Study finds children with vegetarian diet have similar growth and nutrition compared to children who eat meat

Children with a vegetarian diet also had higher odds of underweight weight status

May 2, 2022

Science Daily/St. Michael's Hospital

A study of nearly 9,000 children found those who eat a vegetarian diet had similar measures of growth and nutrition compared to children who eat meat. The study, published in Pediatrics and led by researchers at St. Michael’s Hospital of Unity Health Toronto, also found that children with a vegetarian diet had higher odds of underweight weight status, emphasizing the need for special care when planning the diets of vegetarian kids.

The findings come as a shift to consuming a plant-based diet grows in Canada. In 2019, updates to Canada’s Food Guide urged Canadians to embrace plant-based proteins, such as beans and tofu, instead of meat.

“Over the last 20 years we have seen growing popularity of plant-based diets and a changing food environment with more access to plant-based alternatives, however we have not seen research into the nutritional outcomes of children following vegetarian diets in Canada,” said Dr. Jonathon Maguire, lead author of the study and a pediatrician at St. Michael’s Hospital of Unity Health Toronto.

“This study demonstrates that Canadian children following vegetarian diets had similar growth and biochemical measures of nutrition compared to children consuming non-vegetarian diets. Vegetarian diet was associated with higher odds of underweight weight status, underscoring the need for careful dietary planning for children with underweight when considering vegetarian diets.”

Researchers evaluated 8,907 children age six months to eight years. The children were all participants of the TARGet Kids! cohort study and data was collected between 2008 and 2019. Participants were categorized by vegetarian status – defined as a dietary pattern that excludes meat – or non-vegetarian status.

Researchers found children who had a vegetarian diet had similar mean body mass index (BMI), height, iron, vitamin D, and cholesterol levels compared to those who consumed meat. The findings showed evidence that children with a vegetarian diet had almost two-fold higher odds of having underweight, which is defined as below the third percentile for BMI. There was no evidence of an association with overweight or obesity.

Underweight is an indicator of undernutrition, and may be a sign that the quality of the child’s diet is not meeting the child’s nutritional needs to support normal growth. For children who eat a vegetarian diet, the researchers emphasized access to healthcare providers who can provide growth monitoring, education and guidance to support their growth and nutrition.

International guidelines about vegetarian diet in infancy and childhood have differing recommendations, and past studies that have evaluated the relationship between vegetarian diet and childhood growth and nutritional status have had conflicting findings.

“Plant-based dietary patterns are recognized as a healthy eating pattern due to increased intake of fruits, vegetables, fiber, whole grains, and reduced saturated fat; however, few studies have evaluated the impact of vegetarian diets on childhood growth and nutritional status. Vegetarian diets appear to be appropriate for most children,” said Dr. Maguire, who is also a scientist at MAP Centre for Urban Health Solutions at St. Michael’s Hospital.

A limitation of the study is that researchers did not assess the quality of the vegetarian diets. The researchers note that vegetarian diets come in many forms and the quality of the individual diet may be quite important to growth and nutritional outcomes. The authors say further research is needed to examine the quality of vegetarian diets in childhood, as well as growth and nutrition outcomes among children following a vegan diet, which excludes meat and animal derived products such as dairy, egg, and honey.

https://www.sciencedaily.com/releases/2022/05/220502094813.htm

Gut microbiome may alter response to cancer therapy

April 28, 2022

Science Daily/Brigham and Women's Hospital

Since ancient times, our gut microbiome, home to a vast number of bacteria, viruses, fungi, and other microorganisms, has been thought to influence many aspects of human health. Most recently, sequencing technology has shown that it may also play a role in the treatment of cancer. A review paper published in JAMA Oncology by investigators from Brigham and Women's Hospital captures the current understanding of the connection between the gut microbiome and therapeutic response to immunotherapy, chemotherapy, cancer surgery and more, pointing to ways that the microbiome could be targeted to improve treatment.

"We know that a healthy gut is key to our overall health," said lead author Khalid Shah, MS, PhD, of the Center for Stem Cell and Translational Immunotherapy in the Department of Neurosurgery at the Brigham. "Our gut is so important that we often refer to it as our 'second' brain. In recent years, we've begun to appreciate the many roles of the gut, including the gut-brain connection and the connection between the gut and our immune system. Conversely, gut dysfunction or dysbiosis can have a negative effect on our health."

Shah and colleagues report on an emerging role for gut microbiota in immunotherapy. Immune checkpoint inhibitors and immune checkpoint blockade therapy are novel strategies for treating cancer, but response to these forms of treatment varies considerably between individuals and across cancer types. Several studies have found differences in the species of bacteria found in fecal samples from responders and non-responders, suggesting that different microbiome compositions may influence clinical responses. Other studies suggest that diet and probiotics -- live bacterial species that can be ingested -- as well as antibiotic medications and bacteriophages can influence the composition of the gut microbiome and, in turn, a response to immunotherapy. In particular, the authors highlight recent studies on the effects of ketogenic diets for patients with cancer.

"Today, developing treatments that sync immunotherapies and gut microbiota provides medicine a unique opportunity to truly effect change in patient care," said Shah.

The authors also provide an overview of how microbiota have been implicated in influencing response to chemotherapy and other conventional cancer treatments as well as how cancer therapies may reciprocally affect the microbiome and cause side effects.

"Overall, these findings support the potential of influencing the gut microbiota to diminish the side effects of conventional cancer treatment," said Shah.

The authors note that there is little understanding of what the "ideal" bacteria consortia in the gut looks like and how findings from preclinical models may or may not translate into applications in humans. They note that caution must be exercised before using probiotics or making dietary changes. Many cancer clinical trials are currently exploring the influence of the microbiome to help address some of the limitations and gaps in understanding. These include trials of fecal microbial transplantation, dietary supplements and novel drugs that may influence microbiota composition.

"There is strong evidence that the gut microbiome can have a positive influence on cancer therapies," said Shah. "There remain exciting possibilities to explore, including the influence of healthy diet, probiotics, novel therapies, and more."

https://www.sciencedaily.com/releases/2022/04/220428125422.htm

Reducing sedentary time mitigates the risk of type 2 diabetes and cardiovascular diseases

May 2, 2022

Science Daily/University of Turku

A new study suggests that reducing daily sedentary time can have a positive effect on the risk factors of lifestyle diseases already in three months. Spending just one hour less sitting daily and increasing light physical activity can help in the prevention of these diseases.

Type 2 diabetes and cardiovascular diseases are the most common chronic diseases globally. The risk of developing these diseases is increased particularly by overweight caused by physical inactivity and unhealthy diet, and metabolic disorders often associated with it.

Regular exercise is well known to be beneficial in weight management and disease prevention. However, many adults do not meet the weekly recommendation of 2.5 hours of moderate-intensity exercise, and the majority of the day is typically spent sitting.

In an intervention study of the Turku PET Centre and the UKK Institute in Finland, the researchers investigated whether health benefits can be achieved by reducing daily sedentary time during a three-month intervention period. The research participants were sedentary and physically inactive working-age adults with an increased risk of type 2 diabetes and cardiovascular diseases.

The researchers compared two groups: the intervention group was guided to reduce their sitting time by one-hour per day through increasing standing and light-intensity physical activity, and the control group was instructed to maintain their usual habits and sedentary lifestyle.

"What makes our research design unique is that sedentary time and physical activity of both groups were measured with accelerometers throughout the entire three-month period, whereas in earlier studies activity has typically been measured only for a few days at the beginning and end of the study period. This makes it possible to receive more information on the actual behaviour changes over a longer time period," says Doctoral Candidate Taru Garthwaite from the University of Turku in Finland.

The intervention group managed to reduce sedentary time by 50 minutes per day on average, mainly by increasing the amount of light- and moderate-intensity physical activity. In the three-month period, the researchers observed benefits in health outcomes related to blood sugar regulation, insulin sensitivity and liver health in the intervention group.

"It is an encouraging thought that health benefits can be achieved by reducing the time spent sitting and increasing the amount of even light-intensity physical activity. For many, this may be an easier starting point than increasing actual exercise," says Garthwaite.

Particularly beneficial for physically inactive individuals 

It is likely that people who do not meet the weekly physical activity recommendations will benefit the most from replacing sedentary time with light physical activity. However, reducing sedentary time is probably not enough in itself to prevent diseases if the person has several risk factors of diabetes and cardiovascular diseases.

"Reducing the time spent sitting might still slow down the development of these diseases, but greater benefits can of course be gained by increasing the amount or intensity of physical activity in addition to sitting less," encourages Garthwaite.

The next step for the researchers is to study how changes in daily activity and sedentary time affect energy metabolism and body composition in addition to the risk factors of diabetes and cardiovascular diseases during a six-month study period.

https://www.sciencedaily.com/releases/2022/05/220502094810.htm

Seven hours of sleep is optimal in middle and old age

April 28, 2022

Science Daily/University of Cambridge

Seven hours is the ideal amount of sleep for people in their middle age and upwards, with too little or too much little sleep associated with poorer cognitive performance and mental health, say researchers from the University of Cambridge and Fudan University.

Sleep plays an important role in enabling cognitive function and maintaining good psychological health. It also helps keep the brain healthy by removing waste products. As we get older, we often see alterations in our sleep patterns, including difficulty falling asleep and staying asleep, and decreased quantity and quality of sleep. It is thought that these sleep disturbances may contribute to cognitive decline and psychiatric disorders in the aging population.

