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Misinformation about COVID-19 is spreading from the United States into Canada, undermining efforts to mitigate the pandemic. A study led by McGill University shows that Canadians who use social media are more likely to consume this misinformation, embrace false beliefs about COVID-19, and subsequently spread them.

Many Canadians believe conspiracy theories, poorly-sourced medical advice, and information trivializing the virus--even though news outlets and political leaders in the country have generally focused on providing reliable scientific information. How then, is misinformation spreading so rapidly?

"A lot of Canadians are struggling to understand COVID-19 denialism and anti-vaccination attitudes among their loved ones," says lead author Aengus Bridgman, a PhD Candidate in Political Science at McGill University under the supervision of Dietlind Stolle. According to the study, published in Frontiers in Political Science, these attitudes are partially the result of massive Canadian consumption of information from the United States.

The researchers analyzed the behaviours of the 200,000 most active Canadian Twitter users and conducted surveys on news consumption habits and COVID-19 beliefs of Canadians. They found that those who use social media are relatively more exposed to US-based information than domestic sources of information, and that exposure to US news outlets was associated with misperceptions about COVID-19.

They also found that most of the misinformation circulating on Twitter shared by Canadians was retweeted from US sources. Canadians who followed more American users were more likely to post misinformation.

Canada is not immune to the American infodemic

While there has been a Canadian cross-partisan consensus on battling COVID-19, the political climate in the United States is very different. South of the border there is intense polarization over the severity of the pandemic, with misinformation being reinforced by American media and political figures alike.

Information circulating in the United States also deeply impacts Canadians, for better or worse. This is especially true in social media spaces, where Canadians are among the heaviest users - one out of two are on Instagram, five out of six are on Facebook, and two out of five are on Twitter. Moreover, Canadians pay special attention to American media. "On average, they follow three times as many Americans as they do Canadians on Twitter, and retweet them eight times more often," says co-author Taylor Owen, an Associate Professor at the Max Bell School of Public Policy at McGill University.

According to the researchers, this influence produces a troubling vulnerability for Canada during the pandemic. "It's hard for Canadian journalists, scientists and public health experts to be heard by the average Canadian, given all the noise generated by American sources," says Bridgman. "Countries with journalists and political leaders that don't indulge conspiracy theories or profess anti-science views are simply not immune to dangerous infodemics."

Finding a cure

Although many Canadians choose to consume news from the US, social media platforms likely play a key role in deepening this interest, say the researchers.

Not only do their algorithms saturate information streams with American news, they also propagate false news much faster than factual news. By privileging content that draws emotional responses from users, the algorithms help spread misinformation like wildfire.

Governments wishing to limit the spread of infodemics should consider the ways that social media platforms push out-of-country information to the top of news feeds. "This infodemic has the capacity to change important attitudes and behaviours that influence transmission patterns of COVID-19. Ultimately, it can change the scale and lethality of a pandemic," says Owen.

CHAMPAIGN, Ill. -- Exposure to phthalates, a class of chemicals widely used in packaging and consumer products, is known to interfere with normal hormone function and development in human and animal studies. Now researchers have found evidence linking pregnant women's exposure to phthalates to altered cognitive outcomes in their infants.

Most of the findings involved slower information processing among infants with higher phthalate exposure levels, with males more likely to be affected depending on the chemical involved and the order of information presented to the infants.

Reported in the journal Neurotoxicology, the study is part of the Illinois Kids Development Study, which tracks the effects of hormone-disrupting chemicals on children's physical and behavioral development from birth to middle childhood. Now in its seventh year, IKIDS has enrolled hundreds of participants and is tracking chemical exposures in pregnant women and developmental outcomes in their children. Susan Schantz, a neurotoxicologist and professor emerita of comparative biosciences at the University of Illinois Urbana-Champaign, is the principal investigator of the study. She is a faculty member in the Beckman Institute for Advanced Science and Technology, which houses the IKIDS program at Illinois.

"IKIDS is part of a larger initiative funded by the National Institutes of Health, the Environmental Influences on Child Health Outcomes program. It is tracking the impact of prenatal chemical exposures and maternal psychosocial stress on children's growth and development over time," Schantz said. "We measure numerous birth outcomes, including birth weight and gestational age. We also assess infants' cognition by studying their looking behavior. This allows us to get measures of working memory, attention and information-processing speed."

The researchers analyzed metabolites of three commonly occurring phthalates in urine samples regularly collected from the pregnant women in the study. The chemical exposure data were used in combination with assessments of the women's infants when the children were 7.5 months old.

The researchers used a well-established method that gives insight into the reasoning of children too young to express themselves verbally: Infants typically look longer at unfamiliar or unexpected images or events.

The team used an infrared eye-tracker to follow each infant's gaze during several laboratory trials. With the infant sitting on a caregiver's lap, researchers first familiarized the child with two identical images of a face. After the infant learned to recognize the face, the researchers showed that same face paired with an unfamiliar one.

"In repeated trials, half of the 244 infants tested saw one set of faces as familiar, and half learned to recognize a different set of faces as familiar," Schantz said. "By analyzing the time spent looking at the faces, we could determine both the speed with which the infants processed new information and assess their ability to pay attention."

The assessment linked pregnant women's exposure to most of the phthalates that were assessed with slower information processing in their infants, but the outcome depended on the specific chemical, the sex of the infant and which set of faces the infant viewed as familiar. Male infants, in particular, tended to process information more slowly if their mothers had been exposed to higher concentrations of phthalates known to interfere with androgenic hormones.

