Walking more than five flights of stairs a day can cut risk of heart disease by 20 percent

September 29, 2023

Science Daily/Tulane University

Forget walking 10,000 steps a day. Taking at least 50 steps climbing stairs each day could significantly slash your risk of heart disease, according to a new study from Tulane University.

The study, published in Atherosclerosis, found that climbing more than five flights of stairs daily could reduce risk of cardiovascular disease by 20%.

Atherosclerotic cardiovascular disease (ASCVD) along with coronary artery disease and stroke are the leading causes of morbidity and mortality worldwide.

"Short bursts of high-intensity stair climbing are a time-efficient way to improve cardiorespiratory fitness and lipid profile, especially among those unable to achieve the current physical activity recommendations," said co-corresponding author Dr. Lu Qi, HCA Regents Distinguished Chair and professor at the Tulane University School of Public Health and Tropical Medicine. "These findings highlight the potential advantages of stair climbing as a primary preventive measure for ASCVD in the general population."

Using UK Biobank data collected from 450,000 adults, the study calculated participants' susceptibility to cardiovascular disease based on family history, established risk factors and genetic risk factors and surveyed participants about their lifestyle habits and frequency of stair climbing. Median follow-up time was 12.5 years.

The study found that climbing more stairs daily especially reduced risk of cardiovascular disease in those who were less susceptible. However, Qi said the increased risk of heart disease in more susceptible people could be "effectively offset" by daily stair climbing.

Qi touted the public availability of stairs as a low-cost, accessible way to incorporate exercise into daily routines.

"This study provides novel evidence for the protective effects of stair climbing on the risk of ASCVD, particularly for individuals with multiple ASCVD risk factors," Qi said.

https://www.sciencedaily.com/releases/2023/09/230929131402.htm

How parents' work stress affects family mealtimes and children's development

September 29, 2023

Science Daily/University of Illinois College of Agricultural, Consumer and Environmental Sciences

Family mealtimes are important for parents and children as a space to communicate, socialize, and build attachment relationships. But it can be difficult for busy parents to balance family and work life. A new study from the University of Illinois Urbana-Champaign explores how parents' job stress influences their attendance at family mealtimes, and in turn, children's socioemotional development.

"We all struggle to maintain the balance between work life and family life. But this might be especially challenging for parents, who are engaging in childcare after a busy and stressful day at work. And when it comes to co-parenting in dual-earner families, which comprises 65% of families with children in United States, we do not know much about how mothers and fathers share caregiving roles under work stress," said lead author Sehyun Ju, doctoral student in the Department of Human Development and Family Studies (HDFS) in the College of Agricultural, Consumer and Environmental Sciences (ACES) at U. of I.

The study included data from more than 1,400 dual-earner families, consisting of heterosexual married couples with children, in a nationally representative survey that traced children's development across family, home, child care, and school environments from 9 months to kindergarten. The researchers focused on the interplay of child characteristics, family mealtimes, and parents' job and financial dissatisfaction.

"We found that children of parents who expressed higher work-related stress when the children were 2 years old had lower socioemotional competency at age 4 to 5, measured by lower positive and higher negative social behaviors," Ju explained.

There were significant differences regarding the impact of mothers' and fathers' work stress. For mothers, higher job dissatisfaction did not impact frequency of family mealtimes; however, it was directly associated with lower socioemotional competency in their children.

On the other hand, fathers who had higher job and financial dissatisfaction were less likely to attend family mealtimes with their children, and this in turn resulted in the children having lower socioemotional competency at age 4 to 5.

"Even when the mother increased her mealtime presence to compensate for the father's absence, the child's socioemotional development was still negatively impacted. This indicates fathers may have a unique influence that cannot be replaced by the mother. Future intervention programs should help both parents obtain a better balance between work and family, and highlight the importance of family routines to promote healthy child development," stated co-author Qiujie Gong, a doctoral student in HDFS.

The findings speak to the pervasiveness of traditional gender roles, added Karen Kramer, associate professor in HDFS and co-author on the study. "Mothers are considered primary caregivers, and they are expected to be present and feed their children no matter what. The study showed they didn't adjust their mealtime frequencies in response to job dissatisfaction as fathers did."

Kramer notes the study is unique in combining topics from different disciplines, including psychology, sociology, economics, and nutrition, and connecting them in a holistic way that provides insights for policy measures.

"We have to acknowledge the challenges that families face in creating consistent routines. It's not just an outcome of individual influences. Outside factors, such as parents' work environment and financial situation can affect their interactions, mealtimes, and child development. For example, dinner time for young kids is typically around five or six o'clock, but the expectation that parents are home early in the day doesn't align with being an ideal worker. Policy initiatives to help provide a work environment and community support that facilitate family mealtimes would be important," Kramer concluded.

https://www.sciencedaily.com/releases/2023/09/230929131409.htm

Job loss is linked to increased risk of miscarriage and stillbirth

September 28, 2023

Science Daily/European Society of Human Reproduction and Embryology

Researchers have found a link between a pregnant woman or her partner losing their job and an increased risk of miscarriage or stillbirth.

The study, which is published today (Thursday) in Human Reproduction, one of the world's leading reproductive medicine journals, found a doubling in the chances of a pregnancy miscarrying or resulting in a stillbirth following a job loss.

The researchers, led by Dr Selin Köksal from the Institute for Social and Economic Research at the University of Essex, UK, emphasise that their findings highlight an association between job loss and an increased probability of miscarriage or stillbirth and that the study cannot show that losing a job causes the pregnancy loss.

"Further research would need to be carried out to understand if losing one's job actually causes the increased risk of pregnancy loss," she said. "I would like to analyse socioeconomic factors influencing pregnancy loss in contexts where data for the entire population are available through administrative records. These data can help clarify whether there are solid causal links between job loss and pregnancy loss, and whether there are certain socioeconomic groups in the population that are particularly at risk, such as economically precarious employees.

"Being able to examine the association between job loss and pregnancy loss among different socioeconomic groups could help us to understand how exactly a job loss is related to higher risk of a miscarriage or a stillbirth. Is it because of economic hardship, or an experience of an unexpected event or is it due to loss of social status? These are the questions that I am hoping to answer in the future."

The study is based on data from the "Understanding Society" survey of 40,000 households in the UK between 2009 and 2022. It includes 8142 pregnancies for which there was complete information on the date of conception and pregnancy outcome.

Out of these pregnancies, 11.6% miscarried (947), which may be an underestimate because many pregnancies do not survive beyond the first month and pregnancy loss can go undetected. There were 38 stillbirths, representing 0.5% of conceptions, which is in line with the UK's official statistics for stillbirths.

Out of 136 women who were affected by their own or their partner's job loss, 32 (23.5%) miscarried and one (0.7%) had a still birth. Among 8006 women who were not affected by their own or their partner's job loss, 915 (10.4%) miscarried and 37 (0.5%) had a stillbirth.

Co-author of the paper, Dr Alessandro Di Nallo, from the Dondena Centre for Research on Social Dynamics and Public Policy at Bocconi University, Milan, Italy, said: "The reasons for these associations may be related to stress, reduced access to prenatal care, or changes in lifestyle.

"My previous research indicates that job loss reduces the likelihood of having children. This might be because people postpone their plans to have children under conditions of economic uncertainty, but it could also be due to other reasons. Stress results in a physiological response, releasing hormones that are known to increase the risk of miscarriage or premature delivery. The reduction in income following a job loss could restrict access and compliance with prenatal care, so that at-risk pregnancies are discovered late or are undetected. In addition, the emotional discomfort of job loss could prompt unhealthy behaviours, such as alcohol consumption, smoking or unhealthy eating."

Dr Köksal said: "Our findings are important as we uncover a potential socioeconomic, hence preventable, factor behind pregnancy losses that can be addressed through effective policymaking.

"It is important to raise awareness of women's legal rights and protection in the workplace during pregnancy, so that women can feel safer and more empowered to communicate their pregnancy with their employer. Moreover, stress during pregnancy can have negative effects on both maternal and foetal health. So, provision of psychological support during pregnancy through the public health system is important regardless of women's and their partner's job status.

