Culture

Arlington, Va. (March 12, 2021)--A new supplement offering guidance on severe COVID-19 management in resource-limited settings is now available on the American Journal of Tropical Medicine (AJTMH) website. Pragmatic Recommendations for the Management of Hospitalized COVID-19 Patients in Low- and Middle-Income Countries was coordinated by a COVID-LMIC Task Force headed by Alfred Papali, MD, of Atrium Health, Charlotte, NC, and Marcus Schultz, MD, PhD, of Mahidol University, Bangkok, Thailand; University of Oxford, United Kingdom; and Amsterdam University Medical Centers, The Netherlands.

"We've been working with an international group of healthcare workers from or with experience in LMICs to provide readers a series of sets of recommendations for care of critically ill hospitalized COVID-19 patients," Dr. Schultz said. "This partnership allowed us to come up with helpful and pragmatic advice, and the articles give us great insights into what might be needed to improve the outcome of critically ill COVID-19 patients in resource-limited settings. Some advice may even apply to critically ill patients not having COVID-19."

"COVID-19 has exerted an enormous impact, but most communication on the pandemic has come from high-income countries," said Philip Rosenthal, MD, FASTMH, Editor-in-Chief of the Journal. "This supplement offers a series of pragmatic recommendations from international experts on best practices for the management of COVID-19 in low- and middle-income countries. These articles should offer valuable guidance to clinicians seeking state-of-the-art management strategies while addressing the challenges of constrained healthcare settings."

The articles are as follows:

Editorial

Recommendations for the Management of COVID-19 in Low- and Middle-Income Countries

Articles

Pragmatic Recommendations for Identification and Triage of Patients with COVID-19 in Low- and Middle-Income Countries

Pragmatic Recommendations for Safety while Caring for Hospitalized Patients with COVID-19 in Low- and Middle-Income Countries

Pragmatic Recommendations for Infection Prevention and Control Practices for Healthcare Facilities in Low- and Middle-Income Countries during the COVID-19 Pandemic

Pragmatic Recommendations for the Use of Diagnostic Testing and Prognostic Models in Hospitalized Patients with Severe COVID-19 in Low- and Middle-Income Countries

Pragmatic Recommendations for Therapeutics of Hospitalized COVID-19 Patients in Low- and Middle-Income Countries

Pragmatic Recommendations for the Management of Acute Respiratory Failure and Mechanical Ventilation in Patients with COVID-19 in Low- and Middle-Income Countries

Pragmatic Recommendations for the Management of COVID-19 Patients with Shock in Low- and Middle-Income Countries

Pragmatic Recommendations for the Prevention and Treatment of Acute Kidney Injury in Patients with COVID-19 in Low- and Middle-Income Countries

Pragmatic Recommendations for the Management of Anticoagulation and Venous Thrombotic Disease for Hospitalized Patients with COVID-19 in Low- and Middle-Income Countries

Pragmatic Recommendations for Tracheostomy, Discharge, and Rehabilitation Measures in Hospitalized Patients Recovering From Severe COVID-19 in Low- and Middle-Income Countries

Reston, VA--Immuno-positron emission tomography (PET) imaging can provide early insight into a tumor's response to targeted therapy, allowing physicians to select the most effective treatment for patients who have cancer. The new research was published in the March issue of The Journal of Nuclear Medicine.

The research showed that immuno-PET successfully visualizes changes in different cancer receptors (receptor tyrosine kinases, or RTKs) within tumors during targeted therapies. This gives physicians a tool that can be used to evaluate the effectiveness of a treatment soon after its administration.

"When healthy cells turn into cancer cells, there is a disruption in the RTK signaling. This makes RTKs a valuable therapeutic and imaging target," said Patricia Pereira, Ph.D., a research associate at Memorial Sloan Kettering Cancer Center in New York, New York. "Techniques that allow for real-time monitoring of RTK dynamics, such as immuno-PET, could be very beneficial in informing treatment choice and predicting response."

Immuno-PET uses a "tracer" to follow an antibody directed to a specific tumor. This allows physicians to obtain images of events happening at the tumor site and provides information into whether the tumor responds to the treatment. The physician can then visualize how the tumor is responding.

In this study, researchers used immuno-PET and three different antibodies to visualize three RTKs (MET, EGFR, and HER2) in a kidney tumor. Their results confirmed that immuno-PET visualizes RTKs in ways that determine the level of protein within a tumor. After administering a treatment, immuno-PET can detect changes in RTK levels that indicate whether a tumor is responsive to that treatment.

"Precision medicine involves the identification of certain gene mutations and expressions, as well as other features, that contribute individual tumor signatures," noted Pereira. "Our study shows that immuno-PET is a powerful technique to document RTK changes and predict tumors' response to targeted therapies."

A new study by UC Davis MIND Institute researchers suggests that executive control differences in autism spectrum disorder (ASD) may be the result of a unique approach, rather than an impairment.

Executive control difficulties are common in individuals with autism and are associated with challenges completing tasks and managing time. The study, published in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, sought to tease out whether these difficulties represent a disruption in proactive executive control (engaged and maintained before a cognitively demanding event) or in reactive executive control (engaged as the event occurs).

Using functional magnetic resonance imaging (fMRI), the researchers took brain scans of 141 adolescents and young adults ages 12-22 (64 with autism, 77 neurotypical controls) enrolled in the Cognitive Control in Autism Study. During the scan, the participants completed a task that required them to adapt their behavior.

They were shown a green or red cue, followed by a white arrow (probe) pointing left or right. In half of the trials participants saw a green cue asking them to push a button that matched the direction of the arrow, and in the other half they saw a red cue that asked to push a button that didn't match. Trial order was randomized across the experiment.

