Head injury and concussion in toddlers: Early detection of symptoms is vital

June 1, 2021

Science Daily/University of Montreal

A research team led by scientists at Université de Montréal has developed a unique observational tool for assessing children up to 5 years of age who have had a concussion. The work is explained in a study published in the Journal of Head Trauma Rehabilitation.

Pediatric traumatic brain injury (TBI) is particularly prevalent in toddlers; they're more likely to be injured because they have a lower sense of danger and are still developing physically. But parents and clinicians have trouble detecting symptoms of trauma, given the toddler's limited verbal skills.

"A young child will not tell you that they have a headache or feel dizzy," said Dominique Dupont, an UdeM postdoctoral student in neuropsychology and first author of the study.

"But assessing post-concussion symptoms is the cornerstone for patient management and follow-up," she added. "Without documentation, it's difficult to know whether they're doing well or not."

To address the lack of assessment tools for this age group, UdeM neuropsychology professor Miriam Beauchamp, who conducts research at the UdeM-affiliated CHU Sainte-Justine children's hospital, designed a new observational tool that allows parents and clinicians to assess the child's health status.

Can be damaging

Traditionally, it was suggested that TBI in early childhood did not have significant adverse effects, because the high plasticity of the brain at this time of life allowed for rapid recovery.

"This is true to some extent, but the reverse is also true," said Beauchamp, the study's principal author and director of the ABCs Developmental Neuropsychology Laboratory. "In young children, many things are not yet permanently consolidated. So when a shock disrupts brain function, the response can be as damaging as in older children."

She added: "We felt it was paramount to develop a tool to document the physical, cognitive, and behavioural status of these children and allow for appropriate clinical management."

The tool is also designed to document the progression of symptoms and their severity over time.

The challenge for 0- to 5-year-olds is that they do not have the communication skills to verbalize their condition. In addition, post-concussion symptoms can easily be confused with behaviours typical of this developmental period.

"No one is surprised when a 1-year-old becomes irritable or throws up their snack," said Dupont.

Long list of symptoms

In designing their new tool, the researchers listed all the known symptoms observed in older patients: headaches, memory loss, difficulty concentrating, hypersensitivity to light and noise, irritability, balance or coordination problems, dizziness, and sleep problems are among them.

They then catalogued, with the support of parents of children in the LION cohort and the emergency care staff at CHU Sainte-Justine, post-concussion manifestations observed in very young children. The research team then broke down these symptoms into observations that reflect their child's actual condition.

"Unlike the questionnaires we use with older children, here we include examples to explain how symptoms can manifest in a young child," said Beauchamp. "We also added observations that are potentially unique to this age group and therefore not found in existing questionnaires.

"For example, we asked questions about so-called comfort-seeking: 'Is my baby in my arms more often?' and 'Does my child keep asking for their pacifier or stuffed animal?' We also use 'regression' observations: 'Was my child potty trained, but is no longer?' and 'Did my child sleep through the night, but now wakes up at all hours?'"

She added: "This study is very promising, as it allows us to design patterns to validate our tool.

"We are continuing our research to compare post-concussion symptoms with the behaviour of children who have not been injured in a large multi-centre study in Canada. Ultimately, we'll be able to transfer the tool to clinical use throughout Quebec, and even internationally."

Finally, the study "also highlights the importance for parents to be vigilant in tracking behavioural changes in their child," she said.

https://www.sciencedaily.com/releases/2021/06/210601121801.htm

Scientists say active early learning shapes the adult brain

June 1, 2021

Science Daily/Virginia Tech

An enhanced learning environment during the first five years of life shapes the brain in ways that are apparent four decades later, say Virginia Tech and University of Pennsylvania scientists writing in the June edition of the Journal of Cognitive Neuroscience.

The researchers used structural brain imaging to detect the developmental effects of linguistic and cognitive stimulation starting at six weeks of age in infants. The influence of an enriched environment on brain structure had formerly been demonstrated in animal studies, but this is the first experimental study to find a similar result in humans.

"Our research shows a relationship between brain structure and five years of high-quality, educational and social experiences," said Craig Ramey, professor and distinguished research scholar with Fralin Biomedical Research Institute at VTC and principal investigator of the study. "We have demonstrated that in vulnerable children who received stimulating and emotionally supportive learning experiences, statistically significant changes in brain structure appear in middle age."

The results support the idea that early environment influences the brain structure of individuals growing up with multi-risk socioeconomic challenges, said Martha Farah, director of the Center for Neuroscience and Society at Penn and first author of the study.

"This has exciting implications for the basic science of brain development, as well as for theories of social stratification and social policy," Farah said.

The study follows children who have continuously participated in the Abecedarian Project, an early intervention program initiated by Ramey in Chapel Hill, North Carolina, in 1971 to study the effects of educational, social, health, and family support services on high-risk infants.

Both the comparison and treatment groups received extra health care, nutrition, and family support services; however, beginning at six weeks of age, the treatment group also received five years of high quality educational support, five days a week, 50 weeks a year.

When scanned, the Abecedarian study participants were in their late 30s to early 40s, offering the researchers a unique look at how childhood factors affect the adult brain.

"People generally know about the potentially large benefits of early education for children from very low resource circumstances," said co-author Sharon Landesman Ramey, professor and distinguished research scholar at Fralin Biomedical Research Institute. "The new results reveal that biological effects accompany the many behavioral, social, health, and economic benefits reported in the Abecedarian Project. This affirms the idea that positive early life experiences contribute to later positive adjustment through a combination of behavioral, social, and brain pathways."

During follow-up examinations, structural MRI scans of the brains of 47 study participants were conducted at the Fralin Biomedical Research Institute Human Neuroimaging Lab. Of those, 29 individuals had been in the group that received the educational enrichment focused on promoting language, cognition, and interactive learning.

The other 18 individuals received the same robust health, nutritional, and social services supports provided to the educational treatment group, and whatever community childcare or other learning their parents provided. The two groups were well matched on a variety of factors such as maternal education, head circumference at birth and age at scanning.

Analyzing the scans, the researchers looked at brain size as a whole, including the cortex, the brain's outermost layer, as well as five regions selected for their expected connection to the intervention's stimulation of children's language and cognitive development.

Those included the left inferior frontal gyrus and left superior temporal gyrus, which may be relevant to language, and the right inferior frontal gyrus and bilateral anterior cingulate cortex, relevant to cognitive control. A fifth, the bilateral hippocampus, was added because its volume is frequently associated with early life adversity and socioeconomic status.

The researchers determined that those in the early education treatment group had increased size of the whole brain, including the cortex.

Several specific cortical regions also appeared larger, according to study co-authors Read Montague, professor and director of the Human Neuroimaging Lab and Computational Psychiatry Unit at the Fralin Biomedical Research Institute, and Terry Lohrenz, research assistant professor and member of the institute's Human Neuroimaging Laboratory.

The scientists noted the group intervention treatment results for the brain were substantially greater for males than for females. The reasons for this are not known, and were surprising, since both the boys and girls showed generally comparable positive behavioral and educational effects from their early enriched education. The current study cannot adequately explain the sex differences.

"When we launched this project in the 1970s, the field knew more about how to assess behavior than it knew about how to assess brain structure," Craig Ramey said. "Because of advances in neuroimaging technology and through strong interdisciplinary collaborations, we were able to measure structural features of the brain. The prefrontal cortex and areas associated with language were definitely affected; and to our knowledge, this is the first experimental evidence on a link between known early educational experiences and long-term changes in humans."

"We believe that these findings warrant careful consideration and lend further support to the value of ensuring positive learning and social-emotional support for all children -- particularly to improve outcomes for children who are vulnerable to inadequate stimulation and care in the early years of life," Craig Ramey said.

https://www.sciencedaily.com/releases/2021/06/210601100732.htm

Being born very preterm or very low birthweight is associated with continued lower IQ performance into adulthood

June 1, 2021

Science Daily/University of Warwick

The average IQ of adults who were born very preterm (VP) or at a very low birth weight (VLBW) has been compared to adults born full term by researchers from the Department of Psychology at the University of Warwick. Researchers have found VP/VLBW children may require special support in their education to boost their learning throughout childhood.

Birth before 32 weeks of gestation is classed as very preterm (VP) and those born weighing less than 1500g are classed as very low birthweight (VLBW).