"In the UK, pregnancy is a period that is protected fairly well by labour market legislation. However, there is no job loss protection for the partners of pregnant women who are dismissed without notice.Policymakers, for instance, could consider extending job protection to workers whose partners are pregnant as our results shows that a partner's job stability is equally as important as the woman's job stability for the course of pregnancy. Additionally, it makes sense to increase economic support for individuals -- and their partners -- who lose their jobs because the lack of economic support is shown to be one of the main causes of stress and personal distress, which can eventually increase the risk of pregnancy loss."

Limitations of the study include the fact that pregnancy and job loss were self-reported and may be affected by recall and a bias towards what is socially desirable; other factors might also be correlated with both job loss and pregnancy loss; and finally the researchers do not know if the findings hold true for different socioeconomic groups.

"The UK welfare state has an anti-poverty focus and unemployment benefits are less generous than in the rest of Europe -- on average only 34% of the last job's salary for six months. Therefore, it would be interesting to see if more generous welfare regimes are better at reducing the psychosocial hardship of job loss," concluded Dr Köksal.

https://www.sciencedaily.com/releases/2023/09/230928152436.htm

Grandparent childcare may not help the wellbeing of mums or reduce mother-child conflict

September 28, 2023

Science Daily/University of Exeter

Grandparent childcare for toddlers doesn't have an impact on the wellbeing of their mothers, a new study suggests.

Extra help from another generation alone doesn't help mother- child closeness or reduce mother-child conflict, researchers have found.

Researchers who examined information from a sample of mothers could find no statistical link between their children spending time with grandparents at age three and better social and emotional development when they were seven, or better maternal wellbeing and mother-child relationship at age three.

The academics have called for more investment in child and maternal mental health and wellbeing in early childhood. Parents who took part in the study indicated grandparents were their primary source of childcare, and they had less other support.

The study was carried out by Nevra Atış Akyol, from Sivas Cumhuriyet University, Turkey, Derya Atalan Ergin, from Cappadocia University, Turkey, and Angeliki Kallitsoglou, from the University of Exeter.

The researchers examined information from 1,495 mothers and their children. The findings showed that time spent in the care of grandparents for at least six months was not significantly associated with better maternal mental health and wellbeing and mother-child relationship, or better social and emotional outcomes for children when they were seven.

The study, which used data from the Millennium Cohort Study, shows poor maternal wellbeing at age three predicted poor child social and emotional outcomes at age seven.

A total of 39.3 per cent of the children (587), spent between 1 to 10 hours with their grandparents, 33.7 per cent, (505) spent between 11 and 20 hours, and 27 per cent, (403), spent above 21 hours.The Kessler Screening Scale for Psychological Distress was used to assess maternal psychological wellbeing. The 15-item Child Parent Relationship Scale was used to measure maternal perceptions of mother-child relationship. The parent report of the 25- item Strengths and Difficulties Questionnaire was used to assess child ratings of emotional or behavioural difficulties.

"Poor maternal well-being was linked directly with more mother -- child conflict and less mother-child closeness. Poor maternal wellbeing was associated with higher level of emotional problems, conduct problems and peer problems at age seven. Both mother-child conflict and mother-child closeness were linked directly with child social and emotional difficulties when they were seven.

More mother-child conflict at age three was associated with fewer prosocial behaviours and higher levels of inattention/hyperactivity, emotional problems, peer problems and conduct problems at age seen. Lower mother-child closeness at age three was associated with fewer prosocial behaviours, and higher inattention/hyperactivity, emotional problems, peer problems, and conduct problems at age seven.

Dr Kallitsoglou said: "Our findings suggest that there is no direct relationship between maternal psychological wellbeing and the quantity of support provided to families which rely primarily on grandparental childcare arrangements.''

"While an extra pair of hands may impact maternal outcomes such as stress with child upbringing it may not potentially be enough to alleviate more distal parenting outcomes such as maternal psychological distress.''

"However, the findings are tentative. Grandparental support in the form of childcare may have different implications for maternal mental health for families who may have access to fewer resources of support, for instance, single mothers or across different ethnic groups or mothers in full time employment. So, we cannot rule out the possibility the help of grandparents for mothers with characteristics different to those in our sample to have a different impact.''

"We did not find any evidence to suggest that practical support with childcare as measured by the time children spent time in the care of grandparents during the week is beneficial for the parent-child relationship."

https://www.sciencedaily.com/releases/2023/09/230928151119.htm

Is a longer reproductive lifespan good for your brain?

September 28, 2023

Science Daily/American Academy of Neurology

People with a higher cumulative estrogen exposure throughout their life may have a lower risk of cerebral small vessel disease, according to a new study published in the September 27, 2023, online issue of Neurology®, the medical journal of the American Academy of Neurology.

Cerebral small vessel disease, a form of cerebrovascular disease, results from damage to small blood vessels in the brain. It raises the risk of cognitive impairment and dementia.

"Previous research has shown that rates of cerebrovascular disease increase after menopause, which is often attributed to the absence of hormones," said study author Kevin Whittingstall, PhD, of the University of Sherbrooke in Quebec, Canada. "It remains unknown whether the amount of exposure to hormones before menopause extends that window of protection to after menopause."

Researchers looked at the relationship between lifetime hormone exposure, or the number of times a person has been pregnant and their reproductive lifespan, and white matter hyperintensities, a common biomarker of vascular brain health that develops with age.

The study involved 9,000 postmenopausal female participants with an average age of 64 living in the United Kingdom. They did not have cerebral small vessel disease at the start of the study.

Participants answered questions on reproductive health information, including age at first menstruation and start of menopause, number of pregnancies, oral contraceptive use and hormone therapy.

Participants also had brain scans to look for cerebral small vessel disease by estimating white matter hyperintensities, which indicate injury to the brain's white matter.

Researchers calculated lifetime hormone exposure by adding up the number of years participants were pregnant with the duration of their reproductive lifespan, which is the number of years from first menstruation to menopause. The average lifetime hormone exposure was 40 years.

After adjusting for factors like age, high blood pressure, and smoking, researchers found that participants with higher lifetime hormone exposure had lower white matter hyperintensity volumes. Average total white matter hyperintensity volume was 0.0019 milliliters (ml). They found that people with higher lifetime hormone exposure had a smaller volume of white matter hyperintensities, with a difference of 0.007 ml compared to people with lower lifetime hormone exposure.

Researchers also calculated the lifetime hormone exposure by adding up the number of years participants took oral contraceptives and hormone replacement therapy. These factors did not alter the effect the number of pregnancies and number of reproductive years had on white matter hyperintensities.

The number of pregnancies participants had and their number of reproductive years both affected white matter hyperintensity volumes independently

"Our study highlights the critical role of reproductive history in shaping the female brain across the lifetime," said Whittingstall. "These results emphasize the need to integrate reproductive history into managing brain health in postmenopausal women. Future research should investigate ways to develop better hormonal therapies."

A limitation of the study was that information on reproductive factors was collected mainly based on participants' ability to recall events, and participants may not have remembered such events correctly.

The study does not prove that lower estrogen exposure causes cerebral small vessel disease; it only shows an association.

https://www.sciencedaily.com/releases/2023/09/230928152643.htm

Exposure to air pollution linked to increased risk of stroke within 5 days

September 28, 2023

Science Daily/American Academy of Neurology

Short-term exposure to air pollution may be linked to an increased risk of stroke, according to a meta-analysis published in the September 27, 2023, online issue of Neurology®, the medical journal of the American Academy of Neurology. Short-term exposure was defined as occurring within five days of the stroke.

"Previous research has established a connection between long-term exposure to air pollution and an increased risk of stroke," said study author Ahmad Toubasi, MD, of the University of Jordan in Amman. "However, the correlation between short-term exposure to air pollution and stroke had been less clear. For our study, instead of looking at weeks or months of exposure, we looked at just five days and found a link between short-term exposure to air pollution and an increased risk of stroke."

