Culture

The World Health Organization describes empowerment as a process in which people can take control and make informed decisions about their life and health. Empowerment is important for people with RA since most care is provided by patients themselves.

Andersson and colleagues studied levels of empowerment and associated variables in people with RA, and investigated longitudinal clinical data in those with low and high levels of empowerment. The study involved 2837 people with RA from the BARFOT (Better Anti-Rheumatic PharmacO Therapy) cohort. Everyone was assessed according to a structured protocol at inclusion and after 3, 6, 12, 24, 60, 96, and 180 months. At each follow-up disease activity, function, and pain were assessed. In 2017, a postal survey was sent with questions about disease characteristics, lifestyle habits and the Swedish Rheumatic Disease Empowerment Scale (SWE-RES-23). The 844 patients who answered the SWE-RES-23 made up the study cohort. Differences in empowerment between groups were analysed.

Regarding lifestyle habits, there were no differences between the groups in smoking habits, diet, or drinking. Moderate physical activity for at least 150 minutes per week was reported by 27% in the lowest empowerment group versus 41% in the highest empowerment group - and vigorous physical activity of at least 60 minutes per week was reported by 22% versus 37%, respectively.

In the regression analysis, several factors were associated with low empowerment:1)being a woman; 2)pain-related factors such as higher tender joint count; 3)worse patient global assessment fatigue; 4)function, and5)quality of life. Over time, the group with low empowerment reported worse pain and function at all timepoints, worse disease activity atYear2 and 8, and a worse inflammation at 15 years follow-up compared with the high empowerment group.

An important component in effective self-management may be the use of remote management technologies. Remote management of RA using patient self-assessment of disease and patient-reported outcomes has the potential to inform timely clinical decisions on disease management, reduce burden on busy rheumatology services and promote effective self-management. In a second presentation from the 2021 EULAR congress, Ndosi and colleagues report on a study to determine the agreement between remote treatment decisions based on self-assessment questionnaires assessed blindly by a health professional, and treatment decisions based on routine outpatient monitoring appointments.

Enrolled patients continued with their usual care and clinic monitoring. In addition, they completed at home, self-assessment questionnaires at monthly intervals, including: two self-reported components which are collected as part of routine clinical practice (joint stiffness and flare), visual analogue scales for pain, global health and fatigue; and function and self-efficacy scales. Remote treatment decisions were made by an independent healthcare professional, based on the self-assessment questionnaires from the patient and information collected in the study. In this analysis, the independent blinded clinician did not have the same information as the routine hospital visit clinician (blood results and joints assessment).

The remote decisions were matched with the hospital visit decisions (within 2 weeks) and the measure of agreement between the two raters was evaluated.

A total of 72 RA patients were recruited, and there were 57 matched decisions between the independent healthcare professional and the outpatient clinician. The outpatient clinician made 7 changes to biologic and 18 non-biologic therapy changes, while the remote healthcare professional made 1 change to biologic and 17 changes to a non-biologic DMARD, including bringing in for review. The self-assessment questionnaires reported 34 RA flares of which 21 had resolved. In the matched decisions, there was only one adverse event that required treatment discontinuation, identified by both the remote and the outpatient treatment.

The authors conclude that remote RA monitoring using patient self-assessment and outcome measures is feasible with fair agreement on treatment decisions. Further work is required to understand the importance of adding blood test monitoring to remote decision making.

BALTIMORE (June 14, 2021) - Researchers at the University of Maryland School of Medicine (UMSOM) analyzed data at the 13-hospital University of Maryland Medical System (UMMS) and found public health measures designed to reduce the spread of the COVID-19 virus may have fostered a substantial side benefit: Hospital admissions for chronic obstructive pulmonary disease (COPD) were reduced by 53 percent, according to a new study published in The American Journal of Medicine. This is likely due to a drop in circulating seasonal respiratory viruses such as influenza.

Hospitalizations for COPD, a group of lung diseases that make it hard to breathe and get worse over time, are commonly driven by flare-ups where symptoms are triggered by such factors as tobacco smoke, air pollution and respiratory infections. Seasonal respiratory viruses, including those that cause the common cold or influenza, trigger nearly half of those flare-ups.

In the wake of a marked drop in COPD admissions during the pandemic, the researchers theorized that COVID-19 behavior changes - a mix of stay-at-home orders, social distancing, masking mandates and strict limitations on large gatherings - not only protected against COVID-19, but they may have also reduced exposure to other respiratory infections.

Conversely, they worry that the return to normal behavior may lead to more COPD flare-ups.

"Our study shows there's a silver lining to the behavior changes beyond protecting against COVID-19," said senior author Robert M. Reed, MD, UMSOM Professor of Medicine and pulmonologist at the University of Maryland Medical Center (UMMC). "If we completely eliminate masks and distancing during cold and flu season, we'll allow all those viruses that have been effectively suppressed to come raging back. There could be a lot of illness."

Prior to the COVID-19 pandemic, COPD was the fourth-leading cause of death worldwide and a leading cause of hospital admissions in the United States. The pandemic has led to significant changes in health care delivery, including reduced admissions for COPD and other non-COVID illnesses, some of which may have stemmed from patients' fear of contracting COVID in various hospital settings, as well as a shift toward telemedicine and outpatient COPD management during the pandemic.

To understand what may have occurred to reduce COPD admissions, the researchers compared weekly hospital admissions for COPD in the pre-COVID-19 years of 2018 and 2019, with admissions after the COVID-19 public health measures were instituted. At UMMS, those measures were implemented before April 1, 2020, so the investigators chose the same five-month period in each year for their comparison, April 1 to Sept. 30.

Co-lead author Jennifer Y. So, MD, UMSOM Assistant Professor of Medicine and COPD specialist at UMMC, said electronic medical records from multiple hospitals across a range of communities in the UMMS database facilitated a granular evaluation of changes over time. "We assessed a variety of possible causes that could affect COPD admissions including the presence of multiple diseases or medical conditions and the frequency of COPD exacerbations."