In research published today in Nature Aging, scientists from the UK and China examined data from nearly 500,000 adults aged 38-73 years from the UK Biobank. Participants were asked about their sleeping patterns, mental health and wellbeing, and took part in a series of cognitive tests. Brain imaging and genetic data were available for almost 40,000 of the study participants.

By analysing these data, the team found that both insufficient and excessive sleep duration were associated with impaired cognitive performance, such as processing speed, visual attention, memory and problem-solving skills. Seven hours of sleep per night was the optimal amount of sleep for cognitive performance, but also for good mental health, with people experiencing more symptoms of anxiety and depression and worse overall wellbeing if they reported sleeping for longer or shorter durations.

The researchers say one possible reason for the association between insufficient sleep and cognitive decline may be due to the disruption of slow-wave -- 'deep' -- sleep. Disruption to this type of sleep has been shown to have a close link with memory consolidation as well as the build-up of amyloid -- a key protein which, when it misfolds, can cause 'tangles' in the brain characteristic of some forms of dementia. Additionally, lack of sleep may hamper the brain's ability to rid itself of toxins.

The team also found a link between the amount of sleep and differences in the structure of brain regions involved in cognitive processing and memory, again with greater changes associated with greater than or less than seven hours of sleep.

Having a consistent seven hours' sleep each night, without too much fluctuation in duration, was also important to cognitive performance and good mental health and wellbeing. Previous studies have also shown that interrupted sleep patterns are associated with increased inflammation, indicating a susceptibility to age-related diseases in older people.

Professor Jianfeng Feng from Fudan University in China said: "While we can't say conclusively that too little or too much sleep causes cognitive problems, our analysis looking at individuals over a longer period of time appears to support this idea. But the reasons why older people have poorer sleep appear to be complex, influenced by a combination of our genetic makeup and the structure of our brains."

The researchers say the findings suggest that insufficient or excessive sleep duration may be a risk factor for cognitive decline in ageing. This is supported by previous studies that have reported a link between sleep duration and the risk of developing Alzheimer's disease and dementia, in which cognitive decline is a hallmark symptom.

Professor Barbara Sahakian from the Department of Psychiatry at the University of Cambridge, one of the study's authors, said: "Getting a good night's sleep is important at all stages of life, but particularly as we age. Finding ways to improve sleep for older people could be crucial to helping them maintain good mental health and wellbeing and avoiding cognitive decline, particularly for patients with psychiatric disorders and dementias."

https://www.sciencedaily.com/releases/2022/04/220428125425.htm

Psychedelic experience may not be required for psilocybin's antidepressant-like benefits

So-called 'magic mushroom' drug seems to work through multiple brain mechanisms for its different effects

April 13, 2021

Science Daily/University of Maryland School of Medicine

University of Maryland School of Medicine (UMSOM) researchers have shown that psilocybin -- the active chemical in "magic mushrooms" -- still works its antidepressant-like actions, at least in mice, even when the psychedelic experience is blocked. The new findings suggest that psychedelic drugs work in multiple ways in the brain and it may be possible to deliver the fast-acting antidepressant therapeutic benefit without requiring daylong guided therapy sessions. A version of the drug without, or with less of, the psychedelic effects could loosen restrictions on who could receive the therapy, and lower costs, making the benefits of psilocybin more available to more people in need.

In all clinical trials performed to date, the person treated with psilocybin remains under the care of a guide, who keeps the person calm and reassures them during their daylong experience. This can include hallucinations, altered perception of time and space, and intense emotional and spiritual encounters.

Researchers in the field have long attributed psilocybin's effectiveness to the intense psychedelic experience.

"We do not understand the mechanisms that underlie the antidepressant actions of psilocybin and the role that the profound psychedelic experience during these sessions plays in the therapeutic benefits," says Scott Thompson, Ph.D., Professor and Chair, Department of Physiology at UMSOM and senior author of the study. "The psychedelic experience is incredibly powerful and can be life-changing, but that could be too much for some people or not appropriate."

Several barriers prevent the wide-spread use of psychedelic compounds. For example, there is fear that the psychedelic experience may promote psychosis in people who are predisposed to severe mental disorders, like bipolar disorder and schizophrenia, so the clinical therapy sessions performed to-date have been limited to a highly selected screened group without a family history of these disorders.

Dr. Thompson adds that there may also be an equity issue because not everyone can take several days off work to prepare and engage in the experience. The costs of staffing a facility with at least one trained guide per treated person per day and a private space may also be prohibitive to all but a few. He says it is conceivable that a depression treatment derived from psilocybin could be developed without the psychedelic effects so people can take it safely at home without requiring a full day in a care facility.

For their study, led by UMSOM MD/PhD student Natalie Hesselgrave, the team used a mouse model of depression in which mice were stressed for several hours a day over 2-3 weeks. Because researchers cannot measure mouse moods, they measure their ability to work for rewards, such as choosing to drink sugar water over plain water. People suffering from depression lose the feeling of pleasure for rewarding events. Similarly, stressed mice no longer preferred sugar water over plain water. However, 24 hours after a dose of psilocybin, the stressed mice regained their preference for the sugar water, demonstrating that the drug restored the mice's pleasure response.

Psilocybin exerts its effects in people by binding to and turning on receptors for the chemical messenger serotonin. One of these receptors, the serotonin 2A receptor, is known to be responsible for the psychedelic response. To see if the psychedelic effects of psilocybin were needed for the anti-depressive benefits, the researchers treated the stressed mice with psilocybin together with a drug, ketanserin, which binds to the serotonin 2A receptor and keeps it from being turned on. The researchers found that the stressed mice regained their preference for the sugar water in response to psilocybin, even without the activation of the psychedelic receptor.

"These findings show that activation of the receptor causing the psychedelic effect isn't absolutely required for the antidepressant benefits, at least in mice," says Dr. Thompson, "but the same experiment needs to be performed in depressed human subjects." He says his team plans to investigate which of the 13 other serotonin receptors are the ones responsible for the antidepressant actions.

"This new study has interesting implications, and shows that more basic research is needed in animals to reveal the mechanisms for how these drugs work, so that treatments for these devastating disorders can be developed" says Albert E. Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, University of Maryland Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine.

This work was funded by the National Institute of Mental Health (R01 MH086828) and the National Institute of General Medical Sciences (T32 GM092237).

Although not approved yet, Dr. Thompson and the University of Maryland Baltimore have filed a patent on using psilocybin with drugs that block serotonin 2A receptors to treat depression.

https://www.sciencedaily.com/releases/2021/04/210413114107.htm

Ayahuasca fixings found in 1,000-year-old bundle in the Andes

New evidence that the mind-blowing brew goes back millennia

May 6, 2019

Science Daily/University of California - Berkeley

Today's hipster creatives and entrepreneurs are hardly the first generation to partake of ayahuasca, according to archaeologists who have discovered traces of the powerfully hallucinogenic potion in a 1,000-year-old leather bundle buried in a cave in the Bolivian Andes.

Led by University of California, Berkeley, archaeologist Melanie Miller, a chemical analysis of a pouch made from three fox snouts sewn together tested positive for at least five plant-based psychoactive substances. They included dimethyltryptamine (DMT) and harmine, key active compounds in ayahuasca, a mind-blowing brew commonly associated with the Amazon jungle.

"This is the first evidence of ancient South Americans potentially combining different medicinal plants to produce a powerful substance like ayahuasca," said Miller, a researcher with UC Berkeley's Archaeological Research Facility who uses chemistry and various technologies to study how ancient humans lived.

She is lead author of the study, published today (Monday, May 6) in the journal Proceedings of the National Academy of Sciences.

Miller's analysis of a scraping from the fox-snout pouch and a plant sample found in the ritual bundle -- via liquid chromatography tandem mass spectrometry -- turned up trace amounts of bufotenine, DMT, harmine, cocaine and benzoylecgonine. Various combinations of these substances produce powerful, mind-altering hallucinations.

The discovery adds to a growing body of evidence of ritualistic psychotropic plant use going back millennia, said Miller, a postdoctoral fellow at the University of Otago in New Zealand who conducted the research during her doctoral studies at UC Berkeley.

"Our findings support the idea that people have been using these powerful plants for at least 1,000 years, combining them to go on a psychedelic journey, and that ayahuasca use may have roots in antiquity," said Miller.

The remarkably well-preserved ritual bundle was found by archaeologists at 13,000-foot elevations in the Lipez Altiplano region of southwestern Bolivia, where llamas and alpacas roam. The leather kit dates back to the pre-Inca Tiwanaku civilization, which dominated the southern Andean highlands from about 550 to 950 A.D.

In addition to the fox-snout pouch, the leather bundle contained intricately carved wooden "snuffing tablets" and a "snuffing tube" with human hair braids attached, for snorting intoxicants; llama bone spatulas; a colorful woven textile strip and dried plant material. All the objects were in good shape, due to the arid conditions of the Andean highlands.

Though the cave where the artifacts were found appeared to be a burial site, an excavation did not turn up human remains. Moreover, the plants found in the bundle do not grow at those altitudes, suggesting the bundle's owner may have been a traveling shaman or another expert in the rituals of psychotropic plant use, or someone who was part of an extensive medicinal plant trading network.