The meta-analysis involved a review of 110 studies that included more than 18 million cases of stroke.

Researchers looked at pollutants such as nitrogen dioxide, ozone, carbon monoxide and sulfur dioxide.

They also looked at different sizes of particulate matter, including PM1, which is air pollution that is less than 1 micron (µm) in diameter, as well as PM2.5 and PM10. PM2.5 or smaller includes inhalable particles from motor vehicle exhaust, the burning of fuels by power plants and other industries as well as forest and grass fires. PM10 includes dust from roads and construction sites.

People who had exposure to a higher concentration of various types of air pollution had an increased risk of stroke. Higher concentrations of nitrogen dioxide were linked to a 28% increased risk of stroke; higher ozone levels were linked to a 5% increase; carbon monoxide had a 26% increase; and sulfur dioxide had a 15% increase. A higher concentration of PM1 was linked to a 9% increased risk of stroke, with PM2.5 at 15% and PM10 at 14%.

Higher levels of air pollution were also linked to higher risk of death from stroke. Higher concentrations of nitrogen dioxide were linked to a 33% increased risk of death from stroke, sulfur dioxide, a 60% increase, PM2.5, a 9% increase and PM10, a 2% increase.

"There is a strong and significant association between air pollution and the occurrence of stroke as well as death from stroke within five days of exposure," Toubasi said. "This highlights the importance of global efforts to create policies that reduce air pollution. Doing so may reduce the number of strokes and their consequences."

A limitation of the meta-analysis was most of the studies were conducted in high-income countries, while limited data was available from low- and middle-income countries.

https://www.sciencedaily.com/releases/2023/09/230928152634.htm

Risk of premature birth from smoking while pregnant more than double previous estimates

September 28, 2023

Science Daily/University of Cambridge

Cambridge researchers have found that women who smoke during pregnancy are 2.6 times more likely to give birth prematurely compared to non-smokers -- more than double the previous estimate.

The study, published today in the International Journal of Epidemiology, also found that smoking meant that the baby was four times more likely to be small for its gestational age, putting it at risk of potentially serious complications including breathing difficulties and infections.

But the team found no evidence that caffeine intake was linked to adverse outcomes.

Women are currently recommended to stop smoking and limit their caffeine intake during pregnancy because of the risk of complications to the baby. For example, smoking during pregnancy is associated with an increased risk of fetal growth restriction, premature birth and low birthweight, though it has also been linked to a reduced risk of preeclampsia (high blood pressure during pregnancy).

High caffeine intake has also been shown to be associated with lower birthweights and possibly fetal growth restriction. Caffeine is more difficult to avoid than cigarette smoke as is found in coffee, tea, chocolate, energy drinks, soft drinks, and certain medications.

Studies looking at the links between smoking, caffeine and adverse pregnancy outcomes tend to rely on self-reported data to estimate exposure, which is not always reliable. A more objective measure is to look at levels of metabolites in the blood -- chemical by-products created when substances such as tobacco and caffeine are processed in the body.

Researchers at the University of Cambridge and the Rosie Hospital, part of Cambridge University Hospitals NHS Foundation Trust, recruited more than 4,200 women who attended the hospital between 2008 and 2012 as part of the Pregnancy Outcome Prediction (POP) study. The team analysed blood samples taken from a subset of these women four times during their pregnancies.

To assess exposure to cigarette smoke, the team looked at levels of the metabolite cotinine, which can be detected in blood, urine, and saliva. Only two out of three women with detectable levels of cotinine in every blood sample were self-reported smokers, showing that this measure is a more objective way of assessing smoking behaviour.

A total of 914 women were included in the smoking analysis. Of these, 78.6% were classified as having no exposure to smoking while pregnant, 11.7% as having some exposure and 9.7% as having consistent exposure.

Compared to women who were not exposed to smoking while pregnant, those with consistent exposure were 2.6 times more likely to experience spontaneous preterm birth -- more than double the previous estimate of 1.27 from a meta-analysis of studies -- and 4.1 times as likely to experience fetal growth restriction.

Babies born to smokers were found to be on average 387g lighter than babies born to non-smokers -- that is, more than 10% smaller than the weight of an average newborn. This increases the risk that the baby will have a low birth weight (2.5kg or less), which in turn is linked to an increased risk of developmental problems as well as poorer health in later life.

Unlike in previous studies, however, the team found no evidence that smoking reduced the risk of pre-eclampsia.

Professor Gordon Smith, Head of the Department of Obstetrics and Gynaecology at the University of Cambridge, said: "We've known for a long time that smoking during pregnancy is not good for the baby, but our study shows that it's potentially much worse than previously thought. It puts the baby at risk of potentially serious complications from growing too slowly in the womb or from being born too soon.

"We hope this knowledge will help encourage pregnant mums and women planning pregnancy to access smoking-cessation services. Pregnancy is a key time when women quit and if they can remain tobacco free after the birth there are lifelong benefits for them and their child."

Smoking cessation is offered routinely to all pregnant women and the NHS has local smoking cessation services for anyone, pregnant or not. Further information is available on the NHS website (https://www.nhs.uk/live-well/quit-smoking/nhs-stop-smoking-services-help-you-quit/).

To assess caffeine intake, the researchers looked for the metabolite paraxanthine, which accounts for 80% of caffeine metabolism and is both less sensitive to recent intake and more stable throughout the day.

915 women were included in the caffeine analysis. Of these women, 12.8% had low levels of paraxanthine throughout pregnancy (suggesting low caffeine intake), 74.0% had moderate levels and 13.2% had high levels. There was little evidence of an association between caffeine intake and any of the adverse outcomes.

https://www.sciencedaily.com/releases/2023/09/230928152456.htm

Wearable device data reveals that reduced sleep and activity in pregnancy is linked to premature birth risk

September 28, 2023

Science Daily/Stanford Medicine

A lack of sleep and reduced physical activity during pregnancy are linked to risk of preterm birth, according to new research led by the Stanford School of Medicine.

In the study, which will publish online Sept. 28 in npj Digital Medicine, the researchers collected data from devices worn by more than 1,000 women throughout pregnancy. With a machine learning algorithm, the scientists sifted through participants' activity information to detect fine-grained changes in sleep and physical activity patterns.

"We showed that an artificial intelligence algorithm can build a 'clock' of physical activity and sleep during pregnancy, and can tell how far along a patient's pregnancy is," said senior study author Nima Aghaeepour, PhD, an associate professor of anesthesiology, perioperative and pain medicine and of pediatrics at Stanford Medicine. Normal pregnancy is characterized by progressive changes in sleep and physical activity as the pregnancy advances, he said. "But some patients don't follow that clock." When patients' sleep and activity levels don't change on a typical trajectory, the study showed, it',s a warning sign for premature birth, he added.

The study's lead author is Neal Ravindra, PhD, a former postdoctoral scholar at Stanford Medicine.

As the pregnancies progressed, sleep typically became more disrupted, and women became less physically active, the study showed. However, some women's sleep and activity patterns changed on an accelerated timeline relative to how far along they were in their pregnancies. These individuals were more likely to deliver early, the study found.

"The people who look 'very pregnant' to the AI algorithm -- but are not -- end up being at significantly increased risk of preterm birth," Aghaeepour said.

A struggle to prevent early deliveries

Premature birth, when a baby is born 3 or more weeks early, affects 10.5% of births in the United States; these rates are higher in some other parts of the world. Premature newborns can suffer many medical complications, including diseases of the eyes, lungs, brain and digestive system. Prematurity is the leading cause of death for children under age 5 around the world.

Research has identified a variety of risk factors for premature delivery, including greater levels of inflammation in the pregnant person, specific immune-system changes, African American race, higher levels of stress, history of having a preterm birth and certain types of bacteria in the mother's microbiome.

But doctors still can't reliably determine which pregnancies are at risk for premature delivery. Even when they know a mom is at risk -- because she's previously had a premature delivery, for example -- they still don't have great treatments to extend the pregnancy closer to the due date. Developing medications that could do this would be complex, in part because of ethical concerns regarding testing drugs that might harm the fetus.