Research has previously found that those who were born VP or VLBW had lower cognitive performance in childhood.

In the paper, 'Association of Very Preterm Birth or Very Low Birth Weight with Intelligence in Adulthood: An Individual Participant Meta-analysis', published today, the 28th of May in the journal JAMA Pediatrics, a consortium of researchers led by the Department of Psychology at the University of Warwick have conducted an Individual participant meta-analysis investigating IQ in adulthood.

Participants were 1068 VP/VLBW adults and 1067 term born controls born between 1978-1995 from 6 cohort studies in Europe and 2 from Australia and New Zealand, who had been studied from birth and had their IQ assessed in adulthood (aged 18-30 years).

The average IQ score in the general population is 100. The researchers found that VP/VLBW individuals scored approximately 12 IQ points less (i.e. 88) compared to term born adults (born 37-41 weeks gestation). Even when they removed those who had a childhood neurosensory impairment or learning disability (e.g childhood IQ score below 70) the adult IQ difference between VP/VLBW and term born adults was still on average 9.8 IQ points.

The risk factors that were associated with lower IQ performance for VP/VLBW adults included neonatal severe lung problems (bronchopulmonary dysplasia), neonatal bleeds into their brain (intraventricular haemorrhage) and being born to mothers with lower education.

Robert Eves, first author from the Department of Psychology at the University of Warwick comments:

"We have found that being born very preterm or at a very low birthweight continues to have a highly significant long term impact on the average IQ as compared to their peers in 7 different countries. The multi cohort, international aspect of this research can especially give us confidence in this important finding"

Professor Dieter Wolke, senior author and project lead from the Department of Psychology at the University of Warwick adds: "While most born VP/VLBW show cognitive development within the normal range, many may benefit from better tailored early interventions. These may include reducing bronchopulmonary dysplasia and intraventricular hemorrhage in neonatal care and educational interventions of those born into socially disadvantaged families."

https://www.sciencedaily.com/releases/2021/06/210601100723.htm

These cognitive exercises help young children boost their math skills

May 20, 2021

Science Daily/Karolinska Institutet

Young children who practice visual working memory and reasoning tasks improve their math skills more than children who focus on spatial rotation exercises, according to a large study by researchers at Karolinska Institutet in Sweden. The findings support the notion that training spatial cognition can enhance academic performance and that when it comes to math, the type of training matters. The study is published in the journal Nature Human Behaviour.

"In this large, randomized study we found that when it comes to enhancing mathematical learning in young children, the type of cognitive training performed plays a significant role," says corresponding author Torkel Klingberg, professor in the Department of Neuroscience, Karolinska Institutet. "It is an important finding because it provides strong evidence that cognitive training transfers to an ability that is different from the one you practiced."

Numerous studies have linked spatial ability -- that is the capacity to understand and remember dimensional relations among objects -- to performance in science, technology, engineering and mathematics. As a result, some employers in these fields use spatial ability tests to vet candidates during the hiring process. This has also fueled an interest in spatial cognition training, which focuses on improving one's ability to memorize and manipulate various shapes and objects and spot patterns in recurring sequences. Some schools today include spatial exercises as part of their tutoring.

However, previous studies assessing the effect of spatial training on academic performance have had mixed results, with some showing significant improvement and others no effect at all. Thus, there is a need for large, randomized studies to determine if and to what extent spatial cognition training actually improves performance.

In this study, more than 17,000 Swedish schoolchildren between the ages of six and eight completed cognitive training via an app for either 20 or 33 minutes per day over the course of seven weeks. In the first week, the children were given identical exercises, after which they were randomly split into one of five training plans. In all groups, children spent about half of their time on mathematical number line tasks. The remaining time was randomly allotted to different proportions of cognitive training in the form of rotation tasks (2D mental rotation and tangram puzzle), visual working memory tasks or non-verbal reasoning tasks (see examples below for details). The children's math performance was tested in the first, fifth and seventh week.

The researchers found that all groups improved on mathematical performance, but that reasoning training had the largest positive impact followed by working memory tasks. Both reasoning and memory training significantly outperformed rotation training when it came to mathematical improvement. They also observed that the benefits of cognitive training could differ threefold between individuals. That could explain differences in results from some previous studies seeing as individual characteristics of study participants tend to impact the results.

The researchers note there were some limitations to the study, including the lack of a passive control group that would allow for an estimation of the absolute effect size. Also, this study did not include a group of students who received math training only.

"While it is likely that for any given test, training on that particular skill is the most time-effective way to improve test results, our study offers a proof of principle that spatial cognitive training transfers to academic abilities," Torkel Klingberg says. "Given the wide range of areas associated with spatial cognition, it is possible that training transfers to multiple areas and we believe this should be included in any calculation by teachers and policymakers of how time-efficient spatial training is relative to training for a particular test."

The researchers have received funding by the Swedish Research Council. Torkel Klingberg holds an unpaid position as chief scientific officer for Cognition Matters, the non-profit foundation that owns the cognition training app Vektor that was used in this study.

Examples of training tasks in the study

• In a number line task, a person is asked to identify the right position of a number on a line bound by a start and an end point. Difficulty is typically moderated by removing spatial cues, for example ticks on the number line, and progress to include mathematical problems such as addition, subtraction and division.

• In a visual working memory task, a person is asked to recollect visual objects. In this study, the children reproduced a sequence of dots on a grid by touching the screen. Difficulty was increased by adding more items.

• In a non-verbal reasoning task, a person is asked to complete sequences of spatial patterns. In this study, the children were asked to choose the correct image to fill a blank space based on previous sequences. Difficulty was increased by adding new dimensions such as colors, shapes and dots.

• In a rotation task, a person is asked to figure out what an object would look like if rotated. In this study, the children were asked to rotate a 2D object to fit various angles. Difficulty was moderated by increasing the angle of the rotation or the complexity of the object being rotated.

https://www.sciencedaily.com/releases/2021/05/210520133755.htm

Children's physical activity linked to academic achievement via regulation of emotions

New findings could inform policies to improve educational outcomes and close achievement gaps

May 19, 2021

Science Daily/PLOS

A new study of children in the U.K. suggests that physical activity is linked to emotional regulation in early childhood, which in turn predicts academic achievement. Fotini Vasilopoulos and Michelle Ellefson of the University of Cambridge, U.K. (Vasilopoulos now at University of London, UK), present these findings in the open-access journal PLOS ONE on May 19, 2021.

Previous research suggests that physical activity in childhood can boost self-regulation -- the skill of controlling one's emotions and behavior as required by a given context. However, previous studies of the impact of physical activity on academic outcomes have had mixed findings.

To better understand the interplay between physical activity, self-regulation, and academics, Vasilopoulos and Ellefson used the Millennium Cohort Study, a longitudinal study of 4,043 children in the U.K. Parents and teachers filled out questionnaires to measure the emotional and behavioral components of the children's self-regulation skills at ages 7, 11, and 14. Children's physical activity was assessed according to several parameters, including intensity, duration, and enjoyment.

Statistical analysis of the data showed that a greater degree of physical activity was linked to greater emotional regulation, but not behavioral regulation, across all three time points when measurements were taken. However, when the researchers accounted for the children's socioeconomic status, physical activity was linked to lower emotional regulation and had a negligible link with behavioral regulation.

The analysis also suggested that, for 7-year-olds, physical activity positively predicted emotional regulation skills resulting in higher academic achievement throughout early primary school. For 11-year-olds, physical activity appeared to positively impact academic achievement via behavioral regulation. After accounting for socioeconomic status, these links were even more pronounced.

These findings suggest that early and sustained physical activity is an important element in children's development and schooling. The researchers note that evaluating childhood risks for poor academic achievement is complex, as evidenced, in part, by the influence of socioeconomic status on the results. The findings demonstrate the importance of ensuring that children have access to forms of physical activity, particularly for children from less-advantaged settings who lack the resources or opportunities to participate in physical activity than their better-advantaged peers.

