Body

Published studies have long found a correlation between obesity in children and decreased executive function. New research published in JAMA Pediatrics, based on data mined from a massive national research study, suggests that a change in brain structure - a thinner prefrontal cortex - may help explain that interrelationship.

"Our results show an important connection; that kids with higher BMI tend to have a thinner cerebral cortex, especially in the prefrontal area," said Jennifer Laurent, an associate professor in the Department of Nursing at the University of Vermont and lead author of the study.

The findings are based on data retrieved from a National Institutes of Health-funded research project, the Adolescent Brain Cognitive Development study, or ABCD, which is following 10,000 teens over a 10 year period. Every two years, study subjects are interviewed, take a battery of tests, give blood samples and undergo brain scans.

The study analyzed results from 3,190 nine- and 10-year-olds recruited at 21 ABCD sites in 2017.

The robust study confirmed the findings of its predecessors; that subjects with higher BMI tended to have lower working memory, as measured by a list sorting test.

But it added an important component to that insight - a physiological correlate in the brain that might help explain the connection.

"Our hypothesis going into the study was that the thickness of the cerebral cortex would 'mediate' - or serve as an explanatory link for - the relationship between BMI and executive function," Laurent said.

The findings did confirm the relationship, according to the study's senior author, Scott Mackey, an assistant professor of Psychiatry in the University of Vermont's Larner College of Medicine.

"We found widespread thinning of cerebral cortex" among research subjects with higher BMI, Mackey said, but especially so in the prefontal area.

"That's significant because we know that executive function, things like memory and the ability to plan, are controlled in that area of the brain," he said.

More research is needed to determine the nature of the link between the three variables.

"It could be that a thinner prefrontal cortex is affecting decision-making in some children, and they make unhealthy dietary choices as a result, which could lead to obesity," Laurent said.

Or the causal relationship could work in the opposite direction.

"We know from rodent models and adult studies that obesity can induce low grade inflammatory effects, which actually do alter cellular structure" and can lead to cardiovascular disease, Laurent said.

"With prolonged exposure to obesity, it is possible that children have chronic inflammation, and that may actually be affecting their brain in the long term," she said.

If that were the case, there would be significant public health implications, Laurent said. "We would want to proactively encourage changes in kids' diets and exercise levels at a young age with the understanding that it's not only the heart that is being affected by obesity, it is perhaps also the brain."

The decrease in working memory was a statistical observation, Laurent said, not a clinical one.

"We did not look at behavior. It's very important that this work not further stigmatize people who are obese or overweight," she said.

"What we're saying is that, according to our measures, we are seeing something that bears watching. How and if it translates to behavior is for future research to determine."

Data analysis for the study was done at the University of Vermont and Yale University. Richard Watts, director at the FAS Brain Imaging Center and research associate professor of radiology at Yale, was a co-author of the study.

Mastectomy has historically been the standard treatment for breast cancer patients experiencing recurrence after an initial lumpectomy and whole-breast radiation. Now, a phase 2 clinical trial led by Douglas W. Arthur, M.D., chair and professor in the Department of Radiation Oncology at VCU Massey Cancer Center and VCU School of Medicine, has demonstrated an effective alternative.

The national study, conducted by investigators from 15 institutions, showed that a second lumpectomy followed by partial breast reirradiation was associated with long-term cancer control, low toxic side effects and high rates of breast preservation. The results of the study were published in the November 2019 issue of JAMA Oncology.

"This is exciting data for women experiencing an in-breast recurrence after an initial lumpectomy and whole breast irradiation who desire to continue to preserve their breast," said Arthur, who also is the Florence and Hyman Meyers Endowed Chair in Radiation Oncology, associate director for clinical affairs and member of the Developmental Therapeutics program at Massey. "These women are now able to have a breast-conserving treatment choice that is a viable alternative to mastectomy."

Rates of breast cancer recurrence are less than five to ten percent among patients treated with lumpectomy and whole-breast radiation. Mastectomy has generally been the only option offered to these individuals. However, there has been renewed interest in identifying a salvage treatment for women with a desire to preserve the breast.

The trial tested the efficacy and adverse effects of 3D conformal radiotherapy (3D-CRT) partial reirradiation, which targets the radiation directly on the area where the breast tumor is located and avoids exposing the surrounding tissue.

Researchers studied 58 breast cancer patients experiencing recurrence one year or more after initial breast-conserving therapy. The patients received lumpectomies followed by 3D-CRT partial breast reirradiation treatments delivered twice per day during 15 consecutive working days.

Patients were evaluated for adverse events weekly during treatment and in regular intervals over the course of five years. They were also assessed for mastectomy incidence, distant metastasis-free survival, overall survival and circulating tumor cell incidence.

