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While declines in U.S. hospital admissions during the onset of COVID-19 has been well-documented, little is known about how admissions during the rebound varied by age, insurance coverage and socioeconomic groups. The decline in non-COVID-19 admissions was similar across all demographic subgroups but the partial rebound that followed shows that non-COVID-19 admissions for residents from Hispanic neighborhoods was significantly lower than for other groups. The findings are reported in a new study in Health Affairs (released as a Fast Track Ahead of Print article) conducted by a research team from Sound Physicians, Dartmouth College, and the Dartmouth Institute for Health Policy and Clinical Practice at the Geisel School of Medicine at Dartmouth.

"Our study shows that patients from Hispanic neighborhoods did not have the same rebound in non-COVID-19 admissions as other groups, which points to a much broader issue of healthcare access and equity for lower-income and minority patients," said senior author and health economist Jonathan Skinner, a professor at the Dartmouth Institute for Health Policy and Clinical Practice at the Geisel School of Medicine, and the James O. Freedman Presidential Professor in Economics at Dartmouth. As a result, these barriers may have contributed to higher in-hospital mortality rates in April for this group than for others," he added.

The study drew on data from 1 million hospital admissions (from hospital administrative data and electronic medical and billing records) from Sound Physicians, a large nationally distributed medical group with hospitals throughout the U.S. The data came from 201 hospitals in 36 states, including areas hit hard early on by the pandemic, including Wash., Mich., Ohio, and the greater metropolitan area of New York.

The research team looked at non-COVID-19 admissions for the top 20 acute medical conditions, from early February through early July. They found that non-COVID-19 admissions fell in March and reached its lowest point in April. The rebound leveled off in June/July, which was when there was a resurgence of COVID-19 cases in some regions.

The study's results reports the following:

From February to April 2020, declines in non-COVID-19 admissions were similar across all demographic subgroups exceeding 20 percent for all primary admission diagnoses.

The lowest point in non-COVID-19 admissions was in April during which the overall decline was 43 percent.

By late June/early July 2020, non-COVID-19 admissions had only made a partial rebound at 16 percent below pre-pandemic baseline volume. (Updated data suggests this partial rebound continued through the summer.)

During the June/July rebound period, non-COVID-19 admissions were substantially lower for patients from majority-Hispanic neighborhoods (32 percent below baseline) and remained well below baseline for patients with pneumonia (44 percent below baseline), chronic obstructive pulmonary disease/asthma (40 percent below baseline), sepsis (25 percent below baseline), urinary tract infection (24 percent below baseline) and acute ST-elevation myocardial infarction/heart attack (22 percent below baseline).

These particular diseases are reported in the results, as these were the acute conditions for which the declines were the highest. Most of the majority-Hispanic neighborhoods in this dataset were located in the Southwest and South-- Calif., Ariz., Texas, and Fla.

The research team speculate that the declines in medical admissions may have been due in part to a fear of contracting COVID-19 by both physicians and patients, greater use of telemedicine, and possibly lower transmission rates of non-COVID-19 diseases following stay-at-home orders.

DURHAM, N.C. -- A new drug offers hope for young boys with the progressive neuromuscular disease Duchenne muscular dystrophy (DMD) by potentially offering an alternative to high-dose glucocorticoids that have significant side effects.

Interim results from a 24-month clinical trial at Duke Health and other institutions suggest that the drug, vamorolone, may retain or improve the effects of current steroid treatments but reduces health risks associated with long-term steroid use.

Vamorolone is an anti-inflammatory steroid that differs from all 33 drugs in the corticosteroid class because of a distinct interaction with the body's glucocorticoid receptors. Duke's participation in the study is part of a larger, multi-center global trial.

Published this month in the journal PLOS Medicine, the findings are significant because they offer a potential treatment option for young patients that may reduce the side effects that occur as a result of treatment with high-doses of such steroids as prednisone or deflazacort, while retaining the therapeutic benefit of this class of drugs. Steroid therapy is currently the only treatment that has been shown to slow the effects of DMD, an irreversible, progressive muscle disease that gradually takes the strength of boys.

"This is potentially great news for these boys who are just beginning the steroid regimen that is our standard-of-care treatment," says Edward C. Smith, M.D., a neurologist, co-director of the Duke Children's Neuromuscular Program and a clinical investigator in the trial.