"Our brains are seemingly hardwired to be able to respond to a probe with a matching action more easily than doing the opposite," said Andrew Gordon, a postdoctoral scholar in the Department of Psychiatry and Behavioral Sciences and the lead author on the paper.

Participants with autism show a unique approach

Analyses of the brain scans during both the cue and probe phases found that participants with autism showed significantly greater brain activity than control participants during the cue in networks associated with proactive control processes, but on the less cognitively demanding trials - the ones with the matching arrow. On the more demanding trials - when the arrow didn't match - activity was similar across groups.

"This suggests that proactive control is not in fact impaired, but that those with autism implement it in a unique - and not necessarily maximally efficient - manner, because they employ proactive control to prepare for the easier versus the harder trials," said Marjorie Solomon, a professor in the Department of Psychiatry and Behavioral Sciences and the senior author on the paper.

The researchers also found that during the arrow probe, connectivity between regions associated with reactive control processes was uniquely enhanced on the more-demanding trials in individuals with autism, but not in typically developing participants.

The results were a little surprising, said Gordon. "Previous research suggests that disruption at a neural level may be responsible for behavioral differences. What we actually show is that participants with autism are simply engaging neural control systems differently to those with neurotypical development."

The researchers noted that the results do not explain why the participants with autism engaged in a different, less efficient strategy during the task than the neurotypical controls participants.

"Our findings suggest that, as in many other areas, those with autism use a unique strategy to complete a task," said Solomon. "But it does leave open the question of why they exert more control during the easier task, and it may have to do with reductions in cognitive flexibility."

Solomon and Gordon added that future research would benefit from manipulating the order in which the stimuli are presented.

"These findings stand in contrast to a lot of prior work on this topic," noted Gordon. "Although no one study can be considered enough evidence to change how we think about executive control in autism, these findings suggest we need to be more nuanced with regard to this subject in the future."

March 12, 2021 - Financial strains like debt or unemployment are significant risk factors for becoming homeless, and even help to explain increased risk of homelessness associated with severe mental illness, reports a study in a supplement to the April issue of Medical Care. The journal is published in the Lippincott portfolio by Wolters Kluwer.

The findings "suggest that adding financial well-being as a focus of homelessness prevention efforts seems promising, both at the individual and community level," according to the new research, led by Eric Elbogen, PhD, of the US Department of Veterans Affairs (VA) National Center on Homelessness and Duke University School of Medicine. The study appears as part of a special issue on "Multimorbidity and social drivers of homelessness and health," produced in partnership between the VA National Center on Homelessness and the American Public Health Association Caucus on Homelessness.

Financial strain is a mediator of the link between homelessness and mental illness

Using data on nearly 35,000 participants in a nationally representative longitudinal survey, Dr. Elbogen and colleagues analyzed financial strain as a predictor of homelessness, on its own and in combination with mental illness. Responses to a 2001-02 survey were analyzed to identify factors associated with homelessness at a follow-up survey in 2004-05.

All types of financial strain analyzed - financial crises and debt, lower income, and unemployment - were associated with an increased risk of future homelessness. As expected, severe mental illness - psychotic, bipolar, or depressive disorder - was directly related to an increased risk of homelessness.

In addition, there was a significant "mediating effect" of financial strain, which explained 39 percent of the link between homelessness and mental illness. Homelessness risk was lowest for participants with none of the four types of financial strain, whether or not they had severe mental illness.

"Conversely, participants with all four financial strain variables had significantly higher risk of homelessness," Dr. Elbogen and coauthors write. The risk of becoming homeless increased with each additional type of financial strain, independent of mental illness.

The findings offer a "fresh perspective" on homelessness prevention efforts, the researchers write. "[I]nterventions could be proactively targeted at improving an individual's financial literacy and well-being such that they could prevent situations that may contribute to future homelessness."

The finding that financial strain accounts for part of the impact of severe mental illness "suggests that addressing mental illness without consideration of financial strain may not lead to optimal reduction in homelessness risk," Dr. Elbogen and colleagues add. The study supports efforts to help homeless individuals grow financially through employment, increased financial knowledge, and money management skills - as offered in effective interventions such as Housing First and VA homeless programs.

The special supplement to Medical Care focuses "on the intersection of homelessness, medical illnesses, and related social factors," according to an introductory guest editorial by Jack Tsai, PhD, of the VA National Center on Homelessness and University of Texas Health Science Center at Houston and colleagues. A key focus is on the rising rates of multimorbidity - having multiple medical, mental health, and substance use disorders - amid the ongoing obesity crisis in an aging population.

The supplement includes nine original papers examining special populations such as homeless youth, older adults, and veterans, along with medical and behavioral health conditions such as tuberculosis, HIV, and opioid use disorder. It also presents two editorials commenting on the history of homelessness and its association with suicide. Dr. Tsai and colleagues write: "This special issue illustrates the complex realities of homelessness but also the progress that has been made and the continued efforts and gaps in knowledge that need work."