Results showed that the five-year estimate of re-recurrence was five percent. Late treatment-related adverse events were reported in seven percent of patients and there was a breast conversation rate of 90 percent.

These findings offer evidence that breast-conserving treatment is feasible and effective through a second lumpectomy and 3D-CRT partial breast reirradiation, providing a viable substitute for mastectomy.

BIRMINGHAM, Ala. - In laboratory experiments, a metabolic inhibitor was able to kill a variety of human cancer cells of the skin, breast, lung, cervix and soft tissues through a non-apoptotic route -- catastrophic macropinocytosis.

In mouse xenograft studies, the inhibitor acted synergistically with a common chemotherapy drug, cyclophosphamide, to reduce tumor growth. Thus macropinocytosis, a rarely described form of cell death, may aid in the treatment of cancer.

"Understanding the signaling pathways underlying macropinocytosis-associated cell death is an important step in developing additional effective strategies to treat neoplasms that are resistant to apoptosis induced by chemotherapy," said Mohammad Athar, Ph.D., professor in the University of Alabama at Birmingham Department of Dermatology.

The inhibitor, OSI-027, affects the mTOR pathway, which plays a critical role in regulation cellular growth and metabolism. Significantly, this potent inhibitor simultaneously targets two distinct protein complexes of the mTOR pathway, mTORC1 and mTORC2. Aberrant activation of these components has been associated with many cancer types.

Macropinocytosis starts with formation of ruffles on the surface of a cell that reach out from the cell membrane. These ruffles then fuse back with the cell membrane, creating a bubble that holds extracellular fluid, and the bubble moves inside the cell to become a vacuole filled with fluid. In catastrophic micropinocytosis, large numbers of these vacuoles form inside the cell and then fuse together, causing cell death.

The UAB researchers showed that dual inhibition of the two mTORC1 and -C2 complexes was necessary for highly effective cell death through macropinocytosis.

In early experiments, the researchers found that OSI-027, and a related dual inhibitor, PP242, induced extensive vacuolization in a wide range of human cancer cell lines, including two subtypes of rhabdomyosarcoma. These vacuoles were then shown to be macropinosomes.

Xenograft mouse experiments with human rhabdomyosarcoma tumors showed that OSI-027 blocked tumor growth by inducing macropinocytosis; furthermore, the addition of the chemotherapy agent cyclophosphamide acted synergistically to enhance efficacy of tumor size reduction.

In mechanistic studies, Athar and colleagues found that macropinocytosis depended on activation of the MAP kinase MKK4, which was induced by the presence of reactive oxygen species. However, the full role of MKK4 is not well understood, they say.

Previous work by others had shown that several specific inducers of macropinocytosis induced macropinocytosis mainly in glioblastomas and colorectal cells. "In contrast," Athar said, "our study demonstrates that the dual inhibitors we tested induce catastrophic vacuolization in tumor cell lines from a wide range of organs, including skin, breast, cervix, lung and soft tissues."

The effects were much less pronounced in immortalized human keratinocytes.

"Our data reveal that therapeutic targeting of mTORC1 and mTORC2, together with standard care treatment," Athar said, "may be an effective approach to block the pathogenesis of recurrent rhabdomyosarcoma and perhaps other drug-resistant invasive neoplasms of diverse tissue types as well. The underlying mechanism by which tumors become responsive to treatment involves macropinocytosis, a unique form of cell death."

Most of today's solar panels capture sunlight and convert it to electricity only from the side facing the sky. If the dark underside of a solar panel could also convert sunlight reflected off the ground, even more electricity might be generated.

Double-sided solar cells are already enabling panels to sit vertically on land or rooftops and even horizontally as the canopy of a gas station, but it hasn't been known exactly how much electricity these panels could ultimately generate or the money they could save.

A new thermodynamic formula reveals that the bifacial cells making up double-sided panels generate on average 15% to 20% more sunlight to electricity than the monofacial cells of today's one-sided solar panels, taking into consideration different terrain such as grass, sand, concrete and dirt.

The formula, developed by two Purdue University physicists, can be used for calculating in minutes the most electricity that bifacial solar cells could generate in a variety of environments, as defined by a thermodynamic limit.

"The formula involves just a simple triangle, but distilling the extremely complicated physics problem to this elegantly simple formulation required years of modeling and research. This triangle will help companies make better decisions on investments in next-generation solar cells and figure out how to design them to be more efficient," said Muhammad "Ashraf" Alam, Purdue's Jai N. Gupta Professor of Electrical and Computer Engineering.