The database findings were correlated with data on respiratory viral trends from the U.S. Centers for Disease Control and Prevention for the period of Jan. 1, 2018, through Oct. 1, 2020.

"We found a 53 percent drop in COPD admissions throughout UMMS during COVID-19. That is substantial, but equally significant, the drop in weekly COPD admissions was 36 percent lower than the declines seen in other serious medical conditions, including congestive heart failure, diabetes and heart attack," said Dr. So.

As more and more people are vaccinated against COVID-19 and many of the public health measures of the past year are relaxed, the researchers warn that a full return to normal may again expose COPD patients to the familiar seasonal triggers.

"Our study did not assess which public health components worked to tame seasonal respiratory viruses, but a simple thing like wearing a mask while riding on public transit or working from home when you're sick with a cold could go a long way to reduce virus exposure," said Dr. Reed.

Dr. So, who is from South Korea, said it is a cultural norm to wear masks during the winter in her native country. "The COVID-19 pandemic has helped a lot of people around the world become more aware of the role of masking and social distancing to reduce the spread of disease," she said.

"This is a compelling study that raises some important public health questions about protecting our most vulnerable patient populations after we are finished with the COVID-19 pandemic. I certainly think it warrants a fuller discussion," said UMSOM Dean E. Albert Reece, MD, PhD, MBA, University Executive Vice President for Medical Affairs and the John Z. and Akiko K. Bowers Distinguished Professor.

In many parts of the world, mosquitoes are a common summertime nuisance.

But in places on the front lines of climate change, these disease-spreading insects may one day be a year-round problem, according to new research from the University of Florida.

"In tropical regions, mosquitoes are active all year, but that isn't the case for the rest of the world. Outside of the tropics, winter temperatures cause mosquitoes to go into a kind of hibernation called diapause. We call these mosquitoes 'cold bounded' because their activity is limited by these lower temperatures," said Brett Scheffers, senior author of the study and an assistant professor in the UF/IFAS wildlife ecology and conservation department.

"However, with climate change, we expect summers to get longer and winters to become shorter and warmer. What will that mean for those cold bounded mosquitoes? How will they respond?" Scheffers said.

To help answer those questions, the study's authors conducted experiments with mosquitoes collected in and around Gainesville, a North Central Florida city on the dividing line between subtropical and temperate climates. Their study is published in the journal "Ecology."

The researchers compared how mosquitoes collected during different parts of the year responded to changes in temperature.

"We found that the mosquitoes in our study are what we call 'plastic,' meaning that, like a rubber band, the range of temperatures they can tolerate stretches and contracts at different times of year," Scheffers said.

The researchers found that in the spring, when nighttime temperatures are still cold and daytime temperatures begin to warm up, mosquitoes can tolerate a larger range of temperatures. Come summer, when daily temperatures are warm, that range contracts. In autumn, when temperatures begin to cool off, the range stretches again, Scheffers explained.

"That tells us that as climate change makes our autumns and winters warmer, mosquitoes in more temperate regions are well prepared to be active during those times," Scheffers said.

"Our results suggest that to better understand how well populations and species may be able to tolerate ongoing climate change, we need to measure species thermal responses across different times of the year," said Brunno Oliveira, the study's first author, who conducted the study while a postdoctoral researcher in Scheffers's lab.

"This information would help us to deliver a more accurate representation of the temperature range a species can tolerate," said Oliveira, now a postdoctoral research at University of California Davis.

For their experiment, the researchers collected the mosquitoes at more than 70 sites around Gainesville and the nearby UF/IFAS Ordway-Swisher Biological Station, a 9,500 acre research and conservation area located about 20 miles east of the city.

The scientists lured mosquitoes with special traps that emit carbon dioxide gas, the same gas that humans and animals exhale when we breath. To a mosquito, a strong whiff of carbon dioxide means a meal is nearby.

With these traps, the researchers caught more than 28,000 mosquitoes representing 18 species. From this collection, the scientists randomly sampled about 1,000 mosquitoes to test in the lab.

Each mosquito was placed in a vial that was then put in a water bath. Over time, the researchers changed the water temperature, increasing or decreasing the temperature inside the vials. The scientists monitored each mosquito's activity, noting when mosquitoes became inactive, a signal that either the upper or lower temperature thresholds were met.

"It was surprising to see how well these little creatures could tolerate high temperatures during the experiments, often well above the mean ambient temperatures measured by the weather stations," said Gécica Yogo, one of the study's co-authors.

Yogo helped conduct the study while she was research scholar trainee at UF as part of her master's program at AgroParisTech in France. She is now a soil carbon engineer at INRAE, the French National Institute for Agriculture, Food and Environment.

The researchers say they don't yet know what allows mosquitoes to adjust to rapid changes in temperature.

"Many people do not realize how quickly natural selection can act on short-lived animals," said Daniel Hahn, professor in the UF/IFAS entomology and nematology department and a co-author of the study. "Whether the changes we are seeing in mosquito thermal properties are due to rapid natural selection across seasons, seasonal plasticity - much like a dog changing its coat -- or a combination of both, is what we are working on now."

The researchers say that insights from this study can help communities better prepare for the impacts of climate change as they relate to mosquitoes, which spread diseases that affect humans and animals.

"The more mosquito activity there is, the greater the risk of these diseases spreading. Knowledge is power, and knowing that mosquitoes will be more active for more of the year can inform how we get ready for climate change," Scheffers said.

Peter Jiang, one of the study's co-authors and an entomologist with City of Gainesville's Mosquito Control division, said that residents play an important role in controlling mosquitoes now and in the future.

Simple actions can keep mosquito populations down, Jiang said.

