Researchers at Stockholm University have discovered that sleep affects how old you feel, with important health implications. The study is published in the scientific journal Proceedings of the Royal Society B.
Feeling young is not just a matter of perception: it is actually related to objective health outcomes. Previous studies have shown that feeling younger than one’s actual age is associated with longer, healthier lives. There is even support for subjective age to predict actual brain age, with those feeling younger having younger brains.
“Given that sleep is essential for brain function and overall well-being, we decided to test whether sleep holds any secrets to preserving a youthful sense of age,” says Leonie Balter, researcher at the Department of Psychology, Stockholm University.
In the first study, 429 individuals aged 18 to 70 were asked how old they felt, how many days in the past month they had not gotten enough sleep, and how sleepy they were.
It turned out that for each night with insufficient sleep in the past month, participants felt on average 0.23 years older.
In a second study, the researchers tested whether it was indeed the lack of sleep causing participants to feel older. They conducted an experimental sleep restriction study involving 186 participants aged 18 to 46. Participants restricted their sleep to four hours a night for two nights and another time slept sufficiently for two nights, with nine hours in bed each night.
After sleep restriction, participants felt on average 4.4 years older compared to when having enjoyed sufficient sleep.
The effects of sleep on subjective age appeared to be related to how sleepy they felt. Feeling extremely alert was related to feeling 4 years younger than one’s actual age, while extreme sleepiness was related to feeling 6 years older than one’s actual age.
“This means that going from feeling alert to sleepy added a striking 10 years to how old one felt,” says Leonie Balter, and states that the implications for our daily lives are clear:
“Safeguarding our sleep is crucial for maintaining a youthful feeling. This, in turn, may promote a more active lifestyle and encourage behaviours that promote health, as both feeling young and alert are important for our motivation to be active.”
Scientists have uncovered a key step in the wound healing process that becomes disabled in diseases like diabetes and ageing. Importantly, the research published in Nature reveals a molecule involved in the healing of tissues that leads to a drastic acceleration of wound closure, up to 2.5 times faster, and 1.6 times more muscle regeneration.
The immune system has a critical role in orchestrating tissue healing. As a result, regenerative strategies that control immune components have proved effective. This is particularly relevant when immune dysregulation that results from conditions such as diabetes or advanced age impairs tissue healing following injury. Nociceptive sensory neurons have a crucial role as immunoregulators and exert both protective and harmful effects depending on the context. However, how neuro–immune interactions affect tissue repair and regeneration following acute injury was unclear.
Lead researcher, Associate Professor Mikaël Martino, from Monash University’s Australian Regenerative Medicine Institute (ARMI) in Melbourne, Australia, said the discovery “could transform regenerative medicine, because it sheds light on the crucial role of sensory neurons in orchestrating the repair and regeneration of tissues, offering promising implications for improving patient outcomes.”
The cost of managing poorly healing wounds costs around $250 billion a year.
“In adults with diabetes alone – where poor blood flow can lead to quickly worsening wounds that are often very slow or impossible to heal – the lifetime risk of developing a diabetic foot ulcer (DFU), the most common diabetes-related wound, is 20 to 35 per cent and this number is rising with increased longevity and medical complexity of people with diabetes,” co-lead author, ARMI’s Dr Yen-Zhen Lu said.
Nociceptive sensory neurons, also called nociceptors, are the nerves in our body that sense pain.
These neurons alert us to potentially damaging stimuli in tissues by detecting dangers like tissue damage, inflammation, extremes in temperature, and pressure.
The researchers discovered that, during the healing process, sensory neuron endings grow into injured skin and muscle tissues, communicating with immune cells through a neuropeptide called calcitonin gene-related peptide (CGRP).
“Remarkably, this neuropeptide acts on immune cells to control them, facilitating tissue healing after injury,” Associate Professor Martino said.
Importantly they found that sensory neurons are crucial to the dissemination of CGRP because they showed that the selective removal of sensory neurons in mice reduce CGRP and significantly impairs skin wound healing and muscle regeneration following injury.