The specific characteristics of faces presented to the infants in the familiarization trials also appeared to play a role in the outcome, the researchers reported. Phthalate-exposed children who were first familiarized with faces from Set 2 were more likely to experience slower processing speed than those familiarized with faces from Set 1. The finding is perplexing, Schantz said, but is likely related to differences in the infants' preferences for the faces in the two sets. It also may be an indication that familiarization with the Set 2 faces is a more sensitive detector of changes in processing speed related to phthalate exposure.

"Most previous studies of the relationship between prenatal exposure to phthalates and cognition have focused on early and middle childhood," Schantz said. "This new work suggests that some of these associations can be detected much earlier in a child's life."

Bethesda, MD (April 6, 2021) -- Obesity is a global pandemic, affecting about 40% of adults in the United States. There is an enormous unmet need for an effective weight-loss solution. After a detailed review of available literature, the American Gastroenterological Association (AGA) has released new clinical guidelines recommending the use of intragastric balloons (IGB) for patients with obesity who have not been able to lose weight with traditional weight-loss strategies. This treatment is most successful with accompanying therapy, such as lifestyle modifications and pharmacological agents, and can be used in a sequential manner or along with bariatric surgery. These guidelines are published in Gastroenterology, AGA's official journal.

"Endoscopic bariatric therapies have evolved as an attractive tool for weight loss, however, less than 5% of patients with obesity seeking a weight loss therapy are aware of endoscopic weight loss options," said lead author Thiruvengadam Muniraj, MD, MRCP, from Yale University School of Medicine, New Haven, Connecticut. "Our hope is that this new guideline can lead to shared decision making between patients and providers to determine if intragastric balloons are the best weight loss option for that individual patient."

With the exception of acknowledgement that fluid-filled balloons may be associated with higher efficacy but lower tolerability than air-filled balloons, the guideline makes no recommendations on specific devices.

Key guideline recommendations:

1. Patients with obesity seeking a weight loss intervention should consider using intragastric balloon therapy to augment the effect of moderate to high intensity lifestyle modifications.
2. To minimize gastrointestinal bleeding risk, treat patients undergoing IGB therapy with proton pump inhibitors (PPIs).
3. To avoid nausea, sedate patients for the IGB placement with anesthetics associated with low incidence of nausea, and continue anti-nausea medication for two weeks.
4. While screening for nutritional deficiencies isn't needed, providing 1-2 multivitamins after IGB placement is suggested.
5. To keep weight off after IGB removal, AGA recommends dietary interventions, pharmacotherapy, repeat IGB or bariatric surgery. The choice of this maintenance strategy should be determined based on a shared decision-making approach.

"Shared decision making is a critical component of obesity therapy - for everything from selecting the right IGB device to what concomitant lifestyle modifications, pharmacotherapy or sequential procedures a patient should pursue. This shared decision making should consider the patient's values and preferences, balance benefits and harms within the patient's clinical and behavioral context, and consider cost and availability," added Dr. Muniraj.

Researchers have uncovered pathways involved in the body's response to glucocorticoid treatments and identified a novel biomarker that could be used to monitor how these drugs work in patients, according to a clinical study published today in eLife.

A more reliable indicator of an individual's response to glucocorticoid drugs could be used to develop a clinically applicable test that could help tailor treatments and potentially minimise side-effects.

Glucocorticoids, such as cortisol, are a type of hormone with key roles in the body's response to stress. Glucocorticoid drugs are one of the most commonly prescribed treatments for a range of conditions, including for patients whose adrenal glands are unable to produce enough cortisol. The effects of glucocorticoids are complex, meaning the level of cortisol in the blood does not reliably reflect what is happening in the tissues. This makes it hard for medical professionals to know how to tailor treatments.

"Side effects of glucocorticoid treatments are common in patients, indicating that current methods to monitor their action, which typically focus on clinical response or disease activity, are inadequate," explains first author Dimitrios Chantzichristos, Head Physician at the Section for Endocrinology-Diabetes-Metabolism, Sahlgrenska University Hospital, Sweden. "We wanted to find some kind of biomarker that could be measured to monitor the action of glucocorticoids in individuals, with the hopes this will help clinicians understand how best to treat patients."

The team studied patients with Addison's disease who lack the ability to produce their own cortisol. This allowed them to compare the activity in the tissues of the same patient both when their cortisol levels were low and when they were being restored by glucocorticoid treatments, helping account for variations between individuals.

Rather than focusing only on the metabolic products associated with glucocorticoid exposure, they also looked at gene expression and microRNAs in the patients using new computational approaches developed in collaboration with Dr Adam Stevens at the University of Manchester, UK. MicroRNAs are short strands of ribonucleic acid (RNA) that can regulate the expression of genes by interfering with protein production. The team analysed these different factors in blood cells and body fat, an important metabolic tissue, as the patients' cortisol levels were changed, revealing close relationships between different elements involved in glucocorticoid action.

Among the elements they identified, a microRNA called miR-122-5p closely correlated with genes and metabolites that are regulated by the glucocorticoid treatments. To test this correlation, the team looked at miR-122-5p levels in blood from patients exposed to different levels of glucocorticoids from three independent studies and found the same pattern, supporting the idea that this microRNA could be a useful biomarker of glucocorticoid action.

"This potential biomarker can now be investigated in larger groups of patients with the aim to develop a clinically applicable test," concludes senior author Gudmundur Johannsson, Professor at the Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Sweden. "Our work has also increased our understanding of the action of glucocorticoids, which may help uncover their role in many common diseases such as diabetes, obesity and cardiovascular diseases."

Nursing mothers who receive a COVID-19 vaccine may pass protective antibodies to their babies through breast milk for at least 80 days following vaccination, suggests new research from Washington University School of Medicine in St. Louis.