"Neighbors are encouraged to empty, remove or cover any receptacle that would hold water -- particularly old bottles, tin cans, junk and tires -- repairing leaky pipes, outside faucets and screens, covering or turning small boats upside down, and, twice a week, changing water in wading pools, bird baths, pet dishes and vases holding flowers or cuttings," Jiang said.

Residents looking to learn more about how to control mosquitoes can contact their local UF/IFAS Extension office or their municipal or county mosquito control program.

In addition to informing decision-making, studies like this one bring into focus an aspect of climate change now getting more attention.

"When we talk about how climate change might affect plants and animals, we are often talking about species moving to new areas because the conditions are changing -- in other words, the arrival of something new. However, climate change will also affect species we live with right now, like highly flexible mosquitoes, and that's another aspect to consider," Scheffers said.

KINGSTON, R.I. – June 14, 2021 – The rarest frog in Rhode Island may not be as rare as scientists once thought after a study by University of Rhode Island researchers using a seldom-used methodology turned up many more of the endangered animals than they expected.

Eastern spadefoots – often called spadefoot toads, though they are actually frogs – have long been considered highly secretive and difficult to find outside of their one- or two-day annual breeding periods on rainy nights. In some years, they don’t breed at all. But after scientists reported just 50 sightings of the frogs over the previous 70 years, the Rhode Island researchers observed 42 spadefoots in 10 nights of searching last summer using the new methodology.

“We collected all the myths and misconceptions about spadefoots that have been published or told to us by herpetologists, and we decided to conduct surveys to show that the frogs aren’t secretive, that they don’t only come out when weather is suitable, and they can be detected easily using a noninvasive censusing method,” said Anne Devan-Song, a former URI graduate student who is now a doctoral student at Oregon State University.

While working as a URI research associate in collaboration with Associate Professor Nancy Karraker, Devan-Song led a team that conducted amphibian surveys in Colonial National Historical Park in Virginia from 2015 to 2017 by using a spotlight at night to detect the animals’ eyeshine in forests. A previous researcher conducted amphibian surveys at the park 15 years ago and only detected two Eastern spadefoots, but Devan-Song and her team found up to hundreds of them, even on dry nights, and a total of more than 3,000 individuals.“It completely contradicted everything we’d read about them in the scientific literature, with the exception of recent studies in Massachusetts and Connecticut,” said Devan-Song, whose research was published this month in the Journal of Herpetology. “The perception is that they’re difficult to detect in large numbers outside of rainy weather conditions, but I was stumbling all over them everywhere I went at this particular site, even in drought years when I was nowhere near a known breeding pond.”

To be sure that she could distinguish between the eyeshine of spadefoots and the eyeshine of other creatures active at night – a concern expressed by previous scientists who rejected the spotlighting method – Devan-Song confirmed her ability to accurately identify spadefoot eyeshine by capturing every frog whose eyeshine she detected.

Since the Virginia site may have been home to an uncharacteristically high number of the frogs, Devan-Song collaborated with Rhode Island Department of Environmental Management herpetologist Scott Buchanan to use her spotlighting technique at scattered sites around Rhode Island, where the frogs were believed to be located at only one site and were seldom seen there.

“Spadefoots are at the northern end of their range in Rhode Island and are incredibly rare there,” Devan-Song said. “You can’t just drive around at night and hear them, and there’s little chance of finding them by chance. And yet with just a little bit of spotlighting effort, you can find them.”For sites that were occupied, the frogs were detected on nine out of ten survey nights in Rhode Island, the same rate as they were found in Virginia, and a new breeding population was discovered at a site in Westerly. In both states, the majority of spadefoots observed were sub-adults, an age class seldom detected using traditional survey methods.

“The lack of appropriate methods has hindered the study of this species, which is considered endangered in many states, including Rhode Island,” said Devan-Song. “Without appropriate field methods, you can’t gather information about certain demographic classes and you can’t make accurate population assessments.

“By looking for them only on rainy nights or only near ponds, it has hindered the study of this species for decades,” she added. “There is a huge amount of information that can be collected, especially on these overlooked demographic categories.”

The research team has at least two additional scientific papers in the works that will shed more light on the life history of Eastern spadefoots, both based on the data collected from Rhode Island and Virginia. One describes the social structure of the species, which had been unknown outside the breeding season.

“The general idea had been that these frogs are solitary and don’t interact much except when they go to their ponds to breed,” she said. “But the reality is that they’re doing lots of interesting things in the uplands. Their social structure is much more complex than we imagined.”

DALLAS, June 14, 2021 -- Preserving good cardiovascular health during young adulthood is one of the best ways to reduce risks of premature heart attack or stroke, according to new research published today in the American Heart Association's flagship journal Circulation.

The number of premature deaths from cardiovascular disease is increasing in many countries including the U.S. While there is a wealth of information available on maintaining good heart health during and after midlife to reduce the risks of heart attack and stroke, data about cardiovascular health during young adulthood is scarce.

"Most people lose ideal cardiovascular health before they reach midlife, yet few young people have immediate health concerns and many do not usually seek medical care until approaching midlife," says the study's senior author Hyeon Chang Kim, M.D., Ph.D., a professor in the department of preventive medicine at Yonsei University College of Medicine in Seoul, South Korea. "We need strategies to help preserve or restore heart health in this population because we know poor heart health in young adults is linked to premature cardiovascular disease."

Using the Korean National Health Insurance Services, a nationwide health insurer database, Kim and colleagues analyzed information collected from more than 3.5 million adults who completed routine health exams in 2003 and 2004. A subgroup of approximately 2.9 million participants underwent a follow-up health examination between 2005 and 2008. Patients' ages ranged from 20 to 39 at the time of the first exam, and 65.5% of the study participants were male.