When the scientists administered an engineered version of CGRP to mice with neuropathy similar to that seen in diabetic patients, it led to rapid wound healing and muscle regeneration.
According to Associate Professor Martino, these findings hold significant promise for regenerative medicine, particularly for the treatment of poorly-healing tissues and chronic wounds.
“By harnessing neuro-immune interactions, the team aims to develop innovative therapies that address one of the root causes of impaired tissue healing, offering hope to millions,” he said.
“This study has uncovered significant implications for advancing our understanding of the tissue healing process after acute injury. Harnessing the potential of this neuro-immuno-regenerative axis opens new avenues for effective therapies, whether as standalone treatments or in combination with existing therapeutic approaches. “
Photo by Inzmam Khan: https://www.pexels.com/photo/man-in-black-shirt-and-gray-denim-pants-sitting-on-gray-padded-bench-1134204/
Antipsychotic medications for serious mental illness like schizophrenia or bipolar disorder often causes metabolic side effects such as insulin resistance and obesity, leading some patients to discontinue the treatment.
Now, a pilot study led by Stanford Medicine researchers has found that a ketogenic diet not only restores metabolic health in these patients as they continue their medications, but it further improves their psychiatric conditions. The results, published in Psychiatry Research, suggest that a dietary intervention can be a powerful aid in treating mental illness.
“It’s very promising and very encouraging that you can take back control of your illness in some way, aside from the usual standard of care,” said Shebani Sethi, MD, associate professor of psychiatry and behavioral sciences and the first author of the new paper.
The senior author of the paper is Laura Saslow, PhD, associate professor of health behavior and biological sciences at the University of Michigan.
Making the connection
Sethi, who is board certified in obesity and psychiatry, remembers when she first noticed the connection. As a medical student working in an obesity clinic, she saw a patient with treatment-resistant schizophrenia whose auditory hallucinations quieted on a ketogenic diet.
That prompted her to dig into the medical literature. There were only a few, decades-old case reports on using the ketogenic diet to treat schizophrenia, but there was a long track record of success in using ketogenic diets to treat epileptic seizures.
“The ketogenic diet has been proven to be effective for treatment-resistant epileptic seizures by reducing the excitability of neurons in the brain,” Sethi said. “We thought it would be worth exploring this treatment in psychiatric conditions.”
A few years later, Sethi coined the term metabolic psychiatry, a new field that approaches mental health from an energy conversion perspective.
Meat and vegetables
In the four-month pilot trial, Sethi’s team followed 21 adult participants who were diagnosed with schizophrenia or bipolar disorder, taking antipsychotic medications, and had a metabolic abnormality – such as weight gain, insulin resistance, hypertriglyceridaemia, dyslipidaemia or impaired glucose tolerance. The participants were instructed to follow a ketogenic diet, with approximately 10% of the calories from carbohydrates, 30% from protein and 60% from fat. They were not told to count calories.
“The focus of eating is on whole non-processed foods including protein and non-starchy vegetables, and not restricting fats,” said Sethi, who shared keto-friendly meal ideas with the participants. They were also given keto cookbooks and access to a health coach.
The research team tracked how well the participants followed the diet through weekly measures of blood ketone levels, which are produced when the body breaks down fat instead of glucose for energy. By the end of the trial, 14 patients had been fully adherent, six were semi-adherent and only one was non-adherent.
Physical and mental improvement
The participants underwent a variety of psychiatric and metabolic assessments throughout the trial.
Before the trial, 29% of the participants met the criteria for metabolic syndrome, defined as having at least three of five conditions: abdominal obesity, elevated triglycerides, low HDL cholesterol, elevated blood pressure and elevated fasting glucose levels. After four months on a ketogenic diet, none of the participants had metabolic syndrome.
On average, the participants lost 10% of their body weight; reduced their waist circumference by 11% percent; and had lower blood pressure, body mass index, triglycerides, blood sugar levels and insulin resistance.
