authors acknowledged that the use of weekly data would be expected to underestimate heat-related mortality, and pointed out that daily time-series data are required to accurately estimate the impact of high temperatures on mortality.
The objective of the new study was to develop a theoretical framework that could quantify the errors inherent to aggregated data, such as weekly and monthly temperature and mortality time-series. Models based on temporally aggregated data are useful because the data are available in real-time, allowing analysis of the health hazard within a few days. The researchers aggregated daily temperatures and mortality records from 147 regions in 16 European countries. They then analysed and compared the estimates of heat- and cold-related mortality by different levels of aggregation: daily, weekly, 2-weekly and monthly.
Analysis revealed differences in epidemiological estimates according to the time scale of aggregation. In particular, it was found that weekly, 2-weekly and monthly models underestimated the effects of heat and cold as compared to the daily model, and that the degree of underestimation increased with the length of the aggregation period. Specifically, for the period 1998–2004, the daily model estimated an annual cold and heat-related mortality of 290 104 and 39 434 premature deaths, respectively, while the weekly model underestimated these numbers by 8.56% and 21.56%, respectively.
“It is important to note that the differences were very small during periods of extreme cold and heat, such as the summer of 2003, when the underestimation by the weekly data model was only 4.62%,” explains Joan Ballester Claramunt, the ISGlobal researcher who leads the European Research Council’s EARLY-ADAPT project.
The team used this theoretical framework to revise the mortality burden attributed to the record temperatures experienced in 2022 in their earlier study. According to the calculations made using the new methodological approach, that study underestimated the heat-related mortality by 10.28%, which would mean that the actual heat-related mortality burden in 2022, estimated using the daily data model, was 70,066 deaths, and not 62,862 deaths as originally estimated.
Weekly data to analyse short-term effects of temperatures
“In general, we do not find models based on monthly aggregated data useful for estimating the short-term effects of ambient temperatures,” explains Ballester. “However, models based on weekly data do offer sufficient precision in mortality estimates to be useful in real-time practice in epidemiological surveillance and to inform public policies such as, for example, the activation of emergency plans for reducing the impact of heat waves and cold spells.”
It is an advantage in this area of research to be able to use weekly data since investigators often encounter bureaucratic obstacles that make it difficult or impossible to design large-scale epidemiological studies based on daily data. According to Ballester, when daily data is not available, the use of weekly data, which are easily accessible for Europe in real time, is a solution that can offer “a good approximation of the estimates obtained using the daily data model.”
A new intervention for men with urinary problems trialled across GP practices has shown a sustained reduction in symptoms. Findings from the University of Bristol-led Treating Urinary Symptoms in Men in Primary Healthcare (TRIUMPH) study, involving over 1000 participants and 30 GP practices, have been published in the BMJ. The study was funded by the National Institute for Health and Care Research (NIHR).
The severity and prevalence of lower urinary tract symptoms [LUTS] in men increases with age (up to 30% in men over 65 years), with greater numbers likely to be affected as the population ages. Symptoms can have a substantial impact on quality of life but can also influenced by lifestyle factors.
Current therapies recommended by NICE (National Institute for Health and Care Excellence) include bladder training, controlling fluid intake and lifestyle advice. However, there is a lack of evidence on their effectiveness, and provision by GP practices varies.
Bristol Medical School researchers sought to trial whether a new intervention, comprising a healthcare professional consultation and an information booklet providing conservative and lifestyle guidance, could be more effective than usual care.
Study findings
The team recruited 1077 adult men, each suffering with troublesome urinary tract symptoms between June 2018 and August 2019. Participants were split with 524 in the intervention arm and 553 in the usual care arm. Participants in the intervention arm were directed to relevant sections of the booklet by general practice nurses/healthcare assistants or research nurses following urinary symptom assessment, with subsequent contacts over 12 weeks to ask how the participant was managing.
Overall, the study’s findings showed a range of troublesome urinary tract symptoms improved over 12 months in a population of men with moderate symptom severity, using a standardised booklet and manualised approach to symptom management. Analyses of symptoms in each trial arm found the intervention achieved a greater reduction in symptoms than usual care, and that the difference was maintained in the longer term
Consultant Urologist, Professor Marcus Drake, the study’s Chief Investigator, said: “The assessment of male lower urinary tract symptoms and use of conservative treatments in primary care are inconsistent. Until now, there was limited evidence that conservative treatments are effective, despite their recommendation in national guidelines. The TRIUMPH study aimed to address this need in primary care.
