Publisher Health

Scientists have known for a century that female animals become more active just as they are about to ovulate, a behavior that evolved to enhance their chances of mating when they are fertile.
Now, a team at UC San Francisco has identified the specific neurons and signaling pathway that make sexually receptive females of many species run around at this critical time. The work was done in mice, but researchers expect it will bear out in humans, since the behavior is related to such a fundamental aspect of life.
“Why do you want to get up and move?” asked Holly Ingraham, PhD, the Herzstein Professor of Molecular Physiology at UCSF and senior author of the study published in Nature. “Well, if you activate the circuit in these neurons, maybe that’s why.”
The discovery also illuminates what happens in menopause as the loss of estrogen disrupts this activity circuit, and both mouse and human females become more sedentary, gain weight, and develop metabolic disorders like type 2 diabetes. And it offers the possibility of a new kind of treatment for menopause that sidesteps estrogen and reactivates the circuit with CRISPRa technology.
“As we discover what estrogen does in the brain, we’re probably going to discover more of its benefits,” Ingraham said. “This is just one area in the brain, and it has a powerful effect. We’d also like to know more about other circuits in the brain that affect well-being and cognition.”
When estrogen bathes the brain, it interacts with estrogen receptor ? (ER?) to activate a gene called Mc4r. This produces melanocortin-4 receptors (MC4R) on the surface of estrogen-sensitive neurons in a part of the brain called the ventrolateral ventromedial hypothalamic nucleus (VMHvl) that regulates how energy is used in adult females.

A cell-based influenza vaccine has effectively provided protection against the flu in children and adolescents, according to a new study.
The research found the cell-based quadrivalent influenza vaccine (QIVc) produced a sufficient immune response in children aged two to 18 years. The lead investigator on the study was Professor Terry Nolan, head of the Vaccine and Immunisation Research Group (VIRGo) at the Murdoch Children’s Research Institute (MCRI), and the Peter Doherty Institute for Infection and Immunity at the University of Melbourne.
The findings, published in The New England Journal of Medicine, were the first on the absolute efficacy of a cell-based influenza vaccine in children as young as two years of age.
The randomized controlled study involved 4514 participants across Australia, Thailand, Estonia, Finland, Lithuania, Poland, Spain and the Philippines. The overall vaccine efficacy was 54.6 per cent, meeting the pre-specified endpoint for success and showing benefit across three influenza seasons and all eight countries.
QIVc uses a cell-based flu vaccine production process, an alternative to traditional egg-based manufacturing where reference influenza viruses are grown in the yolk of fertilised hens eggs. But this can result in mutation of the influenza virus leading to an antigenic mismatch between the circulating reference and inactivated strains contained within the seasonal flu vaccine.
Professor Nolan said because cell-based flu vaccines, grown in animal cells, were designed to produce an exact match to the World Health Organization’s selected influenza strains by avoiding egg-adapted changes, they could potentially provide greater effectiveness.
Professor Nolan said cell-based vaccine technology may also offer additional advantages including increased scalability and production speed in the event of an influenza pandemic.
In a typical year, 5-15 per cent of the world’s population contracts influenza and there are up to 650,000 respiratory-related deaths. Deaths most commonly occur in high-risk groups, including young children, the elderly and people with chronic health conditions.
The research was funded by UK-based Seqirus, which announced last year plans to build a cell-based manufacturing facility in Australia, which will be the first facility of its kind in the Southern Hemisphere.
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Materials provided by Murdoch Childrens Research Institute. Note: Content may be edited for style and length.