“We’re seeing huge changes,” Sethi said. “Even if you’re on antipsychotic drugs, we can still reverse the obesity, the metabolic syndrome, the insulin resistance. I think that’s very encouraging for patients.”
The psychiatric benefits were also striking. On average, the participants improved 31% on a psychiatrist rating of mental illness known as the clinical global impressions scale, with three-quarters of the group showing clinically meaningful improvement. Overall, the participants also reported better sleep and greater life satisfaction.
“The participants reported improvements in their energy, sleep, mood and quality of life,” Sethi said. “They feel healthier and more hopeful.”
The researchers were impressed that most of the participants stuck with the diet. “We saw more benefit with the adherent group compared with the semi-adherent group, indicating a potential dose-response relationship,” Sethi said.
Alternative fuel for the brain
There is increasing evidence that psychiatric diseases such as schizophrenia and bipolar disorder stem from metabolic deficits in the brain, which affect the excitability of neurons, Sethi said. The researchers hypothesise that just as a ketogenic diet improves the rest of the body’s metabolism, it also improves the brain’s metabolism.
“Anything that improves metabolic health in general is probably going to improve brain health anyway,” Sethi said. “But the ketogenic diet can provide ketones as an alternative fuel to glucose for a brain with energy dysfunction.”
Likely there are multiple mechanisms at work, she added, and the main purpose of the small pilot trial is to help researchers detect signals that will guide the design of larger, more robust studies.
As a physician, Sethi cares for many patients with both serious mental illness and obesity or metabolic syndrome, but few studies have focused on this undertreated population. She is founder and director of the metabolic psychiatry clinic at Stanford Medicine.
“Many of my patients suffer from both illnesses, so my desire was to see if metabolic interventions could help them,” she said. “They are seeking more help. They are looking to just feel better.”
Replacing sugar with artificial and natural sweeteners in foods has been the subject of a great deal of controversy, due to conflicting reports about their potential to increase appetite. But according to a significant new study published in eBioMedicine, it does not in fact make people hungrier as is often held – and also helps to reduce blood sugar levels.
Previous studies into whether sugar replacement with sweeteners increase appetite have been carried out but did not provide robust evidence. But the researchers say that their study, which meets the gold standard level of proof in scientific investigation, provides very strong evidence that sweeteners and sweetness enhancers do not negatively impact appetite and are beneficial for reducing sugar intake.
The double blind randomised controlled trial found that consuming food containing sweeteners produced a similar reduction in appetite sensations and appetite-related hormone responses as sugary foods. Additionally, it was found to provide some benefits such as lowering blood sugar, which may be particularly important in people at risk of developing type 2 diabetes.
The trial was led by the University of Leeds in collaboration with the The Rhône-Alpes Research Center for Human Nutrition. It is the latest study to be published by the SWEET consortium of 29 European research, consumer and industry partners which is working to develop and review evidence on long term benefits and potential risks involved in switching over to sweeteners and sweetness enhancers in the context of public health and safety, obesity, and sustainability. It was funded by Horizon Europe.
Lead author Catherine Gibbons, Associate Professor in the University of Leeds’ School of Psychology, said: “Reducing sugar consumption has become a key public health target in the fight to reduce the rising burden of obesity-related metabolic diseases such as type 2 diabetes.
“Simply restricting sugar from foods without substitution may negatively impact its taste or increase sweet cravings, resulting in difficulties sticking to a low-sugar diet. Replacing sugars with sweeteners and sweetness enhancers in food products is one of the most widely used dietary and food manufacturing strategies to reduce sugar intake and improve the nutritional profile of commercial foods and beverages.”
Principal investigator Graham Finlayson, Professor of Psychobiology in the University of Leeds’ School of Psychology, said: “The use of sweeteners and sweetness enhancers has received a lot of negative attention, including high profile publications linking their consumption with impaired glycaemic response, toxicological damage to DNA and increased risk of heart attack and stroke. These reports contribute to the current befuddlement concerning the safety of sweeteners and sweetness enhancers among the general public and especially people at risk of metabolic diseases.
