Losing weight via lifestyle adjustments can deliver significant long-term health benefits, without the need for surgery or anti-obesity drugs. Alongside preventing diabetes, it can help ward off chronic conditions including arterial and pulmonary diseases as well as cancers.
A University of Helsinki study tracked 23 000 individuals from Finland and the UK, aged 30 to 50 at the outset, over a period of 12 to 35 years. Health benefits were found in overweight men and women who lost an average of 6.5% of their body weight in early middle age and maintained it throughout the 12–35-year follow-up period. Weight maintenance is crucial.
“The benefits of lifestyle-based weight management are widely discussed even though studies have found it surprisingly difficult to demonstrate health benefits beyond the prevention of diabetes,” notes Professor Timo Strandberg.
The study he led is now filling this gap.
“I hope the findings will inspire people to see that lifestyle changes can lead to major health improvements and a longer life. This is particularly important today as more people are overweight than when the collection of our research data began 35 years ago.”
The study also supports the view that, for optimal health, a lifelong body mass index (BMI) under 25 is ideal.
The study was published in JAMA Network Open, the open-access journal of the American Medical Association.
People with an autism diagnosis are at a higher risk of developing Parkinson’s disease early in life, according to a large-scale study from Karolinska Institutet. The researchers believe that the two conditions can share underlying biological mechanisms.
The study, published in JAMA Neurology, is based on registry data from over two million people born in Sweden between 1974 and 1999 who were followed from the age of 20 up to the end of 2022.
The researchers interrogated a possible connection between the neuropsychiatric diagnosis Autism Spectrum Disorder (ASD), which affects an individual’s thought processes, behaviour and interpersonal communication, and early-onset Parkinson’s disease, a condition that affects locomotion and movement.
Possible dopamine involvment
The results show that people with an autism diagnosis were four times more likely to develop Parkinson’s disease than people without such a diagnosis, a correlation that remained when controlling for socioeconomic status, a genetic predisposition for mental illness or Parkinson’s disease and other such factors.
“This indicates that there can be shared biological drivers behind ASD and Parkinson’s disease,” says first author Weiyao Yin at the Department of Medical Epidemiology and Biostatistics. “One hypothesis is that the brain’s dopamine system is affected in both cases, since the neurotransmitter dopamine plays an important part in social behaviour and motion control.”
It is well-known that dopamine-producing neurons are degraded in Parkinson’s disease. Previous studies have also shown that dopamine is possibly implicated in autism, but more research needs to be done to confirm this.
“We hope that our results will eventually help to bring greater clarity to the underlying causes of both ASD and Parkinson’s disease,” says Dr Yin.
Medical checkups are vital
Depression and the use of antidepressants are common in people with autism, as are antipsychotic drugs, which are known for being able to cause Parkinson’s-like symptoms. When the researchers adjusted for these factors, the correlation between ASD and the later development of Parkinson’s disease was less salient, but the risk was still double.
The researchers point out that they only analysed early-onset Parkinson’s disease before the age of 50 and that the average age of participants by the end of the study was 34. The incidence of Parkinson’s disease was therefore very low. Future studies will need to examine if the elevated risk persists into older age.
“The healthcare services need to keep people with ASD – a vulnerable group with high co-morbidity and a high use of psychotropics – under long-term observation,” says last author Sven Sandin, statistician and epidemiologist at the Department of Medical Epidemiology and Biostatistics. “At the same time, it’s important to remember that a Parkinson’s diagnosis before the age of 50 is very rare, including for people with autism.”
Researchers have discovered how an ion channel in the brain’s neurons has a kind of ‘molecular memory’, which contributes to the formation and preservation of lifelong memories. The researchers have identified a specific part of the ion channel at which new drugs for certain genetic diseases could be targeted.
Learning from past experiences and forming memories depend on the reshaping of connections between neurons in the brain. Synapses are strengthened or weakened throughout life in such a way that the brain is, in a certain sense, constantly being reshaped at the cellular level. This phenomenon is called synaptic plasticity.