A new report finds more than 46,000 cancer cases annually in the United States could be prevented if Americans met the 5 hours per week of moderate-intensity recommended physical activity guidelines. The latest data appearing in the journal Medicine & Science in Sports & Exercise show 3% of all cancer cases in adults in the U.S. aged 30 years and older during 2013 to 2016 were attributable to physical inactivity and the proportion was higher in women (average annual attributable cases 32,089) compared to men (14,277).
For both men and women, states with the highest proportion of cancers attributable to physical inactivity were in the South, such as Kentucky, West Virginia, Louisiana, Tennessee, and Mississippi, whereas the lowest proportions were found in the Mountain region and northern states, such as Utah, Montana, Wyoming, Washington, and Wisconsin.
Led by Adair Minihan, MPH at the American Cancer Society, this is the first study to estimate the number of cancer cases attributable to physical inactivity based on cancer sites (breast, endometrial, colon, stomach, kidney, esophageal adenocarcinoma, and urinary bladder) by state. Data show when focusing on specific cancer sites, 16.9% of stomach cancers, 11.9% of endometrial cancers, 11.0% of kidney cancers, 9.3% of colon cancers, 8.1% of esophageal cancers, 6.5% of female breast cancers, and 3.9% of urinary bladder cancers were associated with lack of exercise. By state, the proportion of cancer cases attributable to physical inactivity ranged from 2.3% in Utah to 3.7% in Kentucky.
While this data shows the importance of physical activity, there are many barriers to recreational physical activity, which include, but are not limited to, lack of time due to long working hours in low-wage jobs, the cost of gym memberships or personal equipment, lack of access to a safe environment in which to be active, and potential childcare costs involved with recreational physical activity. Unfortunately, these barriers are more likely to affect historically marginalized populations, including the Black population and individuals with a limited income, underscoring the importance of enhancing health equity.
“These findings underscore the need to encourage physical activity as a means of cancer prevention and implement individual- and community-level interventions that address the various behavioral and socioeconomic barriers to recreational physical activity,” write the authors. “Understanding and reducing the behavioral and socioeconomic barriers to physical activity is essential for optimizing intervention strategies targeting at risk groups across the country.”
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Materials provided by American Cancer Society. Note: Content may be edited for style and length.

Deaths from tuberculosis, the world’s biggest infectious disease killer until the Covid-19 pandemic arrived, have increased for the first time in more than a decade, totaling more than 1.5 million people in 2020. That trend is expected to worsen in 2021 and 2022, according to a report released on Thursday by the World Health Organization.The report confirmed the warnings from the W.H.O. and other global health organizations that the Covid-19 pandemic would reverse years of progress against other infectious diseases, including TB, H.I.V. and malaria.“This is alarming news that must serve as a global wake-up call to the urgent need for investments and innovation to close the gaps in diagnosis, treatment and care for the millions of people affected by this ancient but preventable and treatable disease,” Dr. Tedros Adhanom Ghebreyesus, the W.H.O.’s director general, said in a statement.Reported diagnoses of TB also dropped sharply, to 5.8 million cases in 2020 from 7.1 million in 2019, suggesting that many more cases than before are going undiagnosed and untreated — a trend that is likely to have a long-term effect on TB deaths. And only 2.8 million people were given preventive treatment for TB in 2020, a 21 percent decrease from 2019.In many poor countries, health care workers, funds and testing equipment that would normally be dedicated to TB were redirected to cope with Covid-19, according to the W.H.O. report. Lockdowns and disruptions in supply chains also interrupted access to treatment and care.At the same time, global funding for TB has fallen to $5.3 billion from $5.8 billion, less than half of what’s needed, according to the W.H.O. report.There were some glimmers of good news amid the sobering statistics. In the Russian Federation, the incidence of TB fell by 6 percent a year between 2010 and 2020, and the W.H.O. European Region overall exceeded the 2020 goal with a decrease of 25 percent.

A new discovery about osteoporosis suggests a potential treatment target for that brittle-bone disease and for bone loss from rheumatoid arthritis.
The findings from University of Virginia School of Medicine researchers and their collaborators help explain why specialized bone cells called osteoclasts begin to break down more bone than the body replaces. With more research, scientists one day may be able to target that underlying cause to prevent or treat bone loss.
The discovery also suggests an answer for why some previous attempts to develop osteoporosis treatments produced disappointing results.
“Bone degradation and subsequent repair are fine-tuned through complex interactions between the cells that degrade the bone, osteoclasts, and those that produce new bone matrix. Simple elimination of osteoclasts is, therefore, not always the best approach to treat pathologic bone loss. Instead, we found a ‘signaling node’ in osteoclasts that regulates their function in degrading the bone but doesn’t reduce osteoclast numbers,” said researcher Sanja Arandjelovic, PhD, of UVA’s Department of Medicine and UVA’s Carter Immunology Center.
Researcher Kodi Ravichandran, PhD, chairman of UVA’s Department of Microbiology, Immunology and Cancer Biology and director of UVA’s Center for Cell Clearance, noted the potential of the findings to inform efforts to develop better treatments for osteoporosis: “In this study,” he said, “we identified previously unappreciated factors that contribute to osteoclast function that is truly exciting and opens up new avenues to pursue.”
Understanding Bone Loss
Osteoporosis affects more than 200 million people around the world, and it causes bone fractures in 1 in 3 women and 1 in 5 men over age 50. Bone loss is also seen in rheumatoid arthritis, a painful inflammatory condition that affects up to 1% of people, including more than 1.3 million Americans.