“Our study provides crucial evidence supporting the day-to-day use of sweeteners and sweetness enhancers for body weight and blood sugar control.”
Until now, virtually all studies of the effects of sweeteners and sweetness enhancers on appetite and glycaemia have been conducted using beverages as the vehicle. Few studies include volunteers with overweight or obesity and few have included volunteers of both sexes.
Most studies have only compared a single sweetener, mostly aspartame, with a control, and very few studies have examined the effect of repeated daily intake of a known sweetener or sweetness enhancer in the normal diet.
The study, which is the first of its kind, looked at the effects of consuming biscuits containing either sugar or two types of food sweetener: natural sugar substitute Stevia, or artificial sweetener Neotame on 53 adult men and women with overweight or obesity. Participants were all aged 18 to 60, with overweight or obesity.
The trial consisted of three two-week consumption periods, where participants consumed biscuits with either fruit filling containing sugar; natural sugar substitute Stevia, or artificial sweetener Neotame, each separated by a break of 14–21 days. Day 1 and day 14 of the consumption periods took place in the lab.
Participants were instructed to arrive in the lab after an overnight fast, a blood sample was taken to establish baseline levels of glucose, insulin and appetite-related hormones. They were also asked to rate their appetite and food preferences.
After consuming the biscuits, they were asked to rate how full they felt over several hours. Glucose and insulin levels were measured, as were ghrelin, glucagon-like peptide 1 and pancreatic polypeptide – hormones associated with the consumption of food.
The results from the two sweetener types showed no differences in appetite or endocrine responses compared to sugar, but insulin levels measured over two hours after eating were reduced, as were blood sugar levels.
Researchers have discovered a gene on the Y chromosome that contributes to the greater incidence of heart failure in men when the Y chromosome is lost to ageing.
Y chromosome loss in men occurs progressively throughout life and can be detected in approximately 40% of 70-year-old men. In 2022, Kenneth Walsh, PhD, at University of Virginia discovered that this loss can contribute to heart muscle scarring and lead to heart failure. (That finding was the first to directly link Y chromosome loss to a specific harm to men’s health; Y chromosome loss is increasingly thought to play a role in diseases ranging from Alzheimer’s to cancer.)
In an important follow-up finding published in Nature Cardiovascular Research, Walsh and his team have discovered how Y chromosome loss triggers changes in heart immune cells that make the cells more likely to cause scarring and heart failure.
Further, the researchers found they could reverse the harmful heart changes by giving lab mice a drug that targets the process of fibrosis that leads to the heart scarring, which could lead to a similar treatment for men.
“Our previous work identified that it was loss of the entire Y chromosome that contributed to heart disease in men,” said Walsh, the director of UVA’s Hematovascular Biology Center. “This new work identified a single gene on the Y chromosome that can account for the disease-promoting effects of Y chromosome loss.”
About Y chromosome loss
Unlike women, who have two X chromosomes, men have an X and a Y. For a long time, the genes found on the Y chromosome were not thought to play important roles in disease. Sex hormones, scientists thought, explained the differences in certain diseases in men and women. But Walsh’s groundbreaking work has helped change that perception. It also suggested an explanation for why heart failure is more common in men than women. (Cardiovascular disease, which includes heart failure, is the leading cause of death worldwide.)
Y chromosome loss occurs in only a small percentage of affected men’s cells. This results in what is called “mosaicism,” where genetically different cells occur within one individual. Researchers aren’t entirely sure why this partial Y chromosome loss occurs, but predominantly it strikes elderly men and men who smoke compared to those who don’t.
To better understand the effects of Y chromosome loss, Walsh and his team examined genes found on the Y chromosome to determine which might be important to heart scarring. One gene they looked at, Uty, helps control the operating instructions for immune cells called macrophages and monocytes, the scientists determined. When the Uty gene was disrupted, either individually or through Y chromosome loss, that triggered changes in the immune cells in lab mice. Suddenly, the macrophages were much more “pro-fibrotic,” or prone to scarring. This accelerated heart failure as well, the scientists found.