There are several processes contributing to synaptic plasticity in the nervous system. One of these processes has to do with a type of molecules called calcium ion channels, which have long been of interest to researchers at Linköping University, LiU.
“I want to uncover the secret lives of these ion channel molecules. Calcium ion channels have very important functions in the body – by opening and closing, they regulate, among other things, nerve-to-nerve signalling. But beyond that, these molecules also have a kind of memory of their own, and can remember previous nerve signals,” says Antonios Pantazis, associate professor at the Department of Biomedical and Clinical Sciences at LiU, who led the study published in Nature Communications.
How can a molecule remember?
The focus of this study was on a specific type of ion channel, the CaV2.1 channel, which is the most common calcium ion channel in the brain. The ion channel is located at the synapse, at the very end of the neuron. When an electrical signal passes through the neuron, the ion channel open, setting in motion a process leading to neurotransmitter being released towards the receiving neuron in the synapse. In this way, CaV2.1 channels are the gatekeepers of synaptic, neuron-to-neuron communication.
Prolonged electrical activity reduces the number of CaV2.1 channels that can open, resulting in less transmitter release, so the receiving neuron receives a weaker message. It is as if the channels can ‘remember’ previous signalling, and in doing so, make themselves unavailable to open by subsequent signals. How this works at the molecular level has been unknown to scientists until now.
The Linköping researchers have now discovered a mechanism for how the ion channel can ‘remember’. The channel is a large molecule made up of several interconnected parts, which can move relative to each other in response to electrical signals. They discovered that the ion channel can take almost 200 different shapes depending on the strength and duration of an electrical signal; it is a very complex molecular machine.
“We believe that during sustained electrical nerve signalling, an important part of the molecule disconnects from the channel gate, similar to the way the clutch in a car breaks the connection between the engine and the wheels. The ion channel can then no longer be opened. When hundreds of signals occur over long enough time, they can convert most channels into this ‘declutched memory state’ for several seconds,” says Antonios Pantazis.
Target for future drugs
If the ion channel can ‘remember’ for just a few seconds, how does it contribute to lifelong learning? This type of collective memory in the ion channels can accumulate over time and reduce the communication between two neurons. This then leads to changes in the receiving neuron, lasting for hours or days. Eventually, it results in much longer-lived changes in the brain, such as the elimination of weakened synapses.
“In this way, a ‘memory’ that lasts for a few seconds in a single molecule can make a small contribution to a person’s memory that lasts for a lifetime,” says Antonios Pantazis.
Increased knowledge of how these calcium ion channels work can in the long term contribute to the treatment of certain diseases. There are many variants of the gene that produces the CaV2.1 channel, CACNA1A, that are linked to rare but serious neurological diseases, that often run in families. To develop drugs against these, it helps to know which part of the large ion channel you want to affect and in what way its activity should be changed.
“Our work pinpoints which part of the protein should be targeted when developing new drugs,” says Antonios Pantazis.
A real-world study based on information from an electronic health records–derived database reveals limited benefits of adding bevacizumab to first-line chemotherapy for patients with ovarian cancer, consistent with previous clinical trials. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.
Bevacizumab is a monoclonal antibody against vascular endothelial growth factor A that acts to inhibit malignant cell growth and blood vessel formation. It’s approved as a treatment for various types of cancer. In clinical trials of patients with ovarian cancer, adding bevacizumab to first-line chemotherapy did not prolong overall survival compared with chemotherapy alone, but this treatment strategy did improve overall survival in analyses limited to patients with high-risk prognostic factors—such as those with advanced disease and those who had residual cancer present after surgery. A final long-term analysis did not find an overall survival benefit associated with bevacizumab in the full patient cohort.
To investigate whether these findings also hold true in real-world clinical practice, researchers examined the electronic health records of 1,752 patients with stage III or IV ovarian cancer who initiated chemotherapy with or without bevacizumab in 2017–2023 and were followed for a median time of 1.5 years.
