Holidays crank up kilos for kids

 On the cusp of summer holidays, Aussie kids are looking forward to some well-deserved time off. But too much downtime could create health problems, as new research shows that holidays are the prime time for excessive weight gain in kids.

Conducted by the University of South Australia's Alliance for Research in Exercise, Nutrition and Activity team, the 'Life on Holidays' study assessed changes to children's fitness and fatness during the holidays.

It found that children's body fat increased at a faster pace during school holidays than in-school periods.

Funded by the NHMRC, the study found that young children (in Grades 4 and 5) expended less energy during holidays than during the school year.

Specifically, children:

• slept 12 minutes less per day
• spent 12 minutes less per being physically active
• spent an additional 70 minutes per day on screen time.

Children's body fat increased at a greater rate during the holidays, and aerobic fitness declined faster than during the in-school periods.

It is the first study of its kind outside of the US.

In Australia, one in four children and teenagers are overweight or obese.

Globally, more than 124 million children and adolescents (6% of girls and 8% of boys) are obese.

Lead researcher, UniSA's Professor Tim Olds says promoting physical activities for children in the school holidays could help address unhealthy weight gain and declining fitness.

"Like all of us, kids (and their parents) deserve some holiday downtime, but the way they spend their time on holidays is very different from the school term -- and in ways which is not always good for children's health," Prof Olds says.

"On school holidays, kids are significantly less active than when they're at school, and this translates into higher body fat percentages and lower levels of fitness.

"During the holidays, kids spend about 12 minutes less each day in moderate to vigorous physical activity -- almost an hour and a half a week -- and get more than an hour's extra screen time each day. They also spend an extra 20 minutes each day in transport, and a quarter of an hour more per day just chilling.

"It's not surprising to find that kids get fatter at a faster rate on school holidays compared to school term, and lose a lot of fitness. If kids spent the whole year on holidays, their percentage of body fat would increase by about 4% more each year than if they had no holidays, and their fitness would decline by about 10% each year.

"Kids who are not getting enough exercise and movement have a greater risk of developing health issues, such as cardiovascular disease and Type 2 diabetes later in life, so it's important that we encourage kids to stay active and embrace a balance of downtime and exercise."

The two-year study focused on children aged 9-10 years, with data collected at the beginning and end of Terms 1 and 4 in both Grades 4 and 5. More than 150 participants from the 'Life on Holidays' study took part in this study.

Co-researcher, UniSA's Dr Dot Dumuid says that one solution could be for Australia to adopt the American institution of summer camps and holiday programs to improve kids' use of time during holidays.

"A defining factor of school holidays is that they're unstructured -- they can get food from the fridge when they want it, and generally have access to computers and devices -- and there's no doubt that screen time plays a key role in increased sedentary time during school holidays," Dr Dumuid says.

"When you compare this to the structure of a school day, where kids have a prepared lunch, and scheduled PE lessons and playtimes, it's vastly different.

"In contrast, summer camps and holiday programs get a big tick of approval as they provide kids with physical activities in a semi-structured way. Already popular in America, summer camps may be worth investigating as a viable option over Australian holidays.

"We all want our kids to be healthy. And while devices and TV may provide a bit of babysitting, is it really worth your child's health?"

Source: ScienceDaily

Body dissatisfaction linked with depression risk in children

 Body dissatisfaction at age 11 is linked to increased risk of depression by age 14, finds a new longitudinal study led by UCL researchers.

The findings, published in The Lancet Psychiatry, show that body image concerns explain a large proportion of an association between body mass index (BMI) and depression in children, particularly in girls.

The study, supported by Wellcome, involved 13,135 participants of the Millennium Cohort Study, a UCL-led nationally representative birth cohort study of people born between 2000 and 2002.

The researchers found that high BMI at age seven was linked with increased depressive symptoms (which can include low mood, loss of pleasure and poor concentration) by age 14, as well as with greater body dissatisfaction at age 11.

They found that body dissatisfaction was a major contributor to the link between BMI at age seven and subsequent depressive symptoms, explaining 43% of the association.

All three of these associations were twice as large in girls compared to boys.

Lead author Dr Francesca Solmi (UCL Psychiatry) said: "Depression has become more common among young people, as have having an overweight BMI, and body dissatisfaction.

"Here we have found strong longitudinal evidence that a high BMI in childhood is linked with an increased risk of depressive symptoms multiple years later.

"But we were particularly interested in how much body dissatisfaction might be the driver of this link. We found strong evidence that being unhappy with one's appearance is linked with increased depressive symptoms years later. Our findings suggest that any efforts to reduce weight in childhood need to consider their potential mental health impacts, so that we can avoid stigmatising weight and instead support children's mental health and wellbeing."

The research did not cover what other factors, besides body dissatisfaction, could explain why children with high BMI are more likely to develop depressive symptoms, but they say that other biological (for instance inflammation) or environmental (for instance bullying) pathways might explain part of the association.

First author Emma Blundell, trainee clinical psychologist at UCL Psychology & Language Sciences, said: "Many public health strategies seek to reduce weight in childhood. Primary school children are being taught about the importance of calories and exercise, and all young people in England are being weighed at school to determine whether weight loss efforts are needed. Whilst promoting healthy diet and exercise is important, it may be that some public health messaging could be fostering feelings of guilt or shame.