“Implementation of this intervention as management in primary care, has the potential to improve care and reduce drug prescriptions. Our study also found the intervention can be delivered by practice nurses or healthcare assistants rather than GPs.”
Dr Jon Rees, GP Partner at Tyntesfield Medical Group, and Chair of the Primary Care Urology Society, added: “In primary care we have often traditionally relied upon pharmaceutical management for men with bothersome urinary symptoms – the TRIUMPH study emphasises the importance of discussing conservative measures with all of these patients – for some men, this will be all that is required, for others these measures can act as an adjunct to any medication prescribed.
“Many men will prefer to avoid long-term medication, so an understanding of the potential benefits of the interventions used in the study is a vital part of the toolkit for any clinician managing these patients.”
Professor Matthew Ridd, at University of Bristol, said: “This is a ‘bread-and-butter’ problem seen by GPs every day and it is great to now have evidence for something other than tablets. It has the additional advantage that it can be done by a practice nurse, freeing up GP time.”
Eating more ultra-processed foods (UPFs) may be associated with a higher risk of developing cancers of the upper aerodigestive tract (ie, the mouth, throat and oesophagus), according to a new study in the European Journal of Nutrition. The authors of this study, led by the University of Bristol and the International Agency for Research on Cancer (IARC), say that obesity associated with the consumption of UPFs may not be the only factor to blame.
Several studies have identified an association between UPF consumption and cancer, including a recent study which looked at the association between UPFs and 34 different cancers in the largest cohort study in Europe, the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which followed 450 111 adults who for approximately 14 years.
As more evidence emerges about the associations between eating UPFs and adverse health outcomes, researchers from the Bristol Medical School and IARC wanted to explore this further.
Since many UPFs have an unhealthy nutritional profile, the team sought to establish whether the association between UPF consumption and head and neck cancer and oesophageal adenocarcinoma in EPIC could be explained by an increase in body fat.
Results from the team’s analyses showed that eating 10% more UPFs is associated with a 23% higher risk of head and neck cancer and a 24% higher risk of oesophageal adenocarcinoma in EPIC.
Increased body fat only explained a small proportion of the statistical association between UPF consumption and the risk of these upper-aerodigestive tract cancers.
Fernanda Morales-Berstein, a Wellcome Trust PhD student at the University of Bristol and the study’s lead author, explained: “UPFs have been associated with excess weight and increased body fat in several observational studies. This makes sense, as they are generally tasty, convenient and cheap, favouring the consumption of large portions and an excessive number of calories. However, it was interesting that in our study the link between eating UPFs and upper-aerodigestive tract cancer didn’t seem to be greatly explained by body mass index and waist-to-hip ratio.”
The authors suggest that other mechanisms could explain the association.
For example, additives including emulsifiers and artificial sweeteners which have been previously associated with disease risk, and contaminants from food packaging and the manufacturing process, may partly explain the link between UPF consumption and upper-aerodigestive tract cancer in this study.
Fernanda Morales-Berstein and colleagues did caution that the associations between UPF consumption and upper-aerodigestive tract cancers found in the study could be affected by certain types of bias.
This would explain why they found evidence of an association between higher UPF consumption and increased risk of accidental deaths, which is highly unlikely to be causal.
Inge Huybrechts, Team head of the Lifestyle exposures and interventions team at IARC, added: “Cohorts with long-term dietary follow-up intake assessments, considering also contemporary consumption habits, are needed to replicate these study’s findings, as the EPIC dietary data were collected in the 1990s, when the consumption of UPFs was still relatively low. As such associations may potentially be stronger in cohorts including recent dietary follow-up assessments.”
Further research is needed to identify other mechanisms, such as food additives and contaminants, which may explain the links observed.
However, based on the finding that body fat did not greatly explain the link between UPF consumption and upper-aerodigestive tract cancer risk in this study, Fernanda Morales-Berstein, suggested: “Focussing solely on weight loss treatment, such as semaglutide, is unlikely to greatly contribute to the prevention of upper-aerodigestive tract cancers related to eating UPFs.”