"Our study showed a huge boost in antibodies against the COVID-19 virus in breast milk starting two weeks after the first shot, and this response was sustained for the course of our study, which was almost three months long," said first author Jeannie Kelly, MD, assistant professor of obstetrics and gynecology. "The antibodies levels were still high at the end of our study, so the protection likely extends even longer."

Based on the small study, involving five mothers who provided frozen breast milk samples after receiving the two-dose Pfizer-BioNTech coronavirus vaccine, the research provides some of the first peer-reviewed evidence that breastfeeding confers a long-lasting immune response in the nursing infants and toddlers of vaccinated mothers.

"There is so much vaccine misinformation out there right now - really scary, misleading posts on social media that are designed to scare moms - so we felt like we needed to look at the science," Kelly said. "We know that these types of antibodies coat babies mouths and throats and protect against disease when a baby is drinking breast milk. So, getting vaccinated while breastfeeding not only protects mom, but also could protect the baby, too, and for months."

Published March 30 in the American Journal of Obstetrics and Gynecology, the study tracked levels of COVID-19 antibodies in breast milk from a baseline before the mothers' first vaccinations and on a weekly basis for 80 days after those initial vaccinations.

While other recent research has shown that COVID-19 vaccines generate antibodies that are passed to nursing infants through breast milk, this is thought to be the first study to track specific levels of these antibodies in breast milk over an extended time period.

The babies of women included in the study ranged in age from one month to 24 months old. To gauge immune response in the breast milk, researchers monitored levels of the immunoglobulins IgA and IgG, which are antibodies deployed by the immune system to fight infections in babies.

Findings confirm that breast milk contains elevated levels of the IgA and IgG antibodies immediately following the first dose of vaccination, with both antibodies reaching immune-significant levels within 14 to 20 days of first vaccination in all participants.

"Our study is limited by a small number of participants, but the findings provide encouraging news about the potential immune benefit to breast-feeding infants after vaccination," said study senior author Misty Good, MD, an assistant professor of pediatrics, also at Washington University. "Our paper is the first that has shown COVID-19 antibodies persist in breast milk for months following the mother's vaccination."

The Washington University findings are similar to prior studies on maternal vaccination, which have shown high levels of antibodies in breast milk for up to six months following vaccination for influenza and whooping cough.

While further studies of maternal COVID-19 vaccination are needed to characterize the length of antibody production in breast milk and the effect on infant infection rates, recent research continues to confirm that the COVID-19 vaccine offers real benefits for protecting both mother and child.

"We do know that COVID-19 infection is more severe during pregnancy and the main benefit of vaccination is to provide protection for moms before they become really sick, which can also be dangerous to their fetus," Kelly said. "There have now been almost 70,000 pregnant people vaccinated against COVID 19 with no evidence of harm."

"We're now seeing a cascade of new data that indicate maternal vaccines are also going to help protect babies -- both through transfer of antibodies through the placenta during pregnancy and through the breast milk during lactation," Kelly said. "This is information we didn't have a few months ago and it's really helping us better counsel our patients who are considering getting the vaccine. I'm telling my pregnant and breastfeeding moms that I strongly recommend that they get vaccinated as soon as possible."

OAK BROOK, Ill. - Body composition information derived from routine chest CTs can provide important information on the overall health of people with chronic obstructive pulmonary disease (COPD), including their risk of all-cause mortality, according to a study published in Radiology.

COPD is a group of chronic, progressive lung diseases like emphysema and chronic bronchitis that affect about 30 million people in the United States alone. It is frequently associated with obesity and sarcopenia, a loss of muscle mass and strength. Obesity is associated with lower mortality in patients with COPD. The longer survival rates of obese patients compared to leaner counterparts, a phenomenon known as the "obesity paradox," has been suggested in several chronic illnesses.

Chest CT is often used to characterize COPD, screen for lung cancer, or plan for surgical options. Beyond lung assessment, these exams offer an opportunity to assess obesity and sarcopenia through soft-tissue biomarkers.

"Chest CT scans have long focused on the lungs or heart," said study coauthor and Radiology editor David A. Bluemke, M.D., Ph.D., from the University of Wisconsin School of Medicine and Public Health in Madison, Wisconsin. "Few prior investigators have evaluated muscle quality, bone density, or degeneration of the spine as an index of overall health. These are readily available and quantifiable in these CT examinations."

For the new study, Dr. Bluemke, along with Farhad Pishgar, M.D., M.P.H., and Shadpour Demehri, M.D., from Johns Hopkins School of Medicine, and colleagues used chest CT exams to study the associations between imaging-derived soft tissue markers and all-cause mortality in COPD.

The study group was made up of 2,994 participants drawn from the Multi-Ethnic Study of Atherosclerosis (MESA), a large trial investigating the roles of imaging-derived soft-tissue and bone markers for predicting outcomes relevant to cardiopulmonary diseases. Of the 265 patients in the study group with COPD, 49 (18%) died over the follow-up period.

A greater amount of intermuscular fat was associated with higher mortality rates. Existing research has linked higher levels of intermuscular fat with diabetes and insulin resistance.

Higher subcutaneous adipose tissue, in contrast, was linked to lower risks of all-cause mortality.

The authors convincingly showed fat in the muscle was much more predictive of bad outcomes than a simple distribution of subcutaneous fat.

The findings point to a role for body composition assessment in people with COPD who undergo chest CT. Such assessments are readily obtainable in clinical practice.

In theory, CT-derived body composition assessments would provide an opportunity for earlier interventions in patients who face a higher risk of adverse health events.