Among patients with high-risk prognostic factors, the median time to next treatment was significantly longer for those receiving chemotherapy plus bevacizumab compared with those receiving chemotherapy alone: 13.6 versus 11.7 months. (Time to next treatment is used to assess the duration of clinical benefit by measuring the time between initiating a treatment and starting the next line of therapy). In these patients, there was also a trend towards longer median overall survival for the combination therapy: 31.1 versus 27.4 months. Among patients without high-risk prognostic factors, outcomes did not differ with the addition of bevacizumab. Benefits therefore seemed limited to special subpopulations, mirroring the findings from clinical trials.
“Our results were similar to results from clinical trials,” said lead author Linda R. Duska, MD, MPH, of the University of Virginia School of Medicine. “Our findings suggest that clinicians should consider a patient’s risk factors before using bevacizumab with first-line chemotherapy in the treatment of advanced ovarian cancer.”
Despite clinicians recommending that many patients with diabetes take statins, nearly one in five opt to delay treatment. In a new study, researchers from Mass General Brigham found that patients who started statin therapy right away reduced the rate of heart attack and stroke by one third compared to those who chose to delay taking the medication. The results, which can help guide decision-making conversations between clinicians and their patients, are published in the Journal of the American Heart Association.
“I see patients with diabetes on a regular basis, and I recommend statin therapy to everyone who is eligible,” said senior author Alexander Turchin, MD, MS, of the Division of Endocrinology at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system. “Some people refuse because they want to first try lifestyle interventions or other drugs. But other interventions are not as effective at lowering cholesterol as starting statin therapy as soon as possible. Time is of the essence for your heart and brain health.”
Heart attacks and strokes remain the leading cause of complications and mortality for patients with diabetes. Statin therapy reduces risk of these cardiovascular events by preventing plaque buildup in the blood vessels.
The researchers used an artificial intelligence method called Natural Language Processing to gather data from the electronic health records of 7239 patients at Mass General Brigham who ultimately started statin therapy during the nearly 20-year study period. The median patient age was 55, with 51% being women, 57% white, and a median HbA1c of 6.9.
Nearly one-fifth (17.7%) of the patients in the study declined statin therapy when it was first recommended by their clinicians, then later accepted the therapy (after a median of 1.5 years) upon repeated recommendation by their clinician. Of those who delayed, 8.5% had a heart attack or stroke. But for patients who started statins immediately, the rate of those cardiovascular events was just 6.4%.
“Clinicians should recognize the increased cardiovascular risk associated with delaying statin therapy for patients with diabetes and use this information to guide shared decision-making conversations with their patients,” said Turchin.
People with a certain heart valve abnormality, mitral annular disjunction, are at increased risk of severe heart rhythm disorders, even after successful valve surgery. This is according to a new study from Karolinska Institutet and Karolinska University Hospital in Sweden published in the European Heart Journal. The condition is more common in women and younger patients with valve disorder and can, in the worst case, lead to sudden cardiac arrest.
Mitral annular disjunction, MAD, is a heart abnormality in which the mitral valve attachment ‘slides’. In recent years, the condition has been linked to an increased risk of severe cardiac arrhythmias. Until now, it has not been known whether the risk of arrhythmias disappears if MAD is surgically corrected.
MAD is often associated with a heart disease called mitral valve prolapse, which affects 2.5% of the population and causes one of the heart’s valves to leak. This can lead to blood being pumped backwards in the heart, causing heart failure and arrhythmias. The disease can cause symptoms such as shortness of breath and palpitations.
Followed patients after surgery
In the current study, researchers at Karolinska Institutet investigated the risk of cardiac arrhythmias in 599 patients with mitral valve prolapse who underwent heart surgery at Karolinska University Hospital between 2010 and 2022. Sixteen percent of the patients also had the cardiac abnormality MAD.