Participants were categorized according to ideal cardiovascular health (CVH) scores based on the American Heart Association's Life's Simple 7® metrics. Patients received "one point" towards a cardiovascular health (CVH) score for each of the following measures from Life's Simple 7: well-maintained blood pressure, low total cholesterol, acceptable blood sugar levels, an active lifestyle, healthy weight and not smoking. Of note: healthy nutrition and diet, the final measure of Life's Simple 7, was not included in this analysis because dietary information was not collected from participants in this database.

Researchers evaluated the total number of first hospitalizations or death from a heart attack, stroke or heart failure by December 31, 2019 to define outcomes. The researchers found:

Rates of premature (younger than 55) cardiovascular events were highest among patients with a CVH score of zero.

A higher CVH score by one point led to reduced risks for heart attack by 42%, heart failure by 30%, cardiovascular death by 25% and stroke by 24%.

While people who improved their CVH score over time reduced their risk of hospitalizations or death from a heart attack, stroke or heart failure, people who began with and maintained a higher CVH score ultimately had the least chance of hospitalization or death from a heart attack or stroke during the study period.

Timely and consistent monitoring of heart health among young adults is important to prevent premature onset of heart disease and reduce the risk of cardiovascular events.

The study's findings may be limited because data was routine health screening data, therefore, it may not be as robust as data collected primarily for a specific study. The study also lacks data on the participants' eating patterns, so researchers modified CVH score metrics to exclude diet. In addition, participants in this study were of Korean ancestry, so the results may not be generalizable to people from other diverse racial or ethnic groups.

The raucous calls of tree hyraxes -- small, herbivorous mammals -- reverberate through the night in the forests of West and Central Africa, but their sound differs depending on the location.

Tree hyraxes living between the Volta and Niger rivers make a barking call that is distinct from the shrieking vocalizations of hyraxes inhabiting other regions of the African forest zone.

A new study in the Zoological Journal of the Linnean Society co-authored by Yale anthropologist Eric Sargis finds that the barking hyraxes are a separate species from their shrieking neighbors. The newly described species, Dendrohyrax interfluvialis, populates the wet and dry forests that lie between the two rivers in coastal regions of southeastern Ghana, southern Togo and Benin, and southwestern Nigeria.

The researchers based their conclusion on the distinctive calls combined with anatomical and genetic differences they identified among tree hyrax populations.

"Sometimes a keen ear is as important as a sharp eye," said Sargis, curator of mammalogy and vertebrate paleontology at the Yale Peabody Museum of Natural History. "My co-authors John Oates and Simon Bearder were in Nigeria in 2009 researching galagos, a group of primates, when they noticed that the hyrax calls were different on one side of the Niger from the other. All the evidence we subsequently studied, including the distinctive vocalizations, points to a unique species in the forests between the Niger and the Volta."

Adult tree hyraxes typically weigh between 5 and 7 pounds -- about the size of a groundhog -- but they are closely related to elephants and manatees. They are usually regarded as nocturnal and tree dwelling, but their behavior has proved difficult to study, in part because, unlike most nocturnal mammals in Africa, their eyes don't shine at night, making them more difficult to spot, the researchers explained.

The researchers studied 418 recordings of tree hyrax calls made between 1968 and 2020 at 42 sites in 12 countries. Bearder, emeritus professor at Oxford Brookes University, produced sonograms from a sample of the 96 clearest and most complete recordings, including 34 from the population between the Niger and Volta and 62 from tree hyrax populations across West, Central, and East Africa, measuring their duration, frequency range, and repetition rates, among other characteristics. This analysis revealed that nearly all the calls recorded between the rivers were "rattle-barks" that differed from the shrieking calls recorded on the western side of the Volta and the eastern side of the Niger.

Sargis and co-author Neal Woodman of the U.S. Geological Survey and the Smithsonian National Museum of Natural History also studied the skulls of 69 adult tree hyrax specimens from six museum collections in Europe and North America. They found subtle but clear differences in the shape and size of skulls from specimens collected between the rivers and those gathered elsewhere. The skulls of D. interfluvialis were shorter and broader than those of their counterparts from outside the interfluvial zone, the study found.

An examination of museum skins, carcasses of hyraxes killed by hunters, and camera-trap imagery obtained in Ghana by co-author Edward Wiafe of the University of Environment and Sustainable Development revealed differences in fur color between D. interfluvialis and other populations, with the flanks and limbs of the former being brindled dark brown and lighter yellow-brown while the latter are dark brown to nearly black. Finally, genetic analyses of 21 samples of hyrax tissue from across the African rainforest found that the interfluvial populations were genetically distinct from other hyrax lineages, according to the study.

Oates, emeritus professor of anthropology at Hunter College in New York City, coordinated the study's various analyses. He has been studying the biogeography of the region inhabited by the newly described species since 1964, when he first heard the nocturnal calls of tree hyraxes on Bioko Island.

"There is increasing evidence that the Niger and Volta Rivers are significant biogeographic barriers to a range of mammals," Oates said. "Hyraxes, for instance, don't cross water easily, so it makes sense that, through millions of years of changing climate, as African forests have expanded and contracted, new species would have differentiated in isolated forest fragments known as refugia, and then have been limited in their subsequent dispersal by large rivers."

As a result, the region between the Volta and Niger now contains many unique animal species, the authors explain. The researchers warn, however, that the wildlife of the region between the Volta and Niger is under severe threat due to large and still growing human populations. Its forests have been reduced to fragments through a combination of commercial logging, tree cutting for firewood and charcoal production, plantation agriculture, and subsistence farming, they note, while most of the larger mammals are hunted for their meat. They call for increased efforts to create effective new nature reserves.

Reston, VA (Embargoed until 4:30 p.m. EDT, Saturday, June 12, 2021)--Positron emission tomography (PET) using a 68Ga-labeled fibroblast activation protein inhibitor (FAPI) can noninvasively identify and monitor pulmonary fibrosis, according to research presented at the Society of Nuclear Medicine and Molecular Imaging 2021 Annual Meeting. By binding to activated fibroblasts present in affected lungs, FAPI-PET allows for direct imaging of the disease process.