Source: ScienceDaily

High cholesterol caused by childhood sedentariness could be reversed with light physical activity

 Increased sedentary time in childhood can raise cholesterol levels by two thirds as an adult, leading to heart problems and even premature death -- but a new study has found light physical activity may completely reverse the risks and is far more effective than moderate-to-vigorous physical activity.

The study was conducted in collaboration between the University of Exeter, University of Eastern Finland, and University of Bristol and published in The Journal of Clinical Endocrinology & Metabolism. Researchers used data from the University of Bristol study Children of the 90s (also known as the Avon Longitudinal Study of Parents and Children), which included 792 children aged 11 years who were followed up until the age of 24.

Results from this study found that accumulated sedentary time from childhood can increase cholesterol levels by two thirds (67 percent) by the time someone reaches their mid-twenties. Elevated cholesterol and dyslipidaemia from childhood and adolescence have been associated with premature death in the mid-forties and heart problems such as subclinical atherosclerosis and cardiac damage in the mid-twenties.

Healthy lifestyles are considered important in the prevention of dyslipidaemia and one of the primary ways of lowering cholesterol, apart from diet, is movement behaviour. For the first time, this study objectively examined the long-term effects of sedentary time, light physical activity, and moderate-to-vigorous physical activity on childhood cholesterol levels.

The World Health Organization currently recommends children and adolescents should accumulate on average 60 minutes of moderate-to-vigorous physical activity a day and reduce sedentary time but have limited guidelines for light physical activity. Yet this new study and other recent studies has found light physical activity -- which includes exercises such as long walks, house chores, or slow dancing, swimming, or cycling -- is up to five times more effective than moderate-to-vigorous physical activity at promoting healthy hearts and lowering inflammation in the young population.

Dr Andrew Agbaje from the University of Exeter led the study and said: "These findings emphasise the incredible health importance of light physical activity and shows it could be the key to preventing elevated cholesterol and dyslipidaemia from early life. We have evidence that light physical activity is considerably more effective than moderate-to-vigorous physical activity in this regard, and therefore it's perhaps time the World Health Organization updated their guidelines on childhood exercise -- and public health experts, paediatricians, and health policymakers encouraged more participation in light physical activity from childhood."

During the research, accelerometer measures of sedentary time, light physical activity, and moderate-to-vigorous physical activity were collected at ages 11, 15, and 24 years. High-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and total cholesterol were repeatedly measured at ages 15, 17, and 24 years. These children also had repeated measurement of dual-energy Xray absorptiometry assessment of total body fat mass and muscle mass, as well as fasting blood glucose, insulin, and high sensitivity C-reactive protein, with smoking status, socio-economic status, and family history of cardiovascular disease.

During the 13-year follow-up, sedentary time increased from approximately six hours a day to nine hours a day. Light physical activity decreased from six hours a day to three hours a day while moderate-to-vigorous physical activity was relatively stable at around 50 minutes a day from childhood until young adulthood. The average increase in total cholesterol was 0.69 mmol/l. It was observed without any influence from body fat.

An average of four-and-a-half hours a day of light physical activity from childhood through young adulthood causally decreased total cholesterol by (-0.53 mmol/l), however, body fat mass could reduce the effect of light physical activity on total cholesterol by up to six percent. Approximately 50 minutes a day of moderate-to-vigorous physical activity from childhood was also associated with slightly reduced total cholesterol (-0.05 mmol/L), but total body fat mass decreased the effect of moderate-to-vigorous physical activity on total cholesterol by up to 48 percent. Importantly, the increase in fat mass neutralised the small effect of moderate-to-vigorous physical activity on total cholesterol.

The paper is entitled Associations of Sedentary Time and Physical Activity from Childhood with Lipids: A 13-Year Mediation and Temporal Studyand published in The Journal of Clinical Endocrinology & Metabolism. These findings come shortly after another study led by Dr Andrew Agbaje published this week in Nature Communications found light physical activity may completely reverse childhood obesity linked to increased sedentary time in more than 6000 children. Sedentary time contributed seven to ten percent of the total fat mass gained during growth from childhood until young adulthood. Light physical activity decreased the overall gain in fat mass by 9.5-15 percent, while moderate-to-vigorous physical activity decreased fat mass by 0.7-1.7 percent.

Source: ScienceDaily

Key to fatty liver disease and its consequences for billions of people

 The global rise in obesity and diabetes is leading to an epidemic in fatty liver disease affecting 20-30 per cent of the world's population. Almost a third of people with fatty liver disease go on to develop an advanced form of the disease, known as non-alcoholic steatohepatitis (NASH) that can progress to cirrhosis and end-stage liver disease, or even liver cancer, and is a major risk factor for cardiovascular disease.

Why some people remain relatively healthy with fatty liver disease and some go onto potentially life-threatening illness has been a mystery.

Until now.

A study published today in The Journal of Clinical Investigation led by Professor Tony Tiganis from Monash University's Biomedicine Discovery Institute, has shown that the levels of the NOX4 protein change as the disease progresses -- rising in the early stages of the disease to protect the liver, but declining as the liver disease gets worse.

The researchers found that removing NOX4 in obese mice led to NASH and liver damage.

And when NOX4 levels were artificially raised in these mice they were protected from NASH and liver damage.