“We have been able to show that people with MAD have a significantly higher risk of suffering from ventricular arrhythmias, a dangerous type of heart rhythm disorder that in the worst case can lead to cardiac arrest in a subset of patients,” says Bahira Shahim, associate professor at the Department of Medicine, Solna, Karolinska Institutet and cardiologist at Karolinska University Hospital
People with MAD were more likely to be female and were on average eight years younger than those without MAD. They also had more extensive mitral valve disease. Although the surgery was successful in correcting MAD, these patients had more than three times the risk of ventricular arrhythmias during five years of follow-up compared to patients without preoperative MAD.
“Our results show that it is important to closely monitor patients with this condition, even after a successful operation,” says Bahira Shahim.
Investigating new hypotheses
The study has led to new hypotheses that the researchers are now investigating further. One hypothesis is that MAD causes permanent changes in the heart muscle over time. Another is that MAD is a sign of an underlying heart muscle disease. The researchers are now continuing to study scarring in the heart using MRI (magnetic resonance imaging) and analyse tissue samples from the heart muscle.
For 30% of people with major depressive disorder (MDD), antidepressants don’t work. When infused at a low dose, ketamine shows remarkable efficacy as a rapidly acting antidepressant, with effects observed within hours even in patients who have been resistant to other antidepressant treatments. One drawback is that consistent infusions of ketamine are needed to maintain symptoms at bay, which could result in side effects, such as dissociative behaviours and the possibility of addiction, and stopping treatment can result in relapse.
In a new study published in Science, Lisa Monteggia’s and Ege Kavalali’s labs show that it is feasible to substantially extend the efficacy of a single dose of ketamine from its current duration of up to a week to a longer period of up to two months.
“The premise of this study, which was led by Zhenzhong Ma, a fantastic research assistant professor, was based on a testable mechanistic model that we developed that accounts for ketamine’s rapid antidepressant action,” Monteggia said.
Previously, researchers in the field had determined that ketamine’s antidepressant effect requires the activation of a key signalling pathway called ERK, but only ketamine’s long-term effects – not its rapid effects – are abolished when ERK is inhibited. As a fast-acting antidepressant, ketamine relies on ERK-dependent synaptic plasticity to produce its rapid behavioural effects. Ma and colleagues hypothesised that they could maintain ketamine’s effects for longer periods by enhancing ERK activity.
In the recent paper, Ma discovered that ketamine’s antidepressant effects could be sustained for up to two months by using a drug called BCI, which inhibits a protein phosphatase and results in increased ERK activity. By inhibiting the phosphatase, the authors retained ERK’s activity and augmented the synaptic plasticity that drives ketamine’s prolonged antidepressant effects.
lthough the use of BCI makes the application of these results to the clinic difficult, Monteggia said that the results provide a proof of principle that ketamine’s antidepressant action can be sustained by targeting intracellular signaling. She and Kavalali, the William Stokes Professor of Experimental Therapeutics and the chair of the Department of Pharmacology, have worked on the project since its inception and hope that it will foster other studies looking to identify specific molecules to enhance and sustain the action of a single dose of ketamine.
Ultimately, this work will be a stepping stone toward improving MDD patients’ lives by reducing the burden of treatment.
A newly published study from the University of Waterloo suggests that increasing the ratio of dietary potassium to sodium intake may be more effective for lowering blood pressure than simply reducing sodium intake.
“Usually, when we have high blood pressure, we are advised to eat less salt,” said Dr Anita Layton, professor at the University of Waterloo. “Our research suggests that adding more potassium-rich foods to your diet, such as bananas or broccoli, might have a greater positive impact on your blood pressure than just cutting sodium.”
Potassium and sodium are both electrolytes – substances that help the body send electrical signals to contract muscles, affect the amount of water in your body and perform other essential functions.
“Early humans ate lots of fruits and vegetables, and as a result, our body’s regulatory systems may have evolved to work best with a high potassium, low sodium diet,” said Melissa Stadt, a PhD candidate in Waterloo’s Department of Applied Mathematics and the lead author of the study.
“Today, western diets tend to be much higher in sodium and lower in potassium. That may explain why high blood pressure is found mainly in industrialised societies, not in isolated societies.”
While previous research found that increasing potassium intake can help control blood pressure, the researchers developed a mathematical model that successfully identifies how the ratio of potassium to sodium impacts the body.