The authors add: "Physical activity is linked to emotional regulation in early childhood and behavioural regulation in middle childhood. This relationship predicts academic attainment, suggesting that early and sustained physical activity is an important element in children's development and schooling. The findings demonstrate the importance of ensuring that children have access to forms of physical activity, particularly for children from less-advantaged settings who lack the resources or opportunities to participate in physical activity than their better-advantaged peers."

https://www.sciencedaily.com/releases/2021/05/210519163656.htm

'Prescription' to sit less, move more advised for mildly high blood pressure and cholesterol

June 2, 2021

Science Daily/American Heart Association

Physical activity is the optimal first treatment choice for adults with mild to moderately elevated blood pressure and blood cholesterol who otherwise have low heart disease risk. About 21% of adults in the US with mild to moderately raised blood pressure and 28-37% of those with mild to moderate elevated cholesterol levels may be best served by a prescription for lifestyle-only treatment, which includes increasing physical activity.

A "prescription" to sit less and move more is the optimal first treatment choice for reducing mild to moderately elevated blood pressure and blood cholesterol in otherwise healthy adults, according to the new American Heart Association scientific statement published today in the American Heart Association's journal Hypertension.

"The current American Heart Association guidelines for diagnosing high blood pressure and cholesterol recognize that otherwise healthy individuals with mildly or moderately elevated levels of these cardiovascular risk factors should actively attempt to reduce these risks. The first treatment strategy for many of these patients should be healthy lifestyle changes beginning with increasing physical activity," said Bethany Barone Gibbs, Ph.D., FAHA, chair of the statement writing group and associate professor in the department of health and human development and clinical and translational sciences at the University of Pittsburgh in Pittsburgh, Pennsylvania.

An estimated 21% of U.S. adults, about 53 million, have systolic (top number) blood pressure between 120-139 mm Hg or diastolic (bottom number) blood pressure between 80-89 mm Hg; both values are abnormally high. Individuals in this range who have an otherwise low risk of heart disease or stroke meet the American College of Cardiology (ACC)/American Heart Association (AHA) High Blood Pressure Guideline criteria for lifestyle-only treatment for elevated blood pressure.

Likewise, the scientific statement authors estimate that 28% of U.S. adults, or about 71 million, have an LDL cholesterol score above 70 mg/dL and otherwise meet criteria for low risk of heart disease or stroke. These people would meet the 2018 AHA/ACC Cholesterol Treatment Guidelines criteria for lifestyle-only treatment. Lifestyle changes highlighted in the blood pressure and cholesterol guidelines include increased physical activity, weight loss, improving diet, stopping smoking and moderating alcohol intake.

"Increasing physical activity can help lower blood pressure and cholesterol, along with many other health benefits." Gibbs said. Physical activity also has benefits beyond cardiovascular health, including a decreased risk of some cancers, improved bone, brain and mental health, and better sleep.

Increasing physical activity results in clinically meaningful reductions in systolic and diastolic blood pressure, typically an average reduction of 3 or 4 mm Hg. Similar improvements are seen with blood cholesterol. For example, increased physical activity typically decreases LDL cholesterol by 3 to 6 mg/dL.

The statement highlights research concluding that physically active people have a 21% lower risk of developing cardiovascular disease and a 36% lower risk of death from cardiovascular diseases compared to those who are not physically active.

To improve health, the U.S. Department of Health and Human Services 2018 Physical Activity Guidelines for Americans suggest individuals participate in either a cumulative 150 minutes of moderate intensity aerobic exercise, or 75 minutes of vigorous aerobic activity weekly plus two or more strength training sessions each week.

However, there is no minimum amount of time to receive benefits from physical activity. "Every little bit of activity is better than none," said Gibbs. "Even small initial increases of 5 to 10 minutes a day can yield health benefits."

The statement provides suggestions for clinicians to provide exercise "prescriptions" such as patient counselling, incorporating health behavior professionals (e.g., health coaches) and connecting patients to local resources like community centers to help meet their physical activity needs.

According to the statement, prescribing exercise includes:

• Screening patients about physical activity at every interaction, as recommended by the American College of Sports Medicine's 'Exercise is Medicine' campaign. Clinicians can ask patients to report their physical activity with a few questions or by using a wearable device.

• Providing ideas and resources for supporting patients to improve and sustain regular physical activity;

• Meeting patients where they are by exploring activities that the patient enjoys and provide ideas for early success; and

• Encouraging and celebrating small increases in physical activity, such as walking more or taking the stairs.

"In our world where physical activity is increasingly engineered out of our lives and the overwhelming default is to sit -- and even more so now as the nation and the world is practicing quarantine and isolation to reduce the spread of coronavirus -- the message that we must be relentless in our pursuit to 'sit less and move more' throughout the day is more important than ever," said Gibbs.

https://www.sciencedaily.com/releases/2021/06/210602091419.htm

Overweight or obesity worsens liver-damaging effects of alcohol

June 1, 2021

Science Daily/University of Sydney

Led by the University of Sydney's Charles Perkins Centre, the study looked at medical data from nearly half a million people and found having overweight or obesity considerably amplified the harmful effects of alcohol on liver disease and mortality.

"People in the overweight or obese range who drank were found to be at greater risk of liver diseases compared with participants within a healthy weight range who consumed alcohol at the same level," said senior author and research program director Professor Emmanuel Stamatakis from the Charles Perkins Centre and the Faculty of Medicine and Health.

"Even for people who drank within alcohol guidelines, participants classified as obese were at over 50 percent greater risk of liver disease."

The researchers drew upon data from the UK Biobank -- a large-scale biomedical cohort study containing in-depth biological, behavioural, and health information from participants in the United Kingdom (UK).

According to the researchers, this is one of the first and largest studies looking at increased adiposity (overweight or obesity) and level of alcohol consumption together, in relation to future liver disease.

Information was examined from 465,437 people aged 40 to 69 years, with medical and health details collected over an average of 10.5 years.

The findings were published in the European Journal of Clinical Nutrition.

Lead author Dr Elif Inan-Eroglu, a postdoctoral research fellow with the Charles Perkins Centre, said the results suggest people carrying excess weight may need to be more aware of risks around alcohol consumption.

"With the most recent data suggesting two in three people -- or 67 percent of the Australian population are in the overweight or obesity range, this is obviously a very topical issue."

Key findings 

The researchers reviewed data on participants classified as overweight/obese based on their body mass index (BMI) and waist circumference, self-reported alcohol consumption according to UK alcohol guidelines, and liver disease incidence and liver disease as cause of death.

BMI is based on both weight and height. A BMI of over 25 denotes overweight, and over 30 denotes obesity. For waist circumference, researchers used the World Health Organization (WHO) classification: normal (<80 cm for women, <94 cm for men), overweight (>80 cm for women, >94 cm for men), and obese (>88 cm for women, >102 cm for men).

The level of risk was given a number called a 'hazard ratio'. The higher the number than 1, the higher the risk.

- People who drank above UK alcohol guidelines had, compared to within guideline drinkers: 

o A nearly 600 percent higher risk of being diagnosed with alcoholic fatty liver disease (5.83 hazard ratio). 

o A nearly 700 percent higher risk of death caused by alcoholic fatty liver disease (6.94 hazard ratio).

- People with overweight or obesity who drank within or above alcohol guidelines had over 50 percent greater risk of developing liver disease compared to normal weight participants who consumed alcohol at the same level.

https://www.sciencedaily.com/releases/2021/06/210601100701.htm

'Good' bacteria show promise for clinical treatment of Crohn's disease, ulcerative colitis

May 28, 2021

Science Daily/University of North Carolina Health Care

A new study published in Nature Communicationsdemonstrates that a consortium of bacteria designed to complement missing or underrepresented functions in the imbalanced microbiome of inflammatory bowel disease (IBD) patients, prevented and treated chronic immune-mediated colitis in humanized mouse models. The study's senior author, Balfour Sartor, MD, Midget Distinguished Professor of Medicine, Microbiology and Immunology, Co-Director of the UNC Multidisciplinary IBD Center, said the results are encouraging for future use treating Crohn's disease and ulcerative colitis patients.

"The idea with this treatment is to restore the normal function of the protective bacteria in the gut, targeting the source of IBD, instead of treating its symptoms with traditional immunosuppressants that can cause side effects like infections or tumors," Sartor said.

The live bacteria consortia, called GUT-103 and GUT-108, were developed by biotech firm Gusto Global. GUT-103 is comprised of 17 strains of bacteria that work together to protect and feed each other. GUT-108 is a refined version of GUT-103, using 11 human isolates related to the 17 strains. These combinations permit the bacteria to stay in the colon for an extended amount of time, as opposed to other probiotics that are not capable of living in the gut and pass through the system quickly.