If researchers can identify sleep and activity patterns that lower prematurity risk, they can design interventions to help expectant mothers adopt better sleep and exercise habits, a potentially low-risk way of reducing preterm births, Aghaeepour said.

Focusing on at-risk moms

The Stanford Medicine team collaborated with scientists at Washington University in St. Louis, who collected the sleep and physical activity data from 1,083 pregnant women treated there. More than half of the cohort (706 participants) were Black. In the United States, the rate of premature birth is about 50% higher in Black women than in white women.

"Our patient population experiences a lot of adversity, and our preterm birth rates are much higher than at Stanford," said study coauthor Sarah England, PhD, professor of obstetrics and gynecology at Washington University School of Medicine in St. Louis. The study participants included women experiencing a variety of stressors linked with higher rates of preterm birth, such as racism, low socioeconomic status and living in areas with higher crime rates, England said, adding that it is important for studies of preterm birth to include populations with the greatest need. "Typically, Black women and women of color have not been included in many large cohort studies," she said.

The participants wore actigraphy devices similar to smartwatches to collect once-a-minute measurements of physical activity and light exposure starting in the first trimester of pregnancy and continuing until their babies were born. The researchers also had data from participants' electronic medical records on gestational age, or how far along each pregnancy was; maternal medical conditions such as high blood pressure, diabetes, heart disease and depression; pregnancy complications such as preeclampsia and infections; and information about the birth, including duration of the pregnancy, the baby's birth weight and newborn medical complications.

With the movement and light exposure data, the research team developed a machine learning model of activity and sleep during pregnancy. The model shows that patterns of sleep and physical activity change over the course of pregnancy, which generally is associated with more sleep disruption and less physical activity as pregnancy progresses.

"Anecdotally, lots of women will say, 'Of course!'" said study coauthor Erik Herzog, PhD, professor of biology at Washington University in St. Louis, adding that, for example, women experience more sleep disruptions as the baby gets larger and more active. "But, surprisingly, the literature has not had a real consensus about what exactly happens to sleep in pregnancy," he said. Using imprecise methods to measure sleep habits, such as questionnaires, has not provided adequate answers.

The researchers were surprised at how strongly deviations from the normal pattern of sleep and physical activity could predict preterm birth. If the machine-learning model classified a woman as sleeping better and being more physically active than usual for her stage of pregnancy, this was linked with a 48% reduction in risk for preterm delivery. Conversely, if the model classified a woman as sleeping worse and being less physically active than usual for her stage of pregnancy, her risk for preterm delivery was 44% higher than for pregnant women with typical sleep and activity patterns.

Strong clues for preventing prematurity

"This is exciting preliminary data," Aghaeepour said. The results suggest that scientists should run studies to test whether tracking and modifying pregnant women's sleep or physical activity could their lower prematurity risk, he said, adding, "It's telling us where to go for future interventions."

The circadian clock regulates several other biological pathways implicated in premature birth, such as those regulating inflammation and the immune response, the scientists said. They plan to test whether improving sleep and physical activity in pregnancy could modify other key pathways, such as those controlling inflammation.

"Our feeling is that if we look at this overarching regulator, we may be able to control individual systems that lead to preterm birth," England said.

Although the findings are at an early stage, and more work is needed to understand their implications for preventing prematurity, there's little risk in advising pregnant women to maintain good sleep habits now, she added. For instance, women should try to maintain consistent bedtimes and wake-up times, get enough sleep, and get some natural light during the day to help regulate their body clock.

"I tell everyone who is pregnant, 'I hope you keep a regular sleep schedule,'" England said.

"If we can use sleep and physical activity to modulate biology in the right direction, it could be a great intervention for reducing the rate of preterm birth," Aghaeepour added.

https://www.sciencedaily.com/releases/2023/09/230928152205.htm

Exercise and muscle regulation: Implications for diabetes and obesity

September 27, 2023

Science Daily/Deutsches Zentrum fuer Diabetesforschung DZD

Prediabetes is a condition that precedes type 2 diabetes and increases the risk of heart attack, kidney and eye disease, and several types of cancer. Currently, there is no approved drug therapy for prediabetes available. Scientists at the German Center for Diabetes Research (DZD) now show how and by which mechanisms prediabetes can be brought into remission, i.e. into a state in which blood glucose levels return to normal. The multicenter study of the DZD also shows that remission of prediabetes protects against type 2 diabetes and is associated with better kidney and vascular function in the long term. Interestingly, the underlying mechanisms are different from those in type 2 diabetes remission, the researchers report in The Lancet Diabetes & Endocrinology.

People with type 2 diabetes have an increased risk of heart attack, kidney disease and stroke, and a higher mortality risk. Type 2 diabetes was thought to be irreversible until a few years ago. We now know that type 2 diabetes can be put into remission in a significant number of individuals through substantial weight loss. However, this remission rarely lasts as most people typically develop type 2 diabetes again within a few years.

"We aimed to explore the feasibility of commencing earlier and implementing preventive measures already at a stage that precedes type 2 diabetes, namely prediabetes, with the aim of reversing it," elucidates senior author Prof. Dr. Andreas Birkenfeld, Medical Director of Medical Clinic IV at Tübingen University Hospital, and Director of the Institute for Diabetes Research and Metabolic Diseases of Helmholtz Munich at the University of Tübingen. This could be crucial for patients with prediabetes as they are at increased risk to develop type 2 diabetes as well as heart, kidney, and eye complications among others.

But what causes prediabetes to go into remission? Scientists from the Institute of Diabetes Research and Metabolic Diseases (IDM) at Helmholtz Munich and the Department of Diabetology, Endocrinology, and Nephrology at the University Hospital of Tübingen, conducted a post-hoc analysis on participants with prediabetes from the Prediabetes Lifestyle Intervention Study (PLIS) to investigate this question.

In this randomized-controlled multicenter study conducted by the DZD, 1,105 individuals with prediabetes underwent a lifestyle intervention involving a healthy diet and increased physical activity for a duration of one year. The researchers then assessed the 298 participants who had achieved a minimum weight loss of five percent as a result of the intervention. Responders were the participants whose fasting blood glucose, 2-hour glucose, and HbA1c levels had normalized within twelve months, indicating that they had gone into remission. Non-responders were individuals who did not achieve remission despite losing weight and still had prediabetes.

Contrary to the researchers' initial assumptions, it was not weight loss that distinguished those who went into remission from those who did not, as there was no difference in relative weight loss between responders and non-responders. However, individuals who achieved remission demonstrated a notable improvement in insulin sensitivity compared to non-responders. In essence, they were able to enhance their sensitivity to insulin, a hormone that lowers blood glucose levels, significantly more than those who did not respond. Nonetheless, the quantity of insulin secreted remained unaltered in both groups. This difference is critical compared to type 2 diabetes remission, which depends primarily on enhanced insulin secretion.

Reducing abdominal fat mass may help reverse prediabetes

To determine the cause of increased insulin sensitivity in responders, the researchers conducted a comparative analysis of the two groups. The responders had lost more abdominal fat compared to non-responders despite losing the same amount of body weight. Visceral abdominal fat is located directly in the abdominal cavity and surrounds the intestines. Its impact on insulin sensitivity is partially attributed to an inflammatory response in adipose tissue.

Indeed, participants who went into remission also had fewer inflammatory proteins in their blood. "Since the responders showed a reduction in abdominal fat in particular, it will be important in the future to identify the factors that promote the loss of this fat depot," says Arvid Sandforth, one of the two lead-authors. Surprisingly, there were no differences between the two groups in the reduction of liver fat, which is also an important risk factor for the development of diabetes.

Participants who achieved remission showed a 73 percent reduced risk of developing type 2 diabetes even two years after the end of the lifestyle intervention. They also showed reduced markers of kidney damage and better status of their blood vessels.

Currently, treatment of prediabetes consists of weight reduction and lifestyle improvement to delay the onset of type 2 diabetes -- but without glucose-based targets to guide the treatment process. The DZD's new analysis fills this gap: "Based on the new data, remission should be the new therapeutic target in people with prediabetes. This has the potential to change treatment practice and minimize the complication rate for our patients," says co-first author Prof. Dr. Reiner Jumpertz-von Schwartzenberg.