In a paper published in the Proceedings of the National Academy of Sciences, Alam and coauthor Ryyan Khan, now an assistant professor at East West University in Bangladesh, also show how the formula can be used to calculate the thermodynamic limits of all solar cells developed in the last 50 years. These results can be generalized to technology likely to be developed over the next 20 to 30 years.

The hope is that these calculations would help solar farms to take full advantage of bifacial cells earlier in their use.

"It took almost 50 years for monofacial cells to show up in the field in a cost-effective way," Alam said. "The technology has been remarkably successful, but we know now that we can't significantly increase their efficiency anymore or reduce the cost. Our formula will guide and accelerate the development of bifacial technology on a faster time scale."

The paper might have gotten the math settled just in time: experts estimate that by 2030, bifacial solar cells will account for nearly half of the market share for solar panels worldwide.

Alam's approach is called the "Shockley-Queisser triangle," since it builds upon predictions made by researchers William Shockley and Hans-Joachim Queisser on the maximum theoretical efficiency of a monofacial solar cell. This maximum point, or the thermodynamic limit, can be identified on a downward sloping line graph that forms a triangle shape.

The formula shows that the efficiency gain of bifacial solar cells increases with light reflected from a surface. Significantly more power would be converted from light reflected off of concrete, for example, compared to a surface with vegetation.

The researchers use the formula to recommend better bifacial designs for panels on farmland and the windows of buildings in densely-populated cities. Transparent, double-sided panels allow solar power to be generated on farmland without casting shadows that would block crop production. Meanwhile, creating bifacial windows for buildings would help cities to use more renewable energy.

The paper also recommends ways to maximize the potential of bifacial cells by manipulating the number of boundaries between semiconductor materials, called junctions, that facilitate the flow of electricity. Bifacial cells with single junctions provide the largest efficiency gain relative to monofacial cells.

"The relative gain is small, but the absolute gain is significant. You lose the initial relative benefit as you increase the number of junctions, but the absolute gain continues to rise," Khan said.

The formula, detailed in the paper, has been thoroughly validated and is ready for companies to use as they decide how to design bifacial cells.

DALLAS, December 18, 2019 -- A pattern of harmful alcohol consumption, or heavy drinking, increases level of blood biomarkers indicating heart tissue damage, according to new research published today in the Journal of the American Heart Association, the open access journal of the American Heart Association.

While previous studies have shown that heavy drinking can increase risks for alcoholic cardiomyopathy (leading to alcohol induced heart failure), high blood pressure, heart attack, arrhythmias, stroke and death, there is limited research on how alcohol consumption can have a such a negative effect on heart health.

For this study, researchers utilized certain signs to define the participants' drinking habits as heavy/harmful: having six or more drinks on one occasion; feeling hungover or drunk; needing a drink first thing in the morning; having experienced adverse consequences in their personal life because of drinking; having a family member or loved one who is concerned about their drinking. Any or all of these signs were indications of a level of drinking that is damaging to cardiovascular health.

"A person can have heart damage before symptoms occur, which we call subclinical heart disease. By measuring the level of certain molecules in the blood, we were able to find that heavy drinkers are much more likely to have subclinical heart damage than people who drink less heavily," said study author Olena Iakunchykova, M.S., a Ph.D. candidate in community medicine at the University in Tromsø, The Arctic University of Norway.

To determine the effects of varying levels of alcohol consumption on the heart, researchers examined blood samples from 2,525 adults, ages 35-69, from the year 2015 to 2018, from the Know Your Heart study. 2,479 of the participants were from the general population of Arkhangelsk, a city in Northwest Russia, while the other 278 participants were patients diagnosed with and being treated for alcoholism at the Arkhangelsk Regional Psychiatric Hospital.

The researchers categorized adults based on their self-reported alcohol consumption habits and included those who drank no alcohol, those who consumed alcohol but didn't experience the signs of heavy/harmful drinking, and heavy drinkers who met the criteria for harmful drinking.

Blood samples included three important measures, or biomarkers, of heart health: 1) high sensitivity cardiac Troponin T, a measure of heart injury; 2) N-terminal pro-B-type natriuretic peptide, a marker of cardiac wall stretch; and 3) high sensitivity C-reactive protein, a measure of inflammation.

Researchers found:

The hospital patient sample, which had the most extreme drinking pattern, had the highest levels of all three biomarkers, compared to non-problem drinkers in the general population;

The hospital patients' biomarkers for heart injury was 10.3% higher; cardiac wall stretch was 46.7% higher; and inflammation 69.2% higher, compared to non-problem drinkers in the general population; and

In the general population sample, the blood marker for cardiac wall stretch was 31.5% higher among drinkers with harmful drinking patterns compared to non-problem drinkers.