“The identification of a single gene on the Y chromosome provides information about a new druggable target to treat fibrotic diseases,” said Walsh, of UVA’s Division of Cardiovascular Medicine and Robert M. Berne Cardiovascular Research Center.
Walsh and his team were able to prevent the harmful changes in the mice’s macrophages by giving them a specially designed monoclonal antibody. This halted the harmful changes in the heart, suggesting the approach might, with further research, lead to a way to treat or avoid heart failure and other fibrotic diseases in men with Y chromosome loss.
“Currently, we are working with our clinician colleagues in the Division of Cardiovascular Medicine at UVA to assess whether loss of the Y chromosome in men is associated with greater scarring in the heart,” Walsh said. “This research will provide new avenues for understanding the causes of heart disease.”
Based on their findings, Walsh and his team believe that a small group of genes found on the Y chromosome may have big effects on a wide array of diseases. Their new work identifies mechanisms that may lead to this, and they are hopeful that further research will provide a much better understanding of unknown causes of sickness and death in men.
“This research further documents the utility of studying the genetics of mutations that are acquired after conception and accumulate throughout life,” Walsh said. “These mutations appear to be as important to health and lifespan as the mutations that are inherited from one’s parents. The study of these age-acquired mutations represents a new field of human genetics.”
Researchers utilise data from Swedish nationwide registers of over 900 000 women
Photo by Sydney Sims on Unsplash
Women affected by premenstrual disorders have a higher risk of perinatal depression compared with those who do not, according to research published March 28th in the open access journal PLOS Medicine. The relationship works both ways: those with perinatal depression are also more likely to develop premenstrual disorders after pregnancy and childbirth. This study suggests that a common mechanism might contribute to the two conditions.
Menstruating women experience cyclical hormone fluctuations through puberty, menstrual cycle, pregnancy and menopause. Some women have difficult to manage symptoms of low mood and depression during these fluctuations. Between a fifth and a third of women are reportedly affected by premenstrual disorders and 11% of mothers suffer perinatal depression – depressive symptoms during pregnancy and up to 12 months after delivery.
Qian Yang and colleagues at the Karolinska Institutet, Sweden and University of Iceland used the Swedish nationwide registers from 2001 to 2018 and identified 84 949 women with perinatal depression and 849 482 unaffected women. The researchers matched the women on age and calendar year, and further controlled for demographic factors, smoking, BMI, parity and history of psychiatric disorders. Among women with perinatal depression, almost 3% had premenstrual disorders before pregnancy compared with 0.6% of matched unaffected women. Women with perinatal depression were also twice as likely to report premenstrual disorders when the menstruation resumed after childbirth, compared to those unaffected by perinatal depression.
The research sheds light on the association between the two conditions and supports a theory that they may share underlying biological mechanisms and/or risk factors. Understanding this association could help healthcare providers to better target support to women most likely to be affected.
The authors add, “This study reveals a strong bidirectional relationship between perinatal depression and premenstrual disorders, using data from over 900 000 pregnancies. The findings suggest that both disorders may exist on a continuum, and emphasise the importance of recognising these susceptibilities in clinical practice.”
Sleeping fewer than seven hours is associated with a higher risk of developing hypertension over time, according to a study presented at the American College of Cardiology’s Annual Scientific Session.
While the association between sleep patterns and hypertension has been reported, evidence about the nature of this relationship has been inconsistent, according to researchers. The current analysis pools data from 16 studies conducted between January 2000 and May 2023, evaluating hypertension incidence in 1 044 035 people from six countries without a prior history of hypertension over a median follow-up of five years (follow-up ranged from 2.4 to 18 years). Short sleep duration was significantly associated with a higher risk of developing hypertension after adjusting for demographic and cardiovascular risk factors, including age, sex, education, BMI, blood pressure, smoking status etc. Furthermore, the association was found to be even stronger for those getting less than five hours of sleep.