GUT-103 and GUT-108 were given orally three times a week to "germ-free" mice (no bacteria present) that had been specially developed and treated with specific human bacteria, creating a humanized mouse model. The therapeutic bacteria consortia worked by addressing upstream targets, rather than targeting a single cytokine to block downstream inflammation responses, and reversed established inflammation.

"It also decreased pathobionts -- bacteria that can cause harm -- while expanding resident protective bacteria, and produced metabolites promoting mucosal healing and immunoregulatory responses," Sartor said. "Simply put -- the treatment increased the good guys and decreased the bad guys."

Because of the robust results seen in this study, and the need for more alternative therapies for Crohn's disease, Sartor would like to see GUT-103 and GUT-108 studied in Phase 1 and 2 clinical trials in the future. He plans to continue his work with Gusto Global to further explore uses of the bacterial consortia.

https://www.sciencedaily.com/releases/2021/05/210528114008.htm

Waking just one hour earlier cuts depression risk by double digits

May 28, 2021

Science Daily/University of Colorado at Boulder

Waking up just one hour earlier could reduce a person's risk of major depression by 23%, suggests a sweeping new genetic study published May 26 in the journal JAMA Psychiatry.

The study of 840,000 people, by researchers at University of Colorado Boulder and the Broad Institute of MIT and Harvard, represents some of the strongest evidence yet that chronotype -- a person's propensity to sleep at a certain time -- influences depression risk.

It's also among the first studies to quantify just how much, or little, change is required to influence mental health.

As people emerge, post-pandemic, from working and attending school remotely -- a trend that has led many to shift to a later sleep schedule -- the findings could have important implications.

"We have known for some time that there is a relationship between sleep timing and mood, but a question we often hear from clinicians is: How much earlier do we need to shift people to see a benefit?" said senior author Celine Vetter, assistant professor of integrative physiology at CU Boulder. "We found that even one-hour earlier sleep timing is associated with significantly lower risk of depression."

Previous observational studies have shown that night owls are as much as twice as likely to suffer from depression as early risers, regardless of how long they sleep. But because mood disorders themselves can disrupt sleep patterns, researchers have had a hard time deciphering what causes what.

Other studies have had small sample sizes, relied on questionnaires from a single time point, or didn't account for environmental factors which can influence both sleep timing and mood, potentially confounding results.

In 2018, Vetter published a large, long term study of 32,000 nurses showing that "early risers" were up to 27% less likely to develop depression over the course of four years, but that begged the question: What does it mean to be an early riser?

To get a clearer sense of whether shifting sleep time earlier is truly protective, and how much shift is required, lead author Iyas Daghlas, M.D., turned to data from the DNA testing company 23 and Me and the biomedical database UK Biobank. Daghlas then used a method called "Mendelian randomization" that leverages genetic associations to help decipher cause and effect.

"Our genetics are set at birth so some of the biases that affect other kinds of epidemiological research tend not to affect genetic studies," said Daghlas, who graduated in May from Harvard Medical School.

More than 340 common genetic variants, including variants in the so-called "clock gene" PER2, are known to influence a person's chronotype, and genetics collectively explains 12-42% of our sleep timing preference.

The researchers assessed deidentified genetic data on these variants from up to 850,000 individuals, including data from 85,000 who had worn wearable sleep trackers for 7 days and 250,000 who had filled out sleep-preference questionnaires. This gave them a more granular picture, down to the hour, of how variants in genes influence when we sleep and wake up.

In the largest of these samples, about a third of surveyed subjects self-identified as morning larks, 9% were night owls and the rest were in the middle. Overall, the average sleep mid-point was 3 a.m., meaning they went to bed at 11 p.m. and got up at 6 a.m.

With this information in hand, the researchers turned to a different sample which included genetic information along with anonymized medical and prescription records and surveys about diagnoses of major depressive disorder.

Using novel statistical techniques, they asked: Do those with genetic variants which predispose them to be early risers also have lower risk of depression?

The answer is a firm yes.

Each one-hour earlier sleep midpoint (halfway between bedtime and wake time) corresponded with a 23% lower risk of major depressive disorder.

This suggests that if someone who normally goes to bed at 1 a.m. goes to bed at midnight instead and sleeps the same duration, they could cut their risk by 23%; if they go to bed at 11 p.m., they could cut it by about 40%.

It's unclear from the study whether those who are already early risers could benefit from getting up even earlier. But for those in the intermediate range or evening range, shifting to an earlier bedtime would likely be helpful.

What could explain this effect?

Some research suggests that getting greater light exposure during the day, which early-risers tend to get, results in a cascade of hormonal impacts that can influence mood.

Others note that having a biological clock, or circadian rhythm, that trends differently than most peoples' can in itself be depressing.

"We live in a society that is designed for morning people, and evening people often feel as if they are in a constant state of misalignment with that societal clock," said Daghlas.

He stresses that a large randomized clinical trial is necessary to determine definitively whether going to bed early can reduce depression. "But this study definitely shifts the weight of evidence toward supporting a causal effect of sleep timing on depression."

For those wanting to shift themselves to an earlier sleep schedule, Vetter offers this advice:

"Keep your days bright and your nights dark," she says. "Have your morning coffee on the porch. Walk or ride your bike to work if you can, and dim those electronics in the evening."

https://www.sciencedaily.com/releases/2021/05/210528114107.htm

Parasites as fountains of youth: Study finds infected ants live much longer

Life expectancy of tapeworm-infected worker ants is significantly higher than that of their uninfected nest-mates and resembles that of ant queens

May 27, 2021

Science Daily/Johannes Gutenberg Universitaet Mainz

Ant workers that are infected with a tapeworm live much longer than their uninfected nest-mates. Parasitic infections are usually harmful to their hosts, but there are some exceptions. According to the results of a multi-year scientific study, ants of the species Temnothorax nylanderi show exceptionally high survival rates when infected with a tapeworm. "The lifespan of the infected ants is significantly prolonged. According to our observations, such workers have a survival rate similar to that of queens," said Professor Susanne Foitzik of Johannes Gutenberg University Mainz (JGU), leader of the study. Queens of this species can live for up to 20 years, while female workers rarely reach the age of two. Among possible explanations for this extended lifespan are the change in the physiology of infected ants caused by the parasites and the fact that infected workers are better supplied with food.

Social care in the nest linked to longer life

In the case of ants, there is a stark divergence in lifespan between female castes. Many ant queens can survive for several decades. They spend almost all their lives safely in the nest where they are cared for by the workers, their daughters. In contrast, ant workers live for only a few weeks or months or, in rare cases, a few years. The infertile workers carry out all tasks in the nest, starting in brood care and progressing to riskier activities outside the colony as they grow older, such as foraging for food. The high life expectancy of queens is due to their low mortality rate, which is attributable to the high levels of social care they receive, their safe environment, and the activation of physiological repair mechanisms.

These factors may also contribute to the extremely high survival rates of Temnothorax-nylanderi workers infected with a tapeworm. This species of ant is common in Central Europe and forms small colonies on the forest floor, inside acorns or wooden branches. The insects are relatively small, with a body length of just two to three millimeters. They serve as an intermediate host for the tapeworm Anomotaenia brevis, whereby a single ant can be infected by up to 70 parasitic larvae. The parasites survive in the hemolymph, the body fluid of insects. Their complex life cycle is completed once they have been ingested by a woodpecker that feeds on the ants.

The research team led by Professor Susanne Foitzik looked at the long-term consequences of the parasitic infection by collecting ant colonies from forests around Mainz and observing them in the laboratory. "We tracked the survival rate of the workers and queens in both infected and uninfected ant colonies over three years, until more than 95 percent of the uninfected workers had died," explained Foitzik. At that point, over half of the infected workers were still alive -- exhibiting a survival rate practically identical to that of the long-lived queens. "It is quite extraordinary that a parasite can trigger such a positive change in its host. This lifespan extension is very unusual," emphasized the JGU-based evolutionary biologist.