"Our results suggest that people who drink heavily are creating higher than normal levels of inflammation in their bodies that have been linked to a wide range of health conditions including cardiovascular disease," Iakunchykova said. "The study adds to what we already know about the health consequences of heavy alcohol consumption. We are now studying ultrasound images of the heart as it beats to help us identify the precise sorts of heart damage associated with heavy and harmful drinking."

Due to the research being confined to one city in Russia and the study population being almost exclusively of Eastern European or Russian descent, the study results may not be generalizable to other races or ethnic populations. More research is needed to show how heavy alcohol use can impact heart health, and the role that inflammation in the body has in the development of heart disease.

High blood levels of the lipid lipoprotein(a) in people with type 1 diabetes add to the already elevated risk of developing cardiovascular disease, researchers from Karolinska Institutet in Sweden report in a paper published in the prestigious journal Diabetes Care. Lipoprotein(a) levels should therefore be measured in patients with type 1 diabetes and form part of the total risk assessment, say the researchers.

"There is currently no readily available treatment for high lipoprotein(a) levels, but the treatment of all other risk factors for cardiovascular disease should be optimised for patients with type 1 diabetes and high levels of lipoprotein(a)," says the study's lead author Karin Littmann, PhD student at the Department of Laboratory Medicine at Karolinska Institutet.

As a consequence of their disease, patients with type 1 diabetes run a higher risk of developing cardiovascular disease. Diabetes and high blood-sugar levels can also eventually cause the leakage of proteins into the urine, reduced kidney function, impaired circulation and retinal damage, leading to impaired vision.

Lipoprotein(a) is a type of blood fat, the levels of which are determined mostly by hereditary factors rather than diet or lifestyle, like other blood lipids. Previous research has shown that high levels of lipoprotein(a) entail a higher risk of cardiovascular diseases, such as myocardial infarction, stroke and calcified aortic valve disease. However, it is not fully known how lipoprotein(a) influences the risk of cardiovascular disease and related complications in patients with type 1 diabetes. It is also not known if there is any connection between lipoprotein(a) levels and high blood-sugar levels in this patient group.

For the present study, the researchers examined 1,860 patients with type 1 diabetes, and gathered data from medical records at Karolinska University Hospital on their lipoprotein(a) and blood-sugar levels, and on the incidence of cardiovascular disease and related complications.

Patients with type 1 diabetes and high lipoprotein(a) levels had a 50 per cent higher risk of developing some form of cardiovascular disease, a 70 per cent higher risk of coronary artery disease and a 100 per cent higher risk of calcified aortic valve disease, than patients with type 1 diabetes and low lipoprotein(a) levels. They also had a 70 per cent higher risk of protein leakage into the urine, which is a sign of reduced kidney function. Patients with high blood glucose (HbA1c) values had higher lipoprotein(a) levels than patients with low blood glucose values.

"Our conclusion is that high levels of lipoprotein(a) in patients with type 1 diabetes add to the already elevated risk of developing cardiovascular disease," says Dr Littmann. "The levels of these blood lipids should therefore be measured and should form part of the total risk assessment."

CLEVELAND, Ohio (December 18, 2019)--The value of a good night's sleep can't be underestimated. Unfortunately, sleep complaints are common during the menopause transition. A new study from Canada compared sleep quality, sleep duration, and sleep disorders between postmenopausal and pre/perimenopausal women and documented increased sleep problems postmenopause. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

Sleep disorders are one of more common complaints during menopause, affecting 40% to 60% of perimenopausal and postmenopausal women. Not only do they impair a woman's quality of life, but they also can lead to major health problems such as cardiovascular disease, diabetes, depression, and anxiety.

Multiple specific sleep disorders are also age related, including obstructive sleep apnea, periodic leg movements during sleep, rapid eye movement sleep behavior, and change in the normal sleep cycle. Although multiple studies have already examined age-related sleep problems, few considered the effect of menopause status. This new study involving more than 6,100 Canadian women sought to demonstrate how sleep was affected as a woman progressed through the menopause transition.

Researchers confirmed that, compared with premenopausal and perimenopausal women, postmenopausal women required more time to fall asleep (in excess of 30 min) and were more likely to suffer from sleep-onset insomnia disorder and obstructive sleep apnea.

Study results appear in the article "Effects of menopause on sleep quality and sleep disorders: Canadian Longitudinal Study on Aging."

"This study highlights links between menopause and insomnia and obstructive sleep apnea. Given the known associations with poorer health, sleep problems should be identified and addressed in menopausal women," says Dr. Stephanie Faubion, NAMS medical director.