Idiopathic pulmonary fibrosis (IPF) causes substantial scarring to the lungs, making it difficult for those impacted to breathe. It is a significant cause of morbidity and mortality in the United States, with more than 40,000 deaths annually. A major challenge in diagnosis and treatment of IPF is the lack of a specific diagnostic tool that can noninvasively diagnose and assess disease activity, which is crucial for the management of pulmonary fibrosis patients.

"CT scans can provide physicians with information on anatomic features and other effects of IPF but not its current state of activity. We sought to identify and image a direct noninvasive biomarker for early detection, disease monitoring and accurate assessment of treatment response," said Carolina de Aguiar Ferreira, PhD, a research associate at the University of Wisconsin-Madison in Madison, Wisconsin.

In the study, researchers targeted the fibroblast activation protein (FAP) that is overexpressed in IPF as a potential biomarker. Two groups of mice--one group with induced pulmonary fibrosis and one control group--were scanned with the FAPI-based PET/CT radiotracer 68Ga-FAPI-46 at multiple time points. Compared to the control group, the mice with induced pulmonary fibrosis had a much higher uptake of the radiotracer, allowing researchers to successfully identify and evaluate areas of IPF.

"Further validation of 68Ga-FAPI-46 for the detection and monitoring of pulmonary fibrosis would make this molecular imaging tool the first technique for early, direct, and noninvasive detection of disease. It would also provide an opportunity for molecular imaging to reduce the frequency of lung biopsies, which carry their own inherent risks," noted Ferreira. "This development will demonstrate that functional imaging can play an invaluable role in evaluation of the disease process."

Abstract 10. "Targeting Activated Fibroblasts for Non-invasive Detection of Lung Fibrosis," Carolina Ferreira, Zachary Rosenkrans, Ksenija Bernau, Jeanine Batterton, Christopher Massey, Alan McMillan, Nathan Sandbo, Ali Pirasteh and Reinier Hernandez, University of Wisconsin - Madison, Madison, Wisconsin; and Melissa Moore, Frank Valla and Christopher Drake, Sofie Biosciences, Dulles, Virginia.

Correction 6/18/21: The original version of this article stated that polymerase theta was the first mammalian polymerase with the ability to transcribe RNA into DNA. In fact, other polymerases have been shown to perform this function, albeit with much lower efficiency than HIV reverse transcriptase. The article has been corrected and we regret the error.

PHILADELPHIA – Cells contain machinery that duplicates DNA into a new set that goes into a newly formed cell. That same class of machines, called polymerases, also build RNA messages, which are like notes copied from the central DNA repository of recipes, so they can be read more efficiently into proteins. But polymerases were thought to only work in one direction DNA into DNA or RNA. This prevents RNA messages from being rewritten back into the master recipe book of genomic DNA. Now, Thomas Jefferson University researchers provide evidence that RNA segments can be written back into DNA via a polymerase called theta, which could have wide implications affecting many fields of biology.

“This work opens the door to many other studies that will help us understand the significance of polymerases that can write RNA messages into DNA,” says Richard Pomerantz, PhD, associate professor of biochemistry and molecular biology at Thomas Jefferson University. “That polymerase theta can do this with high efficiency, raises many questions.” For example, this finding suggests that RNA messages can be used as templates for repairing or re-writing genomic DNA.

The work was published June 11th in the journal Science Advances.

Together with first author Gurushankar Chandramouly and other collaborators, Dr. Pomerantz’s team started by investigating one very unusual polymerase, called polymerase theta. Of the 14 DNA polymerases in mammalian cells, only three do the bulk of the work of duplicating the entire genome to prepare for cell division. The remaining 11 are mostly involved in detecting and making repairs when there’s a break or error in the DNA strands. Polymerase theta repairs DNA, but is very error-prone and makes many errors or mutations.

The researchers therefore noticed that some of polymerase theta’s “bad” qualities were ones it shared with another cellular machine, albeit one more common in viruses -- the reverse transcriptase. Like Pol theta, HIV reverse transcriptase acts as a DNA polymerase, but can also bind RNA and write RNA back into a DNA strand.

In a series of elegant experiments, the researchers tested polymerase theta against the reverse transcriptase from HIV, which is one of the best studied of its kind. They showed that polymerase theta was capable of converting RNA messages into DNA, which it did as well as HIV reverse transcriptase, and that it actually did a better job than when duplicating DNA to DNA. Polymerase theta was more efficient and introduced fewer errors when using an RNA template to write new DNA messages, than when duplicating DNA into DNA, suggesting that this function could be its primary purpose in the cell.

The group collaborated with Dr. Xiaojiang S. Chen’s lab at USC and used x-ray crystallography to define the structure and found that this molecule was able to change shape in order to accommodate the more bulky RNA molecule – a feat unique among polymerases.

“Our research suggests that polymerase theta’s main function is to act as a reverse transcriptase,” says Dr. Pomerantz. “In healthy cells, the purpose of this molecule may be toward RNA-mediated DNA repair. In unhealthy cells, such as cancer cells, polymerase theta is highly expressed and promotes cancer cell growth and drug resistance. It will be exciting to further understand how polymerase theta’s activity on RNA contributes to DNA repair and cancer-cell proliferation.”

BOSTON - Vitamin D deficiency strongly exaggerates the craving for and effects of opioids, potentially increasing the risk for dependence and addiction, according to a new study led by researchers at Massachusetts General Hospital (MGH). These findings, published in Science Advances, suggest that addressing the common problem of vitamin D deficiency with inexpensive supplements could play a part in combating the ongoing scourge of opioid addiction.