Body composition assessments taken from chest CT also present an opportunity for artificial intelligence-derived algorithms that could quickly and automatically add risk assessment to the imaging report.

"I expect that more studies in the future will begin looking at all information on the CT, rather than just one organ at a time," Dr. Bluemke said. "Clinicians will need thresholds when to intervene when fat or bone abnormalities become severe."

The study was just the latest to tap into imaging data from the MESA trial, a collaboration involving more than 6,000 men and women from six communities across the United States.

By 2050 global warming could reduce crop yields by one-third. UC Riverside researchers have identified a gene that could put the genie back in the bottle.

Warmer temperatures signal to plants that summer is coming. Anticipating less water, they flower early then lack the energy to produce more seeds, so crop yields are lower. This is problematic as the world's population is expected to balloon to 10 billion, with much less food to eat.

"We need plants that can endure warmer temperatures, have a longer time to flower and a longer growth period," said UCR botany and plant sciences professor Meng Chen. "But, to be able to modify plants' temperature responses, you first have to understand how they work. So, that's why identifying this gene that enables heat response is so important."

The work that Chen and his colleagues did to uncover the heat-sensing gene was published this week in the journal Nature Communications. It is the second gene they've found involved in temperature sensing.

They located the first gene, called HEMERA, two years ago. Then they did an experiment to see if they could identify other genes involved in controlling the temperature-sensing process.

Ordinarily, plants react to shifts of even a few degrees in weather. For this experiment, the team began with a mutant Arabidopsis plant completely insensitive to temperature, and they modified it to once again become reactive.

Examining the genes of this twice-mutated plant revealed the new gene, RCB, whose products work closely with HEMERA to stabilize the heat-sensing function. "If you knock out either gene, your plant is no longer sensitive to temperature," Chen said.

Both HEMERA and RCB are required to regulate the abundance of a group of master gene regulators that serve multiple functions, reacting to temperature as well as light, and turning plants green. These proteins are distributed to two different parts of plant cells, the nucleus as well as organelles called chloroplasts.

Going forward, Chen says his laboratory will focus on understanding how these two parts of the cell communicate and work together to achieve growth, greening, flowering, and other functions.

"When you change light or temperature, genes in both the nucleus and chloroplasts change their expression. We think HEMERA and RCB are involved coordinating gene expression between these two cell compartments," Chen said.

Ultimately, the goal is to be able to modify temperature response to ensure the future of our food supply.

"We were excited to find this second gene," Chen said. "It's a new piece of the puzzle. Once we understand how it all works, we can modify it, and help crops cope better with climate change."

DALLAS, April 6, 2021 -- A tsunami of chronic health conditions as a result of the SARS-CoV-2 pandemic, especially cardiometabolic disease, may produce an enormous wave of death and disability that demands immediate, comprehensive strategies. In addition, COVID-19 has disrupted cardiovascular science and medicine, yet it presents opportunities to transform and create novel approaches that can yield new successes. These are the opinions of two esteemed leaders in cardiovascular disease care, research and strategy, detailed in two new Frame of Reference articles published today in the American Heart Association's flagship journal Circulation.

While COVID-19 has severely impacted everyone's daily lives, its societal and economic impact will be present for generations. It has prompted urgent responses in many sectors that could be models for rapidly developing real-world solutions that can improve efforts focused on prevention of chronic health conditions. Dramatic transformation in health care research is needed to align with the disruption of cardiovascular care and heart health caused by the COVID-19 pandemic.

The first article, "Avoiding the Coming Tsunami of Common, Chronic Disease: What the Lessons of the COVID-19 Pandemic Can Teach Us," is authored by Robert M. Califf, M.D. He is the head of clinical policy and strategy at Verily Life Sciences and Google Health, a former commissioner of the U.S. Food and Drug Administration, former vice chancellor for health data science at Duke University School of Medicine and the founding director of the Duke Clinical Research Institute.

In his article, Califf urges swift and comprehensive action to avoid the dramatic rise in chronic health conditions, particularly cardiometabolic disease, that are to be expected as a result of COVID-19. Three of the top 10 leading causes of death in the U.S., cardiovascular disease, stroke and type 2 diabetes, are linked to cardiometabolic disease.

He calls for critical shifts in the U.S. health care system to include universal health care, public health and research strategies that incorporate "big data," and improved health data sharing that can inform more effective and efficient prevention and treatment protocols and programs across society."

Califf also notes the impacts of structural racism and that social determinants of health must be incorporated at all levels of research, clinical care and within communities and society at large for equitable, systemic improvement in health outcomes to be realized. He advocates for universal access to broadband internet that could increase access to medical information, digital support programs and telehealth appointments with health care professionals.

He recommends more real time, in-depth tracking of chronic health conditions similar to the rapid data dashboards that were implemented to track COVID-19 cases, hospitalizations and deaths. With better information accessible more quickly, strategies to prevent and treat chronic health conditions can be measured and adapted accordingly.

Califf also proposes a new effort called "Operation Warp Evidence," modeled after the rapid COVID vaccine effort "Operation Warp Speed," to be a speedy, prioritized clinical trial infrastructure that assesses the risks and benefits of new therapies compared to existing therapies for chronic health conditions. This would allow the vast pool of clinical trials to be more focused on immediate interventions that can improve prevention, care and outcomes.

A number of Califf's comments align with the American Heart Association's November 2020 Presidential Advisory, "Call to Action: Structural Racism is a Fundamental Driver of Health Disparities," in which the Association outlined an aggressive and meaningful plan to address structural inequity to eliminate disparities, remove barriers and increase diversity, equity, access and inclusion for all. They also echo the Association's findings in the recent Heart Disease and Stroke Statistics - 2021, showing that COVID-19 will likely influence cardiovascular health and mortality rates for years to come.

