Day: April 19, 2023

Sedentary Time may Significantly Enlarge Teens’ Hearts

Photo by Steinar Engeland on Unsplash

In adolescents, sedentary time may increase heart size three times more than moderate-to-vigorous physical activity, according to a paper published in the Scandinavian Journal of Medicine & Science in Sports. The British and Finnish researchers explored the associations of sedentary time, light physical activity, and moderate-to-vigorous physical activity with cardiac structure and function.

Recent World Health Organization reports and guidelines note that more than 80% of adolescents across the globe have insufficient physical activity per day. Physical inactivity has been associated with several non-communicable diseases in adults such as cardiovascular diseases, type 2 diabetes, and cancer. In the pediatric population, the majority of movement behaviour studies have focused on the effect of sedentary behaviour and physical activity on cardiometabolic health which includes blood pressure, insulin resistance, blood lipids, and body mass index.

There has been a gap in knowledge on the effect of sedentary time and moderate-to-vigorous physical activity on cardiac structure and function in large adolescent populations due to the scarcity of device-measured movement behaviour and echocardiography assessment in the pediatric population. A higher left ventricular mass, which indicates an enlarged or hypertrophied heart, and a reduced left ventricular function, which indicates decreased heart function, may in combination or independently lead to an increased risk of heart failure, myocardial infarction, stroke, and premature cardiovascular death.

The current study, which used data from the University of Bristol study Children of the 90s (also known as the Avon Longitudinal Study of Parents and Children) included 530 adolescents aged 17 years who had complete measurements of fat mass, muscle mass, glucose, lipids, an inflammation marker, insulin, smoking status, socio-economic status, family history of cardiovascular disease, echocardiographic cardiac function and structure measures, and accelerometer-based measure of sedentary time, light physical activity, and moderate-to-vigorous physical activity.

On average, adolescents spent almost 8 hours/day sedentary and about 49 minutes/day in moderate-to-vigorous physical activity in this new study. It was observed that both sedentary time and moderate-to-vigorous physical activity were associated with higher left ventricular mass. However, the increase in cardiac mass (3.8g/m2.7) associated with sedentary time was three times higher than the cardiac mass increase (1.2g/m2.7) associated with moderate-to-vigorous physical activity. This finding was observed in adolescents irrespective of their obesity status, ie among adolescents who had normal weight and those who were overweight or obese. Importantly, light physical activity was not associated with an increase in cardiac mass but was associated with better cardiac function estimated from left ventricular diastolic function.

“This novel evidence extends our knowledge of the adverse effects of sedentary time on cardiac health. It is known among adults that a 5g/mincrease in cardiac mass may increase the risk of cardiovascular disease and death by 7–20%. Engaging in moderate-to-vigorous physical activity also slightly enlarged the heart but it seems an acceptable negative side effect considering several other health benefits of moderate-to-vigorous exercise. Hence, public health experts, health policymakers, high school administrators and teachers, paediatricians, and caregivers are encouraged to facilitate adolescent participation in physical activity to enable a healthy heart,” says Andrew Agbaje, a physician and clinical epidemiologist at the University of Eastern Finland.

Source: University of Eastern Finland

ADHD Stimulant Drugs have Potential for Abuse at Schools that Carry Them

Photo by Myriam Zilles on Unsplash

Researchers have identified a strong association between prevalence of prescription stimulant therapy for attention-deficit/hyperactivity disorder (ADHD) and rates of prescription stimulant misuse by students in US middle and high schools. Published in JAMA Network Open, the study highlights the need for assessments and education in schools and communities to prevent medication-sharing among teens. This is especially important considering non-medical use of prescription stimulants among teens remains more prevalent [PDF] than misuse of any other prescription drug, including opioids and benzodiazepines.  

The study used data collected between 2005 and 2020 by the Monitoring the Future (MTF) study. MTF is a large, multicohort survey of legal and illicit drug use among American adolescents in eighth, 10th, and 12th grade.