"A lot of these plants, if consumed in the wrong dosage, could be very poisonous," Miller said. "So, whoever owned this bundle would need to have had great knowledge and skills about how to use these plants, and how and where to procure them."

Of particular fascination to Miller is the pouch made of three fox snouts. She describes it as "the most amazing artifact I've had the privilege to work with."

"There are civilizations who believe that, by consuming certain psychotropic plants, you can embody a specific animal to help you reach supernatural realms, and perhaps a fox may be among those animals," Miller said.

Ayahuasca is made from brewing the vines of Banisteriopsis Caapi and the leaves of the chacruna (Psychotria viridis) shrub. The leaves release DMT, and the vines release harmine -- and therein lies the secret of the ayahuasca effect.

"The tryptamine DMT produces strong, vivid hallucinations that can last from minutes to an hour, but combined with harmine, you can have prolonged out-of-body altered states of consciousness with altered perceptions of time and of the self," Miller said.

Once the drugs take effect, ayahuasca users typically enter a purgative state, which means they vomit a lot.

Though its use is currently fashionable among Silicon Valley techies, Hollywood celebrities and spiritual awakening-seekers worldwide, Miller says these latest archaeological findings pay homage to ayahuasca's ancient history.

Miller joined the Cueva del Chileno excavation project when archaeologists Juan Albarracín-Jordán of the Universidad Mayor de San Andrés in Bolivia and José Capriles of Pennsylvania State University sought her expertise to identify the plant matter they had found in the bundle.

She traveled for two days to reach the cave site near the remote south Bolivian village of Lipez and helped with the final phases of the excavation. The bundle was transported to a laboratory in La Paz and, once permits were in place, samples were exported to the lab of Christine Moore, chief toxicologist with the Immunalysis Corp. in Pomona, California.

Moore's lab provided the liquid chromatography tandem mass spectrometry technology needed to conduct toxicology tests on the samples. Once the contents of the Andean bundle tested positive for five kinds of psychotropic substances, Miller's research team was over the moon.

"We were amazed to see the incredible preservation of these compounds in this ritual bundle," said Miller. "I feel very lucky to have been a part of this research."

https://www.sciencedaily.com/releases/2019/05/190506151842.htm

New evidence of how exercise can counter diabetes damage

April 26, 2022

Science Daily/Medical College of Georgia at Augusta University

One way exercise can counter the damage of diabetes is by enabling activation of a natural system we have to grow new blood vessels when existing ones are ravaged by this disease, scientists report.

Angiogenesis is the ability to form new blood vessels, and diabetes not only damages existing blood vessels, it hinders this innate ability to grow new ones in the face of disease and injury, say experts at the Vascular Biology Center at the Medical College of Georgia.

Endothelial cells line our blood vessels and are essential to that new blood vessel growth.

Now the MCG scientists have the first evidence that in the face of diabetes, even one 45-minute session of moderate intensity exercise enables more exosomes, submicroscopic packages filled with biologically active cargo, to deliver directly to those cells more of the protein, ATP7A, which can set angiogenesis in motion, they report in The FASEB Journal.

Not unlike the most sophisticated and efficient delivery services we have all come to rely upon, particularly during the pandemic, what exosomes carry depends on where they come from and where they are headed, says Dr. Tohru Fukai, MCG vascular biologist and cardiologist.

While he and co-corresponding author MCG vascular biologist Dr. Masuko Ushio-Fukai are not yet certain of the origin of these helpful exosomes, it's clear that one place they deliver is to endothelial cells, Fukai says.

In both an animal model of type 2 diabetes and a handful of healthy 50-something-year-olds, two weeks of volunteer running on a wheel for the mice and that one cardio session for the humans increased levels of ATP7A in the exosomes that attached to endothelial cells.

At that point, the activity did not significantly impact the weight of the mice, the scientists note, but it did also increase a marker of endothelial function and factors like, vascular endothelial growth factor, needed for angiogenesis.

Exercise also increased the amount of the powerful, natural antioxidant extracellular superoxide dismutase, or SOD3, but it's the heavier payload of ATP7A, which is also known to deliver the essential mineral copper to cells, that is key to making good use of the SOD3 present, Ushio-Fukai says.

SOD3, is an important natural antioxidant produced by vascular smooth muscle cells in the walls of blood vessels as well as skeletal muscle cells, which helps us maintain healthy levels of reactive oxygen species, or ROS. ROS is a natural byproduct of our use of oxygen that is an important cell signal, enabling a variety of functions. But in diabetes, high blood sugar levels result in high ROS levels that instead hinder important normal functions.

The Fukais have shown that ATP7A levels are reduced in diabetes. They also now have some of the first evidence that exosomes circulating in the plasma of sedentary animal models of type 2 diabetes actually impair angiogenesis when placed in a dish with human endothelial cells, as well as in an animal model of wound healing.

The scientists suggest that synthetic exosomes, already under study as drug-delivery mechanisms, could one day work as an "exercise mimetic" to improve patients' ability to grow new blood vessels when diabetes has damaged their innate ability.

In fact, they have already generated exosomes in which SOD3 is overexpressed and found improved angiogenesis and healing in a mouse model of diabetes.

The way it's supposed to work is SOD3 is naturally silenced in endothelial cells, so they must get it from other cells, notes Ushio-Fukai, hence the importance of exosome delivery. SOD3 must then bind to endothelial cells at its natural spot called the heparin-binding domain, and the copper transporter ATP7A must be present to enable SOD3 to be active there, Fukai says. Both ATP7A and the binding site are key, Fukai notes. For example, when they removed the binding site from the endothelial cells, which can happen in nature, the benefits were lost.

Once on the scene and active, SOD3 converts the ROS superoxide into hydrogen peroxide, or H2O2, another signaling ROS that helps support normal endothelial cell function. The Fukais have reported that in human endothelial cells, overexpressing SOD3 promotes angiogenesis by increasing H2O2.

A copper connection also runs throughout this process as endothelial cells regularly use a lot of copper, and ATP7A, known to transport the essential mineral that we consume in foods like nuts and whole grains, is dependent on copper itself.

Physical exercise, like running or walking on treadmill, prompts muscles to contract which in turn prompts release of exosomes into the blood.

When Fukai was a postdoc in the Emory University Section of Cardiology he was part of the research group that was the first to show that exercise increases SOD3 activity. SOD3 levels decrease with age and with some disease states like diabetes and hypertension.

Exosomes are being studied as biomarkers for a wide range of diseases like cancer and diabetes as well as precise treatment delivery tools. For example, exosomes produced by a cancer cell will hone right back to a cancer cell.

About 1 in 10 Americans have diabetes, according to the Centers for Disease Control and Prevention.

https://www.sciencedaily.com/releases/2022/04/220426101747.htm

Stop the clocks: Brisk walking may slow biological aging process

April 20, 2022

Science Daily/University of Leicester

A new study of genetic data published today (Wednesday) of more than 400,000 UK adults has revealed a clear link between walking pace and a genetic marker of biological age.

Confirming a causal link between walking pace and leucocyte telomere length (LTL) -- an indicator of biological age -- the Leicester-based team of researchers estimate that a lifetime of brisk walking could lead to the equivalent of 16 years younger biological age by midlife.

Researchers from the University of Leicester at the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre studied genetic data from 405,981 middle-aged UK Biobank participants and found that a faster walking pace, independent of the amount of physical activity, was associated with longer telomere.

Telomeres are the 'caps' at the end of each chromosome, and hold repetitive sequences of non-coding DNA that protect the chromosome from damage, similar to the way the cap at the end of a shoelace stops it from unravelling.

Each time a cell divides, these telomeres become shorter -- until a point where they become so short that the cell can no longer divide, known as 'replicative senescence'. Therefore, scientists consider LTL a strong marker for 'biological age', independent from when an individual was born.

Although the relationship between telomere length and disease is not fully understood, the build-up of these senescent cells is believed to contribute to a range of symptoms we associate with aging, such as frailty and age-related diseases.

While the physical, mental, social and health benefits of walking are well-documented, this study is one of the first of its kind to compare genetic data with both self-reported walking speeds, as well as actual measurements of movement intensity from wearable activity tracking devices worn by participants.

Dr Paddy Dempsey is a Lecturer and Research Fellow at the University of Leicester and within the NIHR Leicester Biomedical Research Centre, part of the University Hospitals of Leicester (UHL) NHS Trust, and lead author on the study published in Communications Biology. He said:

"Previous research on associations between walking pace, physical activity and telomere length has been limited by inconsistent findings and a lack of high-quality data.

"This research uses genetic data to provide stronger evidence for a causal link between faster walking pace and longer telomere length. Data from wrist-worn wearable activity tracking devices used to measure habitual physical activity also supported a stronger role of habitual activity intensity (e.g. faster walking) in relation to telomere length.

"This suggests measures such as a habitually slower walking speed are a simple way of identifying people at greater risk of chronic disease or unhealthy ageing, and that activity intensity may play an important role in optimising interventions. For example, in addition to increasing overall walking, those who are able could aim to increase the number of steps completed in a given time (e.g. by walking faster to the bus stop). However, this requires further investigation."

Researchers from the University of Leicester have previously shown using UK Biobank that as little as 10 minutes of brisk walking a day is associated with longer life expectancy, and that brisk walkers have up to 20 years' greater life expectancy compared to slow walkers.

This new study demonstrates a causal link between brisk walking and telomere length and, significantly, not the other way round.