Informing how COVID-19 response plans may incorporate digital contact tracing, a model of COVID-19 spread within a simulated French population found that if about 20% of the population adopted a contact tracing app on their smartphones, an outbreak could be reduced by about 35%. If more than 30% of the population adopted the app, the epidemic could be suppressed to manageable levels. Jesús Moreno López and colleagues note that the effectiveness of digital contact tracing would depend on a given population's level of immunity to the virus; the intervention alone would be unable to suppress a COVID-19 epidemic where transmission - and especially asymptomatic transmission - remains high. While many countries have implemented lockdowns and rigorous social distancing measures when COVID-19 activity has crescendoed, these interventions are typically short-lived, with new waves emerging after restrictions are lifted. More sustainable strategies, such as digital contact tracing, are important for keeping outbreaks under control. However, scientists have debated the efficacy of digital contact tracing, since in many countries, a large portion of the population does not have smartphones - particularly the elderly. To investigate digital contact tracing's ability to mediate the spread of COVID-19, Moreno López et al. developed a model that simulates a synthetic French population based on census data from the National Institute of Statistics and Economic Studies (INSEE). The researchers used this synthetic population to explore the impact of digital contact tracing - as well as detection of COVID-19 cases, quarantines, and isolation of household contacts - under scenarios in which the virus was more or less transmissible based on the prevalence of face mask use and hand washing. They found that when the virus was highly transmissible, household isolation alone reduced COVID-19 cases by 27%, while pairing this strategy with digital contact tracing reduced COVID-19 cases by 35% when only 20% of the population adopted the app. Simulating increased rates of app adoption also led to further reductions in cases. Moreno López et al. note that additional information would be required to adapt this approach to a specific outbreak within a particular country.

DURHAM, N.C. -- If you binged on high-calorie snacks and then spent the winter crashed on the couch in a months-long food coma, you'd likely wake up worse for wear. Unless you happen to be a fat-tailed dwarf lemur.

This squirrel-sized primate lives in the forests of Madagascar, where it spends up to seven months each year mostly motionless and chilling, using the minimum energy necessary to withstand the winter. While zonked, it lives off of fat stored in its tail.

Animals that hibernate in the wild rarely do so in zoos and sanctuaries, with their climate controls and year-round access to food. But now our closest hibernating relative has gone into true, deep hibernation in captivity for the first time at the Duke Lemur Center.

"They did not disappoint," said research scientist Marina Blanco, who led the project. "Indeed, our dwarf lemurs hibernated just like their wild kin do in western Madagascar."

The researchers say recreating some of the seasonal fluctuations of the lemurs' native habitat might be good for the well-being of a species hardwired for hibernation, and also may yield insights into metabolic disorders in humans.

"Hibernation is literally in their DNA," Blanco said.

Blanco has studied dwarf lemurs for 15 years in Madagascar, fitting them with tracking collars to locate them when they are hibernating in their tree holes or underground burrows. But what she and others observed in the wild didn't square with how the animals behaved when cared for in captivity.

Captive dwarf lemurs are fed extra during the summer so they can bulk up like they do in the wild, and then they'll hunker down and let their heart rate and temperature drop for short bouts -- a physiological condition known as torpor. But they rarely stay in this suspended state for longer than 24 hours. Which got Blanco to wondering: After years in captivity, do dwarf lemurs still have what it takes to survive seasonal swings like their wild counterparts do? And what can these animals teach us about how to safely put the human body on pause too, slowing the body's processes long enough for, say, life-saving surgery or even space travel?

To find out, Duke Lemur Center staff teamed up to build fake tree hollows out of wooden boxes and placed them in the dwarf lemurs' indoor enclosures, as a haven for them to wait out the winter. To mimic the seasonal changes the lemurs experience over the course of the year in Madagascar, the team also gradually adjusted the lights from 12 hours a day to a more "winter-like" 9.5 hours, and lowered the thermostat from 77 degrees Fahrenheit to the low 50s.

The animals were offered food if they were awake and active, and weighed every two weeks, but otherwise they were left to lie.

It worked. In the March 11 issue of the journal Scientific Reports, the researchers show for the first time that fat-tailed dwarf lemurs can hibernate quite well in captivity.

For four months, the eight lemurs in the study spent some 70% of their time in metabolic slow-motion: curled up, cool to the touch, barely moving or breathing for up to 11 days at a stretch, showing little interest in food -- akin to their wild counterparts.

Now that spring is afoot in North Carolina and the temperatures are warming, the lemurs are waking up. Their first physical exams after they emerged showed them to be 22% to 35% lighter than they were at the start but otherwise healthy. Their heart rates are back up from just eight beats per minute to about 200, and their appetites have returned.

"We've been able to replicate their wild conditions well enough to get them to replicate their natural patterns," said Erin Ehmke, who directs research at the center.

Females were the hibernation champs, out-stuporing the males and maintaining more of their winter weight. They need what's left of their fat stores for the months of pregnancy and lactation that typically follow after they wake up, Blanco said.

Study co-author Lydia Greene says the next step is to use non-invasive research techniques such as metabolite analysis and sensors in their enclosures to better understand what dwarf lemurs do to prepare their bodies and eventually bounce back from months of standby mode -- work that could lead to new treatments for heart attacks, strokes, and other life-threatening conditions in humans.

Blanco suspects the impressive energy-saving capabilities of these lemurs may also relate to another trait they possess: longevity. The oldest dwarf lemur on record, Jonas, died at the Duke Lemur Center at the age of 29. The fact that dwarf lemurs live longer than non-hibernating species their size suggests that something intrinsic to their biological machinery may protect against aging.

"But until now, if you wanted to study hibernation in these primates, you needed to go to Madagascar to find them in the act," Blanco said. "Now we can study hibernation here and do more close monitoring."

Decades of feminist gains in the workforce have been undermined by the COVID-19 pandemic, which has upended public education across the United States, a critical infrastructure of care that parents -- especially mothers -- depend on to work, according to new research from Washington University in St. Louis.

The research, published in Gender & Society, draws on new data from the Elementary School Operating Status (ESOS) database to show that the gender gap between mothers and fathers in the labor force has grown significantly since the onset of the pandemic in states where schools primarily offered remote instruction.

And if these circumstances continue, it could deliver a long-lasting blow to mothers' lifetime earnings and occupational trajectories.