Sunscreen that includes zinc oxide, a common ingredient, loses much of its effectiveness and becomes toxic after two hours of exposure to ultraviolet radiation, according to a collaboration that included Oregon State University scientists.
The toxicity analysis involved zebrafish, which share a remarkable similarity to humans at the molecular, genetic and cellular levels, meaning many zebrafish studies are immediately relevant to people.
Findings were published today in Photochemical & Photobiological Sciences.
The research team, which included College of Agriculture Sciences faculty Robyn Tanguay and Lisa Truong and graduate fellow Claudia Santillan, sought to answer important but largely neglected questions regarding the massive global sunscreen market, predicted by market data firm Statista to be worth more than $24 billion by the end of the decade.
The questions: How stable, safe, and effective are sunscreen ingredients in combination rather than as individual compounds — which is how they are considered for Food and Drug Administration approval — and what about the safety of any chemical products that result from reactions caused by exposure to sunlight?
“Sunscreens are important consumer products that help to reduce UV exposures and thus skin cancer, but we do not know if the use of some sunscreen formulations may have unintended toxicity because of interactions between some ingredients and UV light,” said Tanguay, an OSU distinguished professor and an international expert in toxicology.

An artificial intelligence (AI)-based technology rapidly diagnoses rare disorders in critically ill children with high accuracy, according to a report by scientists from University of Utah Health and Fabric Genomics, collaborators on a study led by Rady Children’s Hospital in San Diego. The benchmark finding, published in Genomic Medicine, foreshadows the next phase of medicine, where technology helps clinicians quickly determine the root cause of disease so they can give patients the right treatment sooner.
“This study is an exciting milestone demonstrating how rapid insights from AI-powered decision support technologies have the potential to significantly improve patient care,” says Mark Yandell, Ph.D., co-corresponding author on the paper. Yandell is a professor of human genetics and Edna Benning Presidential Endowed Chair at U of U Health, and a founding scientific advisor to Fabric.
Worldwide, about seven million infants are born with serious genetic disorders each year. For these children, life usually begins in intensive care. A handful of NICUs in the U.S., including at U of U Health, are now searching for genetic causes of disease by reading, or sequencing, the three billion DNA letters that make up the human genome. While it takes hours to sequence the whole genome, it can take days or weeks of computational and manual analysis to diagnose the illness.
For some infants, that is not fast enough, Yandell says. Understanding the cause of the newborn’s illness is critical for effective treatment. Arriving at a diagnosis within the first 24 to 48 hours after birth gives these patients the best chance to improve their condition. Knowing that speed and accuracy are essential, Yandell’s group worked with Fabric to develop the new Fabric GEM algorithm, which incorporates AI to find DNA errors that lead to disease.
In this study, the scientists tested GEM by analyzing whole genomes from 179 previously diagnosed pediatric cases from Rady’s Children’s Hospital and five other medical centers from across the world. GEM identified the causative gene as one of its top two candidates 92% of the time. Doing so outperformed existing tools that accomplished the same task less than 60% of the time.
“Dr. Yandell and the Utah team are at the forefront of applying AI research in genomics,” says Martin Reese, Ph.D., CEO of Fabric Genomics and a co-author on the paper. “Our collaboration has helped Fabric achieve an unprecedented level of accuracy, opening the door for broad use of AI-powered whole genome sequencing in the NICU.”
GEM leverages AI to learn from a vast and ever-growing body of knowledge that has become challenging to keep up with for clinicians and scientists. GEM cross-references large databases of genomic sequences from diverse populations, clinical disease information, and other repositories of medical and scientific data, combining all this with the patient’s genome sequence and medical records. To assist with the medical record search, GEM can be coupled with a natural language processing tool, Clinithink’s CLiX focus, which scans reams of doctors’ notes for the clinical presentations of the patient’s disease.
“Critically ill children rapidly accumulate many pages of clinical notes,” Yandell says. “The need for physicians to manually review and summarize note contents as part of the diagnostic process is a massive time sink. The ability of Clinithink’s tool to automatically convert the contents of these notes in seconds for consumption by GEM is critical for speed and scalability.”
Existing technologies mainly identify small genomic variants that include single DNA letter changes, or insertions or deletions of a small string of DNA letters. By contrast, GEM can also find “structural variants” as causes of disease. These changes are larger and are often more complex. It’s estimated that structural variants are behind 10 to 20% of genetic disease.
“To be able to diagnose with more certainty opens a new frontier,” says Luca Brunelli, M.D., neonatologist and professor of pediatrics at U of U Health, who leads a team using GEM and other genome analysis technologies to diagnose patients in the NICU. His goal is to provide answers to families who would have had to live with uncertainty before the development of these tools. He says these advances now provide an explanation for why a child is sick, enable doctors to improve disease management, and, at times, lead to recovery.
“This is a major innovation, one made possible through AI,” Yandell says. “GEM makes genome sequencing more cost-effective and scalable for NICU applications. It took an international team of clinicians, scientists, and software engineers to make this happen. Seeing GEM at work for such a critical application is gratifying.”
Fabric and Yandell’s team at the Utah Center for Genetic Discovery have had their collaborative research supported by several national agencies, including the National Institutes of Health and American Heart Association, and by the U of U’s Center for Genomic Medicine. Yandell will continue to advise the Fabric team to further optimize GEM’s accuracy and interface for use in the clinic.