According to the study, remission in prediabetes can be considered to have occurred when fasting blood glucose falls below 100 mg/dl (5.6 mmol/l), 2-hour glucose below 140 mg/dl (7.8 mmol/l), and HbA1c below 5.7 percent. The likelihood of remission increases when body weight is reduced and waist circumference decreases by at least about 4 cm in women and about 7 cm in men. Researchers state that these criteria can now be used as biomarkers.

https://www.sciencedaily.com/releases/2023/09/230927155347.htm

Increasing steps by 3,000 per day can lower blood pressure in older adults

This study sought to determine if older adults with hypertension could receive these benefits by moderately increasing their daily walking, which is one of the easiest and most popular forms of physical activity for this population.

September 27, 2023

Science Daily/University of Connecticut

An estimated 80% of older adults in the U.S. have high blood pressure. Maintaining healthy blood pressure can protect against serious conditions like heart failure, heart attacks, and strokes.

A new study including Linda Pescatello, distinguished professor of kinesiology in UConn's College of Agriculture, Health and Natural Resources, found that adding a relatively minimal amount of movement, about 3,000 steps per day, can significantly reduce high blood pressure in older adults.

Pescatello worked with Elizabeth Lefferts, the lead author of the paper, Duck-chun Lee, and others in Lee's lab at Iowa State University. They published their findings in a recent issue of the Journal of Cardiovascular Development and Disease.

"We'll all get high blood pressure if we live long enough, at least in this country," Pescatello says. "That's how prevalent it is."

Pescatello is an expert on hypertension (the clinical term for high blood pressure) and exercise. Her previous research has demonstrated that exercise can have a significant immediate and long-lasting impact on lowering blood pressure in hypertensive adults.

This study sought to determine if older adults with hypertension could receive these benefits by moderately increasing their daily walking, which is one of the easiest and most popular forms of physical activity for this population.

"It's easy to do, they don't need any equipment, they can do it anywhere at almost any time," Lee says.

The study focused on a group of sedentary older adults between ages 68 and 78 who walked an average of about 4,000 steps per day before the study.

After consulting existing studies, Lee determined that 3,000 steps would be a reasonable goal. This would also put most participants at 7,000 daily steps, in line with the American College of Sports Medicine's recommendation.

"3,000 steps is large enough but not too challenging to achieve for health benefits," Lee says.

The team conducted the study during the height of the COVID-19 pandemic, which meant they had to do everything remotely.

The researchers sent participants a kit with pedometers, blood pressure monitors, and step diaries for participants to log how much they were walking each day.

On average, participants' systolic and diastolic blood pressure decreased by an average of seven and four points, respectively, after the intervention.

Other studies suggest decreases of these magnitudes correspond to a relative risk reduction of all-cause mortality by 11%, and 16% for cardiovascular mortality, an 18% reduction in the risk of heart disease, and a 36% risk reduction of stroke.

"It's exciting that a simple lifestyle intervention can be just as effective as structured exercise and some medications," Lefferts says.

The findings suggest that the 7,000-step regimen the participants in the study achieved is on-par with reductions seen with anti-hypertensive medications.Eight of the 21 participants were already on anti-hypertensive medications. Those participants still saw improvements in systolic blood pressure from increasing their daily activity.

"In a previous study, we found that when exercise is combined with medication, exercise bolsters the effects of blood pressure medication alone," Pescatello says. "It just speaks to the value of exercise as anti-hypertensive therapy. It's not to negate the effects of medication at all, but it's part of the treatment arsenal."

The researchers found that walking speed and walking in continuous bouts did not matter as much as simply increasing total steps.

"We saw that the volume of physical activity is what's really important here, not the intensity," Pescatello says. "Using the volume as a target, whatever fits in and whatever works conveys health benefits."

This work was a pilot study, and the researchers hope to use these data to launch a larger clinical trial.

https://www.sciencedaily.com/releases/2023/09/230927003032.htm

Saturated fat may interfere with creating memories in aged brain

Study finds DHA protects brain cells from fat-related inflammation

September 27, 2023

Science Daily/Ohio State University

New research hints at a few ways fatty foods affect cells in the brain, a finding that could help explain the link between a high-fat diet and impaired memory -- especially as we age.

The Ohio State University study in cell cultures found the omega-3 fatty acid DHA may help protect the brain from an unhealthy diet's effects by curbing fat-induced inflammation at the cellular source.

Separate experiments using brain tissue from aging mice showed a high-fat diet may lead specific brain cells to overdo cell-signaling management in a way that interferes with the creation of new memories.

The same lab found in an earlier study in aging rats that a diet of highly processed ingredients led to a strong inflammatory response in the brain that was accompanied by behavioral signs of memory loss -- and that DHA supplementation prevented those problems.

"The cool thing about this paper is that for the first time, we're really starting to tease these things apart by cell type," said senior author Ruth Barrientos, an investigator in Ohio State's Institute for Behavioral Medicine Research and associate professor of psychiatry and behavioral health and neuroscience in the College of Medicine.

"Our lab and others have often looked at the whole tissue of the hippocampus to observe the brain's memory-related response to a high-fat diet. But we've been curious about which cell types are more or less affected by these saturated fatty acids, and this is our first foray into determining that."

The study was published recently in the journal Frontiers in Cellular Neuroscience.

For this work, the researchers focused on microglia, cells in the brain that promote inflammation, and hippocampal neurons, which are important for learning and memory. They used immortalized cells -- copies of cells taken from animal tissue that are modified to continuously divide and respond only to lab-based stimulation, meaning their behavior may not precisely match that of primary cells of the same type.

Researchers exposed these model microglia and neurons to palmitic acid, the most abundant saturated fatty acid in high-fat foods like lard, shortening, meat and dairy products, to observe how it affected gene activation in the cells as well as functioning of mitochondria, structures inside cells that have a primary metabolic role of generating energy.

Results showed the palmitic acid prompted gene expression changes linked to an increase in inflammation in both microglia and neurons, though microglia had a wider range of affected inflammatory genes. Pre-treatment of these cells with a dose of DHA, one of two omega-3 fatty acids in fish and other seafood and available in supplement form, had a strong protective effect against the increased inflammation in both cell types.

"Previous work has shown that DHA is protective in the brain and that palmitic acid has been detrimental to brain cells, but this is the first time we've looked at how DHA can directly protect against the effects of palmitic acid in those microglia, and we see that there is a strong protective effect," said Michael Butler, first author of the study and a research scientist in Barrientos' lab.

When it came to the mitochondria, however, DHA did not prevent the loss of function that followed exposure to palmitic acid.

"The protective effects of DHA might, in this context, be restricted to effects on gene expression related to the pro-inflammatory response as opposed to the metabolic deficits that the saturated fat also induced," Butler said.

In another set of experiments, the researchers looked at how a diet high in saturated fat influenced signaling in the brains of aged mice by observing another microglial function called synaptic pruning. Microglia monitor signal transmission among neurons and nibble away excess synaptic spines, the connection sites between axons and dendrites, to keep communication at an ideal level.

Microglia were exposed to mouse brain tissue containing both pre- and post-synaptic material from animals that had been fed either a high-fat diet or regular chow for three days.

The microglia ate the synapses from aged mice fed a high-fat diet at a faster rate than they ate synapses from mice fed a regular diet -- suggesting the high-fat diet is doing something to those synapses that gives the microglia a reason to eat them at a higher rate, Butler said.

"When we talk about the pruning, or refinement, that needs to occur, it's like Goldilocks: It needs to be optimal -- not too much and not too little," Barrientos said. "With these microglia eating away too much too soon, it outpaces the ability for these spines to regrow and create new connections, so memories don't solidify or become stable."