Importantly, the discovery provides evidence for a therapeutic avenue for a disease whose prevalence is predicted to balloon by 63 per cent from 2015 to 2030.

According to Professor Tiganis, the precise mechanisms that govern the transition to NASH and liver damage have remained unclear.

"It has been perplexing why the majority of patients with fatty liver disease don't progress to more severe disease," he said.

The researchers have shown that this is because NOX4 is induced when the liver first starts to accumulate fat and activates a complex adaptive program that protects the liver.

It is only when NOX4 levels decline and this adaptive program is abrogated that obese patients with fatty liver progress to NASH and liver damage.

Importantly, previous studies by Professor Tiganis and others have shown that the raising of NOX4 levels in skeletal muscle or in the heart after exercise protects against damage and promote muscle and cardiac function and prevent the metabolic decline otherwise associated with ageing.

"Compounds that bolster the activity of NOX4, or the adaptive program that NOX4 instigates, may be highly beneficial, countering not only the development of NASH, but also improving skeletal and cardiac function, as well as metabolic health," Professor Tiganis said.

Such compounds are found naturally in cruciferous vegetables, such as broccoli or cauliflower.

Source: ScienceDaily

Exercise can boost brain health

 A fascinating link between regular exercise and better brain health has been revealed, according to an international study that included a team of clinical researchers from Pacific Neuroscience Institute's Brain Health Center, located at Providence Saint John's Health Center.

The research, detailed in the paper "Exercise-Related Physical Activity Relates to Brain Volumes in 10,125 Individuals," was published this week in the Journal of Alzheimer's Disease and shows being physically active is related to increased size of brain areas important for memory and learning.The study looked at MRI brain scans from 10,125 people done at Prenuvo imaging centers, a key collaborator in the research.

It found those who regularly engaged in physical activities such as walking, running or sports had larger brain volumes in key areas.

This includes the gray matter, which helps with processing information, and the white matter, which connects different brain regions, as well as the hippocampus, important for memory.

Cyrus A. Raji, M.D., the lead researcher, explains the findings in simple terms: "Our research supports earlier studies that show being physically active is good for your brain. Exercise not only lowers the risk of dementia but also helps in maintaining brain size, which is crucial as we age."

David Merrill, M.D., study co-author and director of the PBHC noted, "We found that even moderate levels of physical activity, such as taking fewer than 4,000 steps a day, can have a positive effect on brain health. This is much less than the often-suggested 10,000 steps, making it a more achievable goal for many people."

Study co-authorSomayeh Meysami, M.D., assistant professor of neurosciences at Saint John's Cancer Institute and the Pacific Brain Health Center noted, "Our research links regular physical activity to larger brain volumes, suggesting neuroprotective benefits. This large sample study furthers our understanding of lifestyle factors in brain health and dementia prevention."

A Lancet Study in 2020 found about a dozen modifiable risk factors increase risk for Alzheimer's disease, including physical activity.

This work builds upon previous work by this group, linking caloric burn from leisure activities to improved brain structure.

"This study demonstrates the influence of exercise on brain health imaging and when added to other studies on the role of diet, stress reduction and social connection offer the proven benefits of drug-free modifiable factors in substantially reducing Alzheimer's disease," said George Perry, Editor-in-Chief of Journal of Alzheimer's Disease.

"With comprehensive imaging scans, our study underscores the interconnected synergy between the body and the brain. It echoes the knowledge of past generations, showcasing that increased physical activity is a predictor of a healthier aging brain," said Dr. Attariwala, senior author of this paper.

Source:ScienceDaily

What happens in the brain while daydreaming?

 You are sitting quietly, and suddenly your brain tunes out the world and wanders to something else entirely -- perhaps a recent experience, or an old memory. You just had a daydream.

Yet despite the ubiquity of this experience, what is happening in the brain while daydreaming is a question that has largely eluded neuroscientists.

Now, a study in mice, published Dec. 13 in Nature, has brought a team led by researchers at Harvard Medical School one step closer to figuring it out.

The researchers tracked the activity of neurons in the visual cortex of the brains of mice while the animals remained in a quiet waking state. They found that occasionally these neurons fired in a pattern similar to one that occurred when a mouse looked at an actual image, suggesting that the mouse was thinking -- or daydreaming -- about the image. Moreover, the patterns of activity during a mouse's first few daydreams of the day predicted how the brain's response to the image would change over time.

The research provides tantalizing, if preliminary, evidence that daydreams can shape the brain's future response to what it sees. This causal relationship needs to be confirmed in further research, the team cautioned, but the results offer an intriguing clue that daydreams during quiet waking may play a role in brain plasticity -- the brain's ability to remodel itself in response to new experiences.

"We wanted to know how this daydreaming process occurred on a neurobiological level, and whether these moments of quiet reflection could be important for learning and memory," said lead author Nghia Nguyen, a PhD student in neurobiology in the Blavatnik Institute at HMS.

An overlooked brain region

Scientists have spent considerable time studying how neurons replay past events to form memories and map the physical environment in the hippocampus, a seahorse-shaped brain region that plays a key role in memory and spatial navigation.

By contrast, there has been little research on the replay of neurons in other brain regions, including the visual cortex. Such efforts would provide valuable insights about how visual memories are formed.