Infected workers differ in appearance, behavior, and physiology

The infected ants are easily distinguished from their brown nest-mates due to their lighter, yellow color, an effect that results from their cuticle being less pigmented. They are also less active and receive enhanced care from other workers in the nest. "The infected insects get more attention and are fed, cleaned, and looked after better. They even benefit from slightly more care than the nest's queen," explained Professor Susanne Foitzik. The tests also revealed that infected ants have metabolic rates and lipid levels similar to those of younger ants. It would seem that these ants remain in a permanent juvenile stage as a result of the infection. This is likely down to both the tapeworm larvae altering the expression of ant genes that affect aging and to the parasites' release of proteins containing antioxidants into the ants' hemolymph.

Even though the mystery of their long life has not yet been fully resolved, the behavior of the infected ants themselves does not seem to be the decisive factor. The research team, which included scientists from the Max Planck Institute for Biology of Ageing and Tel Aviv University, found no evidence that the insects actively beg for better care. However, chemical signals on the cuticle of infected ants were found to elicit more attention of their nest-mates. "The infected insects live a life of luxury, but the fact that they receive more social care cannot alone account for their prolonged lifespan," concluded Foitzik. The scientists will undertake further research in order to identify the factors, particularly on the molecular and epigenetic level, behind the infected workers death-defying attributes.

https://www.sciencedaily.com/releases/2021/05/210527150134.htm

Don't count on caffeine to fight sleep deprivation

May 26, 2021

Science Daily/Michigan State University

Rough night of sleep? Relying on caffeine to get you through the day isn't always the answer, says a new study from Michigan State University.

Researchers from MSU's Sleep and Learning Lab, led by psychology associate professor Kimberly Fenn, assessed how effective caffeine was in counteracting the negative effects of sleep deprivation on cognition. As it turns out, caffeine can only get you so far.

The study -- published in the most recent edition of Journal of Experimental Psychology: Learning, Memory, & Cognition -- assessed the impact of caffeine after a night of sleep deprivation. More than 275 participants were asked to complete a simple attention task as well as a more challenging "placekeeping" task that required completion of tasks in a specific order without skipping or repeating steps.

Fenn's study is the first to investigate the effect of caffeine on placekeeping after a period of sleep deprivation.

"We found that sleep deprivation impaired performance on both types of tasks and that having caffeine helped people successfully achieve the easier task. However, it had little effect on performance on the placekeeping task for most participants," Fenn said.

She added: "Caffeine may improve the ability to stay awake and attend to a task, but it doesn't do much to prevent the sort of procedural errors that can cause things like medical mistakes and car accidents."

Insufficient sleep is pervasive in the United States, a problem that has intensified during the pandemic, Fenn said. Consistently lacking adequate sleep not only affects cognition and alters mood, but can eventually take a toll on immunity.

"Caffeine increases energy, reduces sleepiness and can even improve mood, but it absolutely does not replace a full night of sleep, Fenn said. "Although people may feel as if they can combat sleep deprivation with caffeine, their performance on higher-level tasks will likely still be impaired. This is one of the reasons why sleep deprivation can be so dangerous."

Fenn said that the study has the potential to inform both theory and practice.

"If we had found that caffeine significantly reduced procedural errors under conditions of sleep deprivation, this would have broad implications for individuals who must perform high stakes procedures with insufficient sleep, like surgeons, pilots and police officers," Fenn said. "Instead, our findings underscore the importance of prioritizing sleep."

https://www.sciencedaily.com/releases/2021/05/210526115549.htm

Silver attacks bacteria, gets 'consumed'

Impacts of antibacterial interactions on silver affect applications

May 25, 2021

Science Daily/American Institute of Physics

For millennia, silver has been utilized for its antimicrobial and antibacterial properties. Although its use as a disinfectant is widely known, the effects of silver's interaction with bacteria on the silver itself are not well understood.

As antibiotic-resistant bacteria become more and more prevalent, silver has seen steep growth in its use in things like antibacterial coatings. Still, the complex chain of events that lead to the eradication of bacteria is largely taken for granted, and a better understanding of this process can provide clues on how to best apply it.

In Chemical Physics Reviews, by AIP Publishing, researchers from Italy, the United States, and Singapore studied the impacts an interaction with bacteria has on silver's structure.

When monitoring the interaction of silver nanoparticles with a nearby E. coli culture, the researchers found the silver undergoes several dramatic changes. Most notably, the E. coli cells caused substantial transformations in the size and shape of the silver particles.

It is often assumed the silver stays unmodified in this process, but the work done by the team shows this not to be true.

The electrostatic interaction between the silver and the bacteria causes some of the silver particles to dissolve as it releases ions to penetrate the bacterial cells. This dissolution modifies the shape of the silver particles, shrinking and rounding them out from triangular shapes into circles.

These effects are even more pronounced if the E. coli cells are pretreated with a molecule to increase the permeability of their membranes before they meet the silver.

"It seems from this study that silver is 'consumed' from the interaction," said Guglielmo Lanzani, one of the authors on the paper and director of the Center for Nano Science and Technology of IIT-Instituto di Tecnologia.

Fortunately, this "consumption" likely does not impact silver's antimicrobial properties, because the effect is so small.

"We think this does not affect the efficiency of the biocidal process and, due to the tiny exchange of mass, the lifetime is essentially unlimited," said Giuseppe Paternò, a researcher at IIT and co-author of the study. "The structural modifications, however, affect the optical properties of the metal nanostructures."

Direct investigations of processes like these are difficult, because laboratories are controlled environments that cannot fully capture the complexities of a biological setting of bacterial cells.

Nevertheless, the group is planning further experiments to explore the chemical pathways that lead to the structural changes in silver. They hope to uncover why silver works better than other materials as an antibacterial surface, and why bacterial membranes are particularly vulnerable to silver, while other cells remain less affected.

https://www.sciencedaily.com/releases/2021/05/210525113726.htm

Evacuating under dire wildfire scenarios

May 24, 2021

Science Daily/University of Utah

In 2018, the Camp Fire ripped through the town of Paradise, California at an unprecedented rate. Officials had prepared an evacuation plan that required 3 hours to get residents to safety. The fire, bigger and faster than ever before, spread to the community in only 90 minutes.

As climate change intensifies, wildfires in the West are behaving in ways that were unimaginable in the past -- and the common disaster response approaches are woefully unprepared for this new reality. In a recent study, a team of researchers led by the University of Utah proposed a framework for simulating dire scenarios, which the authors define as scenarios where there is less time to evacuate an area than is required. The paper, published on April 21, 2021 in the journal Natural Hazards Review, found that minimizing losses during dire scenarios involves elements that are not represented in current simulation models, among them improvisation and altruism.

"The world is dealing with situations that exceed our worst case scenarios," said lead author Thomas Cova, professor of geography at the U. "Basically we're calling for planning for the unprecedented, which is a tough thing to do."

Most emergency officials in fire-prone regions develop evacuation plans based on the assumptions that wildfires and residents will behave predictably based on past events. However, recent devastating wildfires in Oregon, California and other western states have shown that those assumptions may no longer hold.

"Wildfires are really becoming more unpredictable due to climate change. And from a psychological perspective, we have people in the same area being evacuated multiple times in the past 10 years. So, when evacuation orders come, people think, 'Well, nothing happened the last few times. I'm staying,'" said Frank Drews, professor of psychology at the U and co-author of the study. "Given the reality of climate change, it's important to critically assess where we are and say, 'Maybe we can't count on certain assumptions like we did in the past.'"

How to predict the unprecedented

The framework allows planners to create a dire wildfire scenario -- when the lead time, defined as the time before the fire reaches a community to respond, is less than the time required to evacuate. The authors developed a scoring system that categorizes each scenario as routine, dire, very dire or extremely dire based on many different factors.

One big factor affecting the direness is the ignition location, as one closer to a community offers less time than one farther away. A second major factor is the wildfire detection time. During the day, plumes of smoke can cue a quick response, but if it starts at night when everyone is asleep, it could take longer to get people moving. Officials may delay their decisions to avoid disrupting the community unnecessarily, but a last-minute evacuation order can cause traffic jams or put a strain on low-mobility households.

Alert system technologies can create dire circumstances if residents do not receive the warning in time due to poor cellphone coverage or low subscription rates to reverse 911 warning systems. If the community has many near misses with wildfire, the public's response could be to enact a wait-and-see approach before they leave their homes.

Using a dire scenario dashboard, the user assigns various factors an impediment level -- low, minor or major -- that can change at any point to lessen or increase a situation's direness.