From here, the researchers plan to expand on findings related to synaptic pruning and mitochondria function, and to see how palmitic acid and DHA effects play out in primary brain cells from young versus aged animals.

https://www.sciencedaily.com/releases/2023/09/230927155308.htm

New research adds evidence to the benefits of ginger supplements for treating autoimmune diseases

Study looked at the impact of ginger supplements on people's white blood cell function

September 22, 2023

Science Daily/University of Colorado Anschutz Medical Campus

New research has revealed a potentially important role ginger supplements can play in controlling inflammation for people living with autoimmune diseases.

The research published today in JCI Insight focused on studying the impact of ginger supplementation on a type of white blood cell called the neutrophil. The study was especially interested in neutrophil extracellular trap (NET) formation, also known as NETosis, and what it may mean for controlling inflammation.

The study found ginger consumption by healthy individuals makes their neutrophils more resistant to NETosis. This is important because NETs are microscopic spider web-like structures that propel inflammation and clotting, which contribute to many autoimmune diseases, including lupus, antiphospholipid syndrome and rheumatoid arthritis.

"There are a lot of diseases where neutrophils are abnormally overactive. We found that ginger can help to restrain NETosis, and this is important because it is a natural supplement that may be helpful to treat inflammation and symptoms for people with several different autoimmune diseases," said senior co-author Kristen Demoruelle, MD, PhD, associate professor of medicine at the University of Colorado School of Medicine on the University of Colorado Anschutz Medical Campus.

In a clinical trial, the researchers found that daily intake of a ginger supplement for seven days (20 mg of gingerols/day) by healthy volunteers boosted a chemical inside the neutrophil called cAMP. These high levels of cAMP then inhibited NETosis in response to various disease-relevant stimuli.

"Our research, for the first time, provides evidence for the biological mechanism that underlies ginger's apparent anti-inflammatory properties in people," said senior co-author Jason Knight, MD, PhD, associate professor in the Division of Rheumatology at the University of Michigan.

The researchers say that many people with inflammatory conditions are likely to ask their health care providers whether natural supplements could be helpful for them or they already take supplements, like ginger, to help manage symptoms. Unfortunately, the precise impact on disease is often unknown. The researchers hope that providing more evidence about ginger's benefits, including the direct mechanism by which ginger impacts neutrophils, will encourage health care providers and patients to more strategically discuss whether taking ginger supplements as part of their treatment plan could be beneficial.

"There are not a lot of natural supplements, or prescription medications for that matter, that are known to fight overactive neutrophils. We, therefore, think ginger may have a real ability to complement treatment programs that are already underway. The goal is to be more strategic and personalized in terms of helping to relieve people's symptoms," Knight adds.

As a next step, the researchers hope to use this study to unlock funding for clinical trials of ginger in patients with autoimmune and inflammatory diseases where neutrophils are overactive, such as lupus, rheumatoid arthritis, antiphospholipid syndrome and even COVID-19.

https://www.sciencedaily.com/releases/2023/09/230922141250.htm

Compound derived from hops reduces abundance of gut microbe associated with metabolic syndrome

September 21, 2023

Science Daily/Oregon State University

Researchers have shown in a mouse model and lab cultures that a compound derived from hops reduces the abundance of a gut bacterium associated with metabolic syndrome.

The findings, published today in the journal Microbiome, are important because an estimated 35 percent of the U.S. adult population suffers from the syndrome, a common and serious condition linked with cognitive dysfunction and dementia as well as being a major risk factor for cardiovascular disease and type 2 diabetes.

A diet high in saturated fat results in chronic low-grade inflammation in the body that in turn leads to the development of metabolic syndrome.

Patients are considered to have metabolic syndrome if they have at least two of the following: abdominal obesity, high blood pressure, high blood sugar, low levels of "good" cholesterol, and high levels of triglycerides.

OSU researchers for years have been studying the potential health benefits of xanthohumol, a chemical found in hops, and its derivatives including tetrahydroxanthohumol. The latter is commonly abbreviated to TXN, the former to XN.

XN is a polyphenol, a type of abundant organic compound existing in plants and used for millennia by practitioners of traditional medicine. XN is one of the flavonoids, natural products found in fruits, vegetables, grains, bark, roots, stems, flowers, tea and wine that are well known for their positive effects on health.

In the most recent study, Andrey Morgun of the OSU College of Pharmacy, Natalia Shulzhenko of the Carlson College of Veterinary Medicine and Adrian Gombart of the Linus Pauling Institute and College of Science demonstrated that TXN can combat metabolic syndrome by reducing the population of Oscillibacter species within the gut microbiome.

More than 10 trillion microbial cells from about 1,000 different bacterial species comprise the human gut microbiome, the community of microorganisms in the digestive tract.

The researchers employed a novel computational method developed earlier by Morgun and Shulzhenko, transkingdom network analysis, to uncover TXN's mechanism for ameliorating metabolic syndrome. The analysis predicts which types of bacteria control the expression of mammalian genes connected to specific medical conditions.

"We found TXN mainly works by reducing the abundance of gut microbes that promote inflammation in the adipose tissue's macrophage cells, and improving glucose metabolism," Morgun said.

Macrophage cells are large cells that are part of the immune system. Glucose metabolism, the body's ability to convert the sugar into fuel, generally suffers impairment as someone becomes obese, which in turn can lead to the person becoming more overweight.

Faulty glucose metabolism also negatively affects brain physiology and is at the root of multiple medical conditions including diabetes and heart disease.

"When exposed to a high-fat diet common to metabolic syndrome, Oscillibacter bacteria help prompt the inflammation of fatty tissue that drives the syndrome," Morgun said. "TXN serves to limit Oscillibacter species' numbers."

The National Institutes of Health, the Linus Pauling Institute, the OSU College of Pharmacy, Hopsteiner, Inc., and the OSU Foundation Buhler-Wang Research Fund supported this study.

The research is a part of a larger collaborative effort spearheaded by Gombart, Fred Stevens of the OSU College of Pharmacy and Claudia Maier of the College of Science, who are exploring ways to improve human health, particularly as it pertains to diet and obesity, through hops compounds.

A little over a year ago, Morgun and Shulzhenko published research showing Oscillibacter and adipose tissue's link to type 2 diabetes, a finding that now suggests TXN may be able to help treat that condition too.

https://www.sciencedaily.com/releases/2023/09/230921154434.htm

Exercise and muscle regulation: Implications for diabetes and obesity

September 20, 2023

Science Daily/Helmholtz Munich

How do our muscles respond at the molecular level to exercise? Researchers at Helmholtz Munich and the German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE) have unraveled the cellular basis and signaling pathways responsible for the positive impact of physical activity on our overall health. Regulatory T cells, a type of immune cell, play a critical role in ensuring proper muscle function. These novel insights are paving the path towards precision medicines targeting metabolic disorders like obesity and diabetes, as well as muscle-related illnesses. Their discoveries are published in Cell Metabolism.

Obesity and type 2 diabetes pose an increasing threat to our global health. Overnutrition and physical inactivity contribute to the development of these conditions. Exercise is not only effective for preventing diseases but also offers numerous health benefits including improving the immune system. Researchers from the German Center for Diabetes (DZD) at Helmholtz Munich and the German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE) revealed new insights on the interconnections between exercise, muscle function, and the immune system. These new findings can not only benefit people living with obesity or type 2 diabetes seeking to improve their health through exercise or patients of muscle-related diseases, but also benefit professional athletes. Importantly, a better understanding of the immune-muscle crosstalk can contribute to the future development of precision immune therapies for diabetes and other complications.

Regulatory T Cells Ensure Proper Muscle Function

Although the beneficial effects of exercise training on metabolic health and the immune system are commonly known, the exact mechanisms of how physical activity affects muscle immune cells remained unknown until now. The team of researchers unraveled the molecular mechanisms by which a specialized subset of immune cells in the human body, the regulatory T cells (Tregs), control muscle crosstalk in a steady state, in response to exercise, as well as upon muscle injury. During exercise highly functional Tregs can be found in the muscles, which are important for proper muscle function, regeneration, and repair.