Children with cerebral palsy can gain greater use of an impaired arm and hand with larger doses of Constraint-Induced Movement Therapy (CIMT) — without increasing stress for parents, according to a new study by researchers at Virginia Tech’s Fralin Biomedical Research Institute at VTC, UVA Children’s, The Ohio State University, and Nationwide Children’s Hospital.
The findings could have far-reaching impacts on treatment of children’s movement disorders.
Scientific findings have supported the benefits of pediatric CIMT, in which a child’s more functional arm and hand are constrained by a lightweight cast, a splint, or a mitt, while a trained therapist uses operant conditioning techniques individualized for each child. But little was known about whether the outcome of therapy was directly linked to the dosage of therapy or method of constraint.
Now, a study funded by the National Institutes of Health’s Eunice Kennedy Shriver National Institute of Child Health and Human Development and published Oct. 14 in Pediatrics shows that higher doses of CIMT therapy — 20 three-hour sessions over four weeks — yield significant and lasting improvement in use of their arms and hands, especially in everyday functional activities. The Children with Hemiparesis Arm-and-hand Movement Project (CHAMP) study is the first to compare different dosage levels of the same type of CIMT intervention for similar children.
“CHAMP provides new findings that are practically useful for clinicians and families in choosing treatment likely to produce meaningful benefits for children with hemiparetic cerebral palsy,” said Sharon Landesman Ramey, Distinguished Research Scholar at the Fralin Biomedical Research Institute and professor of psychiatry, psychology, and neuroscience at Virginia Tech, who led the study and is the paper’s corresponding author.
The study focused on children with hemiparetic cerebral palsy (HCP), the most common childhood neuromotor disorder. Cerebral palsy affects one to four children per 1,000 in the United States, and about 40% of these children will develop hemiparesis — impaired voluntary control on one side of the body, according to the Centers for Disease Control and Prevention.