Earlier work by David E. Fisher, MD, PhD, director of the Mass General Cancer Center's Melanoma Program and director of MGH's Cutaneous Biology Research Center (CBRC), laid the foundation for the current study. In 2007, Fisher and his team found something unexpected: Exposure to ultraviolet (UV) rays (specifically the form called UVB), causes the skin to produce the hormone endorphin, which is chemically related to morphine, heroin and other opioids--in fact, all activate the same receptors in the brain. A subsequent study by Fisher found that UV exposure raises endorphin levels in mice, which then display behavior consistent with opioid addiction.

Endorphin is sometimes called a "feel good" hormone because it induces a sense of mild euphoria. Studies have suggested that some people develop urges to sunbathe and visit tanning salons that mirror the behaviors of opioid addicts. Fisher and his colleagues speculated that people may seek out UVB because they unknowingly crave the endorphin rush. But that suggests a major contradiction. "Why would we evolve to be behaviorally drawn towards the most common carcinogen that exists?" asked Fisher. After all, sun exposure is the primary cause of skin cancer, to say nothing of wrinkles and other skin damage.

Fisher believes that the only explanation for why humans and other animals seek out the sun is that exposure to UV radiation is necessary for production of vitamin D, which our bodies can't formulate on their own. Vitamin D promotes uptake of calcium, which is essential for building bone. As tribes of humans migrated north during prehistoric times, an evolutionary alteration might have been needed to compel them to step out of caves and into the sunshine on bitterly cold days. Otherwise, small children would have died of prolonged vitamin D deficiency (the cause of rickets) and weak bones might have shattered when people ran from predators, leaving them vulnerable.

This theory led Fisher and colleagues to hypothesize that sun seeking is driven by vitamin D deficiency, with the goal of increasing synthesis of the hormone for survival, and that vitamin D deficiency might also make the body more sensitive to the effects of opioids, potentially contributing to addiction. "Our goal in this study was to understand the relationship between vitamin D signaling in the body and UV-seeking and opioid-seeking behaviors," says lead author Lajos V. Kemény, MD, PhD, a postdoctoral research fellow in Dermatology at MGH.

In the Science Advances paper, Fisher, Kemény and a multidisciplinary team from several institutions addressed the question from dual perspectives. In one arm of the study, they compared normal laboratory mice with mice that were deficient in vitamin D (either through special breeding or by removing vitamin D from their diets). "We found that modulating vitamin D levels changes multiple addictive behaviors to both UV and opioids," says Kemény. Importantly, when the mice were conditioned with modest doses of morphine, those deficient in vitamin D continued seeking out the drug, behavior that was less common among the normal mice. When morphine was withdrawn, the mice with low vitamin D levels were far more likely to develop withdrawal symptoms.

The study also found that morphine worked more effectively as a pain reliever in mice with vitamin D deficiency--that is, the opioid had an exaggerated response in these mice, which may be concerning if it's true in humans, too, says Fisher. After all, consider a surgery patient who receives morphine for pain control after the operation. If that patient is deficient in vitamin D, the euphoric effects of morphine could be exaggerated, says Fisher, "and that person is more likely to become addicted."

The lab data suggesting that vitamin D deficiency increases addictive behavior was supported by several accompanying analyses of human health records. One showed that patients with modestly low vitamin D levels were 50 percent more likely than others with normal levels to use opioids, while patients who had severe vitamin D deficiency were 90 percent more likely. Another analysis found that patients diagnosed with opioid use disorder (OUD) were more likely than others to be deficient in vitamin D.

Back in the lab, one of the study's other critical findings could have significant implications, says Fisher. "When we corrected vitamin D levels in the deficient mice, their opioid responses reversed and returned to normal," he says. In humans, vitamin D deficiency is widespread, but is safely and easily treated with low-cost dietary supplements, notes Fisher. While more research is needed, he believes that treating vitamin D deficiency may offer a new way to help reduce the risk for OUD and bolster existing treatments for the disorder. "Our results suggests that we may have an opportunity in the public health arena to influence the opioid epidemic," says Fisher.

The term "doomscrolling" describes the act of endlessly scrolling through bad news on social media and reading every worrisome tidbit that pops up, a habit that unfortunately seems to have become common during the COVID-19 pandemic.

The biology of our brains may play a role in that. Researchers at Washington University School of Medicine in St. Louis have identified specific areas and cells in the brain that become active when an individual is faced with the choice to learn or hide from information about an unwanted aversive event the individual likely has no power to prevent.

The findings, published June 11 in Neuron, could shed light on the processes underlying psychiatric conditions such as obsessive-compulsive disorder and anxiety -- not to mention how all of us cope with the deluge of information that is a feature of modern life.

"People's brains aren't well equipped to deal with the information age," said senior author Ilya Monosov, PhD, an associate professor of neuroscience, of neurosurgery and of biomedical engineering. "People are constantly checking, checking, checking for news, and some of that checking is totally unhelpful. Our modern lifestyles could be resculpting the circuits in our brain that have evolved over millions of years to help us survive in an uncertain and ever-changing world."

In 2019, studying monkeys, Monosov laboratory members J. Kael White, PhD, then a graduate student, and senior scientist Ethan S. Bromberg-Martin, PhD, identified two brain areas involved in tracking uncertainty about positively anticipated events, such as rewards. Activity in those areas drove the monkeys' motivation to find information about good things that may happen.

But it wasn't clear whether the same circuits were involved in seeking information about negatively anticipated events. After all, most people want to know whether, for example, a bet on a horse race is likely to pay off big. Not so for bad news.

"In the clinic, when you give some patients the opportunity to get a genetic test to find out if they have, for example, Huntington's disease, some people will go ahead and get the test as soon as they can, while other people will refuse to be tested until symptoms occur," Monosov said. "Clinicians see information-seeking behavior in some people and dread behavior in others."