By manipulating the Tregs in multiple ways, the authors uncover their pivotal role in regulating muscle function, strength, and repair after injury. The research team identifies a critical mediator of these effects. A signaling pathway involved in the immune response and various other physiological processes, the interleukin-6 (IL6) receptor (IL6R) signaling on T cells, is critical for Treg functionality. The IL6R has to be present on the surface of T cells for the Treg-mediated control of muscle function.

These new findings can additionally offer a possible mechanistic explanation as to why anti-inflammatory treatment targeting IL6R has been associated with the development of muscle weakness as a side effect in the clinic. In conclusion, the new discoveries highlight the importance of dissecting the crosstalk between the immune system and the metabolism in conditions such as diabetes and obesity. These insights will be crucial for developing precision medicines targeting Tregs within distinct niches and contexts in the future.

https://www.sciencedaily.com/releases/2023/09/230920152413.htm

Reducing stress on T cells makes them better cancer fighters

September 20, 2023

Science Daily/Salk Institute

Even for killer T cells -- specialized immune cells -- seeking and destroying cancer cells around the clock can be exhausting. If scientists can understand why killer T cells become exhausted, then they can create more resilient cancer-killing cells.

In a new study, Salk Institute scientists discovered a relationship between killer T cell exhaustion and the body's sympathetic stress response ("fight-or-flight") in varying cancer types in mouse and human tissue samples. What's more, the team found that the interaction between killer T cells and sympathetic stress response hormones can be inhibited with beta-blockers -- a class of drugs already used in humans for controlling blood pressure and heart rate -- to create killer T cells that fight the tumor more efficiently.

The findings, published in Nature on September 20, 2023, establish a new link between the sympathetic stress response and how the immune system responds to cancer. Additionally, they demonstrate the benefit of pairing beta-blockers with existing immunotherapies to improve cancer treatment by bolstering killer T cell function.

"There is no question immunotherapy has revolutionized cancer patient treatment -- but there are many patients for whom it's ineffective," says Professor Susan Kaech, senior author and director of Salk's NOMIS Center for Immunobiology and Microbial Pathogenesis. "Finding that our nervous system can suppress the function of cancer-destroying immune cells opens up entirely new ways to think about how to rejuvenate T cells in tumors."

The sympathetic nervous system is responsible for mediating the body's stress response, also known as the fight-or-flight response. However, little was known about how the nerves regulate the immune response to infections or cancer.

The researchers focused on sympathetic nerves that innervate our organs and produce the messenger hormone noradrenaline, which is also a stress hormone. The scientists used a variety of cancer and chronic illness models in mice and human tissue samples to study when and how killer T cells are influenced by the sympathetic nerves.

They found that the sympathetic nerves were producing noradrenaline, which was binding to killer T cells using a receptor called ADRB1. Exhausted killer T cells expressed more ADRB1 receptors than their functional counterparts, allowing the T cells to "listen" to the noradrenaline released by the nerves.

To test whether killer T cell exhaustion could be prevented, the researchers tested two approaches to intercepting noradrenaline and ADRB1 interaction: either removing ADRB1 altogether or impairing ADRB1 function with beta-blockers, which resulted in more-functional killer T cells that were better at destroying cancer cells.

The authors also found that the exhausted T cells do not just listen to nerves from afar, but cluster right around them in tissues. Surprisingly, the ADRB1 receptor provided the T cells with critical instructions to migrate near the nerves, which in turn suppressed their functions -- making them worse at fighting cancer.

"The innervation of tumors is an understudied area of tumor immunology. Our study has now uncovered that nerves contribute to the process of T cell exhaustion in tumors, where T cells become worn out and less powerful in their fight against the tumor over time," says first author Anna-Maria Globig, a postdoctoral researcher in Kaech's lab. "If we can unravel the details of how nerves suppress the body's immune response to cancer and why the exhausted T cells move towards the nerves, we can begin to target this process therapeutically."

According to Kaech, the researchers hope to expand their understanding of the exhausted killer T cell environment to learn more about why stress makes us sicker.

"We were able to find a new pathway that we can target with beta-blockers to create more resilient killer T cells that resist exhaustion and fight cancer better," says Globig.

Since beta-blockers are already clinically used, the team also hopes to implement their proposed cancer-fighting regimen soon in patients with lung cancer. By partnering with clinicians, they hope to study more human cancer tissue samples to enrich their findings and provide further evidence of the efficacy of beta-blockers in cancer treatment.

https://www.sciencedaily.com/releases/2023/09/230920111129.htm

Morning and afternoon slightly better than evening physical activity for diabetes prevention

September 21, 2023

Science Daily/Diabetologia

New research published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]) shows that morning and afternoon physical activity are associated with a lower risk of developing type 2 diabetes across all population levels of education and income, but found no statistically significant association between evening physical activity and risk type 2 diabetes. The study is by Dr Caiwei Tian, Harvard University, Cambridge, MA, USA, and Dr Chirag Patel, Harvard Medical School, Boston, MA. and colleagues.

Physical activity is a preventive factor for type 2 diabetes, but its timing and consistency (in contrast with overall sum of physical activity) has been relatively unexplored. Accelerometer-based devices that measure physical activity provide a new opportunity to objectively measure behaviour throughout the day and week. It has been shown that midday–afternoon but not evening physical activity is associated with a lower risk of mortality compared with morning physical activity, but the relationship with type 2 diabetes remains understudied. In this new study, the authors analysed the relationship between morning, afternoon, or evening physical activity and consistency (routine) and risk of type 2 diabetes.

A cohort of 93,095 UK Biobank participants (mean age 62 years) without a history of type 2 diabetes wore a wrist-worn accelerometer for 1 week. The authors converted accelerometer information to estimate metabolic equivalent of task (MET) (a common measure of physical activity), summing MET-hours of total physical activity. MET-hour physical activity captures all types of activity undertaken by an individual throughout the day and measured with the accelerometer, including chores, walking, and vigorous activity. The authors measured completed METs within three time segments (morning, afternoon, and evening), divided as 06:00–12:00 hours (morning); 12:00–18:00 hours (afternoon); and 18:00–24:00 hours (evening).

The authors quantified the consistency of physical activity by analysing the variance, or difference of each person’s activity from their own personal average. Those with smaller deviations were more consistent and vice versa. The authors also considered the intensity of exercise: moderate-to-vigorous physical activity (MVPA) and vigorous physical activity (VPA) in association with type 2 diabetes incidence.

The authors observed protective associations of physical activity, with each 1-unit increase in MET being associated with a 10% and 9% reduction in risk of type 2 diabetes in the morning and afternoon, respectively. However, there was no statistically significant association between evening physical activity and risk of type 2 diabetes.

The relationship with morning and afternoon physical activity was largely linear, meaning that those people with more MET-h completed had a much lower risk of developing type 2 diabetes than those with less (10% / 9% per MET-h, for morning and afternoon respectively).

The authors thought that lifestyle factors, such as amount of sleep and dietary intake, would influence the amount of physical activity in the morning, afternoon, and evening undertaken, and therefore the role activity has in diabetes risk. To address how these factors influence physical activity, the authors considered these factors in their analytic models. They found that when adjusting for lifestyle factors, associations for MET-hours with different times of day became more precise.

Consistency of MET-measured physical activity was not associated with type 2 diabetes; but intensity was – both MVPA and VPA were associated with decreased risk for type 2 diabetes at all times of the day. The authors say their study is the first report on the effect of consistency of activity, and explain: “The consistency or routine of physical activity was not strongly associated with type 2 diabetes. In other words, individuals who exercise a smaller amount of time more frequently are at no lesser risk for diabetes than individuals who exercise the same total amount, but with less of a routine.”

https://www.sciencedaily.com/releases/2023/09/230921105751.htm

Posttraumatic brain activity predicts resilience to PTSD

September 21, 2023

Science Daily/Elsevier

After a traumatic experience, most people recover without incident, but some people -- between 2% and 10%- develop posttraumatic stress disorder (PTSD), a mental health condition that can cause debilitating symptoms of anxiety due to emotional dysregulation. PTSD symptoms are present in up to 40% of trauma survivors in the acute aftermath of trauma, but full-blown PTSD develops in only a small subset of cases. Early identification of those at risk is critical for both early treatment and possible prevention.