OAK BROOK, Ill. - A sophisticated type of artificial intelligence (AI) can outperform existing models at predicting which women are at future risk of breast cancer, according to a study published in the journal Radiology.

Most existing breast cancer screening programs are based on mammography at similar time intervals--typically, annually or every two years--for all women. This "one size fits all" approach is not optimized for cancer detection on an individual level and may hamper the effectiveness of screening programs.

"Risk prediction is an important building block of an individually adapted screening policy," said study lead author Karin Dembrower, M.D., breast radiologist and Ph.D. candidate from the Karolinska Institute in Stockholm, Sweden. "Effective risk prediction can improve attendance and confidence in screening programs."

High breast density, or a greater amount of glandular and connective tissue compared to fat, is considered a risk factor for cancer. While density may be incorporated into risk assessment, current prediction models may fail to fully take advantage of all the rich information found in mammograms. This information has the potential to identify women who would benefit from additional screening with MRI.

Dr. Dembrower and colleagues developed a risk model that relies on a deep neural network, a type of AI that can extract vast amounts of information from mammographic images. It has inherent advantages over other methods like visual assessment of mammographic density by the radiologist that may not be able to capture all risk-relevant information in the image.

The new model was developed and trained on mammograms from cases diagnosed between 2008 and 2012 and then studied on more than 2,000 women ages 40 to 74 who had undergone mammography in the Karolinska University Hospital system. Of the 2,283 women in the study, 278 were later diagnosed with breast cancer.

The deep neural network showed a higher risk association for breast cancer compared to the best mammographic density model. The false negative rate--the rate at which women who were not categorized as high-risk were later diagnosed with breast cancer--was lower for the deep neural network than for the best mammographic density model.

"The deep neural network overall was better than density-based models," Dr. Dembrower said. "And it did not have the same bias as the density-based model. Its predictive accuracy was not negatively affected by more aggressive cancer subtypes."

The study findings support a future role for AI in breast cancer risk assessment.

"We are not reporting mammographic density currently," Dr. Dembrower said. "In the introduction of individually adapted screening, we use deep learning networks trained to predict cancer rather than taking the indirect route that density offers."

As an additional benefit, the AI approach can continually be improved with exposure to more high-quality data sets.

"Our deep learning experts at the Royal Institute of Technology in Stockholm are working on an update to the model," Dr. Dembrower said. "After that, we aim to test the model clinically next year by offering MRI to the women who stand to benefit the most."

PHILADELPHIA -- Patients with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) who are treated with anthracyclines are at a heightened risk of heart failure--most often within one year of exposure to the chemotherapy treatment, according to a new study led by researchers at Penn Medicine.

To help identify a patient's risk for heart failure following the treatment, researchers developed a risk score based on clinical and echographic variables, including left ventricular ejection fraction (how much blood the LV pumps out with each contraction), myocardial strain, and cumulative treatment dose. Oncologists, authors say, can use the scoring system to classify patients as low or high risk for heart failure and then tailor their treatment plans accordingly. The risk score model and results of the study were published today in JACC: CardioOncology.

"While we are more effective at treating cancer, the improved survival rates have helped to unmask the cardiotoxic impact of some of the most common cancer therapies," said the study's corresponding author Marielle Scherrer-Crosbie, MD, PhD, director of the Cardiac Ultrasound Laboratory and a professor of Cardiovascular Medicine in the Perelman School of Medicine at the University of Pennsylvania. "Our hope, in creating this risk score system, is to help clinicians identify patients with the highest risk for potential cardiac damage, so they can more closely monitor the patients via a multidisciplinary approach."

Over the past decade, the incidence of acute leukemia in the United States has steadily increased. Advances in treatment during that time, however, have led to drastically improved survival, with mortality rates dropping by one percent each year from 2006 to 2015. Antracyclines remain a standard therapy for acute leukemia, and they are delivered as high doses over a very short period of time--a treatment schedule that increases toxicity. While previous research found patients with hematologic malignancies (cancer that begins in blood-forming tissues) had the highest rates of symptomatic heart failure, there is limited evidence on the comorbidities in adult patients with acute leukemia and little is known about the incidence and risk stratification of symptomatic heart failure in this population.

In this study, researchers analyzed data of 450 patients with ALL (when bone marrow makes too many lymphocytes, a type of white blood cell) or AML (when bone marrow makes abnormal myeloblasts--a type of white blood cell--red blood cells, or platelets). Of the patients studied, 40, or about 9 percent, developed symptomatic heart failure. The patients, on average, developed heart failure 10 months following exposure to treatment. Patients with AML had a higher incidence of heart failure compared to patients with ALL.