At the start of the 2019-20 school year, U.S. mothers' rate of labor participation was, on average, 18 percentage points less than fathers'. By last September, the gap grew to over 23 percentage points in states where schools primarily offered remote instruction. In comparison, in states where in-person instruction was most common, the gender gap in parents' labor force participation grew by less than 1 percentage point, to 18.4%.

"Our research shows schools are a vital source of care for young children, and without full-time, in-person instruction, mothers have been sidelined from the labor force," said Caitlyn Collins, assistant professor of sociology in Arts & Sciences and co-author of the study.

"The longer these conditions remain in place, the more difficult it may be for mothers to fully recover from prolonged spells of non-employment, resulting in reduced occupational opportunities and lifetime earnings."

As the pandemic continues into the spring, states with significantly curtailed in-person learning will likely continue to see low maternal labor force participation with the potential for devastating, long-term employment effects for many women with children, Collins added.

How do school reopening plans impact working parents?

While the primary function of schools is children's education, they also provide an expansive infrastructure of care -- especially for elementary school-age children -- that parents, businesses and the economy rely upon, Collins said. COVID-19 has strained that infrastructure in unprecedented ways.

States have varied considerably in their approaches to slow the virus' spread and reopen schools, resulting in a patchwork structure of K-12 education across the United States.

Collins and co-authors -- Liana Christin Landivar at the Maryland Population Research Center; Leah Ruppanner at the University of Melbourne; and William Scarborough at the University of North Texas -- wanted to understand the nature and magnitude of school closures across states.

They used the ESOS database to measure the percentage of school districts offering in-person, remote and hybrid instruction models for elementary schools by state in September 2020. Then, they linked the data to the Current Population Survey to evaluate the association between school reopenings and parents' labor force participation rates, comparing such 2020 rates with those observed pre-pandemic in 2019.

In the paper, the authors describe results from the 26 states currently available in ESOS, and highlight three states as illustrative examples of the consequences of various reopening statuses.

Their findings illustrate the critical role schools play not only in supporting children's well-being, but also enabling parents, especially mothers, to maintain employment. Absent fathers' equal participation at home, mothers bear the brunt of responsibility for childrearing, both before and during the pandemic, according to Collins.

Maryland - where schools across the state primarily opened remotely in 2020 - experienced the largest drop in mothers' labor force participation. In 2019, Maryland mothers with elementary-age children had a 90% predicted probability of being in the labor force. When schools opened in 2020, that probability dropped to 74%, representing a 16-point drop. In comparison, Maryland fathers' predicted probability of labor force participation dropped by 5 percentage points, from 92% to 87% - a statistically insignificant change, the authors wrote.

Just 200 miles away, New York took a different approach: Nearly half of the elementary schools in the state offered hybrid programs consisting of a mix of remote and in-person education. Researchers found that mothers' labor force participation in New York declined by 7 percentage points, from 79% to 72%. Fathers' labor force participation dropped by 4 percentage points, from 96% to 92%. Neither of these drops was statistically significant.

Finally, in Texas - where more than half of school districts offered full-time, in-person education for elementary students - mothers' labor force participation dropped by 10 percentage points, from 77% to 67%, and fathers' from 96% to 93%. While this was a larger shift than observed in New York, it was still substantially smaller than the changes observed in Maryland.

Across all states, mothers' work attachment fell to a greater extent than fathers', but the gap is widest in states, like Maryland, where schooling was fully remote at the start of the school year.

Upon completion in spring 2021, the ESOS database will be made publicly available via the Open Science Framework, offering the reopening status of all elementary school districts in the country serving more than 500 students, or approximately 9,000 school districts.

'Something had to give'

One in three U.S. women who left employment since the onset of the COVID-19 pandemic cite childcare demands as a primary reason for their departure. Perhaps that's not surprising, though. Preliminary evidence suggests that gender inequality in the domestic division of labor worsened under the pandemic, Collins said.

Collins, Landivar, Ruppanner and Scarborough have been studying the impact of the pandemic on mothers' paid work since the first shutdowns in March 2020. Their early analysis found that mothers were more likely to reduce their work hours or exit the labor force altogether - even when both parents were able to telecommute. They suggest this is likely because mothers picked up a larger share of housework, childcare and homeschooling than fathers.

"Mothers have also reported greater increases in anxiety, depression and disturbed sleep compared to fathers, especially after experiencing a job loss or an increased housework or childcare load," said Ruppanner, associate professor of sociology at the University of Melbourne.

"Without more support from fathers, employers and the government, something had to give under this unsustainable pressure. What seems to be giving is mothers' employment," Collins said.

The fallout will last well beyond the pandemic
When mothers are forced to choose between their families and jobs, it impacts not only their immediate financial stability, but also their psychological well-being, economic independence and lifetime occupational attainment and earnings.

As the current research illustrates, mothers have paid the price of the childcare crisis created by the COVID-19 pandemic.

"This is an injustice with long-term consequences for mothers' job prospects and economic stability," the researchers wrote.

"These are not personal problems, but deeply political issues that require policy interventions. Well-funded and evidence-based reopening plans are necessary to allow children to return to school face-to-face, and to allow parents to engage in paid work.

"Now, more than ever, it is crucial that federal and state governments invest in expanding the public care infrastructure for children of all ages."

A study of the relationship between temperature and yields of various rice varieties, based on 50 years of weather and rice-yield data from farms in the Philippines, suggests that warming temperatures negatively affect rice yields.

Recent varieties of rice, bred for environmental stresses like heat, showed better yields than both traditional rice varieties and modern varieties of rice that were not specifically bred to withstand warmer temperatures. But the study found that warming adversely affected crop yields even for those varieties best suited to the heat. Overall, the advantage of varieties bred to withstand increased heat was too small to be statistically significant.