A new study led by Israel Liberzon, MD, at Texas A&M University, aimed to do just that. The study appears in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, published by Elsevier.

Researchers have long understood that PTSD involves altered brain processing in areas associated with emotion processing and modulation, including the amygdala, insula, and prefrontal cortex. But, it has remained unclear when the PTSD-associated differences arise. In this work, the researchers collected brain scans from 104 survivors of trauma -- usually a car accident -- at 1, 6, and 14 months after the accident. By looking at brain activity so soon after the trauma, the researchers hoped to identify predictors of who would be more at risk or resilient to developing chronic PTSD.

Dr. Liberzon said of the findings, "In this largest-to-date, prospective study of early post-trauma survivors, greater activation in right inferior frontal gyrus, a region linked to cognitive control and emotional reappraisal, predicts better recovery from early PTSD symptoms. These findings highlight the key roles of cortical/cognitive regions in regulation of fear and in PTSD development."

Importantly, the researchers saw changes in the patients' brain activity change over time, reflecting an ongoing, perhaps pathological process.

Cameron Carter, MD, Editor of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, said of the study, "These findings highlight the key role that the prefrontal cortex may play in conferring resilience to the harmful effects of trauma, through its function representing contextual information and regulating emotional responses."

Dr. Liberzon added, "Understanding brain circuits linked to the progression of PTSD from an acute to a chronic condition is critical for understanding its pathophysiology, and eventually for the development of mechanism-informed treatment. The results might also help clinicians to start identifying and treating early trauma survivors at greater risk of developing chronic PTSD a year after the traumatic event."

https://www.sciencedaily.com/releases/2023/09/230921154511.htm

College athletes experience worse post-injury outcomes for concussions suffered outside of sports

Female athletes also had more severe symptoms associated with these injuries

September 20, 2023

Science Daily/Children's Hospital of Philadelphia

Researchers from Children's Hospital of Philadelphia (CHOP) found that college athletes had worse post-injury outcomes related to concussions they experienced outside of sports than those they experienced while playing sports. Additionally, female athletes who sustained their injury outside of sports had more severe symptoms and more days in sports lost to injury relative to male athletes. These findings suggest the need for improved concussion recognition, reporting, and monitoring outside of sports.

The study was recently published online by the Journal of Athletic Training.

Concussions have the potential to impact the daily function and quality of life of those who sustain them. Prompt recognition of symptoms and early access to care can help minimize those effects. Most concussion research has primarily focused on injuries that occur while playing sports, but those studies often exclude concussions that can happen outside of sports, usually the result of falls or car crashes. Some research has indicated that patients with non-sports-related concussions have worse outcomes, but research into those effects in college-age patients is very limited.

"Patients who experience a concussion outside of sports may lack the resources that athletes who sustain their injury on the field have for concussion care, like immediate access to health care providers such as athletic trainers," said study first author Patricia Roby, PhD, an injury scientist who conducted this research while she was a postdoctoral fellow at CHOP.

To help address this gap in knowledge, researchers analyzed data from the National Collegiate Athletic Association-Department of Defense Concussion Assessment, Research, and Education (CARE) Consortium. A total of 3,500 college athletes were included in the study, including 555 that experienced a non-sports-related concussion. More than 40% of athletes included were female so that potential differences in recovery between males and females could be explored.

The study found that athletes who experienced non-sports-related concussions were less likely to report their injuries immediately, potentially due to lack of recognition of symptoms outside of the sport setting or hesitation to report the injury caused by unusual or careless mechanisms. Athletes who sustained non-sports-related concussions reported greater severity of their symptoms, more days with symptoms, and more days in sports lost to injury relative to patients who experienced sports-related concussions, and these findings were even more true in female patients compared with male patients.

"Our findings show that non-sports mechanisms of injury for concussion are an important consideration in college age young adults, something we had already described in our research in younger children. There is an opportunity to improve clinical outcomes by increasing awareness and education around concussions that happen outside of sports and reducing healthcare reporting barriers in this older age group as well," said senior study author Christina L. Master, MD, clinical director of the Minds Matter Concussion Program at CHOP. "Additionally, our findings related to sex differences in the trajectory of these injuries warrant additional investigation to see the extent to which reporting behaviors and access to medical teams are contributing to this disparity in outcomes."

https://www.sciencedaily.com/releases/2023/09/230920152424.htm

Trigonelline derived from coffee improves cognitive functions in mice

September 22, 2023

Science Daily/University of Tsukuba

Trigonelline is derived from coffee; researchers have found that it improves spatial learning and memory in senescence-accelerated mice. The study also suggested that this effect results from inhibiting neuroinflammation and restoring neurotransmitter levels in the brain.

The search for functional natural compounds that can improve age-related cognitive decline has recently emerged as an important research focus to promote healthy aging. Trigonelline (TG), a plant alkaloid found in coffee, as well as in fenugreek seed and radish, was anticipated to possess cognitive enhancement properties.

In this study, researchers led by the University of Tsukuba investigated the effects of TG on memory and spatial learning (acquiring, retaining, structuring, and applying information related to the surrounding physical environment) from both a cognitive and molecular biology perspective in an integrated manner using a senescence-accelerated mouse prone 8 (SAMP8) model.

Following oral administration of TG to SAMP8 mice for 30 days, the Morris water maze test indicated a significant improvement in spatial learning and memory performance compared with SAMP8 mice that did not receive TG. Next, the researchers performed whole-genome transcriptomic analysis of the hippocampus to explore the underlying molecular mechanisms. They found that signaling pathways related to nervous system development, mitochondrial function, ATP synthesis, inflammation, autophagy, and neurotransmitter release were significantly modulated in the TG group.

Furthermore, the research team found that TG suppressed neuroinflammation by negatively regulating signaling factor Traf6-mediated activation of the transcription factor NF-κB. Additionally, quantitative protein analysis confirmed that the levels of inflammatory cytokines TNF-α and IL-6 were significantly decreased and the levels of neurotransmitters dopamine, noradrenaline, and serotonin were significantly increased in the hippocampus. These findings suggest the efficacy of TG in preventing and improving age-related spatial learning memory impairment.

https://www.sciencedaily.com/releases/2023/09/230922110815.htm

A network that spreads light and the role of thalamus in our brain

September 22, 2023

Science Daily/University of Liège

New research conducted at the University of Liège, using ultra-high field 7 Tesla MRI, provides a better understanding of how light stimulates our brain and could provide new insights into how it works.

A research team at the ULiège GIGA Institute tried to understand better how light stimulates our cognition. Light acts like a cup of coffee and helps keep us awake. That's why we recommend not using too much light on our smartphones and tablets in the evening. This can disrupt our sleep. On the other hand, the same light can help us during the day. Many studies have shown that good lighting can help students in schools, hospital staff and patients, and company employees. It's the blue part of the light that's most effective for this, as we have blue light detectors in our eyes that tell our brains about the quality and quantity of light around us.

Once again, the brain regions responsible for this stimulating impact of light (also known as the 'non-visual' impact of light) are not well understood. "They are small and located in the subcortical part of the brain," explains Ilenia Paparella, doctoral student in the GIGA CRC IVI laboratory and first author of the article published in Communications Biology. The team of researchers from the GIGA-CRC-IVI was once again able to take advantage of the higher resolution of 7 Tesla MRI to show that the thalamus, a subcortical region located just below the corpus callosum (that connects our two hemispheres), plays a role in relaying non-visual light information to the parietal cortex in an area known to control attention levels. "We knew of its important role in vision, but its role in non-visual aspects was not yet certain. With this study, we have demonstrated that the thalamus stimulates the parietal regions and not the other way around, as we might have thought."

These new advances in our knowledge of the role of the thalamus will ultimately enable us to propose lighting solutions that will help cognition when we need to be fully awake and focused, or that will contribute to better sleep through relaxing light.

https://www.sciencedaily.com/releases/2023/09/230922110728.htm