Researchers then developed a risk score, which ranged from 0 to 21, based on six clinically relevant variables and myocardial strain--a measure of strain on the heart muscles that can be calculated by echocardiography. The team assigned points to each of the variables: a baseline global longitudinal strain of greater than -15 percent (6 points); baseline LV ejection fraction of less than 50 percent, preexisting heart disease, AML (4 points each); cumulative anthracycline dose of greater than or equal to 250 mg/m (2 points) and older than 60 years of age (1 point).

The patients were divided into three subgroups based on their risk scores: low (0 to 6), moderate (7 to 13) and high (14 to 21). The majority of patients (318) were classified as low risk, while 112 were considered moderate and 20 classified as high risk for heart failure. The team found that 65 percent of patients classified as high risk developed heart failure, while only 1 percent of the patients in the low risk group did.

"While this is a significant step toward identifying patient risk for heart failure, additional studies are needed to determine the effectiveness of such a risk score in clinical practice," said the study's lead author Yu Kang, MD, PhD, a post-doctoral research fellow at Penn.

WASHINGTON--Weight may affect doctors' ability to correctly interpret routine blood tests in children, according to new research published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

The number of U.S. youth who are overweight or obese has risen dramatically over the past three decades. The State of Obesity reports about 18.5 percent of children are obese. With the rising rates of obesity in children and teens becoming a major public health concern, it is important for patients and doctors to understand the potential influence of weight on routine blood tests.

"We performed the first comprehensive analysis of the effect of obesity on routine blood tests in a large community population of children and found that almost 70 percent of the blood tests studied were affected," said the study's first author, Victoria Higgins, Ph.D. of The Hospital for Sick Children and The University of Toronto in Ontario, Canada. "As clinical decisions are often guided by normative ranges based on a large healthy population, understanding how and which routine blood tests are affected by obesity is important to correctly interpret blood test results."

The researchers studied over 1,300 otherwise healthy children and teens from the community in the Greater Toronto Area and found that 24 routine blood tests are affected by obesity, including liver function tests, inflammation markers, lipids, and iron.

While it is unknown whether this effect of pediatric obesity reflects early disease, doctors should be aware of these findings when interpreting several blood tests in children.

"We hope our study results will assist pediatricians and family physicians to better assess children and adolescents with different degrees of overweight or obesity," Higgins said.

CINCINNATI - Scientists describe in Nature Immunology an entirely new molecular process in mice that triggers T cell-driven inflammation and causes different auto-immune diseases.

In a study published online Dec. 17, researchers at Cincinnati Children's Hospital Medical Center say their data have implications for Multiple Sclerosis, Type 1 diabetes and Inflammatory Bowel Disease. It also will help efforts to find better treatments for autoimmune disease, still an urgent need in medicine.

"This study opens new avenues for developing more effective autoimmune therapies. To this end, we now are testing the molecular process we identified in different kinds of human cells, including building collaborations with others researchers to collect donated cell samples from people who have multiple sclerosis, arthritis and other autoimmune diseases," said lead investigator Chandrashekhar Pasare, DVM, PhD, a member of the Division of Immunobiology at Cincinnati Children's and co-director of the Center for Inflammation and Tolerance.

A Mystery Resolved

For the past decade or so, scientists and physicians have linked the immune system protein IL-1b (cytokine interleukin-1 beta) with several autoimmune diseases. Drugs and antibodies that block or inhibit IL-1b are currently used to manage symptoms in people with different types of autoimmune disease, according to researchers.

But until the current study, it wasn't known how IL-1b is made in the body, especially during autoimmunity. This limits the ability to develop effective therapeutics for autoimmune diseases, according to researchers.

Previously it was thought that IL-1b production required activation of a group of immune system protein molecules that make up structures called the inflammasomes. It turns out the inflammasomes, which act as system sensors that activate inflammation, can cause what are called auto-inflammatory diseases. These are distinct from auto-immune diseases.

Pasare and his colleagues found out that instead of inflammasomes, a different molecular pathway cranks up inflammation during autoimmunity while working completely independent from inflammasomes. That molecular process was triggered by interactions between myeloid cells and CD4-positive T cells, which become primed to attack harmful bacteria, viruses and other microorganisms. Unfortunately, in the case of autoimmunity, the immune system attacks and eventually destroys healthy tissues erroneously targeted as harmful.

When it's not fulfilling its role in driving autoimmunity, IL-1b usually works as a stimulator of anti-microbial immunity. But during autoimmune processes, the authors report they discovered in their mouse models that autoreactive T cells, macrophage and dendritic cells in the immune system work through two other molecules--TNF (tumor necrosis factor) and FasL (fas ligand)--to produce overabundant amounts of IL-1b.