Tom Yates, senior author and Professor of Physical Activity, Sedentary Behaviour and Health at the University of Leicester and NIHR Leicester Biomedical Research Centre, added:

"Whilst we have previously shown that walking pace is a very strong predictor of health status, we have not been able to confirm that adopting a brisk walking pace actually causes better health. In this study we used information contained in people's genetic profile to show that a faster walking pace is indeed likely to lead to a younger biological age as measured by telomeres."

https://www.sciencedaily.com/releases/2022/04/220420133538.htm

Obsession with failure and hunt for perfection linked to burnout, sports study uncovers

April 22, 2022

Science Daily/University of Essex

Athletes who strive for perfection and fixate on their mistakes risk burning out, a University of Essex-led study has revealed.

More than 250 sportspeople -- across individual and team sports -- were examined and it was discovered hyper self-critical competitors who react negatively to even minor failings are at risk of psychological difficulty.

It was discovered perfectionistic concerns -- an obsession and excessive reaction to perceived failure -- were strongly related to athlete burnout.

This fixation on failure may see them view any achievement as inadequate and upcoming competitions, as disproportionately stressful, and create a self-fulfilling performance prophecy.

It is hoped the study led by Luke Olsson, from the University's School of Sport, Rehabilitation and Exercise Sciences will help shine a light on burnout.

He said: "Most people have come across the term burnout, with a lot of research focussing on the reason why it develops.

"There are many studies that have shown if an individual pursues perfection, whether that be in work, sport, or school, it can lead to burnout.

"However, our study was able to determine one potential explanation as to why this is the case in sport, which suggests that the stresses of pursuing perfection can lead those to mentally disengage with their sporting activities."

Mr Olsson worked with academics from York St John University on the Journal of Clinical Sport Psychology-published study which examined those competing or training in the UK.

All men and women in the study had been competing for more than eight years and were on average 21 years old, spanning levels from university to international. They were measured for levels of stress, burnout and perfectionism.

The athletes competed in a variety of sports -- including athletics, golf, weightlifting, football, netball, and hockey.

Burnout is defined as athletes having a reduced sense of accomplishment, prolonged exhaustion, and falling out of love with their sport.

Cognitive behavioural therapy, mindfulness and developing a kinder mindset are all thought to reduce perfectionistic concerns and potentially prevent burnout.

Mr Olsson added: "There is a need to prevent athletes from experiencing burnout.

"In the case of our research, the athletes themselves should be wary that pursuing perfection and being overly self-critical is likely to be doing more harm than good.

"I believe athletes may be better served by being less self-critical which should allow them to celebrate successes in performance and embrace failures as an opportunity to reflect and improve rather than beat themselves up."

https://www.sciencedaily.com/releases/2022/04/220422094337.htm

Calming overexcited neurons may protect brain after stroke

New data prompts reconsideration of decades-old theory about brain injury due to stroke

April 21, 2022

Science Daily/Washington University School of Medicine

A new study has prompted scientists to reconsider a once-popular yet controversial idea in stroke research.

Neuroscientists believed that, in the aftermath of a stroke, calming overexcited neurons might prevent them from releasing a toxic molecule that can kill neurons already damaged by lack of oxygen. This idea was supported by studies in cells and animals, but it lost favor in the early 2000s after numerous clinical trials failed to improve outcomes for stroke patients.

But a fresh approach has yielded evidence that the idea may have been discarded too hastily. The new findings are available online in the journal Brain.

By scanning the whole genomes of nearly 6,000 people who had experienced strokes, researchers at Washington University School of Medicine in St. Louis identified two genes associated with recovery within the pivotal first 24 hours after stroke. Events -- good or bad -- that occur in the first day set stroke patients on their courses toward long-term recovery. Both genes turned out to be involved in regulating neuronal excitability, providing evidence that overstimulated neurons influence stroke outcomes.

"There's been this lingering question about whether excitotoxicity really matters for stroke recovery in people," said co-senior author Jin-Moo Lee, MD, PhD, the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology. "We can cure stroke in a mouse using blockers of excitotoxicity. But in humans we performed numerous clinical trials, and we couldn't move the needle. Every last one of them was negative. In this study, out of 20,000 genes, the top two genetic hits point to mechanisms involving neuronal excitation. That's pretty remarkable. This is the first genetic evidence that shows excitotoxicity matters in people and not just in mice."

Every year nearly 800,000 people in the U.S. have ischemic strokes, the most common kind of stroke. Ischemic strokes occur when a clot blocks a blood vessel and cuts off oxygen to part of the brain, triggering sudden numbness, weakness, confusion, difficulty speaking or other symptoms. Over the next 24 hours, some people's symptoms continue to worsen while others' stabilize or improve.

In the 1990s, Dennis Choi, MD, PhD, then head of the Department of Neurology at Washington University, performed groundbreaking research on excitotoxicity in stroke. He and others showed that stroke can cause neurons to release large amounts of glutamate, a molecule that transmits excitatory messages between neurons. Glutamate is constantly being released by neurons as part of the normal functioning of the nervous system, but too much all at once can be toxic. Efforts to translate this basic research into therapies for people did not pan out, and eventually pharmaceutical companies let their anti-excitotoxic drug development programs lapse.

But Lee, who formerly worked on excitotoxicity with Choi, did not give up. He teamed up with genetics researcher and co-senior author Carlos Cruchaga, PhD, the Barbara Burton and Reuben M. Morriss III Professor of Neurology and a professor of psychiatry; first author Laura Ibañez, PhD, an assistant professor of psychiatry; and co-author Laura Heitsch, MD, an assistant professor of emergency medicine and of neurology, to tackle the question of what drives post-stroke brain injury. The team identified people who had experienced strokes, and they looked for genetic differences between those who naturally recovered substantial function in the first day and those who did not.

As members of the International Stroke Genetics Consortium, the research team was able to study 5,876 ischemic stroke patients from seven countries: Spain, Finland, Poland, the United States, Costa Rica, Mexico and South Korea. They measured each person's recovery or deterioration over the first day using the difference between their scores on the National Institutes of Health (NIH) Stroke Scale at six and 24 hours after symptoms first appeared. The scale gauges a person's degree of neurological impairment based on measures such as the ability to answer basic questions such as "How old are you?"; to perform movements such as holding up the arm or leg; and to feel sensation when touched.

The researchers performed a genomewide association study by scanning the participants' DNA for genetic variations related to the change in their NIH stroke scale scores. The top two hits were genes that coded for the proteins ADAM23 and GluR1. Both are related to sending excitatory messages between neurons. ADAM23 forms bridges between two neurons so that signaling molecules such as glutamate can be passed from one to the other. GluR1 is a receptor for glutamate.

"We started with no hypotheses about the mechanism of neuronal injury," Cruchaga said. "We started with the assumption that some genetic variants are associated with stroke recovery, but which ones they are, we did not guess. We tested every single gene and genetic region. So the fact that an unbiased analysis yielded two genes involved in excitotoxicity tells us that it must be important."

In the years since anti-excitotoxic drug development was abandoned, clot-busting drugs have become the standard of care for ischemic stroke. Such drugs aim to restore blood flow so that oxygen -- and anything else in the bloodstream, including medication -- can reach affected brain tissue. Consequently, experimental neuroprotective therapies that failed in the past might be more effective now that they have a better chance of reaching the affected area.

"We know that that first 24-hour period has the greatest impact on outcomes," Lee said. "Beyond 24 hours, there's diminishing returns in terms of influence on long-term recovery. Right now, we don't have any neuroprotective agents for that first 24 hours. Many of the original studies with anti-excitotoxic agents were performed at a time when we weren't sure about the best trial design. We've learned a lot about stroke in the last few decades. I think it's time for a re-examination."

https://www.sciencedaily.com/releases/2022/04/220421181207.htm

Risky driving behaviors increase as common sleep disorder worsens

Diagnosing, treating sleep apnea may make driving safer for older adults

April 20, 2022

Science Daily/Washington University School of Medicine

People with sleep apnea wake up tired in the morning, no matter how many hours they actually sleep. The condition causes them to briefly stop and restart breathing dozens or even hundreds of times a night. Even though such breathing interruptions often don't awaken those with apnea, they prevent them from sinking into deep, refreshing sleep.

A new study puts a number on how dangerous such chronic tiredness can be, at least in regard to driving. For every eight additional breathing interruptions per hour, the odds of making a dangerous driving move such as speeding, braking hard or accelerating suddenly increase by 27%, according to a study by researchers at Washington University School of Medicine in St. Louis.

Older adults are more likely to develop sleep apnea. They also are more likely to be seriously injured or killed in a car accident. The findings, available online in the journal Sleep, suggest that screening older adults for sleep apnea and for treatment, if needed, may help older people continue driving safely for longer.

"The percentage of older adults with mild sleep apnea is 30% to 50%, but if such adults don't have daytime sleepiness or other evidence of impairment, they may not come to medical attention," said co-senior author Brendan Lucey, MD, an associate professor of neurology and director of Washington University's Sleep Medicine Center. "However, these findings suggest that we might want a lower threshold to evaluate older adults for sleep apnea and track their breathing interruptions. If their conditions worsen by just eight interruptions an hour, that could have significant adverse effects on their driving and their risk of suffering serious injury."