The second article, titled "Incremental Change versus Disruptive Transformation: COVID-19 and the Cardiovascular Community," is from Nanette K. Wenger, M.D., FAHA, professor of medicine in the division of cardiology at Emory University School of Medicine, consultant to the Emory Heart and Vascular Center, founding consultant to the Emory Women's Heart Center and director of the Cardiac Clinics and Ambulatory Electrocardiographic Laboratory at Grady Memorial Hospital in Atlanta.

Wenger has been at the forefront of advancing patient care for the last 60-plus years, and she was among the first physicians to focus on coronary heart disease in women and to evaluate the different cardiovascular risk factors, symptoms and conditions for women compared to men. She was one of the first women to graduate from Harvard Medical School and has received numerous accolades throughout her distinguished career for her pioneering work on cardiovascular disease in women. Notably, she was an author of the Association's 2007 Guidelines for Cardiovascular Disease in Women, and she has received multiple awards from the Association including the Gold Heart Award, the Lifetime Achievement Award and, most recently, the 2020 Eugene Braunwald Academic Mentorship Award.

Wenger's article documents her perspective that the U.S. has been experiencing three simultaneous pandemics: COVID-19, economic disruption and social injustice. The COVID-19 pandemic magnified societal and health care disparities; millions of people lost jobs; numerous industries and small businesses have been financially decimated; and every aspect of scientific research and medicine has been altered - education, research and clinical care. Yet, she acknowledges there were numerous successes and critical shifts, such as the quick adoption of telemedicine, that can lead to broad transformation in health care delivery and potentially improve access to care for more patients.

Disparities were revealed to include patient hesitancy to receive care. Many improvements achieved over the past five decades in acute coronary and stroke care were compromised because patients self-quarantined to avoid the emergency room and exposure to COVID-19.

While COVID-19 drove research urgency to understand the disease, its course, treatments and vaccines, it opened the door for successful new public-private partnerships that realized rapid results. Wenger asks, "Could these be a model for future advancements?"

Academic education moved to virtual settings, many labs were closed and some programs fast-tracked students to join the pool of professionals providing emergency patient care. Career opportunities for medical students and professionals shifted in unexpected ways, and women scientists have been disproportionately affected by quarantines because of historic childcare responsibilities. "What will the long-term effects be on science and discovery?" Wenger noted.

In scientific publishing, COVID-19 research was accelerated through the peer-review process to meet the pressures and yielded an effective model for greater efficiencies that should be continued. Health registries that were implemented quickly to track COVID-19 patients could be expanded to include cardiovascular disease measures, treatment and outcomes, particularly since there are still so many unknowns about long-haul COVID and lasting cardiovascular effects.

The recognition of social injustice and its correlation to poorer health outcomes were unmasked by the disproportionate COVID-19 deaths in African American, Hispanic/Latino, American Indian/Alaska Native and Pacific Islander communities this past year. COVID-19 magnified these disparities and has catalyzed critical commitments to dismantle structural racism, as addressed in the previously mentioned AHA 2020 Presidential Advisory.

Wenger concludes, "The convergence of all of these issues, their impact on cardiovascular disease and care, presents unique opportunities for transformation in cardiovascular medicine, clinical care and research. We must remain focused and flexible during this unprecedented time to maximize innovation and achieve equity for all."

As the toll of COVID-19 continues to climb, newly released poll data suggest an opportunity to use the pandemic as a prompt for discussing and documenting older adults' wishes for their care, if they get seriously ill or injured for any reason.

Overall, 59% of the 50- to 80-year-olds polled said they had had a conversation with loved ones about their preferences in case they became severely ill. That percentage was even higher -- 70% -- among those over age 65. Just 7% of all older adults polled said COVID-19 had motivated them to have such a conversations.

When it came to documenting their preferences in a legally binding way that can guide families and care teams, 46% of those polled said they had completed at least one of two legal documents that could help their loved ones make decisions for them if they can't do it for themselves. The poll asked about medical durable powers of attorney, and advance directives, often called "living wills."

Among the 7% of older adults who had completed one or both of these forms in the early months of the pandemic, one-third said COVID-19 had motivated them to do so. But this was a very small percentage - just 1% -- of the entire poll sample.

The new findings come from the National Poll on Healthy Aging, based at the University of Michigan's Institute for Healthcare Policy and Innovation. The poll receives support from AARP and Michigan Medicine, and draws from the answers of a national sample of more than 2,000 adults aged 50 to 80.

The poll data released today were gathered in June 2020, when the higher risk of severe illness and death among older adults who developed COVID-19 was already well known.

"Our study adds to growing body of scholarly research that supports the need for more effective, innovative, and targeted approaches to ensure increased completion of advance care planning among all older adults. The fact that so few of the respondents cited COVID-19 as motivation to have these critical conversations and update or complete their advance directives is concerning," says Chithra R. Perumalswami, M.D., M.Sc. a research felllow at the U-M Center for Bioethics and Social Sciences in Medicine who worked with the poll team on the new report.

"It can be difficult for patients, families and providers to navigate these conversations in the hospital setting, especially when visitor restriction policies are in place to reduce the spread of COVID-19," she says. "It is incredibly helpful to have advance care planning completed before a person becomes seriously ill and potentially unable to communicate their preferences."