To find the neural circuits involved in deciding whether to seek information about unwelcome possibilities, first author Ahmad Jezzini, PhD, and Monosov taught two monkeys to recognize when something unpleasant might be headed their way. They trained the monkeys to recognize symbols that indicated they might be about to get a puff of air to the face. For example, the monkeys first were shown one symbol that told them a puff might be coming but with varying degrees of certainty. A few seconds after the first symbol was shown, a second symbol was shown that resolved the animals' uncertainty. It told the monkeys that the puff was definitely coming, or it wasn't.

The researchers measured whether the animals wanted to know what was going to happen by whether they watched for the second signal or averted their eyes or, in separate experiments, letting the monkeys choose among different symbols and their outcomes.

Much like people, the two monkeys had different attitudes toward bad news: One wanted to know; the other preferred not to. The difference in their attitudes toward bad news was striking because they were of like mind when it came to good news. When they were given the option of finding out whether they were about to receive something they liked -- such as juice -- they both consistently chose to find out.

"We found that attitudes toward seeking information about negative events can go both ways, even between animals that have the same attitude about positive rewarding events," said Jezzini, who is an instructor in neuroscience. "To us, that was a sign that the two attitudes may be guided by different neural processes."

By precisely measuring neural activity in the brain while the monkeys were faced with these choices, the researchers identified one brain area, the anterior cingulate cortex, that encodes information about attitudes toward good and bad possibilities separately. They found a second brain area, the ventrolateral prefrontal cortex, that contains individual cells whose activity reflects the monkeys' overall attitudes: yes for info on either good or bad possibilities vs. yes for intel on good possibilities only.

Understanding the neural circuits underlying uncertainty is a step toward better therapies for people with conditions such as anxiety and obsessive-compulsive disorder, which involve an inability to tolerate uncertainty.

"We started this study because we wanted to know how the brain encodes our desire to know what our future has in store for us," Monosov said. "We're living in a world our brains didn't evolve for. The constant availability of information is a new challenge for us to deal with. I think understanding the mechanisms of information seeking is quite important for society and for mental health at a population level."

Researchers at University of California San Diego School of Medicine used an artificial intelligence (AI) algorithm to sift through terabytes of gene expression data -- which genes are "on" or "off" during infection -- to look for shared patterns in patients with past pandemic viral infections, including SARS, MERS and swine flu.

Two telltale signatures emerged from the study, published June 11, 2021 in eBiomedicine. One, a set of 166 genes, reveals how the human immune system responds to viral infections. A second set of 20 signature genes predicts the severity of a patient's disease. For example, the need to hospitalize or use a mechanical ventilator. The algorithm's utility was validated using lung tissues collected at autopsies from deceased patients with COVID-19 and animal models of the infection.

"These viral pandemic-associated signatures tell us how a person's immune system responds to a viral infection and how severe it might get, and that gives us a map for this and future pandemics," said Pradipta Ghosh, MD, professor of cellular and molecular medicine at UC San Diego School of Medicine and Moores Cancer Center.

Ghosh co-led the study with Debashis Sahoo, PhD, assistant professor of pediatrics at UC San Diego School of Medicine and of computer science and engineering at Jacobs School of Engineering, and Soumita Das, PhD, associate professor of pathology at UC San Diego School of Medicine.

During a viral infection, the immune system releases small proteins called cytokines into the blood. These proteins guide immune cells to the site of infection to help get rid of the infection. Sometimes, though, the body releases too many cytokines, creating a runaway immune system that attacks its own healthy tissue. This mishap, known as a cytokine storm, is believed to be one of the reasons some virally infected patients, including some with the common flu, succumb to the infection while others do not.

But the nature, extent and source of fatal cytokine storms, who is at greatest risk and how it might best be treated have long been unclear.

"When the COVID-19 pandemic began, I wanted to use my computer science background to find something that all viral pandemics have in common -- some universal truth we could use as a guide as we try to make sense of a novel virus," Sahoo said. "This coronavirus may be new to us, but there are only so many ways our bodies can respond to an infection."

The data used to test and train the algorithm came from publicly available sources of patient gene expression data -- all the RNA transcribed from patients' genes and detected in tissue or blood samples. Each time a new set of data from patients with COVID-19 became available, the team tested it in their model. They saw the same signature gene expression patterns every time.

"In other words, this was what we call a prospective study, in which participants were enrolled into the study as they developed the disease and we used the gene signatures we found to navigate the uncharted territory of a completely new disease," Sahoo said.

By examining the source and function of those genes in the first signature gene set, the study also revealed the source of cytokine storms: the cells lining lung airways and white blood cells known as macrophages and T cells. In addition, the results illuminated the consequences of the storm: damage to those same lung airway cells and natural killer cells, a specialized immune cell that kills virus-infected cells.

"We could see and show the world that the alveolar cells in our lungs that are normally designed to allow gas exchange and oxygenation of our blood, are one of the major sources of the cytokine storm, and hence, serve as the eye of the cytokine storm," Das said. "Next, our HUMANOID Center team is modeling human lungs in the context of COVID-19 infection in order to examine both acute and post-COVID-19 effects."

The researchers think the information might also help guide treatment approaches for patients experiencing a cytokine storm by providing cellular targets and benchmarks to measure improvement.

To test their theory, the team pre-treated rodents with either a precursor version of Molnupiravir, a drug currently being tested in clinical trials for the treatment of COVID-19 patients, or SARS-CoV-2-neutralizing antibodies. After exposure to SARS-CoV-2, the lung cells of control-treated rodents showed the pandemic-associated 166- and 20-gene expression signatures. The treated rodents did not, suggesting that the treatments were effective in blunting cytokine storm.

"It is not a matter of if, but when the next pandemic will emerge," said Ghosh, who is also director of the Institute for Network Medicine and executive director of the HUMANOID Center of Research Excellence at UC San Diego School of Medicine. "We are building tools that are relevant not just for today's pandemic, but for the next one around the corner."