One of the top 10 countries globally in rice production, the Philippines is also a top-10 rice importer, as domestic supply cannot meet demand.

Roderick Rejesus, a professor and extension specialist of agricultural and resource economics at North Carolina State University and the corresponding author of a paper that describes the study, says that teasing out the effects of temperature on rice yields is important to understand whether rice-breeding efforts have helped address the environmental challenges faced by modern society, such as global warming.

The study examined rice yields and atmospheric conditions from 1966 to 2016 in Central Luzon, the major rice-growing region of the Philippines. Rejesus and study colleagues were able to utilize farm-level data of rice yields and area weather conditions in four-to-five-year increments over the 50-year period, a rare data trove that allowed the researchers to painstakingly examine the relationship between rice yield and temperature in actual farm environments.

"This rich data set allowed us to see what was actually happening at the farm level, rather than only observing behavior at higher levels of aggregation like in provinces or districts," Rejesus said.

The study examined three general rice varieties planted during those 50 years: traditional rice varieties; "early modern varieties" planted after the onset of the Green Revolution, which were bred for higher yields; and "recent modern varieties" bred for particular characteristics, like heat or pest resistance, for example.

Perhaps as expected, the study showed that, in the presence of warming, recent modern varieties had the best yields when compared with the early modern and traditional varieties, and that early modern varieties outperformed traditional varieties. Interestingly, some of the early modern varieties may have also mitigated heat challenges given their smaller "semi-dwarf" plant architecture, even though they were not bred to specifically resist heat.

"Taken all together, there are two main implications here," Rejesus said. "The first is that, at the farm level, there appears to be a 'yield gap' between how rice performs in breeding trials and on farms, with farm performance of recent varieties bred to be more tolerant to environmental stresses not being statistically different relative to the older varieties.

"The second is that rice breeding efforts may not have reached their full potential such that it may be possible to produce new varieties that will statistically perform better than older varieties in a farm setting."

Rejesus also acknowledged that the study's modest sample size may have contributed to the inability to find statistical significance in the differences in warming impacts between rice varietal yields.

"This paper has implications for other rice-breeding countries, like Vietnam, because the timing of the release of various rice varieties is somewhat similar to that of the Philippines," Rejesus said. "Plant-breeding institutions can learn from this type of analysis, too. It provides guidance as to where research funding may be allocated by policymakers to further improve the high temperature tolerance of rice varieties available to farmers."

Rejesus plans to further study other agricultural practices and innovations that affect crop yields, including an examination of cover crops, or plants grown on cropland in the off season that aim to keep soils healthy, to gauge whether they can mitigate the adverse impacts of a changing climate.

The Affordable Care Act (ACA) dramatically increased children's preventive healthcare while reducing out-of-pocket costs, according to a new Boston University School of Public Health (BUSPH) study.

Published in JAMA Network Open, the study found that checkups with out-of-pocket costs dropped from 54.2% of visits in 2010 (the year the ACA passed) to 14.5% in 2018.

"This is a great feather in the cap of the ACA, even though there is still some work to do," says study lead author Dr. Paul Shafer, assistant professor of health law, policy & management at BUSPH.

"We found that one in seven families were still charged something for their children's well visits," he says, "and costs can be a barrier to parents keeping their kids up-to-date with preventive care."

Shafer and colleagues analyzed national health insurance claims data from 2006 through 2018 for children 0 to 17 years old.

Even before the ACA became law in 2010, the researchers saw improving trends in preventive pediatric care. The proportion of children who went to the doctor at least once per year without having a preventive checkup dropped from 39.3% in 2006 to 29.0% in 2018. The researchers also found a 60% increase in the proportion of so-called "sick" visits (for anything other than a checkup) that included one or more preventive services, such as immunizations or recommended screenings. The researchers write that this may mean pediatricians are increasingly taking advantage of any opportunity they can to provide preventive care.

"As deductibles and copays continue to rise, the promise of free preventive care has become a very popular benefit of the ACA," Shafer says. "According to our results, we are continuing to get better at delivering on that promise for children."

CLEVELAND--Scientists at the Case Western Reserve University School of Medicine have determined the structure of protein "fibrils" linked to Lou Gehrig's disease and other neurodegenerative disorders--findings that provide clues to how toxic proteins clump and spread between nerve cells in the brain.

Their results may also lead to developing drugs to treat diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).

"These devastating brain disorders that affect tens of thousands of Americans?are on the rise worldwide, and there are no effective treatments to stop their progression," said Witold Surewicz, a professor in the Department of Physiology and Biophysics at the School of Medicine and the study's senior author.

The study was published March 12 in the online journal Nature Communications. Qiuye Li, a graduate student in the department, was lead author; Case Western Reserve medical student Michael Babinchak contributed.

The study was supported by the National Institutes of Health.

TDP-43 is normally a soluble protein that interacts with nucleic acids. However, in several neurodegenerative disorders, this protein forms large, harmful rope-like clumps that accumulate in brains of afflicted patients.

These abnormal structures, known as amyloid fibrils, are a signature of brain pathology in amyotrophic lateral sclerosis (ALS; also called Lou Gehrig's disease) and FTD, the most common cause of dementia in people at younger ages--in their 50s and 60s.

Similar fibrilar structures of TDP-43 are also linked to other brain disorders, including Alzheimer's disease and chronic traumatic encephalopathy, a condition caused by repeated brain injuries and often found in athletes who played football and other contact sports.

By using a technique of electron microscopy at very low temperature (cryo-electron microscopy), the authors analyzed thousands of images of fibrils formed in the test tube by the key fragment of TDP-43. They determined the complex architecture of these elongated structure at a resolution close to individual atoms. This structural insight revealed, among other findings, the nature of the template on which more copies of TDP-43 can lock.