The role of health providers

Perumalswami studies end-of-life care and decision-making, and is trained in internal medicine and palliative care. She worked on the poll with neurologists and IHPI members James F. Burke, M.D., M.S. and Lesli E. Skolarus, M.D., M.S. They co-lead a study of the use of advance care planning coverage under Medicare, and how it relates to older adults' health outcomes.

"Health care professionals can use the COVID-19 pandemic as a starting point for discussing advance care planning with older adults, and policymakers may want to look for opportunities to encourage more discussions within families and between patients and providers," says poll director Preeti Malani, M.D., a Michigan Medicine infectious disease physician also trained in geriatrics.

She notes that of those who had completed at least one form, 15% said they had done it because they had had a hospitalization or operation, or a concern related to their own health, and 8% said a member of their health care team had suggested it.

A difficult topic

The new poll confirms past research finding that just bringing up the topic of end-of-life care and medical decisionmaking is uncomfortable or hard to broach for older adults. Nearly a quarter (23%) of the poll respondents who hadn't yet had a conversation about their wishes said they don't like talking about such things, and 56% said they hadn't gotten around to it.

Among those who hadn't completed at least one of the two legal forms, 13% said they do not like talking about such things, and 15% said they didn't know how. But 62% said they just hadn't gotten around to it.

The poll also finds that a sizable percentage of adults may need more information about why it's important for everyone to have at least discussed their wishes with a loved one, even if they haven't signed a form to authorize someone to make medical decisions for them, or laid out their general preferences in advance. One in five older of those who hadn't had a conversation said they didn't think it was necessary.

"This research confirms that many people are uncomfortable talking about severe illness and death, yet it's important to have those discussions and document your wishes for medical treatment," says Alison Bryant, Ph.D., senior vice president of research for AARP. "Many organizations, including AARP, offer resources to help start a conversation with your loved ones and complete the correct paperwork for your state."

Hamilton, ON (April 6, 2021) - If you are one of the millions of people worldwide suffering from allergies, you may take an antihistamine pill to ward off hives, sneezing and watery eyes.

But you may be taking your medications incorrectly, says Derek Chu, a McMaster University allergy expert and clinical scholar.

"People need to rethink what they stock in their home cabinets as allergy medicines, what hospitals keep on formulary, and what policymakers recommend. The message needs to get out. This publication is on time for the spring allergy season and as COVID vaccines roll out, for which rashes are common and antihistamines can be helpful," said Chu.

Co-author Gordon Sussman, professor of medicine at University of Toronto's Temerty Faculty of Medicine, agrees.

"There are new modern second generation antihistamines that are potent, specific, fast acting and of proven safety which everyone should be using to treat allergic rhinitis and hives," he said.

This team's study is published in the Canadian Medical Association Journal (CMAJ), and list five facts to know:

1. Antihistamines are among the most commonly and incorrectly used medicines worldwide.
Antihistamines are best used to relieve symptoms of hay fever and outbreaks of hives, but not for asthma, eczema, coughs or insomnia.

2. First-generation antihistamines are associated with substantial and sometimes fatal side effects.
Antihistamines with diphenhydramine, chlorpheniramine or hydroxyzine are first-generation antihistamines that can cause drowsiness and affect cognitive functions such as school performance. Overdosing can cause death and they are potentially dangerous for both young and older people.

3. Newer antihistamines are safer, as affordable and as effective as first-generation antihistamines.
Later-generation antihistamines are proven to be more effective and last longer with less side-effects like drowsiness.

4. Antihistamines should not be used instead of epinephrine to treat anaphylaxis.
Oral drugs can be used together with epinephrine injections to treat anaphylactic reactions, but they are not a substitute.

5. Most antihistamines are safe to use during pregnancy and breastfeeding.
Medical research has shown that antihistamines at standard doses do not harm fetuses during pregnancy and may be used during breastfeeding. They are also safe for children to use.

Below please find a summary and link to new coronavirus-related content published today in Annals of Internal Medicine. All coronavirus-related content published in Annals of Internal Medicine is free to the public. A complete collection is available at https://annals.org/aim/pages/coronavirus-content.

Graded dosing protocol may help patients with first dose reactions tolerate second dose of vaccine

Abstract: https://www.acpjournals.org/doi/10.7326/L21-0104

Researchers from Rochester Regional Health used graded doses to successfully administer a second dose of the Moderna vaccine to two patients who had an immediate hypersensitivity reaction with the first dose. Their case report is published today in Annals of Internal Medicine.

The first patient, a 64-year-old woman with a history of shellfish allergy, received dose 1 of the Moderna vaccine and experienced skin irritation, hives, and a rapid heartbeat within 10 minutes. She was treated successfully by medical personnel at the vaccination site. Patient 2, a 39-year-old woman with a history of allergic rhinitis, received dose 1 of the Moderna vaccine and developed hives on her chest and neck within 15 minutes. Medical personnel treated her symptoms at the vaccination site, but she went on to develop mild facial swelling and was transported by ambulance to the emergency department. After brief treatment, her symptoms resolved and she was discharged to home in stable condition.

Before having a second dose of the vaccine, both patients were referred to the authors' allergy practice for further evaluation. Skin prick and intradermal showed reaction to the Moderna vaccine. But since both patients worked in the health care setting with repeated exposure to patients with COVID-19, they wanted to make an educated decision with their health care provider about proceeding with the second dose of the vaccine. The authors administered the vaccine without premedication through a graded dosing protocol that used smaller doses of vaccine over 5 injections given every 15 minutes with patients being observed for reaction throughout the process. Both patients responded well to the graded dosing protocol and reported no additional symptoms over the following 24 hours. In addition, 3 to 4 weeks after receiving the second dose, both patients had IgG antibodies directed against the spike protein of COVID-19, suggesting vaccination was efficacious despite the graded dosing protocol.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. The corresponding author, S. Shahzad Mustafa, MD, can be reached through Veronica Chiesi Brown at Veronica.ChiesiBrown@rochesterregional.org.