For centuries, scientists, aeronautic designers and adventure-seekers have sought to replicate the qualities that allow birds to fly, namely wing-structure and balance. However, without an external mechanism such as a hot air balloon or airplane, humans have remained earth-bound, unable to use their own bodies to propel themselves into the stratosphere.

While researchers have long-focused on structural factors, like wings, that define the category of bird, a recent study published Science Advances by Professor Avihu Klar at the Hebrew University of Jerusalem's Faculty of Medicine and Prof. Claudio Mello from Oregon Health and Science University found that there are specific molecular characteristics that distinguish birds from animals, and these differences allow birds to flap their wings and take to the sky.

In previous studies, researchers found that the ability of mammals and reptiles to walk is embedded within their spinal cord. In this new study, the scientists found that the ability to fly is embedded in birds' spinal cords. The team closely examined the neural networks of chicken and mice embryos and discovered that the genetic coding of the ephrin-B3 molecule in birds is fundamentally different than those of mammals and reptiles.

"The molecule ephrin-B3 is present in mammals but mutated or absent in birds. This simple but profound difference is what allows birds to flap their wings and take flight," shared Klar. Animals, such as rodents, present this molecule in its fullest form and therefor move in a stepping motion from left to right with their front and back limbs. On the other hand, mice with an ephrin-B3 mutation move with a synchronous jumping motion of both left and right sides at the same time, similar to birds.

These findings reinforced their theory that evolution--genetic changes over time--helped birds to develop a network of neurons that activates a very coordinated movement pattern, namely: the simultaneous flapping of wings.

"Our study provides a clue to the evolutionary enigma: How did the nervous system evolve to support stepping, flying and swimming," said Klar. "It paves the way for future experiments to reveal the evolution of neuronal networks that enable the different modes of movement of legs and hands, a characteristic of bipedal animals, such as birds and human."

What The Study Did: Researchers examined the associations between Medicare Advantage star ratings, which are created using data from all enrollees in a plan, and disparities in care for racial/ethnic minorities and enrollees with lower income and less education.

Authors: David J. Meyers, Ph.D., M.P.H., of the Brown University School of Public Health in Providence, Rhode Island, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamahealthforum.2021.0793)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Reston, VA (Embargoed until 6:15 p.m. EDT, Friday, June 11, 2021)--An advanced artificial intelligence technique known as deep learning can predict major adverse cardiac events more accurately than current standard imaging protocols, according to research presented at the Society of Nuclear Medicine and Molecular Imaging 2021 Annual Meeting. Utilizing data from a registry of more than 20,000 patients, researchers developed a novel deep learning network that has the potential to provide patients with an individualized prediction of their annualized risk for adverse events such as heart attack or death.

Deep learning is a subset of artificial intelligence that mimics the workings of the human brain to process data. Deep learning algorithms use multiple layers of "neurons," or non-linear processing units, to learn representations and identify latent features relevant to a specific task, making sense of multiple types of data. It can be used for tasks such as predicting cardiovascular disease and segmenting lungs, among others.

The study utilized information from the largest available multicenter SPECT dataset, the "REgistry of Fast myocardial perfusion Imaging with NExt generation SPECT" (REFINE SPECT), with 20,401 patients. All patients in the registry underwent SPECT MPI, and a deep learning network was used to score them on how likely they were to experience a major adverse cardiac event during the follow-up period. Subjects were followed for an average of 4.7 years.

The deep learning network highlighted regions of the heart that were associated with risk of major adverse cardiac events and provided a risk score in less than one second during testing. Patients with the highest deep learning scores had an annual major adverse cardiac event rate of 9.7 percent, a 10.2-fold increased risk compared to patients with the lowest scores.

"These findings show that artificial intelligence could be incorporated in standard clinical workstations to assist physicians in accurate and fast risk assessment of patients undergoing SPECT MPI scans," said Ananya Singh, MS, a research software engineer in the Slomka Lab at Cedars-Sinai Medical Center in Los Angeles, California. "This work signifies the potential advantage of incorporating artificial intelligence techniques in standard imaging protocols to assist readers with risk stratification."

Abstract 50. "Improved risk assessment of myocardial SPECT using deep learning: report from REFINE SPECT registry," Ananya Singh, Yuka Otaki, Paul Kavanagh, Serge Van Kriekinge, Wei Chih-Chun, Tejas Parekh, Joanna Liang, Damini Dey, Daniel Berman and Piotr Slomka, Department of Imaging, Cedars-Sinai Medical Center, Los Angeles, California; Robert Miller, Department of Cardiac Sciences, University of Calgary, Calgary, Alberta, Canada, and Department of Imaging, Cedars-Sinai Medical Center, Los Angeles, California; Tali Sharir, Department of Nuclear Cardiology, Assuta Medical Centers, Tel Aviv, and Ben Gurion University of the Negev, Beer Sheba, Israel; Andrew Einstein, Division of Cardiology, Department of Medicine and Department of Radiology, Columbia University, Irving Medical Center and New York-Presbyterian Hospital, New York, New York; Mathews Fish, Oregon Heart and Vascular Institute, Sacred Heart Medical Center, Springfield, Oregon; Terrence Ruddy, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Philipp Kaufmann, Department of Nuclear Medicine, Cardiac Imaging, University Hospital Zurich, Zurich, Switzerland; Albert Sinusas and Edward Miller, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine New Haven, Connecticut; Timothy Bateman, Department of Imaging, Cardiovascular Imaging Technologies LLC, Kansas City, Missouri; Sharmila Dorbala and Marcelo Di Carli, Department of Radiology, Division of Nuclear Medicine and Molecular Imaging, Brigham and Women's Hospital, Boston, Massachusetts.

What The Study Did: Editorial team composition by gender, race, ethnicity and sexual orientation was assessed at 25 leading medical and scientific journals in this survey study.

Authors: James W. Salazar, M.D., M.A.S., of the University of California San Francisco, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamainternmed.2021.2363)

Editor's Note: The article includes conflicts of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.