People 65 and over are the most responsible drivers on the road. They obey speed limits. They drive defensively. They avoid driving at night, in bad weather and in unfamiliar places. But the changes that often come with advancing age -- such as deteriorating vision, slower reflexes and, yes, difficulty sleeping -- can undermine even the safest habits.

Lucey teamed up with driving researcher Ganesh M. Babulal, PhD, OTD, an assistant professor of neurology and the paper's co-senior author, to investigate the relationship between sleep apnea and risky driving behaviors. Participants were recruited from ongoing studies at Washington University's Charles F. and Joanne Knight Alzheimer Disease Research Center (Knight ADRC).

Babulal and Lucey monitored the driving and sleep habits of 96 older adults under real-world conditions. They used a commercially available take-home test to identify people with sleep apnea and measure its severity. Less than five breathing interruptions per hour is considered normal, five to 15 is mild sleep apnea, 15 to 30 is moderate, and greater than 30 is severe.

To assess driving habits, the researchers installed a chip developed by Babulal and colleagues into participants' personal vehicles and monitored their driving for a year, focusing on episodes of hard braking, sudden acceleration and speeding. In total, they collected data on more than 100,000 trips. Participants also were evaluated by researchers at the Knight ADRC for cognitive impairments and molecular signs of early Alzheimer's disease.

Even though all participants were cognitively normal, about a third had brain changes indicative of early Alzheimer's disease. The researchers found that the frequency with which drivers made dangerous moves behind the wheel rose in parallel with the frequency with which their sleep was interrupted at night, regardless of whether their brains bore the marks of early Alzheimer's.

"We didn't have cameras in the vehicles, so we don't know exactly what happened that caused someone to, say, brake hard suddenly," Babulal said. "But it could be something like a stoplight that they didn't realize was red until they got close and had to stomp on the brakes. The more tired you are, the less attention you have to deploy to the task at hand, especially if it is novel and constantly changing."

The study helps untangle the ways aging-associated risk factors such as poor sleep and Alzheimer's disease put older adults in danger while driving, and could aid efforts to find ways to maximize years of safe driving, the researchers said.

"Driving always carries the risk of crashing, and older adults are at risk of more severe injury than younger adults if they experience a crash," Babulal said. "But we can't just tell them to give up their keys. When older people stop driving, they lose a lot of their independence and mobility, which is often associated with negative health and social outcomes. What we want to understand is what puts them at a higher risk so we can intervene and help them stay behind the wheel, safely, for as long as possible."

https://www.sciencedaily.com/releases/2022/04/220420170509.htm

Scientists discover mechanism behind chemically induced suppression of fearful memories

April 25, 2022

Science Daily/Tokyo University of Science

Fearful events negatively impact the brain. For instance, war veterans often go through post-traumatic stress disorder months after the cessation of the triggering event. Now, in a study led by Tokyo University of Science researchers, the precise mechanism of suppression of such fearful memories has been uncovered. Using a mouse model, the researchers identified the associated biochemical pathways, thus paving the way for the development and clinical evaluation of therapeutic compounds such as KNT-127.

Tragic events like wars, famines, earthquakes, and accidents create fearful memories in our brain. These memories continue to haunt us even after the actual event has passed. Luckily, researchers from Tokyo University of Science (TUS) have recently been able to understand the hidden biochemical mechanisms involved in the selective suppression of fearful memories, which is called fear extinction. The researchers, who had previously demonstrated fear extinction in mice using the chemically synthesized compound "KNT-127," have now identified the underlying mechanism of this compound's action. Their findings have been published recently in Frontiers in Behavioral Neuroscience.

Prof. Akiyoshi Saitoh, lead author of the study, and Professor at TUS, muses, "Drugs that treat fear-related diseases like anxiety and posttraumatic stress disorder must be able to help extinguish fear. We previously reported that KNT-127, a selective agonist of the d-opioid receptor or DOP, facilitates contextual fear extinction in mice. However, its site of action in the brain and the underlying molecular mechanism remained elusive. We therefore investigated brain regions and cellular signaling pathways that we assumed would mediate the action of KNT-127 on fear extinction."

"We investigated the molecular mechanism of KNT-127-mediated suppression of fearful memories. We administered KNT-127 to specific brain regions and identified the brain regions involved in promoting fear extinction via delta receptor activation," elaborates Dr. Daisuke Yamada, co-author of the study, and Assistant Professor at TUS.

Using a mouse model, the research team performed fear conditioning test on laboratory mice. During fear conditioning, mice learn to associate a particular neutral conditioned stimulus with an aversive unconditioned stimulus (e.g., a mild electrical shock to the foot) and show a conditioned fear response (e.g., freezing).

After the initial fear conditioning, the mice were re-exposed to the conditioning chamber for six minutes as part of the extinction training. Meanwhile, the fear-suppressing therapeutic "KNT-127" was microinjected into various regions of the brain, 30 minutes prior to re-exposure. The treated brain regions included the basolateral nucleus of the amygdala (BLA), the hippocampus (HPC), and the prelimbic (PL) or infralimbic subregions (IL) of the medial prefrontal cortex. The following day, the treated mice were re-exposed to the chamber for six minutes for memory testing. The fear-suppressing "KNT-127" that infused into the BLA and IL, but not HPC or PL, significantly reduced the freezing response during re-exposure. Such an effect was not observed in mice that did not receive the KNT-127 treatment, thus confirming the fear-suppressing potential of this novel compound.

Chemical compounds known to inhibit the actions of key intracellular signaling pathways like PI3K/Akt and MEK/ERK pathways reversed the therapeutic effect, thereby suggesting the key roles of these two pathways in influencing KNT-127-mediated fear extinction.

The first author of the study, Ayako Kawaminami, who is currently pursuing research at TUS, says, "The selective DOP antagonist that we used for pretreatment antagonized the effect of KNT-127 administered into the BLA and IL. Further, local administration of MEK/ERK inhibitor into the BLA and of PI3K/Akt inhibitor into the IL abolished the effect of KNT-127. These findings strongly indicated that the effect of KNT-127 is mediated by MEK/ERK signaling in the BLA, by PI3K/Akt signaling in the IL, and by DOPs in both brain regions. We have managed to show that DOPs play a role in fear extinction via distinct signaling pathways in the BLA and IL."

PTSD and phobias are thought to be caused by the inappropriate or inadequate control of fear memories. Currently, serotonin reuptake inhibitors and benzodiazepines are prescribed during therapy. However, many patients do not derive significant therapeutic benefits from these drugs. Therefore, there is an urgent need for the development of new therapeutic agents that have a different mechanism of action from existing drugs.

Dr. Hiroshi Nagase, a Professor at University of Tsukuba and a coauthor of the study, concludes, "We have succeeded in creating KNT-127 by successfully separating convulsion- and catalepsy-inducing actions, which has so far been extremely difficult. Our findings will provide useful and important information for the development of evidence-based therapeutics with a new mechanism of action, that is targeting DOP."

Fighting fear with the right therapeutic is the need of the hour, as anxiety and stress increase globally, and the findings of this study could help us achieve this objective. We have our fingers crossed.

https://www.sciencedaily.com/releases/2022/04/220425104337.htm

Study: Economic burden of PTSD 'staggering'

U.S. civilian, military populations combine for more than $230 billion in annual costs

April 25, 2022

Science Daily/Veterans Affairs Research Communications

A new study finds that the national economic burden of PTSD goes beyond direct health care expenses and exceeds the costs of other common mental health conditions, such as anxiety and depression.

The researchers estimated the cost of PTSD at $232.2 billion for 2018, the latest year for which data were available at the time of the study. They called for increased awareness of PTSD, more effective therapies, and the expansion of evidence-based strategies to "reduce the large clinical and economic burden" of that mental health condition.

The results appeared online in the Journal of Clinical Psychiatry on April 25, 2022.

"The $232 billion annual economic burden of PTSD in the U.S. demonstrated in this study is staggering and fuels the urgency for public and private stakeholders to work together to discover new and better treatments, reduce stigma, improve access to existing treatments, and expand evidence-based recovery and rehabilitation programs," the researchers write.

Dr. Lori Davis, the associate chief of staff for research at the Tuscaloosa Veterans Affairs Medical Center in Alabama, led the study. She and her team used insurance claims data, academic literature, and government publications to estimate the costs of PTSD in both the U.S. civilian and military populations. The latter cohort included active-duty military and veterans.

Understanding the complex nature of posttraumatic stress disorder, commonly known as PTSD, is one of VA's most pressing challenges. The agency says many veterans who fought in Vietnam, the Gulf War, and the post-9/11 conflicts in Iraq and Afghanistan have had that mental health condition sometime in their lives.

PTSD symptoms are well documented: re-experiencing of trauma through flashbacks and nightmares; avoidance of reminders of a traumatic event; changes in thoughts and feelings, such as guilt and emotional numbing; insomnia; and hyperarousal.

In the study, the investigators brought to light the extent to which PTSD not only impacts veterans, but civilians, as well. The research team found that civilians accounted for 82% of the total PTSD costs, compared with 18% for the military population. That disparity is predicated on the fact that the number of civilians far exceeds that of active-duty military and veterans. Although PTSD is more prevalent in the military, the number of civilians with PTSD still tops the number of Veterans with that condition.

Davis and her colleagues noted that more studies on PTSD and its treatments are needed to address the rise in civilians with PTSD, calling that phenomenon a "rapidly accumulating societal burden." Improved access to effective treatments is also needed, especially for people in economically vulnerable situations," she noted.