"One of our biggest concerns about high-dose steroid treatment in these patients is the effect on linear growth and bone development," Smith said. "So far, based on the interim results from this trial, we may be seeing a much less negative impact on bone health among patients using vamorolone."

High-dose steroid use halts the development of growth plates in young patients and inhibits the lengthening of bones, Smith says. Despite the side effects, steroid therapy has been shown to extend patients' mobility and lives. Patients now frequently live into their 30s, but eventually experience heart and respiratory failure.

A severe type of muscular dystrophy, DMD is caused by a genetic inability to create dystrophin, a protein that protects skeletal and heart muscle from injury caused by normal contraction and relaxation. The disorder is caused by an X chromosome mutation and affects mostly boys. There is no cure.

Smith says young patients typically present with some degree of delayed motor development and neurocognitive issues. Behavioral development may also be hampered.

"The boys tend to do relatively well until about ages four to six," he says. "Then weakness becomes more pronounced and eventually impacts their ability to stand and then their ability to walk."

Following completion of the six-month study, the 46 trial participants were given the option to transition to standard of care using prednisone or deflazacort or continue treatment with vamorolone through enrollment in a two-year long-term extension study. All participants opted to continue treatment with vamorolone.

"We saw statistically significant improvements in the outcome measures in this part of the overall trial in boys treated with the two highest doses of vamorolone for 18 months, with improvements in strength and function," Smith said. "These improvements appear to be similar to what is seen on steroid-treated boys, based on data from DMD natural history studies. Additionally, vamorolone appears it may have a much better side effect profile than traditional glucocorticoids, even at the highest doses tested."

"Although this particular trial was not placebo-controlled, I am encouraged by the safety and efficacy data and look forward to results from the larger placebo-controlled trial (VBP15-004) that is currently underway at Duke and other sites," Smith said.

CHAPEL HILL, N.C.--New cancer research by scientists at UNC Lineberger Comprehensive Cancer Center, and colleagues, shows the potential for targeting a specific circular RNA, known as CDR1as, to attack lung squamous cell cancer. Lung squamous cell cancers comprise up to 30% of all lung cancers and are responsible for about 70,000 new cases and approximately 40,000 deaths each year in the U.S.

The results from this study are published in Cancer Research, a journal of the American Association for Cancer Research.

"Cancer is revealing, at a rapid pace, that it has many more vulnerabilities than we previously believed, including the one we've elucidated, which undoubtedly means better treatment options ahead," said study senior author UNC Lineberger's Chad V. Pecot, MD, an associate professor at the UNC School of Medicine. "I'm very hopeful, based on our work and much of what is being done in the field of drug development, that many new medicines are on the horizon."

For decades, scientists dismissed RNAs that joined ends to form circles as splicing errors. Research by former UNC Lineberger director Ned Sharpless, MD, and current director of the National Cancer Institute, among others, revealed that these RNAs are highly abundant and compromise a new class of RNA called circRNAs.

Many circRNAs, including the one in this study (CDR1as), are thought to work by targeting and inhibiting other RNAs. However, after many years of investigation, the researchers discovered that one of the keys to how CDR1as works was through an unstudied protein called CDR1. With the help of several collaborators, they found the answer came by looking at Golgi trafficking.

Golgi bodies in a cell ensure that the proteins a cell produces get to where they need to go and exert their designed function. For cancer cells, this means that Golgi must reposition themselves so that cells can metastasize, or spread, to other parts of the body. Most cellular behavior is ultimately regulated by proteins, so if Golgi trafficking is altered, this can be hugely consequential to what happens in the cell. This new research uncovers some of the first connections of circRNAs with Golgi trafficking.

"We found that CDR1as plays a large role in driving metastasis in lung squamous cancer," said Pecot. "However, because nothing was really known about CDR1, the protein regulated by CDR1as, our journey was just beginning. We eventually determined that CDR1 in part operates by increasing Golgi trafficking, which we found to be critical to its role in helping cancer spread."

The researchers say they will continue to explore the intricate biology of both CDR1as and CDR1. According to Pecot, these both represent very enticing drug targets because they are usually not turned on in the rest of the body. So blocking them would be destructive to cancer cells but should not cause much toxicity to the rest of the body.

"The study of CDR1as is only just beginning, and our research highlights a new mechanism for circRNA function that has implications beyond cancer biology," said study first author Emily B. Harrison, PhD, postdoctoral research associate at UNC Lineberger and UNC Eshelman School of Pharmacy. "This has been a huge team effort across UNC, including many Lineberger members as well as researchers across several departments. It truly exemplifies a successful team effort."