“Based on the most updated data, the less you sleep – that is less than seven hours a day – the more likely you will develop high blood pressure in the future,” said Kaveh Hosseini, MD, assistant professor of cardiology at the Tehran Heart Center in Iran and principal investigator of the study. “We saw a trend between longer sleep durations and a greater occurrence of high blood pressure, but it was not statistically significant. Getting seven to eight hours of sleep, as is recommended by sleep experts, may be the best for your heart too.”
The study found that sleeping less than seven hours was associated with a 7% increased risk of developing hypertension, which spiked to 11% when reported sleep duration was less than five hours. By comparison, diabetes and smoking are known to heighten one’s risk of hypertension by at least 20%, Hosseini said.
While the study did not look at why this might be the case, Hosseini said that disrupted sleep could be to blame. For example, he said lifestyle habits or comorbid conditions such as overeating, alcohol use, nightshift work, certain medication use, anxiety, depression, sleep apnoea or other sleep disorders may be factors.
Researchers were surprised there were no age-based differences in the association between sleep duration and hypertension given that sleep patterns tend to shift with age. Participants ranged in age from 35.4 years to 60.9 years and 61% were female. When compared with men, females who reported less than seven hours of sleep had a 7% greater risk of developing hypertension.
“Getting too little sleep appears to be riskier in females,” Hosseini said. “The difference is statistically significant, though we are not sure it’s clinically significant and should be further studied. What we do see is that lack of good sleep patterns may increase the risk of high blood pressure, which we know can set the stage for heart disease and stroke.”
It’s important for people to talk with their health care team about their sleep patterns, especially if they have disrupted sleep that might be due to obstructive sleep apnoea. Sleep apnoea has been tied to higher rates of high blood pressure, stroke and coronary artery disease.
This study has several limitations, including that sleep duration was based on self-reported questionnaires, so changes in sleep duration over the follow-up period were not assessed. Moreover, there were variations in how short sleep duration was defined between the studies (fewer than five or six hours).
“Further research is required to evaluate the association between sleep duration and high blood pressure using more accurate methods like polysomnography, a method for evaluating sleep quality more precisely,” Hosseini said. “Moreover, the variations in reference sleep duration underline the need for standardised definition in sleep research to enhance the comparability and generalisability of findings across diverse studies.”
Natural products have unique chemical structures and biological activities and can play a pivotal role in advancing pharmaceutical science. In a pioneering study, researchers from Shinshu University discovered Inaoside A, an antioxidant derived from Laetiporus cremeiporus mushrooms. This breakthrough, published in the journal Heliyon, sheds light on the potential of mushrooms as a source of therapeutic bioactive compounds.
The search for novel bioactive compounds from natural sources has gained considerable momentum in recent years due to the need for new therapeutic agents to combat various health challenges. Among a diverse array of natural products, mushrooms have emerged as a rich reservoir of bioactive molecules with potential pharmaceutical and nutraceutical applications. The genus Laetiporus has attracted attention for its extracts exhibiting antimicrobial, antioxidant, and antithrombin bioactivities. The species Laetiporus cremeiporus, spread across East Asia, has also been reported to show antioxidant properties. However, the identification and characterisation of specific antioxidant compounds from this species have not been conducted.
In a groundbreaking study, researchers led by Assistant Professor Atsushi Kawamura from the Department of Biomolecular Innovation, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, along with Hidefumi Makabe from the Department of Agriculture, Graduate School of Science and Technology, Shinshu University, and Akiyoshi Yamada from the Department of Mountain Ecosystem, Institute for Mountain Science, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, recently discovered the antioxidant compound derived from L. cremeiporus.
The researchers collected fresh fruiting bodies of L. cremeiporus from the Ina campus of Shinshu University. The obtained extracts were concentrated and partitioned between water and ethyl acetate. After this, the extracts were subjected to advanced chromatographic techniques, which led to the successful isolation of Inaoside A, a new antioxidant phenolic compound, along with three other well-characterised bioactive compounds, i.e., 5′-S-methyl-5′-thioadenosine (MTA), nicotinamide, and adenosine.