"My lab became interested in whether we could record from enough neurons in the visual cortex to understand what exactly the mouse is remembering -- and then connect that information to brain plasticity," said senior author Mark Andermann, professor of medicine at Beth Israel Deaconess Medical Center, and professor of neurobiology at HMS.

In the new study, the researchers repeatedly showed mice one of two images, each consisting of a different checkerboard pattern of gray and dappled black and white squares. Between images, the mice spent a minute looking at a gray screen. The team simultaneously recorded activity from around 7,000 neurons in the visual cortex.

The researchers found that when a mouse looked at an image, the neurons fired in a specific pattern, and the patterns were different enough to discern image one from image two. More important, when a mouse looked at the gray screen between images, the neurons sometimes fired in a similar, but not identical, pattern, as when the mouse looked at the image, a sign that it was daydreaming about the image. These daydreams occurred only when mice were relaxed, characterized by calm behavior and small pupils.

Unsurprisingly, mice daydreamed more about the most recent image -- and they had more daydreams at the beginning of the day than at the end, when they had already seen each image dozens of times.

But what the researchers found next was completely unexpected.

Throughout the day, and across days, the activity patterns seen when the mice looked at the images changed -- what neuroscientists call "representational drift." Yet this drift wasn't random. Over time, the patterns associated with the images became even more different from each other, until each involved an almost entirely separate set of neurons. Notably, the pattern seen during a mouse's first few daydreams about an image predicted what the pattern would become when the mouse looked at the image later.

"There's drift in how the brain responds to the same image over time, and these early daydreams can predict where the drift is going," Andermann said.

Finally, the researchers found that the visual cortex daydreams occurred at the same time as replay activity occurred in the hippocampus, suggesting that the two brain regions were communicating during these daydreams.

Source: ScienceDaily

Researchers, Coast Salish people analyze 160-year-old indigenous dog pelt in the Smithsonian's collection

 Researchers from the Smithsonian's National Museum of Natural History led a new analysis that sheds light on the ancestry and genetics of woolly dogs, a now extinct breed of dog that was a fixture of Indigenous Coast Salish communities in the Pacific Northwest for millennia. Anthropologist Logan Kistler and evolutionary molecular biologist Audrey Lin analyzed genetic clues preserved in the pelt of "Mutton," the only known woolly dog fleece in the world, to pinpoint the genes responsible for their highly sought-after woolly fur.

The study's findings, published today, Dec. 14, in the journal Science, include interviews contributed by several Coast Salish co-authors, including Elders, Knowledge Keepers and Master Weavers, who provided crucial context about the role woolly dogs played in Coast Salish society.

"Coast Salish traditional perspective was the entire context for understanding the study's findings," said Kistler, the museum's curator of archaeobotany and archaeogenomics.

Coast Salish tribal nations in Washington state and British Columbia bred and cared for woolly dogs for thousands of years. Prized for their thick undercoats, the dogs were sheared like sheep and often kept in pens or on islands to carefully manage their breeding and to care for the canines' health and vitality. Coast Salish weavers used the dogs' wool to craft blankets and other woven items that served a variety of ceremonial and spiritual purposes. Woolly dogs themselves possessed spiritual significance and were often treated as beloved family members. As emblems for many Coast Salish communities, woolly dogs adorned woven baskets and other art forms.

By the mid-19th century, this once thriving dog wool-weaving tradition was in decline. In the late 1850s, naturalist and ethnographer George Gibbs cared for a woolly dog named Mutton. When Mutton died in 1859, Gibbs sent his pelt to the nascent Smithsonian Institution, where the fleece has resided ever since. However, few were aware of the pelt's existence until it was rediscovered in the early 2000s.

Lin first learned about Mutton when she was a Peter Buck postdoctoral fellow at the museum in 2021.

"When I saw Mutton in person for the first time, I was just overcome with excitement," said Lin, who is now a postdoctoral researcher at the American Museum of Natural History. "I had heard from some other people that he was a bit scraggly, but I thought he was gorgeous."

She was surprised to find out that virtually no work had been done on the genetics of woolly dogs, which disappeared around the turn of the 20th century. She teamed up with Kistler and they reached out to several Coast Salish communities to gauge their interest in working together on a potential research project on woolly dogs.

Many in the Coast Salish communities were eager to share their knowledge.

Source: ScienceDaily

Measuring long-term heart stress dynamics with smartwatch data

 Biomedical engineers at Duke University have developed a method using data from wearable devices such as smartwatches to digitally mimic an entire week's worth of an individual's heartbeats. The previous record covered only a few minutes.

Called the Longitudinal Hemodynamic Mapping Framework (LHMF), the approach creates "digital twins" of a specific patient's blood flow to assess its 3D characteristics. The advance is an important step toward improving on the current gold standard in evaluating the risks of heart disease or heart attack, which uses snapshots of a single moment in time -- a challenging approach for a disease that progresses over months to years.

The research was conducted in collaboration with computational scientists at Lawrence Livermore National Laboratory and was published on November 15, 2023, at the International Conference for High Performance Computing, Networking, Storage, and Analysis (SC23). The conference is the leading global conference in the field of high-performance computing.