Close2U, an electronic device application, has been developed by researchers at the Complutense University (UCM) and the University of Zaragoza (UZA) to monitor cancer patients' physical and mental health using gamification.

Users answer a series of daily questions about their mood and where they are experiencing pain. In return, the app rewards them in the form of advice or songs, resources intended to increase their motivation.

"The use of gamification enables more continuous monitoring of cancer patients by obtaining frequent information about their mood. Among other things, this lets us know if they are depressed, stressed or in pain", explained Iván García-Magariño, a researcher in the Department of Software Engineering and Artificial Intelligence at the UCM.

The study was conducted in collaboration with the Spanish Cancer Association (Spanish initials: AECC), primarily at its branch in Teruel, where patients tested the app.

Researchers from both universities have reported development of the app and the results obtained in the Journal of Biomedical Informatics and Journal of Healthcare Engineering.

Exchange of resources among patients

For example, for the question "How did you sleep?", users mark a point on a horizontal line between the two extremes "very badly" and "very well", while for the question "Where in your body are you experiencing pain?", the screen displays an image of a body on which patients mark areas affected by pain.

The information obtained from their answers is sent to a hospital or association physician.

In return, patients are rewarded with advice or songs which "are intended to amuse and entertain them, and which they can also share with other cancer patients to provide mutual support", observed García Magariño.

He also noted that the researchers were working on incorporating the app on other devices such as smart furniture or watches. "We don't know exactly when our products will be available to the general public because that will depend on our resources and interest from potential users", he concluded.

Close2U is an e-Health action and meets objectives such as automatic data capture without requiring any explicit action on the part of users, and smart data analysis, alerting healthcare staff when appropriate.

Medications often have unwanted side-effects. One reason is that they reach not only the unhealthy cells for which they are intended, but also reach and have an impact on healthy cells. Researchers at the Technical University of Munich (TUM), working together with the KTH Royal Institute of Technology in Stockholm, have developed a stable nano-carrier for medications. A special mechanism makes sure the drugs are only released in diseased cells.

The human body is made up of billions of cells. In the case of cancer, the genome of several of these cells is changed pathologically so that the cells divide in an uncontrolled manner. The cause of virus infections is also found within the affected cells. During chemotherapy for example, drugs are used to try to destroy these cells. However, the therapy impacts the entire body, damaging healthy cells as well and resulting in side effects which are sometimes quite serious.

A team of researchers led by Prof. Oliver Lieleg, Professor of Biomechanics and a member of the TUM Munich School of BioEngineering, and Prof. Thomas Crouzier of the KTH has developed a transport system which releases the active agents of medications in affected cells only. "The drug carriers are accepted by all the cells," Lieleg explains. "But only the diseased cells should be able to trigger the release of the active agent."

Synthetic DNA keeps the drug carriers closed

The scientists have now shown that the mechanism functions in tumor model systems based on cell cultures. First they packaged the active ingredients. For this purpose, they used so-called mucins, the main ingredient of the mucus found for example on the mucus membranes of the mouth, stomach and intestines. Mucins consist of a protein background to which sugar molecules are docked. "Since mucins occur naturally in the body, opened mucin particles can later be broken down by the cells," Lieleg says.

Another important part of the package also occurs naturally in the body: deoxyribonucleic acid (DNA), the carrier of our genetic information. The researchers synthetically created DNA structures with the properties they desired and chemically bonded these structures to the mucins. If glycerol is now added to the solution containing the mucin DNA molecules and the active ingredient, the solubility of the mucins decreases, they fold up and enclose the active agent. The DNA strands bond to one another and thus stabilize the structure so that the mucins can no longer unfold themselves.

The lock to the key

The DNA-stabilized particles can only be opened by the right "key" in order to once again release the encapsulated active agent molecules. Here the researchers use what are called microRNA molecules. RNA or ribonucleic acid has a structure very similar to that of DNA and plays a major role in the body's synthesis of proteins; it can also regulate other cell processes.

"Cancer cells contain microRNA strands whose structure we know precisely," explains Ceren Kimna, lead author of the study. "In order to use them as keys, we modified the lock accordingly by meticulously designing the synthetic DNA strands which stabilize our medication carrier particles." The DNA strands are structured in such a way that the microRNA can bind to them and as a result break down the existing bonds which are stabilizing the structure. The synthetic DNA strands in the particles can also be adapted to microRNA structures which occur with other diseases such as diabetes or hepatitis.