Mouse models of neurodevelopmental disorders possess unique, sex-specific metabolic dysfunctions, according to a new study in eNeuro. Understanding the unique metabolic effects of each disorder in both animal models and humans may lead to more personalized treatments and diagnostic methods.

Any disorder affecting the brain also impacts the body. People with neurodevelopmental disorders -- including Down syndrome and autism spectrum disorders -- are at increased risk for developing diabetes, obesity, and hypertension. Yet the impact of these three disorders on metabolism has not been studied.

Menzies et al. measured the resting energy metabolism of three neurodevelopmental disorder mouse models: Down syndrome, 16p11.2 deletion syndrome, and Fragile X syndrome. The mice spent 48 hours in a special cage that tracked gas exchange, activity, food consumption, and heat production. The research team also measured metabolites in the blood. Despite similar food consumption and physical activity levels, each mouse model exhibited a unique, sex-specific metabolic signature. The signatures varied in terms of energy expenditure, fat and carbohydrate utilization, body composition, and metabolite levels. The results suggested all three mouse models may be showing signs of mitochondrial dysfunction, meaning their cells have issues using and producing energy.

PHILADELPHIA - A team led by scientists at the Perelman School of Medicine at the University of Pennsylvania has illuminated the functions of mysterious structures in cells called "nuclear speckles," showing that they can work in partnership with a key protein to enhance the activities of specific sets of genes.

The discovery, which will be published on April 5 in Molecular Cell, is an advance in basic cell biology; the key protein it identifies as a working partner of speckles is best known as major tumor-suppressor protein, p53. This avenue of research may also lead to a better future understanding of cancers, and possibly better cancer treatments.

"This study shows that nuclear speckles work as major regulators of gene expression, and suggests that they have a role in some cancers," said study senior author Shelley Berger, PhD, the Daniel S. Och University Professor in the Department of Cell and Developmental Biology.

Nuclear speckles, tiny structures within the nucleus of every mammalian cell, were first observed with a microscope in 1910, but in the ensuing 111 years, scientists have discovered little about their functions.

One early theory was that the speckles are essentially storage depots, since they do contain important molecules needed to copy out the DNA in genes into RNA transcripts and then to process those transcripts into the finished "messenger RNAs" that can be translated into proteins. In recent years, scientists have begun to find evidence that speckles play a more direct role in gene transcription.

Nevertheless, identifying their precise functions and how those are regulated has been difficult, due to the basic challenges of studying speckles.

In the study, Berger and colleagues, including first author Katherine Alexander, PhD, a postdoctoral researcher in the Berger Laboratory who did most of the experiments, overcame some of these challenges to reveal that speckles work with p53 to directly enhance the activity of certain genes.

While p53 has long been known as a "transcription factor" or master switch that controls the activity of a broad set of genes, the researchers showed that it exerts this effect on a subset of its target genes via nuclear speckles. The protein acts as a matchmaker, bringing together speckles and DNA containing these target genes. When the speckles and genes get close, the level of transcription of the genes jumps significantly.

The researchers went even further to show that the p53 target genes whose activity is boosted via speckles have a set of functions that are broadly distinct from those of other p53 target genes.

"Speckle-associated p53 target genes, compared to other p53 target genes, are more likely to be involved in tumor-suppressing functions such as stopping cell growth and triggering cell suicide," Alexander said.

These findings not only confirm nuclear speckles as enhancers of gene activity, but also implicate them in the functions of a key tumor-suppressor protein, which is known to be disrupted in about half of all cancers. In some cancers, p53 is mutated in a way that causes it not only to lose its tumor-suppressor function but also to actively drive cancerous growth. The researchers are now working to determine if nuclear speckles are involved in mediating this cancer-driving effect of mutant p53.

"If that proves to be the case," Berger said, "then in principle we could develop treatments to interfere with this association between p53 and speckles--an association that might turn out to be a real Achilles heel for cancer."

SARS-CoV-2 showed the world with devastating clarity the threat undetected viruses can pose to global public health. SpillOver, a new web application developed by scientists at the University of California, Davis, and contributed to by experts from all over the world, ranks the risk of wildlife-to-human spillover for newly-discovered viruses.

SpillOver is the first open-source risk assessment tool that evaluates wildlife viruses to estimate their zoonotic spillover and pandemic potential. It effectively creates a watchlist of newly-discovered viruses to help policymakers and health scientists prioritize them for further characterization, surveillance, and risk-reducing interventions.

The tool is linked to a study published in the journal PNAS, in which the authors identified the most relevant viral, host and environmental risk factors for virus spillover. Then the team ranked the risk from 887 wildlife viruses using data collected from a variety of sources, including viruses detected by the USAID Emerging Pandemic Threats PREDICT project, which UC Davis' One Health Institute led from 2009 to 2020.

CORONAVIRUSES RANK HIGH

Topping the list were 12 known human pathogens, which was expected and validates the tool's utility. Interestingly, SpillOver ranked several newly-discovered coronaviruses as higher risk for spillover than some viruses already known to be zoonotic. This watchlist includes a novel coronavirus provisionally named PREDICT_CoV-35, which ranked within the top 20.

The power of the tool lies in the fact that it is open-source--the more data entered, the more robust the ranking. SARS CoV-2 currently ranks second out of the 887 viruses analyzed, between Lassa and Ebola viruses.