"This means our findings have two previously unknown implications," Pasare explained. "We show for the first time that IL-1b can be made in the absence of infection and that T cells are major drivers of IL-1b in an autoimmune setting."

The study also underscores that therapies targeting IL-1b production by inflammasomes are going to be limited in their effectiveness in treating autoimmune disease. This is because the Pasare team's findings show that auto-reactive T cells have their own mechanisms to drive inflammation and work independently of inflammasomes.

Pasare said that targeting the TNF and FasL pathway of IL-1b production is more likely to be an effective way of treating auto-immune diseases in humans.

Work Remains Preclinical

The researchers stressed that because the preclinical findings were obtained by studying laboratory models, it is still too early to determine whether the results will translate to treating patients in clinic. A great deal of additional preclinical research is needed first. Anti-TNF therapies are already used in the clinic for some auto-immune diseases, and additional blockade of FasL, as suggested in the current study, may be a more effective way of treating auto-immune diseases. Pasare and his collaborators will continue to test this in their preclinical models.

Approximately $50 billion dollars of the annual healthcare cost of cardiometabolic disease in the US population could be associated with poor diet, according to a research article published this week in the open access journal PLOS Medicine. The results of the study, conducted by Renata Micha and Thomas Gaziano of Tufts University and the Brigham and Women's Hospital, Boston, United States and colleagues, suggest that the highest costs associated with cardiometabolic disease may be attributable to suboptimal consumption of foods such as nuts and seeds, and seafood-derived omega-3 fats.

While unhealthy diet contributes to the risk of developing diseases such as type 2 diabetes, stroke, and coronary heart disease, the related healthcare costs are unknown. In the new study, which was part of the National Institutes of Health- funded Food-PRICE (Policy Review and Intervention Cost Effectiveness) Project to improve diet-related health in the US population, Micha, Gaziano and colleagues used a microsimulation modeling approach to estimate cardiometabolic disease costs associated with suboptimal consumption of ten food groups in US adults between 35 and 85 years of age. In their model, the authors incorporated dietary intake and cardiovascular disease risk factor data from the 2009-2012 National Health and Nutrition Examination Survey (NHANES), a program of studies assessing health and nutrition in the US.

The study estimated that the annual cardiometabolic disease cost associated with suboptimal diet is $301 per person, and $50.4 billion for the US population, corresponding to 18.2% of the total cardiometabolic disease cost. Further, the results suggest that the largest estimated annual costs per person are associated with lower than recommended consumption of foods such as nuts and seeds ($81), and omega-3 fats derived from seafood ($76). It is important to note that the study diet data are derived from individuals' recollections of recent food consumption, and could be subject to recall errors, or may not reflect an individual's long-term dietary habits.

These results suggest that improvements in diet may help to reduce the cost burden associated with cardiometabolic diseases in the US. The authors explain that the high costs attributable to specific dietary groups in this study, such as nuts and seeds, are in part related to the fact that individual consumption of these food components is relatively low, noting that "...from the economic perspective, intervention policies focused not just on the benefit or harm of dietary factors, but also focused on how far the population is from achieving ideal consumption are more likely to have economic benefit."

PULLMAN, Wash--Young adults say that Instagram helps them develop friendships in real life, especially those who are more hesitant to try new experiences, according to a recent study by Washington State University researchers.

In the study published online in Computers in Human Behavior, the researchers analyzed survey responses of nearly 700 college-age adults about their perceptions and use of the social media site.

The analysis found that the young adults liked how Instagram was easy to use as well as the many features of the highly visual platform. This encouraged them to express themselves on the social media site, which in turn led to new and deeper relationships offline.

"Our findings are optimistic: that self-disclosure on Instagram could facilitate friendship development, even if followers were just casual acquaintances at the start," said Danielle Lee, the study's lead author and current doctoral student in WSU's Edward R. Murrow College of Communication.

The results of the study suggested that Instagram had a greater effect on people who ranked low on the personality trait of "openness," meaning they tend to be more reserved and closed to new experiences than those who ranked high in this trait.

"Studies have shown that in general people who are not extroverted, who might be somewhat shy, find social media platforms an easier way to interact with other people," said Associate Professor Porismita Borah, co-author on the paper. "Instagram is such a visually rich platform and that really helps in self-presentation."

A large majority, 71%, of young Americans age 18 to 24 use Instagram, according to a 2018 Pew Research Center survey. As the WSU study notes, users can follow other people on Instagram without their approval, if their accounts are public, allowing for people to interact who don't have strong social ties outside of the platform. Instagram also distinguishes itself from other social networks with its focus on images: users cannot create a post without a visual as they can on Facebook and Twitter. The platform also provides easy ways to control how users present themselves.