"Much of the research and legislative response on PTSD has focused on combat-exposed populations due to the high prevalence of the condition among the military population," the researchers write. "However, the military population composed a small proportion of the overall U.S. population with PTSD.

"With the increasing occurrence of national and societal traumatic events around the world, including COVID-19, civil unrest, and climate change, there is mounting concern of an increase in PTSD and burden in the civilian population. As such, the current cost estimate is likely an underestimation given these recent global traumas, the effects of which would not have been captured and are likely to result in increasing negative repercussions."

Although civilians accounted for more than three times the total PTSD costs, the annual costs per civilian with PTSD ($18,640) were lower than that in the military population ($25,684). In the civilian population, direct health care and unemployment costs accounted for the economic burden, while disability and direct health care costs drove the burden in the military population. Non-direct health costs such as disability payments are higher in military populations, according to Davis. The expansion of supported employment services for PTSD patients is overdue and could address the growing disability and unemployment crisis in veterans, she says.

The researchers also found that women represented 66% and 74% of the overall and civilian population with PTSD, respectively, thereby contributing disproportionally to the national costs. Research has shown that trauma-exposed women show higher levels of PTSD symptoms than trauma-exposed men. Plus, traumas such as sexual assault and domestic violence tend to affect more women than men and represent important areas for prevention and treatment.

The study notes that the substantial economic burden of PTSD highlights the "urgent and unmet" need for treating and rehabilitating people with the disorder.

"Experts agree that there is a long-standing crisis in pharmacologic drug development for the treatment of PTSD, as no medication has been FDA-approved for PTSD since the only two marketed agents were approved 20 years ago," the researchers write. "Additionally, there is a scarcity of evidence on the impact of available pharmacologic and psychological treatments and the interplay between the two on patient-centered outcomes, such as quality of life, well-being, interpersonal relationships, and occupational functioning. A burden that is often ignored in economic calculations is the cost for psychotherapy not covered under health plans, which represents a significant out-of-pocket [expense] for someone with PTSD, as demonstrated in the current study."

What does all of this mean for getting PTSD costs under control in the future?

"It is important to remember that we have effective treatments for PTSD," says Dr. Paula Schnurr, executive director of VA's National Center for PTSD. "One potential implication of this study's findings is that increasing treatment could reduce not only the symptom burden on people but also the economic costs to society as a whole."

https://www.sciencedaily.com/releases/2022/04/220425135929.htm

Viruses in the gut may warn of a deadly disease in preterm infants

April 25, 2022

Science Daily/Arizona State University

Immediately after birth, human infants begin to develop a complex, interwoven fabric of microbes in their gut. Known collectively as the gut microbiome, this diverse ecosystem consists of bacteria, archaea, viruses and fungi, numbering in the billions. All have important roles to play in health and disease and researchers are racing to better understand their enigmatic activities.

In a new study published in the journal Nature Microbiology, Efrem Lim and his colleagues explore the galaxy of viruses present in the gut, known as the gut virome. They find that some preterm infants undergo marked alterations in their pattern of gut viruses shortly before developing a serious and often fatal disease known as necrotizing enterocolitis (NEC).

Professor Lim is a researcher in the Biodesign Center for Fundamental and Applied Microbiomics. He is also the principal investigator of the Center for Viral Genomics at ASU and an assistant professor at ASU's School of Life Sciences.

The study was conducted in collaboration with ASU colleagues and researchers from the Washington University School of Medicine.

Although the bacterial component of the gut microbiome has received considerable research attention, viruses inhabiting the gut remain a largely hidden realm. The viral signature highlighted in the study, along with changes in gut bacterial communities, could provide an early warning signal that an infant is at risk of developing NEC, allowing clinicians to take emergency action.

"For many years now, there's been some inkling that the microbiome is implicated in this rapidly developing disease," Lim says. "Studies have shown that changes in the microbiome of the gut in these preterm infants seem to predict the progression to NEC disease."

Yet teasing out the specific microbial changes leading to the disease has been challenging and the precise mechanism causing the affliction is still unknown. The current study is the first to comprehensively investigate changes in the viral microbiome that appear to set the stage for the development of NEC in preterm infants.

A microbial world is born

Microbes begin colonizing the infant gut during birth, when a baby encounters a variety of microorganisms from its mother's vaginal tract. As the baby suckles, it picks up additional microbes from its mother's skin as well as those that have infiltrated her breast milk.

The infant will acquire new microbes from other family and non-family members and even from household pets. These all become incorporated into the developing gut microbiome, composed of some 20-100 billion microbes.

This vast microbial community will go on to shape many aspects of an individual's health, throughout the person's life. Unsurprisingly, abnormal alterations in the gut microbiome can spell serious trouble and premature infants are particularly vulnerable to such disruptions.

Before their time

Preterm birth usually refers to infants born after less than 37 weeks of pregnancy. The condition appears to be on the rise, though the causes of this are not fully understood. In many low-income countries, factors including HIV, infections, malaria, and high adolescent pregnancy rates have all been implicated.

In 2020, preterm birth affected 1 of every 10 infants born in the United States. Babies born too early (particularly before 32 weeks), have higher rates of death and disability. Those that survive may experience lasting health issues, including feeding difficulties; breathing, vision and hearing problems; and abnormalities including developmental delays and cerebral palsy.

Babies born prematurely are also at risk of NEC. The disease often strikes suddenly. When babies are born after fewer than 32 weeks of gestation, the incidence of NEC ranged from 2-7% in high-income countries. Mortality among infants with necrotizing enterocolitis ranges from 22-38%.

A stealthy disease

While rarely occurring in full-term infants, this largely mysterious disease affects 1 in 1,000 premature babies. The condition strikes without warning and can cause an infant to go from appearing healthy to a dire state of illness within hours. The disease usually occurs two to six weeks after birth.

The disease produces severe inflammation of intestinal tissue, causing it to die. Such afflictions are known as necro-inflammatory diseases. A perforation may also form in the intestine, allowing bacteria to leak into the abdomen or bloodstream. The sequence of steps leading to NEC remain unclear, though risk factors are believed to include the prolonged use of antibiotics early in life and formula feeding (in addition to preterm birth).

Although studies have strongly implicated changes in the gut microbiome as contributors to the development of NEC, no single bacterial genus has been consistently associated with the disease.

Babies who survive the affliction often face lifelong health issues, which can include neurodevelopmental disabilities and a condition known as short bowel syndrome.

The role of viruses

In the current study, 138 stool samples were collected over the first 11 weeks of life. The samples were from 23 preterm infants in a neonatal intensive care unit in St. Louis, Missouri. Nine of these infants developed NEC, while 14, matched for weight and gestational age, did not.

The study explored the samples using metagenomics, a sequencing method that allows researchers to comprehensively sample genes from all organisms present in a sample. This allows microbiologists like Lim to evaluate bacterial diversity and detect microbial abundance in various environments. The technique also enables the detailed study of microorganisms that are difficult or impossible to culture in the laboratory. (In early 2020, Lim used metagenomic sequencing to rapidly probe the 30,000 letter code of the SARS CoV-2 virus, identifying a unique mutation.)

The study demonstrates that the NEC infants showed a convergence of viral and bacterial signatures in the gut virome. Notably, babies with NEC showed a reduced diversity in viral composition between communities in the gut, a feature known as ?-diversity. The diminishing viral ?-diversity occurred over a 10-day period preceding the onset of NEC, providing a potential biomarker, alerting clinicians to the looming danger. The findings suggest that the developing virome holds vital clues reflecting on the health of preterm infants.

Microbial horizons

The research could lead not only to faster diagnosis and better therapies for NEC but also for a broad range of diseases mediated by the microbiome. Further, existing therapies directed at modifying the gut microbiome, for example, fecal transplant therapy, could be further improved by taking stock of the viral component.

The study demonstrates that the underexplored viral constituents of the microbiome have much to teach us and almost certainly play an important role not only in the transition to NEC in preterm infants but also in other diseases. With new and rapidly evolving sequencing technologies, researchers can begin to mine the virome for valuable diagnostic signposts of disease and develop more effective therapies.

https://www.sciencedaily.com/releases/2022/04/220425172138.htm

Automated cognitive behavioral therapy for insomnia delivered over the internet shown to be highly effective in Black women

April 20, 2022

Science Daily/Boston University School of Medicine

Black women are disproportionately affected by poor sleep, which is associated with increased risk of adverse outcomes such as cardiovascular disease, depression and worse quality of life. The gold standard treatment for insomnia is cognitive behavioral therapy for insomnia (CBT-I), which specifically targets the individual's problematic sleep behaviors and beliefs.

Internet-delivered CBT-I programs for insomnia have been developed to increase patient access to treatment. While these programs have been shown to be very effective, the vast majority of this research has been conducted among non-Hispanic White participants. This can be an issue for minority groups who understandably may not trust the healthcare system. In particular, Black women were less likely than White women to initiate internet-delivered CBT-I, or to stay engaged with treatment once they began. Now, a study led by researchers from the Slone Epidemiology Center (SEC) at Boston University and the Division of Sleep Medicine at Harvard Medical School shows that internet-delivered CBT-I is highly effective in Black women, and that a version of the program tailored specifically for Black women improves their engagement with treatment.