Based on this structural model, the researchers also discussed how the fibril structure could be controlled by amino acid mutations in TDP-43 linked to hereditary forms of ALS and FTD, as well as by aging-dependent modifications of the protein.

"This is really an exciting development because it reveals a mechanism for the growth of these toxic aggregates," Li said.

"This, in turn, provides important clues as to how these aggregates may spread between the cells in affected brains."

"Detailed knowledge about fibrillar structures formed by TDP-43 may also lead to the development of drugs to treat these devastating brain disorders," Surewicz said.

A new study led by University of Maryland and UCLA researchers found that DNA from tissue samples can be used to accurately predict the age of bats in the wild. The study also showed age-related changes to the DNA of long-lived species are different from those in short-lived species, especially in regions of the genome near genes associated with cancer and immunity. This work provides new insight into causes of age-related declines.

This is the first research paper to show that animals in the wild can be accurately aged using an epigenetic clock, which predicts age based on specific changes to DNA. This work provides a new tool for biologists studying animals in the wild. In addition, the results provide insight into possible mechanisms behind the exceptional longevity of many bat species. The study appears in the March 12, 2021, issue of the journal Nature Communications.

"We hoped that these epigenetic changes would be predictive of age," said Gerald Wilkinson, a professor of biology at UMD and co-lead author of the paper. "But now we have the data to show that instead of having to follow animals over their lifetime to be sure of their age, you can just go out and take a tiny sample of an individual in the wild and be able to know its age, which allows us to ask all kinds of questions we couldn't before."

The researchers looked at DNA from 712 bats of known age, representing 26 species, to find changes in DNA methylation at sites in the genome known to be associated with aging. DNA methylation is a process that switches genes off. It occurs throughout development and is an important regulator for cells. Overall, methylation tends to decrease throughout the genome with age. Using machine learning to find patterns in the data, the researchers found that they could estimate a bat's age to within a year based on changes in methylation at 160 sites in the genome. The data also revealed that very long-lived bat species exhibit less change in methylation overall as they age than shorter-lived bats.

Wilkinson and his team then analyzed the genomes of four bat species--three long-lived and one short-lived--to identify the specific genes present in those regions of the genome where age-related differences in methylation correlated with longevity. They found specific sites on the genome where methylation was more likely to increase rather than decrease with age in the short-lived bats, but not in long-lived bats, and that those sites were located near 57 genes that mutate frequently in cancerous tumors and 195 genes involved in immunity.

"What's really interesting is that the sites where we found methylation increasing with age in the short-lived bats are near genes that have been shown to be involved in tumorigenesis--cancer--and immune response," Wilkinson said. "This suggests there may be something to look at in these regions regarding mechanisms responsible for longevity."

Wilkinson said analyzing methylation may provide insight into many age-related differences between species and lead to a better understanding of the causes for age-related declines across many species.

"Bats live a long time, and yet their hearing doesn't decay with age, the way ours does," he said. "You could use this method to see whether there are differences in methylation that are associated with hearing. There are all kinds of questions like this we can ask now."

Chest pain is misdiagnosed in women more frequently than in men, according to research presented today at ESC Acute CardioVascular Care 2021, an online scientific congress of the European Society of Cardiology (ESC).1 The study also found that women with chest pain were more likely than men to wait over 12 hours before seeking medical help.

"Our findings suggest a gender gap in the first evaluation of chest pain, with the likelihood of heart attack being underestimated in women," said study author Dr. Gemma Martinez-Nadal of the Hospital Clinic of Barcelona, Spain. "The low suspicion of heart attack occurs in both women themselves and in physicians, leading to higher risks of late diagnosis and misdiagnosis."

This study examined gender differences in the presentation, diagnosis, and management of patients admitted with chest pain to the chest pain unit of an emergency department between 2008 and 2019. Information was collected on risk factors for a heart attack including high blood pressure and obesity. The researchers recorded the physician's initial diagnosis after the first evaluation of each patient, which is based on clinical history, physical examination, and an electrocardiogram (ECG) and occurs before other examinations like blood tests.

"We had the first impression of the doctor as to whether the chest pain had a coronary cause or another origin such as anxiety or a musculoskeletal complaint," explained Dr. Martinez-Nadal.

A total of 41,828 patients with chest pain were included, of which 42% were women. The median age was 65 years in women and 59 years in men. Women were significantly more likely to present late to the hospital (defined as waiting 12 hours or longer after symptom onset): this occurred in 41% of women compared to 37% of men.

"This is worrying since chest pain is the main symptom of reduced blood flow to the heart (ischaemia) because an artery has narrowed," said Dr. Martinez-Nadal. "It can lead to a myocardial infarction which needs rapid treatment."

In the physician's initial diagnosis, acute coronary syndrome was more likely to be considered the cause of chest pain in men compared to women. Specifically, in 93% of patients, the ECG did not provide a definitive diagnosis. In those patients, the doctor noted a probable acute coronary syndrome (ACS) in 42% of cases - when analysed according to gender, probable ACS was noted in 39% of women and 44.5% of men (p

Dr. Martinez-Nadal said: "In the doctor's first impression, women were more likely than men to be suspected of a non-ischaemic problem. Risk factors like hypertension and smoking should instil a higher suspicion of possible ischaemia in patients with chest pain. But we observed that women with risk factors were still less likely than men to be classified as 'probable ischaemia'."