The way a person’s brain responds to stress following a traumatic event, such as a car accident, may help to predict their long-term mental health outcomes, according to research supported by the National Institute of Mental Health (NIMH), part of the National Institutes of Health. The research, published in the American Journal of Psychiatry, is part of the NIMH-funded AURORA study, a large-scale, multisite study that followed more than 3,000 people for up to a year after exposure to a traumatic event.
Evidence from previous studies suggests that it’s common for people to show a wide range of responses after a traumatic experience, such as a natural disaster or serious accident. One person may show initial symptoms that diminish naturally over time, while another may have long-lasting symptoms that make it difficult to carry out everyday activities. These different responses do not fall neatly into existing diagnostic categories and, although there are known risk and resilience factors associated with mental health outcomes, researchers aren’t yet able to predict how a specific person will fare after experiencing a traumatic event.
Using a variety of neurobiological, behavioral, and self-report measures, the AURORA study researchers hope to develop a comprehensive picture of the factors that play a role in trauma survivors’ mental health over time. To help advance this effort, AURORA study data will be made available to the broader research community through the NIMH Data Archive.
As part of the study, Jennifer Stevens, Ph.D., of Emory University in Atlanta, led an investigation of post-trauma brain activity in an initial group of 69 AURORA participants who were seen in an emergency department following a car crash. Stevens and colleagues hypothesized that different patterns of stress-related brain activity may predict participants’ long-term mental health symptoms across a range of diagnoses.
Two weeks after the accident, the participants had their brain activity measured via functional MRI while they completed a series of standard computer-based tasks. The tasks assessed their brain activity in response to social threat cues, reward cues, and situations that required them to inhibit a response.
Over the next six months, the participants also completed digital surveys in which they self-reported symptoms of post-traumatic stress disorder (PTSD), depression, dissociation, anxiety, and impulsivity.
Analyses of the participants’ brain activity data revealed four distinct profiles: Reactive/disinhibited: High activity related to both threat and reward; little activity related to response inhibition Low-reward/high-threat: High activity related to threat; low activity related to reward High-reward: No activity related to threat; little activity related to response inhibition; high activity related to reward Inhibited: De-activation related to threat; some activity related to inhibition; low activity related to rewardThe researchers then performed the same analyses with a separate group of 77 AURORA participants who also were seen in an emergency department following exposure to a range of traumatic events not limited to car crashes. In this group, they found evidence for three of the four profiles: reactive/disinhibited, low-reward/high-threat, and inhibited. These profiles were not correlated with other demographic, health-related, trauma-related, or site-specific characteristics.
Looking at participants’ brain activity profiles in relation to their mental health outcomes, Stevens and co-authors found that participants with the reactive/disinhibited profile — those who showed high activity related to both threat and reward — reported higher levels of symptoms of both PTSD and anxiety over the six-month follow-up period compared with the other profiles.
The researchers found no association between any of the brain activity profiles and other mental health outcomes, such as symptoms of depression, dissociation, or impulsivity.
The link between high reward reactivity (as part of the reactive/disinhibited profile) and long-term symptoms was unexpected, as previous studies indicated an association between low reward reactivity and post-trauma PTSD and depression. The divergent findings could be explained by the fact that reactivity to reward and threat are rarely examined together in trauma-related studies. The researchers suggest that reward reactivity warrants greater attention in future studies as a potential risk factor for stress-related symptoms following trauma.
These findings are preliminary and additional research with larger samples will be needed to confirm and refine these brain-based profiles. However, these initial findings suggest that the profiles could provide meaningful information about a person’s vulnerability to stress after experiencing a traumatic event. Establishing reliable, predictive profiles of stress response could improve clinical care, helping providers deliver effective interventions that are tailored to trauma survivors’ individual needs and circumstances.

A commonly available pesticide has been associated with an increased risk of chronic kidney disease (CKD) in a University of Queensland study.
Researchers analysed links between pesticide exposure and the risk of kidney dysfunction in 41,847 people, using data from the USA National Health and Nutrition Examination Survey (NHANES).
School of Public Health Associate Professor, Nicholas Osborne said the study found people exposed to higher amounts of the insecticide Malathion, known as Maldison in Australia, had 25 per cent higher risk of kidney dysfunction.
“Nearly one in 10 people in high income countries show signs of CKD, which is permanent kidney damage and loss of renal function,” Dr Osborne said.
Risk factors of developing CKD include age, hypertension and diabetes.
Dr Osborne said CKD with no known cause was rising in low-to-middle income countries such as India, Sri Lanka and Mesoamerica.