In a randomized trial, 333 women with insomnia from BU's Black Women's Health Study (BWHS) -- (a large follow-up study of Black women in progress since 1995), were randomized to three internet-delivered treatments: Sleep Healthy Using the Internet (SHUTi); SHUTi-BWHS, a culturally-tailored version of SHUTi developed specifically for Black women, guided by a team of stakeholders including Black women; and patient education about sleep (PE).

The trial participants were unaware of the program to which they had been assigned. The PE group was provided with sleep education materials, such as sleep hygiene recommendations, while the women assigned to SHUTi and SHUTi-BWHS worked their way through the interactive program that contained six "modules" addressing various aspects of sleep. The modules delivered CBT-I using psychoeducational content, customized recommendations based on the participant's reported sleep, videos highlighting common challenges that insomnia patients experience when implementing CBT-I, and advice from experts. The SHUTi-BWHS program addressed key issues that may be more likely to affect a Black woman's sleep, with all of the program's visual content revamped to include only Black patients and sleep physicians.

Participants in both SHUTi and SHUTi-BWHS had greater improvements in their insomnia symptoms compared with the PE group, with these gains sustained at 6 months after program completion. Significantly more women receiving SHUTi-BWHS completed the program than those receiving SHUTi. This is important as women who completed either SHUTi or SHUTi-BWHS were more likely to see their sleep improve.

"While Internet-delivered interventions offer better access to evidence-based care, patient adherence with automated programs that are designed to change health behaviors can be an issue. The development of a culturally tailored intervention may be the key to better engaging minority patients with proven insomnia treatment," explains senior author Lynn Rosenberg, ScD, epidemiologist at the SEC and a principal investigator of the BWHS.

The leaders of the study were encouraged that efforts to address sleep problems facing Black women was successful. "Profound health inequities affect the lives of so many racial/ethnic minority patients. We are proud to have conducted research designed specifically to address sleep health disparities in Black women, and are hopeful that this work spurs further interest and investment into research in this critical domain," said corresponding author Eric Zhou, PhD, clinical psychologist, Dana-Farber Cancer Institute.

https://www.sciencedaily.com/releases/2022/04/220420113004.htm

Fetal exposure to meds may affect infants' brain development

April 20, 2022

Science Daily/University of Helsinki

New study demonstrates that in utero exposure to mother's antiepileptic or antidepressant medication may affect development of the newborn brain networks. In the study, novel mathematical methods were developed to allow future research on how commonly used drugs or other environmental conditions affect the newborn brain.

Pregnant mothers may need treatment for their medical conditions, such as mood disorder or epilepsy. The effects of such drug treatment on newborn brain network functions was examined in a study conducted at the BABA Center, a research unit in University of Helsinki and New Children's Hospital of HUS Helsinki University Hospital. The study used electroencephalography (EEG) to measure electrical brain activity during sleep, and cortical network properties were calculated using advanced mathematical techniques.

"In prior studies, we have shown that changes in cortical activity across sleep states may provide important information on infants' neurological condition," Senior Researcher Anton Tokariev says.

The study demonstrated that exposure to antiepileptics and antidepressants during the fetal period leads to widespread changes in the cortical networks, and these effects may be specific to the type of drug exposure. In the case of antidepressants, the effect was more pronounced in local cortical networks. In contrast, exposure to antiepileptics had drug-specific effects on brain wide networks. Both drug types affected brain networks that are reactive to changes in sleep stages.

"What was clinically significant in the findings was that, some EEG findings linked to children's subsequent neuropsychological development. Stronger changes in neural networks predicted a greater deviation in development at two years of age," says Mari Videman, specialist in paediatric neurology at HUS Helsinki University Hospital.

Shedding new light on early brain development

The studies offer an entirely new way of assessing the effects of pharmaceutical agents on the development of child's brain function.

"The EEG measurement technique developed at the BABA Center and its associated state-of-the-art mathematical assessment of the brain's neural networks constitute breakthroughs in clinical research on early neurodevelopment," Professor Sampsa Vanhatalo says.

Vanhatalo considers it particularly important that these EEG -based measures open a window into mechanisms that operate between neuronal cell. This leads to an opportunitity to compare results observed in human children with research conducted using laboratory-animal models. Such translational work is needed to understand the mechanistic underpinnings of the drug effects. For instance, identical animal work is required to study how the amount or timing of maternal drug treatment would affect brain function of the offspring.

"Our novel methods provide a general analytical framework to support extensive future research on the questions how fetal brain development is affected by changes in intrauterine environment. Such studies may go far beyond maternal drug treatment, including also mother's nutrition and overall physical condition, as well as myriad of further environmental factors," Vanhatalo summarises.

https://www.sciencedaily.com/releases/2022/04/220420092203.htm

Childhood abuse linked to higher risk for high cholesterol as an adult

April 27, 2022

Science Daily/American Heart Association

The likelihood of developing high cholesterol -- a risk factor for heart disease and stroke -- was higher among white men and white women who experienced abuse during childhood, according to a study of more than 5,000 Black and white adults in the U.S. In contrast, growing up in a well-managed household with family members who were involved and engaged in the child's life offset the higher risk of high cholesterol among white women and Black men who reported abuse during childhood.

A new study found risk factors for heart disease and stroke were higher among adults who said they experienced childhood abuse and varied by race and gender. However, those who described their family life as well-managed and had family members involved in their lives during childhood were less likely to have increased cardiovascular risk factors as adults, according to new research published today in the Journal of the American Heart Association, an open access, peer-reviewed journal of the American Heart Association.

Although cardiovascular disease, which includes heart disease and stroke, is more common among older people, the risks often begin much earlier in life. Previous research confirms physical and psychological abuse and other adverse experiences in childhood increase the risk of developing obesity, Type 2 diabetes, high blood pressure and high cholesterol, which, in turn, increase the risk for cardiovascular diseases, as detailed in the 2018 American Heart Association Scientific Statement: Childhood and Adolescent Adversity and Cardiometabolic Outcomes.

Conversely, healthy childhood experiences -- nurturing, loving relationships in a well-managed household, including having family members who are involved and engaged in the child's life -- may increase the likelihood of heart-healthy behaviors that may decrease the cardiovascular disease risks. In this study, researchers explored whether nurturing relationships and well-managed households may offset the likelihood of higher cardiovascular risk factors.

"Our findings demonstrate how the negative and positive experiences we have in childhood can have long-term cardiovascular consequences in adulthood and define key heart disease risk disparities by race and sex," said study lead author Liliana Aguayo, Ph.D., M.P.H., social epidemiologist and research assistant professor at Emory University's Rollins School of Public Health in Atlanta.

Researchers examined information from the Coronary Artery Risk Development in Young Adults (CARDIA) Study, an ongoing, long-term study among 5,115 Black and white adults enrolled from 1985-1986 to 2015-2016. Study enrollment occurred in four U.S. cities: Birmingham, Alabama; Chicago; Minneapolis; and Oakland, California. More than half of the study participants were women, and nearly half were Black adults. At the start of the study, participants were 25 years old, on average. All participants received initial clinical examinations and eight additional examinations every few years to assess cardiovascular risks over 30 years.

At ages 33 to 45, participants completed a survey of questions to assess areas of their family life during childhood. For this analysis, three areas were examined:

• Abuse: how often a parent or adult in their home pushed, grabbed, shoved or hit them so hard that they were injured; and how often a parent or adult in their home swore at them, insulted them or made them feel threatened.

• Nurturing: how often a parent or adult made them feel loved, supported or cared for; and how often a parent or adult in the family expressed gestures of warmth and affection.

• Household organization: did they feel the household was well-managed, and did their family know where they were and what they were doing most of the time. (No definitions or criteria were provided for the term "well-managed;" study participants were instructed to determine if the term described their childhood family experience.)

Participants were categorized based on their responses to the survey questions:

• Roughly 30% of participants reported experiencing "occasional/frequent abuse," which included those who responded, "occasionally or moderate amount of time" or "most or all of the time" to questions related to abuse.

• About 20% of participants reported they experienced abuse "some or little of the time," which was categorized as "low abuse."

• About half of the participants reported no childhood abuse and described their family life during childhood as nurturing and well-managed.

Among the adults who reported experiencing abuse during childhood, the risk of Type 2 diabetes and high cholesterol -- but not obesity and high blood pressure -- was higher, compared to the adults who reported no abuse in childhood. The increase in risk, however, appeared to vary depending on gender and race.

Researchers noted:

• The risk of high cholesterol was 26% higher among white women and 35% higher among white men who reported low levels of abuse in childhood, compared to same sex and race adults who reported no abuse in childhood.

• The risk of Type 2 diabetes was 81% higher among white men who reported occasional/frequent abuse during childhood, compared to adults who reported no abuse in childhood.

• Black men and white women who said they experienced abuse and grew up in a dysfunctional household were more than 3.5 times as likely to develop high cholesterol as those who reported no abuse during childhood. In contrast, among people who reported growing up in a well-managed household, the risk of high cholesterol decreased by more than 34%.

• An unexpected finding: The risk for cardiovascular disease risk factors was not higher among Black women who reported experiencing abuse in childhood.

Several limitations may have affected the study's results. This study was a retrospective analysis of data collected in the CARDIA study in 2015-2016; no new surveys were conducted with the CARDIA study participants. The questionnaires about childhood family experiences were completed when the participants were adults, relying on memories, which may include some inaccuracies or incomplete recollections. In addition, participants' BMI (body mass index), which is a measurement of weight according to height, was recorded only in adulthood, with no data on BMI during childhood for comparison.