“Our study marks the pioneering discovery of Inaoside A from an extract of the edible mushroom Laetiporus cremeiporus. To date, there has been only one prior report on the biological function of an extract of L. cremeiporus. We are the first to uncover the isolation of an antioxidant compound from L. cremeiporus,” states Professor Kawamura, highlighting the breakthrough research.
Next, the researchers wanted to determine the structure of the newly found antioxidant compound. For this, they utilised one and two- dimensional NMR and other spectroscopic analyses. The structure of Inaoside A revealed a planar configuration. With a molecular formula of C17H24O7, the compound was found to feature a distinctive ribose moiety, identified as α-ribofuranoside through stereochemical analysis. Subsequent investigation into the absolute stereochemistry confirmed the D-ribose configuration, thereby reinforcing the planar structure of this compound.
The mushroom extracts were then isolated into fractions to determine the antioxidant activities of the four isolated bioactive compounds. These fractions were then examined by DPPH radical scavenging and superoxide dismutase assays. The findings were noteworthy as the DPPH radical scavenging activity exhibited by Inaoside A was significant, showing 80% inhibition at 100μg/mL, indicative of its significant antioxidant properties. The IC50 value of Inaoside A was determined to be 79.9μM, further highlighting its efficacy as an antioxidant agent.
What are the objectives of the researchers following the discovery of Inaoside? Professor Kawamura reveals, “We are now focusing on investigating the chemical compositions and biological properties of natural compounds obtained from mushrooms. Our goal is to uncover the potential of edible mushrooms as functional foods through this discovery.”
The identification of Inaoside A as an antioxidant from Laetiporus cremeiporus marks a significant breakthrough in natural product research, highlighting the potential of mushrooms as a source of therapeutic bioactive compounds. These findings may lead to the development of novel antioxidant-based therapies for various health conditions. Further studies should focus on synthetic research and detailed investigations into the biological activity of Inaoside A, aiming to harness its potential as a pharmaceutical lead compound.
Simply asking patients to get the flu vaccine, and combining it with helpful video and print messages, is enough to persuade many who visit emergency departments to roll up their sleeves, according to a new study published in NEJM Evidence.
Researchers led by UC San Francisco found a 32% vaccine uptake in patients who were asked if they’d be interested in getting the flu shot and told their health providers would be informed.
They saw a 41% uptake for those who were asked about receiving a flu shot and received a pamphlet, watched a three-minute video of a physician with a similar ethnic background discussing the vaccine and were told about the benefits of the vaccine.
The researchers say this type of systematic approach could lead to more underserved people receiving vaccines, especially those whose primary health care occurs in emergency departments.
Flu can be fatal
Annual mortality rates from flu are typically in the tens of thousands in the U.S., especially when combined with pneumonia – but vaccination is particularly low among underserved populations and those whose primary care occurs in emergency departments.
Such patients often face general vaccine hesitancy or a lack of opportunities for the flu shot.
“This research arose from our desire to address the health disparities that we see every day in our emergency department, especially among homeless persons, the uninsured and immigrant populations,” said first author, Robert M. Rodriguez, MD, a professor of Emergency Medicine with the UCSF School of Medicine.
The researchers designed the clinical trial to span a single flu season between October 2022 and February 2023.
Investigators in the study created flu vaccine messaging – including a brief video, flyer and a scripted health provider question, “Would you be willing to accept the influenza vaccine?” – and assessed their effectiveness among nearly 800 patients in five cities: San Francisco, Houston, Philadelphia, Seattle and Durham, North Carolina.
The median age was 46, and more than half the participants in the trial were Black or Latino, 16 % lacked health insurance, nearly a third had no primary care and 9% were homeless or living in severely inadequate housing. These demographic characteristics are similar to patient populations often served by urban emergency departments.
“Overall, our study adds to the growing body of knowledge showing that a number of important public health interventions can and should be delivered to underserved populations in emergency departments,” said Rodriguez, whose previous research has found the effectiveness of delivering similar COVID-19 vaccine messaging to emergency department patients.