“The drug supply has rapidly changed, and what looks like medications – bought online or shared among friends or family members – can contain fentanyl or other potent illicit substances that can result in overdoses. It’s important to raise awareness of these new risks for teens,” said NIDA Director Nora Volkow, MD. “It’s also essential to provide the necessary resources and education to prevent misuse and support teens during this critical period in their lives when they encounter unique experiences and new stressors.”

Stimulant therapy is an evidence-based treatment for ADHD, but it can also be harmful if used without prescription or guidance from clinicians. Prolonged stimulant misuse can lead to several detrimental health effects including cardiovascular conditions, depressed mood, overdoses, psychosis, anxiety, seizures, and stimulant use disorder.

Previous studies have shown that more than half of adolescents who misuse prescription stimulants get the medication for free from friends or relatives. While diagnoses of ADHD and prescribing of stimulant therapy for ADHD have increased significantly in the United States over the past 20 years, few studies have looked at the relationship between stimulant therapy and prescription stimulant misuse in schools. This is the first large, national study to examine prevalence of prescription stimulant misuse and factors correlating with prevalence among students in eighth, 10th, and 12th grade across the U.S.

Researchers at the University of Michigan examined both school- and individual-level characteristics associated with prescription stimulant misuse. Across 231 141 student participants surveyed at 3,284 secondary schools, the school-level prevalence of nonmedical use varied from 0% to over 25% of students. Schools with a greater number of students (12% or higher) reporting prescription stimulant therapy for ADHD tended to have the highest percentages of their student body reporting prescription stimulant misuse (8% of total student body). By comparison, schools with fewer students (0 to 6% of student body) reporting stimulant therapy for ADHD were associated with lower rates of prescription stimulant misuse (4 to 5% of student body).

Other features of schools that were associated with increased rates of misuse included having a higher proportion of parents with higher levels of education, being located in non-Northeastern regions of the US and in suburban areas, having a higher proportion of non-Hispanic white students, and showing “medium-level” (10-19% of total student body) binge drinking. However, the association between school prevalence of stimulant therapy for ADHD and prescription stimulant misuse remained strong when accounting for prevalence of other types of substance use and numerous other individual- and school-level sociodemographics.

Recent research from this team expands on the associations found in this study, including a study that suggested teens with a history of taking both stimulant or non-stimulant medications for ADHD are at high risk for prescription stimulant misuse, as well as cocaine and methamphetamine use. The researchers note that it is important to interpret these results as associations, not causations, and that the primary goal of these kinds of studies is to inform effective preventative and support [PDF] strategies for teens.

“The key takeaway here is not that we need to lessen prescribing of stimulants for students who need them, but that we need better ways to store, monitor, and screen for stimulant access and use among youth to prevent misuse,” said study author Sean Esteban McCabe, PhD. “There’s variation in stimulant misuse across different schools, so it’s important to assess schools and implement personalised interventions that work best for each school. It’s also critical to treat and educate teens on prescription stimulants as the medications they are intended to be and limit their availability as drugs of misuse.”

Source: National Institutes of Health

Dopamine’s Role in Exercise Feeling ‘Hard’ or ‘Easy’

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Dopamine, long associated with pleasure, motivation and reward-seeking, also appears to play an important role in why exercise and other physical efforts feel ‘easy’ to some people and exhausting to others. These are the findings of of a study of people with Parkinson’s disease, which is published in NPG Parkinson’s Disease. Parkinson’s disease is marked by a loss of dopamine-producing cells in the brain over time.

According to the researchers, the findings might eventually lead to more effective ways to help people establish and stick with exercise regimens, new treatments for fatigue associated with depression and many other conditions, and a better understanding of Parkinson’s disease.

“Researchers have long been trying to understand why some people find physical effort easier than others,” says study leader Vikram Chib, Ph.D., associate professor in the Department of Biomedical Engineering at the Johns Hopkins University School of Medicine and research scientist at the Kennedy Krieger Institute. “This study’s results suggest that the amount of dopamine availability in the brain is a key factor.”