"Modeling a patient's 3D blood flow for even a single day would take a century's worth of compute time on today's best supercomputers," said Cyrus Tanade, a PhD candidate in the laboratory of Amanda Randles, the Alfred Winborne and Victoria Stover Mordecai Associate Professor of Biomedical Sciences at Duke. "If we want to capture blood flow dynamics over long periods of time, we need a paradigm-shifting solution in how we approach 3D personalized simulations."

Over the past decade, researchers have steadily made progress toward accurately modeling the pressures and forces created by blood flowing through an individual's specific vascular geometry. Randles, one of the leaders in the field, has developed a software package called HARVEY to tackle this challenge using the world's fastest supercomputers.

One of the most commonly accepted uses of such coronary digital twins is to determine whether or not a patient should receive a stent to treat a plaque or lesion. This computational method is much less invasive than the traditional approach of threading a probe on a guide wire into the artery itself.

While this application requires only a handful of heartbeat simulations and works for a single snapshot in time, the field's goal is to track pressure dynamics over weeks or months after a patient leaves a hospital. To get even 10 minutes of simulated data on the Duke group's computer cluster, however, they had to lock it down for four months.

"Obviously, that's not a workable solution to help patients because of the computing costs and time requirements," Randles said. "Think of it as taking three weeks to simulate what the weather will be like tomorrow. By the time you predict a rainstorm, the water would have already dried up."

Source: ScienceDaily

Heart over head? Stages of the heart's cycle affect neural responses

 Optimal windows exist for action and perception during the 0.8 seconds of a heartbeat, according to research published November 28 in the open access journal PLOS Biology. The sequence of contraction and relaxation is linked to changes in the motor system and its ability to respond to stimulation, and this could have implications for treatments for depression and stroke that excite nerve cells.

The ways in which we perceive and engage with the world are influenced by internal bodily processes such as heartbeats, respiration and digestion.

Cardiac activity can influence auditory and visual perception, and touch and sensory perceptions have been shown to be impaired during the systolic phase of the cardiac cycle when blood vessels are briefly distended.

Esra Al of the Max Planck Institute for Human Cognitive and Brain Sciences, Germany, and colleagues, wanted to understand whether there were changes in cortical and corticospinal excitability -- the ability to respond to stimuli -- across the cardiac cycle.

37 healthy human volunteers aged between 18 and 40 years received a series of transcranial magnetic stimulation (TMS) pulses -- non-invasive short magnetic pulses that stimulate nerve cells -- above the right side of the brain.

Motor and cortical responses as well as heartbeats were measured during the pulses and the authors found that higher excitability was recorded during the systolic phase.

These simultaneous recordings of brain activity, heart activity, and muscle activity, suggest the timing of heartbeats and their neural processing are linked to changes in the excitability of the motor system.

TMS is used in treatments for depression and recovery after stroke.

The research raises questions about whether these could be fine-tuned to improve results, as well as contributing to a greater understanding of brain-body interactions in health and in disease.

The authors add, "Intriguingly, this study uncovers a remarkable connection between the human heart and brain, revealing distinct time windows tailored for action and perception."

Source: ScienceDaily

Radiation therapy may be potential heart failure treatment

 Cardiologists and radiation oncologists at Washington University School of Medicine in St. Louis pioneered the use of radiation therapy -- a strategy typically used against cancer -- to treat patients with a life-threatening abnormal heart rhythm called ventricular tachycardia.

Now, after studying the cardiac effects of radiation in a small number of these patients and modeling the effects of low-dose radiation in mice with heart failure, the research team has found that low-dose radiation therapy appears to improve heart function in various forms of heart failure.

More research is needed before the investigators can evaluate this therapy in patients with heart failure, but the study suggests that radiation's effects on injured hearts with high levels of inflammation may be more varied -- and perhaps beneficial -- than previously understood.

The study, published Nov. 28 in the journal Med, suggests that low-dose radiation therapy improves heart function, at least in part, by reducing the number of inflammatory immune cells in the heart muscle.

"The radiation therapy used to treat ventricular tachycardia is targeted to a specific location in the heart; however, a large portion of the rest of the heart gets a low-dose exposure," said co-senior author and cardiologist Ali Javaheri, MD, PhD, an assistant professor of medicine.

"We wanted to understand the effects of that low-dose radiation on these patients' hearts. There was concern that it could be harmful to overall heart function, even though it treats dangerous arrhythmia. We were surprised to find the opposite: Heart function appeared to be improved after radiation therapy, at least in the short term."

About 6.2 million American adults currently live with heart failure, according to the Centers for Disease Control and Prevention.

More than half of heart failure patients hospitalized for the condition die within five years of that first hospitalization, demonstrating a need for better therapies.

A failing heart gradually loses its ability to properly supply the body with oxygenated blood.

A complex condition, heart failure can have diverse triggers, including a past heart attack, viral infection or chronic arrhythmias such as ventricular tachycardia.

A group of nine patients with ventricular tachycardia was evaluated with cardiac MRI before and after radiation treatment, with the MRIs showing improved heart function soon after radiation.

In particular, the patients' hearts showed improved pumping capacity of the left ventricle, which supplies blood to the entire body.

The improvement was seen a few days after treatment, so it was deemed unlikely to be due to the reduction of the arrhythmia, which happens more gradually over the ensuing weeks and months.

The researchers also studied the effects of similar low-dose radiation to the heart in groups of mice with heart failure from three different causes.