"Usually when we run computer simulations, nothing ever goes wrong. But in the real world, things can get much worse half-way through an evacuation," said Cova. "So, what happens when you don't have enough time? The objective switches from getting everyone out to instead minimizing casualties. It's dark."

"More people began working remotely from home during the pandemic, which then led to them moving out of large cities into rural areas," explained assistant professor Dapeng Li of the South Dakota State University Department of Geography and Geospatial Sciences, a co-author and U alumnus who helped develop the computer simulations. "These rural communities typically have fewer resources and face challenges in rapidly evacuating a larger number of residents in this type of emergency situation."

Reducing dire scenarios

Simulating dire wildfire scenarios can improve planning and the outcomes in cases where everything goes wrong. For example, creating fire shelters and safety zones inside of a community can protect residents who can't get out, while reducing traffic congestion for others who can evacuate. During the 2018 Camp Fire, people improvised temporary refuges in parking lots and community buildings. Modeling could help city planners construct permanent safety areas ahead of time.

A common human response during wildfires are improvisations and creative thinking, which are difficult to model but can be literally lifesaving. For example, during the 2020 Creek Fire in California, a nearby military base sent a helicopter to rescue trapped campers. Another crucial component is individuals helping others, such as people giving others rides or warning neighbors who missed the official alert. During the Camp Fire, Joe Kennedy used his bulldozer to singlehandedly clear abandoned cars that were blocking traffic.

"It is very common for families and neighbors to assume a first responder role and help each other during disasters," said Laura Siebeneck, associate professor of emergency management and disaster science at the University of North Texas and co-author of the study. "Many times, individuals and groups come together, cooperate, and improvise solutions as needed. Though it is difficult to capture improvisation and altruism in the modeling environment, better understanding human behavior during dire events can potentially lead to better protective actions and preparedness to dire wildfire events."

Studying and modeling dire scenarios is necessary to improve the outcomes of unprecedented changes in fire occurrence and behavior. This study is the first attempt to develop a simulation framework for these scenarios, and more research is needed to incorporate the unpredictable elements that create increasingly catastrophic wildfires.

https://www.sciencedaily.com/releases/2021/05/210524161657.htm

Narcissism linked to aggression in review of 437 studies

Study found relationship 'across the board' all over the world

May 25, 2021

Science Daily/Ohio State University

A comprehensive analysis of 437 studies from around the world provides the best evidence to date that narcissism is an important risk factor for both aggression and violence, researchers said.

The link between narcissism and aggression was found for all dimensions of narcissism and for a variety of types of aggression. Results were similar regardless of gender, age, whether they were college students, or country of residence.

And, to have an impact, narcissism doesn't have to be at levels so high as to be pathological. Findings showed that even when narcissism was within what is considered a normal range, higher levels were linked to aggression.

"It is a pretty straightforward message: Narcissism is a significant risk factor for aggressive and violent behavior across the board," said Brad Bushman, co-author of the study and professor of communication at The Ohio State University.

The study was led by Sophie Kjaervik, a graduate student in communication at Ohio State. It was published yesterday (May 24, 2021) in the journal Psychological Bulletin.

"The link we found between narcissism and aggression was significant -- it was not trivial in size," Kjaervik said. "The findings have important real-world implications."

The researchers combined and analyzed data from many studies to provide a comprehensive view of this research area. In this meta-analysis, they examined data from 437 independent studies with a total of 123,043 participants.

Narcissism is characterized by an overblown sense of self-importance, Bushman said. The key component of narcissism is entitlement. Narcissism also has two peripheral components: grandiose (those with high self-esteem) and vulnerable (those with low self-esteem). The study found all of these components were linked to aggression.

Narcissism was related to all forms of aggression measured in the studies the researchers analyzed, including physical, verbal, bullying, direct or indirect, and displaced onto innocent targets.

"Individuals who are high in narcissism are not particularly picky when it comes to how they attack others," Kjaervik said.

Findings showed that narcissism was linked to online cyberbullying, as well as bullying offline.

"That's a highly important finding now that we live in an online world," she said.

People higher in narcissism were not only more likely to lash out in anger, but were also more likely to be "cold, deliberate and proactive" in their aggression, Bushman said.

People high in narcissism were more likely than others to be aggressive whether they were provoked or not, the study found. But the risk for aggression was significantly higher when they felt provoked, such as being ignored or insulted.

The researchers were somewhat surprised to find that the link between narcissism and violence was nearly as strong as its link with less serious forms of aggression. Violence is more rare than and is generally more difficult to predict than lesser forms of aggression, Bushman said. In this study, violence was defined as aggression intended to cause physical harm such as injury or death.

But these results are consistent with research suggesting that narcissism might be a risk factor for extremely violent acts such as mass shootings, he said.

One argument could be that the narcissism-aggression link would be more likely to occur in individualistic countries, like the United States, where people emphasize their personal rights. But the analysis found that narcissism and aggression were related even in more collectivist countries.

And findings were similar whether the research participants were college students or a more general population.

It might be tempting to think these results apply only to people who are "narcissists," but that would be wrong, Bushman said.

For one, you can't separate people into those who are narcissists and those who are not. Nearly everyone has some degree of narcissism, even though only a minority have levels high enough to be called pathological.

Findings in this study suggest that higher levels of narcissism are related to more aggression even before it reaches pathological levels.

"All of us are prone to being more aggressive when we are more narcissistic," Bushman said.

One thing that clearly stood out in the analysis, he said, was how people high in narcissism respond when they feel threatened.

"Our results suggest provocation is a key moderator of the link between narcissism and aggression," Bushman said.

"Those who are high in narcissism have thin skins, and they will lash out if they feel ignored or disrespected."

https://www.sciencedaily.com/releases/2021/05/210525084324.htm

Taking more steps daily may lead to a longer life

May 20, 2021

Science Daily/American Heart Association

Taking more steps per day, either all at once or in shorter spurts, may help you live longer, according to preliminary research to be presented at the American Heart Association's Epidemiology, Prevention, Lifestyle & Cardiometabolic Health Conference 2021. The meeting is virtual, May 20-21, and offers the latest science on population-based health and wellness and implications for lifestyle.

Walking is one of the safest and easiest ways to improve fitness and health including heart health. The American Heart Association's fitness guidelines for adults recommend at least 150 minutes per week of moderate or 75 minutes of vigorous physical activity, or a combination of both. Popular fitness apps and step counters make it easy to count steps, so researchers used a wearable step counting device to compare the effects of uninterrupted bouts of steps (10 minutes or longer) to occasional short spurts, such as climbing the stairs and general daily activities throughout the day.

"Technological advances made in recent decades have allowed researchers to measure short spurts of activity. Whereas, in the past we were limited to only measuring activities people could recall on a questionnaire," said lead study author Christopher C. Moore, M.S., a Ph.D. student in epidemiology at the University of North Carolina at Chapel Hill. "With the help of wearable devices, more research is indicating that any type of movement is better than remaining sedentary."

From 2011-2015, 16,732 women wore a waist step counter that measured their daily steps and walking patterns for four to seven days. The women were all over age 60 (average age of 72; mostly non-Hispanic white women) and were participants in the Women's Health Study, a large, national study of heart disease, cancer and other long-term disease prevention.

The researchers divided the total number of steps for each study participant into two groups: 1) 10 minutes or longer bouts of walking with few interruptions; and 2) short spurts of walking during regular daily activities such as housework, taking the stairs, or walking to or from a car. In follow-up, they tracked deaths from any cause for an average of six years, through December 31, 2019.

Researchers found:

• Overall, 804 deaths occurred during the entire study period of 2011-2019.

• Study participants who took more steps in short spurts lived longer, regardless of how many steps they had in longer, uninterrupted bouts. The benefits leveled off at about 4,500 steps per day in short spurts.

• Compared to no daily steps, each initial increase of 1,000 steps per day was associated with a 28% decrease in death during the follow-up period.

• A 32% decrease in death was noted in participants who took more than 2,000 steps daily in uninterrupted bouts.

A prior analysis of the same women reported that those who took 4,500 steps per day had a significantly lower risk of death compared to the least active women. "Our current results indicate that this finding holds even for women who did not engage in any uninterrupted bouts of walking. Taking 2,000 or more additional steps during bouts was associated with further benefits for longevity," Moore said.

"Older adults face many barriers to participating in structured exercise programs, so some may find it more convenient and enjoyable to increase everyday walking behaviors, like parking slightly further from their destination or doing some extra housework or yardwork," Moore said.