Just as you can’t make an omelette without breaking eggs, scientists at Albert Einstein College of Medicine have found that you can’t make long-term memories without DNA damage and inflammation in the brain. Their surprising findings were published online today in the journal Nature.
“Inflammation of brain neurons is usually considered to be a bad thing, since it can lead to neurological problems such as Alzheimer’s and Parkinson’s disease,” said study leader Jelena Radulovic, MD, PhD, professor of psychiatry and behavioural sciences at Einstein. “But our findings suggest that inflammation in certain neurons in the brain’s hippocampal region is essential for making long-lasting memories.”
The hippocampus has long been known as the brain’s memory centre. Dr Radulovic and her colleagues found that a stimulus sets off a cycle of DNA damage and repair within certain hippocampal neurons that leads to stable memory assemblies, ie clusters of brain cells representing past experiences.
From shocks to stable memories
The researchers discovered this memory-forming mechanism by giving mice brief, mild shocks sufficient to form an episodic memory of the shock event. Then, they analysed neurons in the hippocampal region and found that genes participating in an important inflammatory signalling pathway had been activated.
“We observed strong activation of genes involved in the Toll-Like Receptor 9 (TLR9) pathway,” said Dr Radulovic, who is also director of the Psychiatry Research Institute at Montefiore Einstein (PRIME). “This inflammatory pathway is best known for triggering immune responses by detecting small fragments of pathogen DNA. So at first we assumed the TLR9 pathway was activated because the mice had an infection. But looking more closely, we found, to our surprise, that TLR9 was activated only in clusters of hippocampal cells that showed DNA damage.”
Brain activity routinely induces small breaks in DNA that are repaired within minutes. But in this population of hippocampal neurons, the DNA damage appeared to be more substantial and sustained.
Triggering inflammation to make memories
Further analysis showed that DNA fragments, along with other molecules resulting from the DNA damage, were released from the nucleus, after which the neurons’ TLR9 inflammatory pathway was activated; this pathway in turn stimulated DNA repair complexes to form at an unusual location: the centrosomes. These organelles are present in the cytoplasm of most animal cells and are essential for coordinating cell division. But in neurons – which don’t divide – the stimulated centrosomes participated in cycles of DNA repair that appeared to organise individual neurons into memory assemblies.
“Cell division and the immune response have been highly conserved in animal life over millions of years, enabling life to continue while providing protection from foreign pathogens,” Dr. Radulovic said. “It seems likely that over the course of evolution, hippocampal neurons have adopted this immune-based memory mechanism by combining the immune response’s DNA-sensing TLR9 pathway with a DNA repair centrosome function to form memories without progressing to cell division.”
Resisting inputs of extraneous information
During the week required to complete the inflammatory process, the mouse memory-encoding neurons were found to have changed in various ways, including becoming more resistant to new or similar environmental stimuli. “This is noteworthy,” said Dr Radulovic, “because we’re constantly flooded by information, and the neurons that encode memories need to preserve the information they’ve already acquired and not be ‘distracted’ by new inputs.”
“This is noteworthy,” said Dr Radulovic, “because we’re constantly flooded by information, and the neurons that encode memories need to preserve the information they’ve already acquired and not be ‘distracted’ by new inputs.”
Importantly, the researchers found that blocking the TLR9 inflammatory pathway in hippocampal neurons not only prevented mice from forming long-term memories but also caused profound genomic instability, ie, a high frequency of DNA damage in these neurons.
“Genomic instability is considered a hallmark of accelerated aging as well as cancer and psychiatric and neurodegenerative disorders such as Alzheimer’s,” Dr Radulovic said.
“Drugs that inhibit the TLR9 pathway have been proposed for relieving the symptoms of long COVID. But caution needs to be shown because fully inhibiting the TLR9 pathway may pose significant health risks.”
PhD Student Elizabeth Wood and Ana Cicvaric, a postdoc in the Radulovic lab, were the study’s first authors at Einstein.