Source: ScienceDaily

First multi-chamber heart organoids unravel human heart development and disease

 Heart disease kills 18 million people each year, but the development of new therapies faces a bottleneck: no physiological model of the entire human heart exists -- so far. A new multi-chamber organoid that mirrors the heart's intricate structure enables scientists to advance screening platforms for drug development, toxicology studies, and understanding heart development. The new findings, using heart organoid models developed by Sasha Mendjan's group at the Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences, are presented in the journal Cell on November 28.

Cardiovascular disease is the leading cause of death worldwide, but only a few new therapies are on the horizon. Similarly, one in every 50 babies born suffers from a congenital heart defect -- and again, therapies are few and far between, as we know little why they arise. What is missing in understanding both heart disease and cardiac malformations is a model comprising the major regions of the human heart. Now, the Mendjan team at IMBA presents the first physiological organoid model that includes all the principal developing heart structures and allows researchers to study cardiac disease and development.

In 2021, the Mendjan lab presented the first chamber-like organoid heart model formed from human induced pluripotent stem cells. These self-organizing heart organoids, or Cardioids, recapitulated the development of the heart's left ventricular chamber in the very early days of embryogenesis. "These Cardioids were a proof-of-principle and an important step forward," says Mendjan. "While most adult diseases affect the left ventricle, which pumps oxygenated blood through the body, congenital defects affect mostly other heart regions essential to establish and maintain circulation."

In the new study, the team at IMBA expanded on their previous work. The researchers first derived organoid models of each developing heart structure individually. "Then we asked: If we let all these organoids co-develop together, do we get a heart model that co-ordinately beats like the early human heart?," Mendjan explains.

Unraveling human heart development

After growing left and right ventricular and the atrial organoids together, the researchers were in for a surprise: "Indeed, an electrical signal spread from the atrium to the left and then the right ventricular chambers -- just like in early fetal heart development in animals," Mendjan recalls. "We now observed this fundamental process in a human heart model for the first time, with all its chambers."

While the previous Cardioid model allowed the researchers to study the chamber's shape and tissue organization, the newly developed multi-chamber Cardioids enabled them to go beyond, studying how regional gene expression differences lead to specific chamber contraction patterns and intricate communication between them.

The researchers have already gained insight into early heart development, particularly how the human heart starts beating -- which has not been understood so far. "We saw that as the organoid chambers developed, they performed an intricate dance of lead and follow. At first, the left ventricular chamber leads the budding right ventricular and atrium chambers at its rhythm. Then, as the atrium develops- two days later- the ventricles follow the atrial lead. This mirrors what is seen in animals before the final leaders, the pacemakers, control the heart rhythm," explains Alison Deyett, a PhD student in the Mendjan group and one of the study's first authors.

Source: ScienceDaily

Coronary heart disease before age 45 may increase risk of dementia later in life

 Adults diagnosed with coronary heart disease, especially before the age of 45, may be at increased risk of developing dementia, Alzheimer's disease and vascular dementia later in life, according to new research published today in the Journal of the American Heart Association, an open access, peer-reviewed journal of the American Heart Association.

"Coronary heart disease has previously been associated with dementia risk in older adults, however, this is believed to be the first large-scale study examining whether the age of coronary heart disease onset may impact the risk of developing dementia later in life," said Fanfan Zheng, Ph.D., senior study author and researcher in the School of Nursing at the Chinese Academy of Medical Sciences & Peking Union Medical College in Beijing, China.

"In previous research, we found that adults experienced accelerated cognitive decline after new diagnoses of coronary heart disease," she said.

The researchers assessed the potential relationship between age at coronary heart disease onset and the development of dementia by analyzing health data from the UK Biobank.

The analysis found:

• Among the 432,667 participants in the study, there were 5,876 cases of dementia, 2,540 cases of Alzheimer's disease and 1,220 cases of vascular dementia that occurred over an average of 13 years of follow-up.
• Compared with participants who did not have coronary heart disease, participants with coronary heart disease had higher risks of developing dementia from any cause, Alzheimer's disease and vascular dementia.
• After adjusting the analysis for demographic and lifestyle factors, participants with coronary heart disease had a 36% increased risk of developing dementia, a 13% increased risk of developing Alzheimer's and a 78% greater risk of developing vascular dementia.
• Earlier coronary heart disease-onset was associated with a 25% increased risk of dementia, a 29% increased risk of Alzheimer's disease and a 22% increased risk of vascular dementia.
• The risk of dementia rose in direct proportion to the younger age of coronary heart disease onset (per 10-year decrease in age).
• Participants diagnosed with coronary heart disease before age 45 had a significantly increased risk of developing dementia compared to their counterparts who did not have coronary heart disease.

"What surprised us most was the linear relationship between age of coronary heart disease onset and dementia. This shows the huge detrimental influence of premature coronary heart disease on brain health," Zheng said. "As more people live longer and are diagnosed with coronary heart disease at a younger age, it's likely there will be a large increase in the number of people living with dementia in years to come. Health care professionals should be aware of individuals diagnosed with coronary heart disease at a young age. The next step is to determine whether modifying cardiovascular risk early in life will promote better brain health later in life."