Chib explains that after a bout of physical activity, people’s perception and self-reports of the effort they expended varies, and also guides their decisions about undertaking future exertions. Previous studies have shown that people with increased dopamine are more willing to exert physical effort for rewards, but the current study focuses on dopamine’s role in people’s self-assessment of effort needed for a physical task, without the promise of a reward.

For the study, Chib and his colleagues from Johns Hopkins Medicine and the Kennedy Krieger Institute recruited 19 adults diagnosed with Parkinson’s disease, a condition in which neurons in the brain that produce dopamine gradually die off, causing unintended and uncontrollable movements such as tremors, fatigue, stiffness and trouble with balance or coordination.

In Chib’s lab, 10 male volunteers and nine female volunteers with an average age of 67 were asked to perform the same physical task, that of squeezing a hand grip equipped with a sensor, on two different days within four weeks of each other. On one of the days, the patients were asked to take their standard, daily synthetic dopamine medication as they normally would. On the other, they were asked not to take their medication for at least 12 hours prior to performing the squeeze test.

On both days, the patients were initially taught to squeeze a grip sensor at various levels of defined effort, and then were asked to squeeze and report how many units of effort they put forth.

When the participants had taken their regular synthetic dopamine medication, their self-assessments of units of effort expended were more accurate than when they hadn’t taken the drug. They also had less variability in their efforts, showing accurate squeezes when the researchers cued them to squeeze at different levels of effort.

In contrast, when the patients hadn’t taken the medication, they consistently over-reported their efforts, meaning they perceived the task to be physically harder, and had significantly more variability among grips after being cued.

In another experiment, the patients were given a choice between a sure option of squeezing with a relatively low amount of effort on the grip sensor or flipping a coin and taking a chance on having to perform either no effort or a very high level of effort. When these volunteers had taken their medication, they were more willing to take a chance on having to perform a higher amount of effort than when they didn’t take their medication.

A third experiment offered participants the choice between getting a small amount of guaranteed money or, getting either nothing or a higher amount of money on a coin flip. Results showed no difference in the subjects on days when they took their medication and when they did not. This result, researchers say, suggests that dopamine’s influence on risk-taking preferences is specific to physical effort-based decision-making.

Together, Chib says, these findings suggest that dopamine level is a critical factor in helping people accurately assess how much effort a physical task requires, which can significantly affect how much effort they’re willing to put forth for future tasks. For example, if someone perceives that a physical task will take an extraordinary amount of effort, they may be less motivated to do it.

Understanding more about the chemistry and biology of motivation could advance ways to motivate exercise and physical therapy regimens, Chib says. In addition, inefficient dopamine signalling could help explain the pervasive fatigue present in conditions such as depression and long COVID, and during cancer treatments. Currently, he and his colleagues are studying dopamine’s role in clinical fatigue.

Source: John Hopkins Medicine

Changes in Hyaluronic Acid Properties Drive Osteoarthritis

Source: CC0

The composition of synovial fluid changes significantly in osteoarthritis: The concentration and molecular weight of hyaluronic acid tends to decrease and is commonly used to diagnose the disease. An international group of researchers explored the disease-driven breakdown of hyaluronan and the mechanistic implications of these changes on the lubrication and subsequent wear of joints.

“One of the most important properties of the synovial fluid is its viscosity,” said Rosa Maria Espinosa-Marzal, co-author of the study published in the journal Biointerphases. “Viscosity is a measure of the internal frictional force between adjacent layers of a fluid in relative motion, or, more simply, a fluid’s resistance to flow. Large, high molecular weight polymers such as hyaluronic acid play a significant role in maintaining a high viscosity of the synovial fluid, which helps maintain a fluid film and reduces friction between articulating surfaces during motion.”

Through analysis with neutron and light scattering, the team determined that the structure of the lipid-hyaluronic-acid complexes in the bulk solution is a function of concentration and its molecular weight.