The model also identifies how sex differences affect the relationship between potassium and blood pressure. The study found that men develop high blood pressure more easily than pre-menopausal women, but men are also more likely to respond positively to an increased ratio of potassium to sodium.
The researchers emphasise that mathematical models like the one used in this study allow these kinds of experiments to identify how different factors impact the body quickly, cheaply, and ethically.
Findings in the Journal of Investigative Dermatology reinforce the role of weight management in psoriasis care
Source: Pixabay CC0
Researchers have found that central body fat, especially around the abdomen, is more strongly linked to psoriasis risk than total body fat, particularly in women. This link between central fat and psoriasis remained consistent regardless of genetic predisposition, indicating that abdominal fat is an independent risk factor. The study in the Journal of Investigative Dermatology, published by Elsevier, provides insights that could help improve early risk prediction and guide personalised prevention strategies.
While it is well established that increasing levels of body fat raise the risk of developing psoriasis, the impact of specific fat distribution and genetics remains unclear.
Researchers of the current study analysed data from over 330 000 participants with White British ancestry in the UK Biobank, including more than 9000 people with psoriasis. They examined 25 different measures of body fat using both traditional methods and advanced imaging techniques, assessing how each was associated with psoriasis.
Lead investigator Ravi Ramessur, MD, St John’s Institute of Dermatology, King’s College London, explains, “Our research shows that where fat is stored in the body matters when it comes to psoriasis risk. Central fat – especially around the waist – seems to play a key role. This has important implications for how we identify individuals who may be more likely to develop psoriasis or experience more severe disease, and how we approach prevention and treatment strategies.”
Senior author Catherine H. Smith, MD, also at King’s College London, adds, “As rates of obesity continue to rise globally, understanding how different patterns of body fat influence chronic inflammatory conditions such as psoriasis is important. Our findings suggest that central body fat contributes to psoriasis risk irrespective of genetic predisposition and reinforces the importance of measuring waist circumference and pro-active healthy weight strategies in psoriasis care.”
Because this study only included individuals of White British ancestry from the UK Biobank, the generalisability of these findings to more diverse populations may be limited. Future studies incorporating datasets with dermatologist-confirmed diagnoses and broader ethnic representation will be important to further validate these associations and refine risk stratification approaches.
Dr Ramessur notes, “We were surprised by how consistently strong the association was across different central fat measures and how much stronger the effect was in women. The observed links between central body fat and psoriasis suggest that there may be underlying biological mechanisms contributing to the disease that are not yet fully understood and which warrant further investigation.”
In an accompanying editorial Joel M. Gelfand, MD, MSCE, FAAD, at the University of Pennsylvania Perelman School of Medicine, points to the potential of incretin therapy for psoriatic disease. Incretins are gut-derived hormones, principally glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), that regulate glucose, digestion, and appetite, and are approved for treatment of diabetes, obesity, and obesity-associated obstructive sleep apnoea.
Dr Gelfand comments, “The strong relationship between psoriasis and obesity and the emerging promise of glucagon-like peptide-1 receptor agonists (GLP1RA) for reducing psoriasis morbidity is a call to action for large scale clinical trials of GLP1RA monotherapy for treatment of psoriasis. Our current paradigm of just focusing on the skin and joint manifestations when treating psoriasis is outdated in the context of our evolving understanding of the tight relationship of psoriasis, obesity, and cardiometabolic disease.“
When a physician says a procedure is “rarely risky,” what does that really mean? Although terms like “common” and “unlikely” may sound descriptive enough, experts in medical decision-making suggest that leaving out numbers may be misleading for patients.
In a paper published in the Journal of General Internal Medicine, a team of researchers and clinicians explained that patients often overestimate risk estimates, like possible side effects or medical conditions, when given only verbal descriptions. They encourage doctors not to shy away from including numbers, offering a list of five science-backed tricks on how to make those numbers count.