Alcohol consumption may have positive and negative effects on cardiovascular disease risk

 While past research has indicated that moderate alcohol consumption can lower one's risk of cardiovascular disease (CVD), more recent studiessuggest that moderate levels of drinking may be hazardous to heart health. A new analysis led by Boston University School of Public Health and Friedman School of Nutrition Science and Policy at Tufts University (Friedman School) now sheds new insight on this complex relationship between alcohol consumption and the progression of CVD.

Published in the journal BMC Medicine, the study found that alcohol consumption may have counteractive effects on CVD risk, depending on the biological presence of certain circulating metabolites -- molecules that are produced during or after a substance is metabolized and studied as biomarkers of many diseases.

The researchers observed a total of 60 alcohol consumption-related metabolites, identifying seven circulating metabolites that link long-term moderate alcohol consumption with an increased risk of CVD, and three circulating metabolites that link this same drinking pattern with a lower risk of CVD.

The findings provide a better understanding of the molecular pathway of long-term alcohol consumption and highlight the need for and direction of further research on these metabolites to inform targeted prevention and treatment of alcohol-related CVD.

"The study findings demonstrate that alcohol consumption may trigger changes of our metabolomic profiles, potentially yielding both beneficial and harmful outcomes," says Dr.Chunyu Liu, assistant professor of biostatistics at BUSPH and co-corresponding/co-senior author of the study along with Dr.Jiantao Ma, assistant professor in the Division of Nutrition Epidemiology and Data Science at the Friedman School.

"However, rather than definitively settling that debate, this study underscores the intricate effects of alcohol consumption on cardiovascular health and generates a useful hypothesis for future investigations," Dr. Liu says.

For the study, the researchers examined blood samples to measure the association between the cumulative average consumption of beer, wine, and liquor and 211 metabolites among 2,428Framingham Heart Study Offspring Study participants, who are the children of participants in the long-running Boston University-basedFramingham Heart Study, over 20 years.

Among the participants, 636 developed CVD over the study period.

Among the 60 drinking-related metabolites, 13 metabolites had a stronger association with alcohol consumption in women than in men, perhaps due to women's generally smaller body size and likely higher blood alcohol concentration after consuming the same amount of alcohol as men.

The results also showed that consumption of different types of alcohol was linked to different metabolomic responses, with beer consumption generating a slightly weaker association overall than wine and liquor.

In roughly two-thirds of the 60 metabolites, higher plasma levels were detected in participants who consumed greater amounts of alcohol.

Source: ScienceDaily

Novel study finds aspirin-free regimen benefits patients with LVAD

 The ARIES-HM3 Randomized Clinical Trial assessed the safety and efficacy of excluding aspirin from the antithrombotic regimen in patients with advanced heart failure who have undergone implantation of a fully magnetically levitated left ventricular assist device (LVAD).

"We can now safely say that not giving aspirin is not only safe from a thromboembolic risk profile but results in improved adverse event rate by a significant reduction in non-surgical bleeding which is a well-known complication related to LVAD therapy," said Mirnela Byku, M.D., Ph.D., MBA, co-author of the study and director of the UNC Durable Mechanical Circulatory Device Program at the UNC School of Medicine.

"Improving not only longevity but also reducing morbidity and improving quality of life is a big focus in the field of MCS."

Until this study, there had been no consensus in the field about use of or dose of aspirin in the LVAD population.

The paper was published in JAMA.

The international clinical trial followed a randomized, double-blind, placebo-controlled design and involved 628 patients across 51 centers in 9 countries.

The patients were divided into two groups: one receiving aspirin (100mg/d) and the other receiving a placebo in addition to vitamin K antagonist (VKA) therapy.

A focus was to determine if the likelihood a patient experiences major nonsurgical hemocompatibility-related adverse events (such as stroke, pump thrombosis, major bleeding, or arterial peripheral thromboembolism) within 12 months differed between the two groups.

The results showed not giving aspirin to patients with advanced heart failure, treated with a fully magnetically levitated LVAD who are receiving VKAs, did not make their survival worse. Furthermore, aspirin avoidance was associated with a significant reduction (34%) in major nonsurgical bleeding events.

Source: ScienceDaily

Pulling an all-nighter? Don't follow with an important decision

 Research gives insight into importance of sleep on cognitive performance and emotional well-being to those who find themselves under stress

Politicians, military generals and first responders are just some high-stress positions which should avoid taking important decisions after a night without sleep, new research from the University of Ottawa indicates.

We all understand the power of sleep and the vital role it plays in human health, cognitive performance and in regulating our emotional well-beingNumerous studies into a lack of sleep have shown drops in neurocognitive functions, particularly vigilant attention, motor responses, inhibition control, and working memory.

Despite this, sleep loss continues to challenge public health and affect people of all ages.

Sleep and risky decision-making

With little insight into the impact of a lack of sleep on risky decision-making at the neuroimaging level, researchers from the University of Ottawa and the University of Pennsylvania found a 24-hour period of sleep deprivation significantly impacted individuals' decision-making processes by dampening neural responses to the outcomes of their choices.

In other words, people tend to exhibit reduced positive emotions in response to winning outcomes and diminished negative emotions when faced with losses after pulling an all-nighter compared to their well-rested baseline condition.

"Common sense does dictate if people incur sleep loss, sleep disturbance or a sleep disorder that their cognitive function will be impacted, their attention and efficiency will decrease. But there is an emotional impact, too," says Zhuo Fang, a Data Scientist in the Department of Psychology at the Faculty of Social Sciences.