That may seem counterintuitive, the authors note, given the pandemic's current global devastation. They explain that the tool is ranking the potential for another spillover beyond what has happened historically. In addition, key information remains undiscovered about SARS CoV-2 and its spillover risk, such as the number and range of its host species. As scientists learn more about this virus, it is possible SARS CoV-2 will move to No. 1.

"SARS-CoV-2 is just one example of many thousands of viruses out there that have the potential to spillover from animals to humans," said lead author Zoë Grange, who led the development of SpillOver as a postdoctoral researcher with the UC Davis One Health Institute. "We need to not only identify but also prioritize viral threats with the greatest spillover risk before another devastating pandemic happens. Our SpillOver Viral Risk Ranking tool is the starting point for building proactive solutions."

VIRUS 'CREDIT SCORE'

SpillOver was inspired by risk assessments used by banks and insurance companies. It creates a "credit-like" score for viruses by looking at key risk factors and using them to prioritize those viruses posing the greatest potential threats to human health for a watchlist. Users can customize the watchlist to their own circumstances, such as country of interest.

Previous virus-ranking tools have been limited in the number or types of viruses analyzed, with minimal risk factors considered. SpillOver considers 32 risk factors about the virus and hosts, including associated environment and human behaviors. It also includes 25 different viral families, from coronaviruses to the viral family that causes ebolaviruses.

RANK YOUR VIRUS

SpillOver produces a detailed risk report for each virus, and its 'Risk Comparison' tool allows users to compare and contrast ranked viruses, as well as filter viruses on a selection of key attributes, including virus species, host species and country of detection.

As an open-source tool, SpillOver provides a living platform for ongoing ranking of spillover risk. Scientists can contribute data to existing viruses or assess risk of new viruses using the 'Rank Your Virus' application.

"This tool is intended to start a global conversation that will allow us to go far beyond how we thought about ranking viruses in the past and allow real-time scientific collaboration to identify new threats early," said corresponding author Jonna Mazet, a professor at the UC Davis School of Veterinary Medicine, founding director of the One Health Institute and former global director of PREDICT. "SpillOver can help advance our understanding of viral health threats and enable us to act to reduce the risk of spillover before pandemics can catch fire."

SpillOver engages and enables scientists who are discovering viruses to collaborate in a One Health framework that is focused not only on viral characteristics but also on all of the circumstances present at high-risk areas for disease emergence. This allows the tool to be a catalyst for rapidly identifying and ranking newly-discovered viruses and their animal-human transmission interfaces.

This paradigm shift can facilitate collaboration early, across disciplinary and national boundaries. Identifying and ranking viruses for human-health risks can help scientists identify critical control points and address human behaviors that put humans and animals at risk for novel viral infection.

New Haven, Conn. -- In a new study, Yale Cancer Center researchers have defined the genetic landscape of uterine leiomyosarcomas (uLMS). Furthermore, using fully sequenced patient-derived xenografts, the team has preclinically validated new treatment modalities, which may point to new treatments for uterine cancer. Study results were published online in an early edition of the Proceedings of the National Academy of Science (PNAS).

Uterine cancer is the most common gynecologic malignancy and uterine leiomyosarcomas (uLMS) are highly lethal sarcomas arising from the myometrium, the smooth muscle layer of the uterus. They represent the most common type of uterine sarcomas, which overall account for three to seven percent of all uterine cancers. uLMS have poor prognosis and are characterized by aggressive biological behavior leading to early local and distant metastatic spread.

A collaborative team--which included researchers with expertise in gynecological cancer, genomics, pathology, pharmacology, and computational biology from the United States of America, South Korea, Spain, and Italy-- identified a number of genes that are frequently mutated in uLMS. Using an integrated and comprehensive genetic approach, scientists identified multiple genes with recurrent alterations in uLMS including the homologous-recombination DNA-repair deficiency (HRD), the alternative lengthening of telomere (ALT), C-MYC/BET, and PI3K-AKT-mTOR pathway as potential targets.

"Using two fully sequenced patient-derived-xenografts (PDXs) harboring deranged C-MYC/BET and PTEN/PIK3CA pathways and/or an HRD signature, we found olaparib (PARPi), GS-626510 (BETi), and copanlisib (PIK3CAi) monotherapy to significantly inhibit in vivo uterine leiomyosarcomas growth," said senior author of the study Alessandro Santin, MD, Professor of Obstetrics, Gynecology and Reproductive Sciences at Yale School of Medicine and Disease Aligned Research Team Leader for the Gynecological Cancers Program at Yale Cancer Center and Smilow Cancer Hospital. "Our integrated genetic analysis combined with in vivo preclinical validation experiments suggests that a large subset of uLMS may potentially benefit from existing PARPi/BETi/PIK3CAi targeted drugs."

The team reported results from 83 women diagnosed with uLMS from the U.S. and Italy to determine the molecular basis of the tumor's aggressive behavior. They sequenced the genes from the tumors and identified mutations that are crucial for these tumors to grow. The team also studied the copy number variations--genes that are not mutated but are amplified in the tumors to give them a growth advantage over normal tissues as well as tumor RNA expression levels and gene fusion products.

"The establishment of 2 PDXs with different mutation profiles provided the opportunity for in vivo assessment of whether a mutation profile is predictive of drug response," said corresponding author Joseph Schlessinger, PhD, William H. Prusoff Professor and Chairman of the Department of Pharmacology at Yale School of Medicine and Co-Director of the Yale Cancer Biology Institute. "These preclinical validation studies have suggested new opportunities for personalized therapy."