“One of the purposes of this paper is to help physicians figure out how to communicate numeric information about risks so that patients can understand and use them to make better choices, take charge of their health and be healthier long term,” said Ellen Peters, a professor at the University of Oregon School of Journalism and Communication and Department of Psychology.
Peters draws on two decades of research on how patients understand numbers and make decisions. She said it’s a common concern that patients won’t understand numerical information, as about a third of American adults have limited numerical skills.
But she’s found that people often prefer getting numbers. According to her previous studies, people rated messages more trustworthy and their messenger more expert when they provided data.
In collaboration with physicians Paul K.J. Han of the National Cancer Institute and Clara N. Lee at the University of North Carolina, Peters hopes their recommended strategies will facilitate stronger shared decision-making between patients and their health care providers.
“There’s a whole raft of strategies that you can use, some of which might be more appropriate in one situation versus the other,” she said. “But by choosing one of them, you can help people use statistics more than they typically would. Otherwise, numbers are just abstract and meaningless.”
Communicate with numbers, not just words
Physicians often default to verbal terms, knowing that a sizable portion of American adults struggle with simple numeric concepts, Peters said. But research has shown that people better understand risks and react appropriately when numbers are discussed alongside verbal descriptions.
“When you present numeric evidence, like the likelihood of side effects for a prescription medication, what ends up happening is that it helps correct people’s original expectation,” Peters said. “They’re much less likely to overestimate the risk and are more likely to take on a physician’s recommendations.”
Do: “Headache is a common side effect and occurs in 7 percent of people.”
Don’t: “Headache is a common side effect.”
Make numbers more manageable
When patients are overwhelmed by medical information, they may rely on mental problem-solving techniques, like gut feelings, pre-existing beliefs and anecdotes they’ve heard from others. To avoid cognitive overload, Peters suggests limiting information to what’s important. If a disease has three intervention options but a patient has a condition that eliminates one as a viable option, she advises not to mention that option.
The authors also suggest clinicians do the math for their patients. For example, they can calculate the risk of birth control based on the number of years the patient expects to use it instead of the annual risk.
Do: Highlight only the key facts and tailor information to the patient’s situation.
Don’t: Provide information that isn’t relevant to a specific patient.
Provide context to statistics
Numbers said alone can be meaningless, so Peters suggests using evaluative labels, like “a 6 percent risk is generally considered poor,” or comparisons to indicate whether it’s high or low risk.
Do: “Ninety-three percent of patients survive with treatment A compared to 99 percent who survive with treatment B.”
Don’t: “Ninety-three percent of patients survive with treatment A.”
Acknowledge uncertainty
Risk information is an estimate. In some cases, being upfront about the uncertainty of whether a patient will be a part of the 40 percent side or the 60 percent side of a risk, for example, can help convey to patients how seriously they should take it.
Do: “Estimates of the chance of something happening are only a best guess based on the scientific knowledge we have right now. We do not know your personal real risk because of things about you that have never been studied and we don’t yet understand.”
Don’t: Present numeric risk information as unerringly precise and correct.
Test your communication through the teach-back technique
Experts tend to overestimate how much other people know and how clearly they’ve communicated. So doctors can use the teach-back technique, Peters said, in which they ask their patient to repeat what they understood and found important. The physician can then insert more information to either correct what’s wrong or remind them of something.
Do: “This can be hard to understand. I’d like to make sure I’ve explained it clearly. Could you tell me how you understand the pros and cons of taking drug X?”
Don’t: “What questions do you have?”
Such strategies also can be used by patients to advocate for themselves, Peters said. If told about a possible side effect, they can ask how statistically likely it is. If given too many possible side effects or treatments, they can request to simplify the information to the most important facts.
Peters plans to conduct a series of studies to test which of the five strategies is the most effective. She also is interested in how storytelling and anecdotes affect patient decision-making.
“Physicians have very limited time in any one appointment and are often faced with a similar patient over and over,” Peters said. “What that means is, if you’re trying to help them better communicate with patients, you’ve got to provide things that are fast and scripted so that everyone can make informed decisions about their care.”