Since all study participants were older and mostly non-Hispanic white women, more research is needed to determine if the results apply to men, younger women and people from diverse racial and ethnic groups.

https://www.sciencedaily.com/releases/2021/05/210520145353.htm

Study raises new alarm over long-term exposure to second-hand smoke

Researchers measure chronic exposure in mice over 10 months

May 19, 2021

Science Daily/Oregon Health & Science University

Chronic exposure to second-hand smoke results in lower body weight and cognitive impairments that more profoundly affects males, according to new research in mice led by Oregon Health & Science University.

The study published today in the journal Environmental Health Perspectives.

"The hope is that we can better understand these effects for policymakers and the next generation of smokers," said lead author Jacob Raber, Ph.D., professor of behavioral neuroscience in the OHSU School of Medicine. "Many people still smoke, and these findings suggest that that the long-term health effects can be quite serious for people who are chronically exposed to second-hand smoke."

The research examined daily exposure of 62 mice over a period of 10 months. Researchers used a specially designed "smoking robot" that went through a pack of cigarettes a day in ventilated laboratory space at OHSU. The longest previous study of this kind lasted three months.

"Nobody has done this, ever. This study is unique," Raber said. "It really gives you the ability to look at long-term effects."

"This study more accurately replicates the human experience by daily exposing mice to cigarette smoke," added senior author Glen Kisby, Ph.D., professor of pharmacology at Western University of Health Sciences in Lebanon, Oregon.

Second-hand smoke is already considered a risk factor for dementia in people, but the new study put the theory to the test.

Researchers first divided mice into two groups -- one wild-type and one expressing the human tau protein, important in Alzheimer's-like dementia. Starting in April of 2018, they exposed mice to cigarette smoke for 168 minutes a day, then conducted behavioral and cognitive testing. They also examined lung and brain tissue.

Key findings:

• Smoke harms 'healthy' mice. Researchers theorized that second-hand smoke would be especially harmful for mice with the human tau protein. However, "we actually found the opposite," Raber said. In many of the behavioral and cognitive tests -- including swimming speeds and migrating through a maze -- wild-type mice were more affected than human tau mice after both groups were exposed to second-hand smoke.

• Smoke especially harms males. Researchers discerned a clear sex-related difference in cognition, with clearly discernable changes in the hippocampus region of the brain among males compared to females.

• Loss in body weight. Researchers found lower body weights in wild-type mice following second-hand smoke compared with human tau mice. Further, they also noticed that males were disproportionately impacted by a loss in body weight compared to females.

• Brain changes: Researchers discovered more profound changes in metabolic pathways, which are linked chemical reactions, in the brains of wild-type males than females. Researchers also found more profound effects in the brains of wild-type than the human tau mice.

Although smoking rates have declined in recent generations in some countries, smoking -- and exposure to second-hand smoke -- remains widespread in much of the world. The World Health Organization estimates 1.5 to 1.9 billion people worldwide will be smokers in 2025.

"Long-term exposure to second-hand smoke triggers detrimental changes," Raber said. "Based on our study, it seems that males might be more susceptible than females. People should take that into consideration."

https://www.sciencedaily.com/releases/2021/05/210519080435.htm

Alcohol problems severely undertreated

Heavy drinkers see doctors regularly, but few receive treatment for disorder

May 17, 2021

Science Daily/Washington University School of Medicine

Some 16 million Americans are believed to have alcohol use disorder, and an estimated 93,000 people in the U.S. die from alcohol-related causes each year. Both of those numbers are expected to grow as a result of heavier drinking during the COVID-19 pandemic.

Yet, in a new study involving data from more than 200,000 people with and without alcohol problems, researchers at Washington University School of Medicine in St. Louis found that although the vast majority of those with alcohol use disorder see their doctors regularly for a range of issues, fewer than one in 10 ever get treatment for drinking.

The findings are published in the June issue of the journal Alcoholism: Clinical & Experimental Research.

Analyzing data gathered from 2015 through 2019 via the National Survey on Drug Use and Health, the researchers found that about 8% of those surveyed met the current criteria for alcohol use disorder, the medical diagnosis for those with an addiction to alcohol. Of these people who met the criteria, 81% had received medical care in a doctor's office or spent time in a hospital or clinic during the previous year. But only 12% reported they had been advised to cut down on their drinking, 5% were offered information about treatment, and 6% received treatment, some of whom were not referred by their doctors but sought out treatment on their own.

"It's not that these people aren't in the health-care system," said first author Carrie M. Mintz, MD, an assistant professor of psychiatry. "But although they see doctors regularly, the vast majority aren't getting the help they need."

Mintz and her colleagues evaluated data from 214,505 people. The researchers first wanted to learn whether people with alcohol use disorder had access to health care and if they did, whether they had been screened about their alcohol use; they were considered to have been screened if their doctors simply had asked how much they drink. The researchers also evaluated whether people with drinking problems had been advised to cut down on drinking, had received additional information about treatment, or had received treatment or counseling.

The researchers found that although most people with alcohol use disorder had access to health care and although 70% reported they had been asked about alcohol use, that's where the care stopped.

"Some primary care doctors may not feel comfortable telling patients they should cut down on drinking, prescribing medication to help them cut back or referring them to treatment because they don't specialize in treating alcohol misuse; but the result is that many people who need treatment aren't getting it," said senior author Laura Jean Bierut, MD, the Alumni Endowed Professor of Psychiatry. "We used to see the same thing with smoking, but when physicians became educated about smoking and learned that many of their patients wanted to quit or cut back, doctors began offering more treatment, and more people were able to quit. We think the same thing may be possible with alcohol."

Among treatments that could be prescribed are the FDA-approved medications naltrexone, acamprosate and disulfiram, as well as psychotherapy and mutual-aid approaches, such as the 12-step program used by Alcoholics Anonymous.

"Alcohol use disorder is a chronic disease, but compared to other chronic diseases, it's wildly untreated," Bierut said. "For example, two-thirds of patients with HIV and 94% of patients with diabetes receive treatment, compared with only 6% of people with alcohol use disorder."

The researchers noted that during the pandemic, alcohol sales in the U.S. increased by 34%. Consequently, they expect that as the country emerges from COVID-19 and returns to normal, the number of people with alcohol use disorder will have climbed.

"We know alcohol use and misuse have increased during the pandemic," Mintz said. "It seems there has been a shift toward heavier drinking. Plus, many doctor's offices, AA groups and other support groups were shut down for a period of time, so we would hypothesize that even the relatively small percentage of people in treatment may have declined during the past year."

Mintz, C, Hartz S, Fisher S, Ramsey A, Geng E, Grucza R, Bierut L. A cascade of care for alcohol use disorder: using 2015-2019 National Survey on Drug Use and Health data to identify gaps in past 12-month care. Alcoholism: Clinical & Experimental Research, published online May 16, 2021.

https://www.sciencedaily.com/releases/2021/05/210517144730.htm

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Studies reveal skull as unexpected source of brain immunity

Immune cells from skull bone marrow guard the brain, spinal cord

June 3, 2021

Science Daily/Washington University School of Medicine

The immune system is the brain's best frenemy. It protects the brain from infection and helps injured tissues heal, but it also causes autoimmune diseases and creates inflammation that drives neurodegeneration.

Two new studies in mice suggest that the double-edged nature of the relationship between the immune system and the brain may come down to the origins of the immune cells that patrol the meninges, the tissues that surround the brain and spinal cord. In complementary studies published June 3 in the journal Science, two teams of researchers at Washington University School of Medicine in St. Louis unexpectedly found that many of the immune cells in the meninges come from bone marrow in the skull and migrate to the brain through special channels without passing through the blood.

These skull-derived immune cells are peacekeepers, dedicated to maintaining a healthy status quo. It's the other immune cells, the ones that arrive from the bloodstream, that seem to be the troublemakers. They carry genetic signatures that mark them as likely to promote autoimmunity and inflammation, and they become more abundant with aging or under conditions of disease or injury. Taken together, the findings reveal a key aspect of the connection between the brain and the immune system that could inform our understanding of a wide range of brain disorders.