In women, 5% of ACS were initially misdiagnosed, whereas in men, 3% of ACS were initially misdiagnosed (p

Dr. Martinez-Nadal said: "Heart attack has traditionally been considered a male disease, and has been understudied, underdiagnosed, and undertreated in women, who may attribute symptoms to stress or anxiety. Both women and men with chest pain should seek medical help urgently."

University of Otago researchers have discovered one of the reasons why more than 50 per cent of people with type 2 diabetes die from heart disease.

And perhaps more significantly, they have found how to treat it.

Associate Professor Rajesh Katare, of the Department of Physiology, says it has been known that stem cells in the heart of diabetic patients are impaired. While stem cell therapy has proved effective in treating heart disease, it is not the case in diabetic hearts.

It has not been known why; until now.

It comes down to tiny molecules called microRNA which control gene expression.

"Based on the results of laboratory testing, we identified the number of microRNAs that are impaired in stem cells of the diabetic heart," Associate Professor Katare says.

"Among several microRNAs we identified that one particular microRNA called miR-30c - which is crucial for the stem cells' survival, growth and new blood vessel formation - is reduced in the diabetic stem cells. All these functions are required for stem cell therapy to be successful in the heart.

"Importantly, we also confirmed that this microRNA is decreased in the stem cells collected from the heart tissue of the patients undergoing heart surgery at Dunedin Hospital."

Researchers were able to then increase the level of the lacking miR-30c in the heart by a "simple injection".

"This resulted in significantly improving the survival and growth of stem cells in the diabetic heart," Associate Professor Katare says.

"This fascinating discovery has newly identified that impairment in the microRNAs is the underlying reason for the stem cells being not functional in the diabetic heart. More importantly, the results have identified a novel therapy for activation of stem cells in the heart using microRNA, without the need to inject stem cells, which is a time and cost consuming process."

Associate Professor Katare calls the finding "significant" and says it could help diabetes- sufferers - who are ten per cent of New Zealanders - lead a longer, quality life.

"Apart from identifying the reasons for poor stem cells function in a patient with diabetes, the novel therapy of using microRNA could change the treatment method for heart disease in diabetic individuals."

Researchers will now undertake more laboratory testing before moving on to humans.

"Our initial analysis revealed that there might be another four potential candidate microRNAs. Therefore, it is essential to test the function of those microRNAs as well. It may be possible that combination therapy with more than one microRNA could further increase the beneficial effects."

The impact of the COVID-19 pandemic on public health is staggering; more than one hundred million cases and two million deaths worldwide. In response, most countries and local governments have taken substantial measures -- such as travel restrictions and physical distancing -- to keep their citizens safe. Both the pandemic and related protective measures pose challenges for ongoing clinical research studies seeking to treat and prevent the world's greatest public health emergencies including COVID-19, but also Alzheimer's disease and other dementia.

In a new paper from the World-Wide FINGERS network in Alzheimer's & Dementia: Translational Research and Clinical Interventions, first author Susanne Röhr, Ph.D., clinical psychologist at the Institute of Social Medicine, Occupational Health and Public Health, University of Leipzig, Germany, and colleagues provide timely guidance on the design and management of clinical research during COVID-19 -- specifically on the conduct of lifestyle-based risk reduction studies in people at risk for cognitive decline and dementia.

The article describes the COVID-19-related experiences of three trials - each at a different stage of the study process - conducted in conjunction with the World-Wide FINGERS (WW-FINGERS), the first global network of lifestyle-based multidomain trials for dementia risk reduction and prevention, which includes over 30 countries.

J-MINT: Japan-multimodal intervention trial for prevention of dementia -- mainly in the recruitment process (~December, 2020) and intervention delivery.

U.S. POINTER: U.S. study to protect brain health through a lifestyle intervention to reduce risk -- recruitment process and intervention delivery.

German AgeWell.de study -- intervention adherence and post-intervention follow-up.

"The COVID-19 pandemic has profoundly altered the landscape for the design and conduct of clinical trials of multidomain lifestyle interventions. This is especially true in studies focused on cognition, Alzheimer's and other dementia, where the study population has some of the greatest health risks," said Röhr, who also is an Atlantic Fellow for Equity in Brain Health at the Global Brain Health Institute.

"With this collaborative publication, we bring together and discuss our experiences of the challenges we've faced, and continue to face, and how we've responded to them. By sharing our collective knowledge about the lessons learned so far, we can provide real-world, evidence-based recommendations to similar ongoing and prospective lifestyle intervention trials," Rohr added.

In response to COVID-19, the WW-FINGERS network created a shared space for its members to discuss the challenges of research during the pandemic. They gathered international teams with expertise to address, almost in real-time, the challenges that cut across the research. This allows studies at earlier stages to adjust to these potential challenges, while more advanced studies will still be able to access expertise to adapt to their specific circumstances.

"By working together, we can address and solve common problems and find effective strategies to prevent cognitive decline and Alzheimer's disease," said Mark Espeland, Ph.D., professor of Internal Medicine at Wake Forest School of Medicine and senior author on the newly published article.

"The WW-FINGERS collaborative efforts are needed more than ever in the current landscape. The network's joint knowledge and expertise is shaping lifestyle interventions both during and in the post-pandemic scenario," said Miia Kivipelto, M.D., Ph.D., professor of Clinical Geriatrics at Karolinska Institute, founder and scientific leader of the WW-FINGERS network and co-author of the article.

"Looking at the impact of COVID-19 across the WW-FINGERS network of clinical trials enables us to evaluate the effectiveness of our responses to the pandemic across different cultures, local environments, and phases of the pandemic," said Maria C. Carrillo, Ph.D., Alzheimer's Association chief science officer and a co-author of the article. "The lessons learned through WW-FINGERS might be helpful for other lifestyle intervention research as well."