The researchers found the hyaluronic acid’s concentration and molecular weight both play a role in how the lubricant reacts with different surfaces.

“Our results show low molecular weight hyaluronic acid, which mimics osteoarthritis-diseased joints, hinders the adsorption of the hyaluronic-acid-lipid complex,” said Espinosa-Marzal, of the University of Illinois Urbana-Champaign. “The lack of the formation of an amorphous film on the surface may reflect a consequence of osteoarthritis, since this film should help reduce friction and wear.”

Their hypothesis is that this film’s absence may increase wear of the cartilage surface. In contrast, high molecular weight hyaluronic-acid-lipid complexes form an amorphous film, which presumably helps maintain the mechanical integrity and longevity of efficient lubrication in healthy cartilage.

Studies on hyaluronic acid itself and hyaluronic-acid-lipid complexes “do not entirely support hyaluronic acid’s role in providing high lubricity to the cartilage’s articular surface, which is still a bit controversial,” Espinosa-Marzal said. “Our results indicate that for low molecular weight hyaluronic acid, this is likely the case.”

By exploring the complex interplay between phospholipid and hyaluronic acid self-assembly, and the role of molecular weight on surface affinity, “our study illuminates a mechanism whereby the ‘vicious circle’ of osteoarthritis can be explained,” said co-author Mark Rutland, from KTH Royal Institute of Technology.

Source: American Institute of Physics

Scientists ‘Poke the Bear’ to Gain a Better Understanding of Blood Clotting

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It’s generally good advice not to “poke the bear” as they say, but that’s exactly what a multinational team of scientists have been doing, to discover the secrets of blood clotting. Hibernating bears, paralysed humans, and pigs kept in small enclosures all avoid dangerous blood clots, despite being immobile for extremely long periods.

Their new study published in Science shows that reduction of a key protein inhibits the formation of blood clots in all three mammal species when they are immobile for days, months or even years.

Passengers on long haul flights run the risk of developing deep vein thrombosis if they do not take some time to walk around and use compression socks. Some people are predisposed to blood clots, due to genetic factors.

Yet, when humans – and other mammals such as bears – are immobilised for a much longer period than a flight, the researchers found that a protein known as Hsp47 is reduced by 55 times. This could lead to new medicines to help those who have inherited blood clotting disorders that put them at risk for pulmonary embolism, heart attack, and stroke.

Professor Jon Gibbins led the work at the University of Reading. He said: “It seems counterintuitive that people who have severe paralysis don’t appear to be at higher risk of blood clots. This tells us that something interesting is happening. And it turns out that reducing levels of Hsp47 plays a key role in preventing clots, not just in humans, but in other mammals, including bears and pigs.

“When we see something like this in multiple species, that reinforces its importance. Having Hsp47 must have been an evolutionary advantage.”

Hsp47 is released by platelets – the sticky blood cells that trigger blood clotting.  Usually clotting is an important response to an injury, to prevent blood loss, and Hsp47 is one of the necessary ingredients to enable platelets to do their job. Examining the role of Hsp47 in clotting function the team found that when released into the blood of bears, mice and humans that it promoted conditions that may give rise to deep vein thrombosis.

Professor Gibbins said, “We aren’t totally sure how, but it appears that there is something about movement that keeps Hsp47 at an appropriate level. It could be that the mechanical forces involved in moving around actually have an impact on gene expression, dramatically increasing the amount of Hsp47 that circulates in the blood.”

The team took blood samples from bears in winter, while hibernating, and in summer, while awake and moving around. They also compared people who were immobilised with those who can move and walk. And finally, pigs kept in small pens were compared with others that were free to move around in barns. In all three cases, proteomics experiments showed that the absence of movement was associated with having far less Hsp47.

Professor Gibbins continued: “Now we know that Hsp47 is so important, we can begin to look for new or existing medicines that might be able to inhibit the function of this protein in blood clotting and protect mobile people who are prone to clots.”

Source: University of Reading