"In Instagram, you can change the image the way you want with filters and many different tools before posting it," said Borah. "Both media richness and user-friendliness come together in Instagram, which is probably what makes it so appealing to the younger generation."

Barcelona, 17 December 2019. Women who live less than 300 metres from green space may be at lower risk of excess weight or obesity. This is the main finding of a study led by the Barcelona Institute for Global Health (ISGlobal), a centre supported by "la Caixa", and published in the International Journal of Hygiene and Environmental Health.

Using information from the MCC-Spain multi-case control study, the researchers analysed data on 2,354 people from seven Spanish provinces (Asturias, Barcelona, Cantabria, Madrid, Murcia, Navarre and Valencia). The study participants, who ranged in age from 20 to 85 years, answered survey questions about their residential history, lifestyle (physical activity, leisure time, etc.), weight and height. In addition, hip and waist circumference was measured and blood or saliva samples were collected. To determine whether or not participants were overweight or obese, the researchers used two markers that are commonly used in epidemiologic studies: body mass index and waist-hip ratio.

The study found a strong association between overweight or obesity in women and lack of access to urban green spaces such as parks and gardens. However, no such association was found in men. "We do not have a clear understanding of the biological determinants behind the observed gender differences," commented ISGlobal researcher Cristina O'Callaghan-Gordo, the lead author of the study. "There are probably social factors, such as differences in how men and women use green spaces, that explain this disparity."

Using the DNA samples collected from the participants' saliva and blood, the researchers analysed the role of genetics in this association. "We studied genetic polymorphisms that have been associated with obesity in previous research," commented O'Callaghan-Gordo. "In general, we observed a more marked reduction in risk of obesity in people with a genetic predisposition to this condition. This finding points to the existence of gene-environment interactions that could either trigger or prevent excess weight gain."

Overweight and Obesity: Catalysts of Disease

According to the World Health Organisation, in 2016 more than 1.9 billion adults were overweight. Of these, more than 650 million were obese--a preventable condition. "Excess weight is an important risk factor for various non-communicable diseases, including cardiovascular, kidney and liver disease, diabetes, various musculoskeletal disorders, and some types of cancer," commented study leader Manolis Kogevinas, a researcher in the Non-communicable Diseases and Environment programme at ISGlobal. "It is also associated with increased all-cause mortality."

Natural outdoor environments, including green spaces within urban settings, promote health and well-being by increasing levels of physical activity, reducing exposure to noise and reducing psychological stress, which is an important driver of weight gain. "This study highlights the important role played by green space in the risk of excess weight and obesity in Spanish women. Understanding the mechanisms that explain this association is crucial to plan effective and successful public health interventions," concluded Kogevinas.

High intensity interval training (HIIT) is only effective for improving fitness when performed at 60-second intervals, according to new research from Liverpool John Moores University, presented today (Tuesday 17 December) at The Physiological Society early career conference, Future Physiology 2019: Translating Cellular Mechanisms into Lifelong Health Strategies.

Currently 40% of people in the UK do not meet the Government's physical activity guidelines, with a lack of time cited as the most common barrier.

HIIT, meaning short burst (anywhere from 20 to 90 seconds) of intense cardio exercises is a time-efficient alternative that has been making headlines in the last decade. Specifically, home-based HIIT, which involves doing HIIT training at home using simple body weight exercises, has become popular because it gets rid of the barriers such as the time and money required to go to the gym..

Researchers at Liverpool John Moores University compared two popular HIIT protocols (60HIIT and 30HIIT) performed for six weeks, three times per week, in a sample of 26 previously sedentary men and women. 60HIIT means 6-10 60-second intervals with 60 seconds of rest, whereas 30HIIT means 4-8 30 seconds intervals with 120 seconds of rest.

They kept track of training adherence and intensity remotely via a heart rate monitor that fed info through a mobile app. The researchers looked at three parameters of fitness: aerobic capacity, stiffness of arteries, and body composition (meaning how much muscle and fat they had) during the six weeks of HIIT.

Aerobic capacity increased after six weeks of 60HIIT but there was no difference for 30HIIT on any of the three parameters. This means that 60HIIT should be used over 30HIIT because the former improves fitness whereas the latter doesn't.

Hannah Church, one of the researchers involved said:

"In order for people to get the most out of HIIT, which may be the answer to the difficulties of paying for and getting to the gym, we need to get the timing right. Our research showed just how important this is, because we found that 30 second intervals with 120 seconds of rest meant that participants' heart rates didn't stay up. 120 seconds is just too long to be resting for!"