"Further research is needed to better understand the potential mechanisms linking childhood abuse and family environment to higher heart disease risk factors, as well as the impact of structural racism and social determinants of health, which likely influenced the differences we found by race and sex," Aguayo said. "This information is critical to strengthening cardiovascular disease prevention interventions and policies, particularly those that focus on people who experienced abuse or other trauma during childhood."

https://www.sciencedaily.com/releases/2022/04/220427100503.htm

Tree-filled spaces are more favorable to child development than paved or grassy surfaces

Areas with tree cover may provide greater mitigation of air pollution, noise and heat than more open green spaces

April 21, 2022

Science Daily/Barcelona Institute for Global Health (ISGlobal)

A study recently published in Environment International has found that living in a tree-filled environment is associated with better early childhood development than living in an environment where vegetation takes the form of grass cover. The analysis -- led by Matilda van den Bosch, senior researcher at the Barcelona Institute for Global Health (ISGlobal), a centre supported by the "la Caixa" Foundation -- also found that both varieties of green space are associated with better child development outcomes than areas dominated by paved surfaces.

The study reinforces the notion -- supported by a growing body of research -- that green spaces are associated with better attention and memory in early childhood, higher academic achievement, and fewer emotional and behavioural problems. However, the research team wanted to go further and explore whether the type of vegetation makes a difference in these positive associations. All green spaces appear to promote health, but tree-filled areas may mitigate air pollution, noise and heat better than more open green spaces, while also doing more to support restoration from mental fatigue and the capacity for directed attention. Grassy spaces, in contrast, may do more to encourage group activities and therefore foster social well-being. Paved surfaces, meanwhile, are associated with more heat exposure and traffic-related air and noise pollution.

How the Study Was Conducted

The analysis was carried out in the Vancouver metropolitan area (Canada) and was based on a large birth cohort containing data on 27,539 children. These data were collected between 2000 and 2005 by various government bodies, including the British Columbia Ministry of Health. The children were followed from birth to age five years, at which time their kindergarten teachers rated their physical health and well-being, social competence, emotional maturity, language and cognitive development, communication skills and general knowledge. The teachers performed this assessment using a tool known as the Early Development Instrument (EDI).

The researchers used a high-spatial-resolution land cover map to determine whether the areas where the children lived were vegetated or non-vegetated and whether the vegetated land consisted of grass or trees (predominantly deciduous). The mean percentage of total vegetation exposure was found to be 36%, while the mean percentage of paved surfaces exposure was slightly lower at 32.2%.

Conclusion

Children with the greatest exposure to vegetation (either trees or grass) had the highest developmental scores. This positive association was especially notable for exposure to tree-filled areas. In contrast, early-life exposure to paved surfaces was associated with poorer child development.

"Because we assessed different types of vegetation, our findings contribute to an improved understanding of associations between exposure to green spaces and early childhood development," commented Ingrid Jarvis, researcher at the University of British Columbia (Canada) and first author of the study.

Although more research is needed, these findings may be useful to urban planners. "Taken together, our findings suggest that converting paved surfaces to green spaces and, in particular, increasing the amount of trees in neighbourhoods may have positive effects on early childhood health and development," noted ISGlobal researcher Matilda van den Bosch who led the research. Such efforts would not only reap the benefits associated with green spaces, but potentially also "reduce the adverse effects associated with urbanisation and impervious environments," she added. Although the observed associations between environmental exposure and childhood development were relatively small, "even minor individual gains in childhood could lead to important public health benefits across the life course," she concluded.

https://www.sciencedaily.com/releases/2022/04/220421141608.htm

Micronutrients (vitamins + minerals) show benefit for children with ADHD and emotional dysregulation

Evidence from a randomized clinical trial shows broad-spectrum micronutrient supplementation with all known vitamins and essential minerals resulted in global improvement of attention and mood based on blinded clinician ratings

April 26, 2022

Science Daily/Elsevier

A study in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP), published by Elsevier, reports that children with ADHD and emotional regulation randomized to take a micronutrient formula were three times more likely to show symptomatic improvement on blinded clinician ratings, compared to those in the placebo group (54% versus 18%). The micronutrient formula, consisting of all known vitamins and essential minerals, was administered for eight weeks.

"Supplementing with all known vitamins and essential minerals, at doses between Recommended Daily Allowance and Upper Tolerable Limit, may improve mood and concentration in children with ADHD and emotional dysregulation," said lead author Jeanette Johnstone, PhD, Assistant Professor, Department of Child and Adolescent Psychiatry, Oregon Health & Science University and Helfgott Research Institute, National University of Natural Medicine.

"These findings, replicating results of a previous randomized trial of micronutrients in children with ADHD conducted in New Zealand, confirm that supplementation with a broad range of nutrients may benefit some children. These findings may offer guidance to doctors and families seeking integrative treatments for their children with ADHD and related emotional dysregulation," Dr. Johnstone noted.

The triple-blinded study enrolled 135 medication-free children and their parents at three sites (Portland, Oregon; Columbus, Ohio; Alberta, Canada) and randomized participants to either micronutrient or placebo capsules for eight weeks. Three-quarters of the participants were adherent to the study protocol. The intervention was well-tolerated, with no significant differences in adverse events between the micronutrient and placebo groups, or safety concerns based on blood and urine tests. Parents, children and clinicians were blinded to treatment allocation and were not able to guess assignment better than chance.

In addition to behavioral and emotional benefits, children taking micronutrients grew 6mm more in height than those taking placebo after adjusting for baseline height. "The growth finding, also a replication from the previous child micronutrient study, is particularly encouraging, as height suppression is a concern with first-line ADHD medication," Dr. Johnstone added.

In contrast to clinician ratings, parents, who were also blinded to their child's treatment allocation, reported significantly improved behavior that was equal in both the micronutrient and placebo groups, with no significant between-group differences, highlighting the importance of blinded clinician ratings.

"No treatment is 100% effective for all with ADHD," commented L. Eugene Arnold, MD, Professor Emeritus of Psychiatry & Behavioral Health at Ohio State University and one of the senior co-authors. "For example, about 2/3 respond to the first stimulant drug tried, which is an established first-line ADHD treatment despite emotional, appetite, and growth side effects. So, it's encouraging that a good half of the children responded to this relatively safe treatment."

"Future studies will focus on the micronutrients' mechanisms of action and subgroup responses to understand for whom and why this intervention works. Mechanistic hypotheses to be tested include changes in the gut microbiome and its metabolome, reductions in inflammatory markers (e.g. cytokines), replenishment of minerals, and optimization of neurotransmission. In order to increase parent sensitivity to child behavior changes, we plan to utilize real-time data reporting methods such as 'ecological momentary assessment' using a phone or other device to capture behaviors when they occur," added Dr. Johnstone.

https://www.sciencedaily.com/releases/2022/04/220426101650.htm

Differences in children's behavior predict midlife health behaviors

April 21, 2022

Science Daily/University of Jyväskylä - Jyväskylän yliopisto

A recent study by the Faculty of Sport and Health Sciences at the University of Jyväskylä and the Gerontology Research Center (Finland) investigated the paths from childhood socioemotional behaviour to midlife health behaviour decades later. Socioemotional behaviour at age 8 predicted health behaviour both directly and indirectly through education.

There are a wide variety of factors behind health behaviour and one of them is personality. Differences in behaviour and response style between individuals are already visible in young children. A recent paper examined the role of socioemotional behaviour in children in relation to physical activity, smoking, alcohol consumption and body mass index assessed up to 42 years later.

Well-controlled behaviour in girls, indicating a tendency to behave kindly and constructively in conflicting situations, predicted more physical activity in middle age. Social activity, which was seen, for example, as an eagerness to talk and play with other children, predicted heavier alcohol consumption in girls and smoking in boys. 

“Well-controlled behaviour may appear as good self-discipline and the ability to follow the exercise plans in adulthood,” says postdoctoral researcher Tiia Kekäläinen. “Social activity, on the other hand, may have led later to social situations where smoking and alcohol consumption were started.”

The educational path matters

Some paths between childhood socioemotional behaviour and midlife health behaviours went through education. Social activity in girls and well-controlled behaviour in both girls and boys predicted better school success in adolescence and higher education in adulthood. High educational achievement was linked, in turn, to less smoking and alcohol use.

“The results are in line with previous results based on this same longitudinal data and other studies,” says Kekäläinen. “In particular, well-controlled behaviour has been found to contribute to school success and education. These may provide information and skills that help to make healthy choices. The results of this paper suggest that differences in individuals' behaviour already visible in childhood are reflected in adulthood both directly and through various mediating mechanisms.”

The study was part of the Jyväskylä Longitudinal Study of Personality and Social Development (JYLS) in which the same individuals have been followed since 1968 when they were 8 years old. This study used data on socio-emotional behaviour and parental socioeconomic status at age 8, school success at age 14, educational background at age 27, personality traits at age 33, and health behaviours at age 36, 42, and 50. The data collection in JYLS at various stages has been funded by the Academy of Finland (latest funding number 323541) and the writing of this publication was funded by the Ministry of Education and Culture (PATHWAY-project).

https://www.sciencedaily.com/releases/2022/04/220421181217.htm