"There has been this gap in our knowledge that applies to almost every neurological disease: neuro-COVID, Alzheimer's disease, multiple sclerosis, brain injury, you name it," said Jonathan Kipnis, PhD, the Alan A. and Edith L. Wolff Distinguished Professor of Pathology & Immunology and a BJC Investigator. Kipnis is the senior author on one of the papers. "We knew immune cells were involved in neurological conditions, but where were they coming from? What we've found is that there's a new source that hasn't been described before for these cells."

Earlier this year, Kipnis showed that immune cells stationed in the meninges keep tabs on the brain. As part of these new studies, Kipnis and Marco Colonna, MD, the Robert Rock Belliveau, MD, Professor of Pathology and the senior author on the other paper, independently launched projects to find where such cells come from. Kipnis focused on the innate arm of the immune system and Colonna on the adaptive arm. Innate immune cells are responsible for inflammation, which helps defend against infection and heal injuries, but also can damage tissues and contribute to degenerative conditions such as Alzheimer's and Parkinson's disease. Adaptive immune cells are capable of specifically targeting undesirables such as viruses and tumors, but they also can mistakenly home in on the body's own healthy tissues, resulting in autoimmune diseases such as multiple sclerosis.

Colonna and colleagues -- including co-first authors Simone Brioschi, PhD, a postdoctoral researcher, Wei-Le Wang, PhD, a postdoctoral researcher, and Vincent Peng, a graduate student -- traced the development of B cells, antibody-producing members of the adaptive immune system. They found that most B cells in the meninges arose and matured in the skull bone marrow. As B cells mature, they must be taught to distinguish between normal proteins from the body, which pose no threat, and foreign proteins that signal infection or disease and require a response. For B cells destined for a life patrolling the boundaries of the central nervous system, the skull is a convenient site for this education.

"B cells in the bone marrow of the skull come into contact with the central nervous system and are educated by the central nervous system," said Colonna, who is also a professor of medicine. "That would not happen if they were released into the blood. Because they are directly in contact with the brain, they learn to be tolerant of brain proteins."

Along with the tolerant B cells derived from the skull, the researchers also discovered a population of B cells that come into the meninges from the blood. These blood-derived B cells are not trained to ignore normal central nervous system proteins. Some of these cells may wrongly recognize harmless central nervous system proteins as foreign and produce antibodies against them, Colonna said. Moreover, the number of these blood-derived B cells increases with age, providing a clue to why the risk of neuro-immune conditions is higher in older people.

Meanwhile, Kipnis' team -- led by co-first authors Andrea Cugurra, a graduate student, Tornike Mamuladze, MD, a visiting researcher, and Justin Rustenhoven, PhD, a postdoctoral researcher -- was searching for the source of meningeal myeloid cells, a group of innate immune cells. They found that myeloid cells arose in the bone marrow of the skull and spinal vertebrae and entered the meninges via direct channels through the bone.

Using mouse models of multiple sclerosis and of brain and spinal cord injuries, Kipnis and colleagues found that myeloid cells swarm into the brain and spinal cord in response to injury or disease. Most of the entering cells are drawn from the resident population of myeloid cells in the meninges. These are biased toward regulating and modulating the immune response. But some myeloid cells come in from the blood, and these are more inflammatory, capable of causing damage if not properly controlled.

"Understanding where these cells come from and how they behave is a critical part of understanding the basic mechanisms of neuro-immune interactions, so we can design new therapeutic approaches for neurological conditions associated with inflammation," said Kipnis, who is also a professor of neurosurgery, of neurology and of neuroscience. "The location of these cells in the skull makes them relatively accessible, and opens up the possibility of designing therapies to alter the behavior of these cells and treat neuro-immune conditions."

https://www.sciencedaily.com/releases/2021/06/210603171058.htm

Secondary infections inflame the brain, worsening cognition in Alzheimer's disease

June 3, 2021

Science Daily/Trinity College Dublin

New research into Alzheimer's disease (AD) suggests that secondary infections and new inflammatory events amplify the brain's immune response and affect memory in mice and in humans -- even when these secondary events occur outside the brain.

Scientists believe that key brain cells (astrocytes and microglia) are already in an active state due to inflammation caused by AD and this new research shows that secondary infections can then trigger an over-the-top response in those cells, which has knock-on effects on brain rhythms and on cognition.

In the study, just published in Alzheimer's & Dementia, the journal of the Alzheimer's Association, mice engineered to show features of AD were exposed to acute inflammatory events to observe the downstream effects on brain inflammation, neuronal network function and memory.

These mice showed new shifts in the output of astrocytes and microglia and displayed new cognitive impairment and disturbed 'brain rhythms' that did not occur in healthy, age-matched, mice. These new onset cognitive changes are similar to acute and distressing psychiatric disturbances like delirium, that frequently occur in elderly patients.

Although it is difficult to replicate these findings in patients, the study additionally showed that AD patients who died with acute systemic infection showed heighted brain levels of IL-1β -- a pro-inflammatory molecule that was important in causing the heightened immune response and the new onset disruptions seen in the AD mice.

Colm Cunningham, Associate Professor in Trinity's School of Biochemistry and Immunology, and the Trinity Biomedical Sciences Institute, led the research. He said:

"Alzheimer's disease is the most common form of dementia, affecting more than 5% of those over 60 and this distressing, debilitating condition causes difficulties for a huge number of people across the globe. The more we know about the disease and its progression the better chance we have of treating those living with it. We believe our work adds to this knowledge base in a few ways. Primarily, we show that the Alzheimer's-affected brain has a greater vulnerability to acute inflammatory events, even if they occur outside the brain.

Placing this within the context of the slowly evolving progression of AD, we propose that these hypersensitive responses, now seen in multiple cell populations, may contribute to the negative outcomes that follow acute illness in older patients, including episodes of delirium and the accelerated cognitive trajectory that has been observed in patients who experience delirium before or during their dementia."

The research was supported by the US National Institutes of Health (NIH) and by the Wellcome Trust.

https://www.sciencedaily.com/releases/2021/06/210603083545.htm

Healthy lifestyle linked to better cognition for oldest adults -- regardless of genetic risk

New study suggests importance of maintaining healthy lifestyle even after age 80

June 1, 2021

Science Daily/PLOS

A new analysis of adults aged 80 years and older shows that a healthier lifestyle is associated with a lower risk of cognitive impairment, and that this link does not depend on whether a person carries a particular form of the gene APOE. Xurui Jin of Duke Kunshan University in Jiangsu, China, and colleagues present these findings in the open-access journal PLOS Medicine.

The APOE gene comes in several different forms, and people with a form known as APOE ε4 have an increased risk of cognitive impairment and Alzheimer's disease. Previous research has also linked cognitive function to lifestyle factors, such as smoking, exercise, and diet. However, it has been unclear whether the benefits of a healthy lifestyle are affected by APOE ε4, particularly for adults over 80 years of age.

To clarify the relationship between APOE ε4 and lifestyle, Jin and colleagues examined data from 6,160 adults aged 80 or older who had participated in a larger, ongoing study known as the Chinese Longitudinal Healthy Longevity Survey. The researchers statistically analyzed the data to investigate links between APOE ε4, lifestyle, and cognition. They also accounted for sociodemographics and other factors that could impact cognition.

The analysis confirmed that participants with healthy lifestyles or intermediately healthy lifestyles were significantly less likely to have cognitive impairment than those with an unhealthy lifestyle, by 55 and 28 percent, respectively. In addition, participants with APOE ε4 were 17 percent more likely to have cognitive impairment than those with other forms of APOE.

A previous study suggested that in individuals at low and intermediate genetic risk, favorable lifestyle profiles are related to a lower risk of dementia compared to unfavorable profiles. But these protective associations were not found in those at high genetic risk. However, the investigation showed the link between lifestyle and cognitive impairment did not vary significantly based on APOE ε4 status which represented the genetic dementia risk. This suggests that maintaining a healthier lifestyle could be important for maintaining cognitive function in adults over 80 years of age, regardless of genetic risk.

This cross-sectional study emphasized the importance of a healthy lifestyle on cognitive health. While further research will be needed to validate these findings among different population, this study could help inform efforts to boost cognitive function for the oldest of adults.

In the next step, the team will explore this association using the AD polygenetic risk score (AD-PRS) and explore the interactive relationship between AD-PRS and lifestyle on cognition with the longitudinal data.

https://www.sciencedaily.com/releases/2021/06/210601152005.htm