"If you experience even just one night of sleep deprivation, there will be an impact, even on a neural level. So, we wanted to combine brain imaging and behaviour to see that impact," adds Fang, who is affiliated with uOttawa's Brain and Mind Research Institute and The Royal.

The study, which evaluated the impact of one night of total sleep deprivation on 56 healthy adults, found:

• A single night of total sleep loss significantly decreased the brain activation to win and loss outcomes, suggesting that acute sleep loss can have a dampening effect on neural responses to decision outcomes during risk-taking.
• Total sleep deprivation had the detrimental effect by disrupting the relationship between neural response and individual's risk-taking behavior, which might be related to the altered perception for risk-taking.

While numerous studies have previously illustrated the wide-ranging effects of sleep deprivation on various brain and cognitive functions, including attention processing, memory consolidation, and learning, this study addresses the specific impact of sleep loss on decision-making.

sources-science daily

.

Researchers identify cell signaling pathway controlling melanoma cell metastasis to the brain

 Melanoma is the deadliest form of skin cancer because of its ability to quickly grow and spread throughout the body. More than half of those with advanced melanoma will see the disease spread to the brain, where it rapidly progresses, often leading to death in only three to four months. Researchers in Moffitt Cancer Center's Donald A. Adam Melanoma and Skin Cancer Center of Excellence have been working to better understand what drives melanoma brain metastasis. In a new study published in Nature Communications, they report on the identification of a cell signaling pathway that regulates the metastatic spread of melanoma cells to the brain.

Melanoma tumors are composed of subgroups of cells with different gene expression patterns with varied abilities to invade surrounding tissues and survive anticancer treatments.

It is unclear how these different melanoma subgroups contribute to tumor development and progression.

n previous studies, Moffitt researchers determined that the protein HDAC8 regulated resistance to BRAF and MEK inhibitors commonly used to treat melanoma.

HDAC8 removes chemical modifications called acetyl groups from other proteins, leading to alterations in gene expression patterns.

The Moffitt team hypothesized that HDAC8 may also be involved in the regulation of gene expression patterns of melanoma cell subgroups.

The researchers performed laboratory experiments and demonstrated that HDAC8 activity increased melanoma cell survival under stress conditions, including low oxygen, UV radiation, and BRAF/MEK inhibitor treatment.

HDAC8 activity also changed the gene expression pattern of melanoma cells and caused the cells to develop characteristics associated with cell subgroups that were able to migrate into and invade surrounding sites.

Their pre-clinical experiments found that increased HDAC8 expression and activity enhanced the ability of melanoma cells to metastasize to the brain, while no significant impact was observed in the number of metastatic tumors to other organs, such as the liver or lung.

The researchers further investigated the molecular pathways of HDAC8-mediated brain metastasis and discovered that HDAC8 chemically modified the protein EP300, which subsequently caused cells to develop invasive characteristics.

sources-science daily

Human behavior guided by fast changes in dopamine levels

What happens in the human brain when we learn from positive and negative experiences? To help answer that question and better understand decision-making and human behavior, scientists are studying dopamine.

Dopamine is a neurotransmitter produced in the brain that serves as a chemical messenger, facilitating communication between nerve cells in the brain and the body. It is involved in functions such as movement, cognition and learning. While dopamine is most known for its association with positive emotions, scientists are also exploring its role in negative experiences.

Now, a new study from researchers at Wake Forest University School of Medicine shows that dopamine release in the human brain plays a crucial role in encoding both reward and punishment prediction errors. This means that dopamine is involved in the process of learning from both positive and negative experiences, allowing the brain to adjust and adapt its behavior based on the outcomes of these experiences.

The study was published today in Science Advances.

"Previously, research has shown that dopamine plays an important role in how animals learn from 'rewarding' (and possibly 'punishing') experiences. But, little work has been done to directly assess what dopamine does on fast timescales in the human brain," said Kenneth T. Kishida, Ph.D., associate professor of physiology and pharmacology and neurosurgery at Wake Forest University School of Medicine. "This is the first study in humans to examine how dopamine encodes rewards and punishments and whether dopamine reflects an 'optimal' teaching signal that is used in today's most advanced artificial intelligence research."

For the study, researchers on Kishida's team utilized fast-scan cyclic voltammetry, an electrochemical technique, paired with machine learning, to detect and measure dopamine levels in real-time (i.e., 10 measurements per second). However, this method is challenging and can only be performed during invasive procedures such as deep-brain stimulation (DBS) brain surgery. DBS is commonly employed to treat conditions such as Parkinson's disease, essential tremor, obsessive-compulsive disorder and epilepsy.

Kishida's team collaborated with Atrium Health Wake Forest Baptist neurosurgeons Stephen B. Tatter, M.D., and Adrian W. Laxton, M.D., who are also both faculty members in the Department of Neurosurgery at Wake Forest University School of Medicine, to insert a carbon fiber microelectrode deep into the brain of three participants at Atrium Health Wake Forest Baptist Medical Center who were scheduled to receive DBS to treat essential tremor.

While the participants were awake in the operating room, they played a simple computer game. As they played the game, dopamine measurements were taken in the striatum, a part of the brain that is important for cognition, decision-making, and coordinated movement

sources-science daily