"Conducting a clinical trial such as J-MINT is a huge challenge during the pandemic, but we have learned a lot about how to prevent the infection. Applying this knowledge to this and other clinical trials should be useful for improving future implementation of lifestyle-based dementia prevention measures," said Hidenori Arai, M.D., Ph.D., President, National Center for Geriatrics and Gerontology, and co-author of the newly published article.

Lifestyle intervention research may be particularly susceptible to disruption from the pandemic. Traditionally, lifestyle interventions focus on strong bonds through group and individual face-to-face sessions. Social isolation -- which can result from physical distancing -- can also challenge lifestyle interventions. Research studies focused on preventing cognitive decline often recruit individuals for whom COVID-19 poses greater risks due to their older age and greater burden of age-related noncommunicable diseases.

Each of the four WW-FINGERS studies adapted by altering designs and analysis plans -- changing recruitment plans, timelines, and modes of delivery for interventions and assessments. For example:

Due to the COVID-19 pandemic, J-MINT was forced to halt recruitment and initial evaluation of participants from late February to mid-May 2020. Enrollment activities resumed in late May 2020 with appropriate measures to defend against infection. To help ensure safety of participants and study staff, new rules and procedures for testing and intervention were implemented. This added extra time and cost. As a result, progress of the study was delayed more than half a year. Nonetheless, by December 2020, planned recruitment was completed. The potential statistical problem caused by the four-month gap on average from the initial evaluation to the intervention will be addressed through additional analysis to see if this is correlated with the magnitude of cognitive changes. If the time between the initial evaluation and the start of the intervention is longer than 6 months, the team will conduct a reevaluation and may conduct a sub-analysis that excludes the study participants who were reevaluated.

During a study-wide pause from March to July 2020, U.S. POINTER researchers maintained contact with study participants through phone calls that encouraged participants to continue to meet their study intervention goals. Intervention delivery shifted from in-person meetings to video conferencing. Some data were accumulated continuously during the pause, but others were postponed and rescheduled. Following the pause, intervention meetings were held remotely and full adherence monitoring was resumed.

In Germany, infection control measures, including the first nationwide lockdown, largely coincided with AgeWell.de's intervention period. As the quarantine measures put restrictions on lifestyles, concerns specifically arose regarding social and physical activity and mental wellbeing. In addition, face-to-face post-intervention assessments were at risk; and changing the assessment mode would violate the data integrity. Therefore, a safety and hygiene protocol was developed, including an option to be interviewed at the study site instead of at home. To better understand the pandemic impact, the researchers mailed a survey to participants during the first lockdown to measure changes to everyday life, social and mental health and resilience. The survey will be repeated to gain a longitudinal perspective of the pandemic impact.

Firefly beetles rank among the world's most charismatic creatures, with luminous courtship displays that have now turned them into a popular attraction for wildlife tourists. In the first comprehensive review of firefly tourism, published in the journal Conservation Science and Practice, an international team of biologists led by a Tufts University researcher, reveal that an estimated 1 million people now travel each year to witness bioluminescent performances starring some two dozen firefly species around the world.

But the authors also point out that while this unique, insect-based tourism can bring economic, social, and psychological benefits to local communities and tourists alike, it also threatens to extinguish some local firefly populations unless adequate protections are put in place.

"With this review of the current state of firefly tourism and the declining health of their habitats, we are putting out a call to action to engage local communities and governments, as well as the tourists themselves, to act as guardians of the fireflies," said lead author Sara Lewis, professor of biology at Tufts University and co-chair of the International Union for the Conservation of Nature's (IUCN) Firefly Specialist Group, which conducted the review. The IUCN firefly group works to identify key threats and conservation issues facing fireflies in different geographic regions, and advocates for the most threatened species at national and global levels. Lewis' earlier work on fireflies with the IUCN has drawn considerable attention and fascination among the public and other researchers, with media coverage including CNN and The Washington Post.

In recent years, the number of tourists has skyrocketed at several sites in Mexico, India, Taiwan, Malaysia, Thailand, and the United States. "In Mexico, the rapid growth of firefly tourism over the past decade is thrilling but also alarming," said Tania López-Palafox, graduate student at Universidad Nacional Autónoma de México and co-author of the review. "The COVID pandemic gave them a momentary respite, but we have witnessed the harm that too much tourism can do."

Aimed at site managers, tour guides, and tourists, the report highlights the need to recognize ecological requirements across all firefly life stages. To promote the breeding success of firefly adults, sites should minimize light pollution: bright lights from buildings, vehicles, flashlights, and even cell phones - all of which can disrupt firefly courtship rituals.

Protection of nearby habitats also plays an essential role. Fireflies spend most of their life cycle in a juvenile, larval stage. These juveniles require several months or even years to develop into their adult form and, depending on the species, spend this time living below ground, in leaf litter or sometimes underwater. The authors describe former firefly sites along mangrove rivers where commercial development and excessive motorboat traffic have degraded riverbank habitat that had been essential for supporting firefly larvae.

At some sites, the reproductive cycle of firefly populations is threatened by tourists inadvertently trampling female fireflies and degrading larval habitats. Females in many species can't fly, and so are particularly susceptible to tourist foot traffic. Learn more about the mating rituals of fireflies studied by the Tufts research team in this video.

The report noted the popularity of displays created by several kinds of synchronous fireflies found in Southeast Asia and North America, where hundreds or thousands of firefly males captivate females - and tourists, too - by flashing their lights together in unison. According to co-author Anchana Thancharoen, lecturer at Kasetsart University in Bangkok, "With such mesmerizing lights, the firefly display trees make tourists fall in love at first sight. Our aim with this call to action is to channel that love into support for conservation efforts."