The clinical application of the new mechanism has not yet been tested; additional laboratory investigations with more complex tumor model systems are necessary first. The researchers also plan to investigate further modifying this mechanism to release active agents in order to improve existing cancer therapies.

BOSTON - A novel mobile health program created in early 2018 by the Kraft Center for Community Health at Massachusetts General Hospital (MGH) has proven to be an effective model for bringing opioid addiction treatment services directly to marginalized individuals, particularly the homeless, a population that faces the highest risk of near-term death from drug overdose. The early success of the program, known as Community Care in Reach, in breaking down traditional barriers of care and serving as an entry point for people disconnected from the healthcare system was detailed in a community case study published in Frontiers in Public Health. The program, made possible by contributions from Robert K. Kraft and family, brings together the resources of the Kraft Center, the Boston Health Care for the Homeless Program (BHCHP) and the Boston Public Health Commission's (BPHC) syringe access program, AHOPE.

"Through a non-traditional combination of clinical care and harm reduction services, the program's clinical van and street outreach have produced a model that flips the notion of 'the doctor will see you now' on its head," says Craig Regis, MPH, investigator with the Kraft Center for Community Health and lead author of the study. "Community Care in Reach has shown a unique ability to improve access to evidence-based services among a vulnerable population that must cope routinely with barriers to essential healthcare."

By the end of 2019, the program's 24-foot mobile medical unit had recorded 9,098 contacts with people living with addiction in areas identified as overdose hot spots in and around Boston, distributing 96,600 syringes and 2,956 naloxone kits to rapidly reverse opioid overdose. Addiction care medications prescribed and administered on the van by primary care physicians from BHCHP include buprenorphine, used to reduce substance craving, and naltrexone, a synthetic opioid antagonist taken orally or through injection. Other services offered to people with opioid use disorders are naloxone training, disposal of used syringes, HIV/HCV testing, education around safe injection practices, wound care management and referrals to various substance use treatment facilities. Outreach and harm reduction work are conducted by BPHC's Access Harm Reduction, Overdose Prevention and Education (AHOPE) program.

"Our analyses of Community Care in Reach showed a high demand for addiction services among people with opioid use disorders, particularly as the program became more established and built trust within the community," reports Elsie Taveras, MD, MPH, executive director of the Kraft Center for Community Health and senior author of the study. "Patients said they appreciated the convenience and ease of accessing the program, along with the compassionate care and proactive street outreach initiated by our team of experienced clinicians." Helping to confirm the success of the model was the recent decision by the Massachusetts Department of Public Health to expand mobile addiction services, including the Kraft Center's program, as well as a report in March 2019 by the state's Harm Reduction Commission that praised Community Care in Reach as a best practice program for addressing opioid addiction.

A major contributor to the success of the mobile treatment program, according to its organizers, is a data-driven approach that ensures its addiction care services are reaching areas of the city where they are most needed. "We constantly monitor EMS and population health data to determine where sustained high levels of overdose exist in the Greater Boston area," explains Regis. "This gives us the flexibility to rapidly deploy the van to opioid hot spots. Just as importantly, it allows us to develop data to demonstrate to others that this model can be just as effective as a brick-and-mortar setting for treating individuals with opioid use disorder."

If the healthcare system is truly committed to helping some of society's most vulnerable members - statistics show the rate of death from opioid overuse among the homeless is 20 times higher than the general population - then it must create innovative approaches that leapfrog the traditional models of healthcare delivery, maintains Taveras. "As we've shown, one potential solution to this massive challenge is to shift some addiction care services to a mobile health setting," she says. "That way, we're able to not only increase access to these essential services, but customize them to the needs of patients most critically in need."

Taveras is also professor of pediatrics at Harvard Medical School. Regis is program manager at the Kraft Center for Community Health. Co-authors include Jessie Gaeta, MD, with Boston Health Care for the Homeless Program; Sarah Mackin, MPH, who leads the needle exchange program for Boston Public Health Commission; Travis Baggett, MD, MPH, faculty clinician-investigator in the Division of General Internal Medicine, MGH; and Joan Quinlan, MPA, vice president for community health at MGH.

Cocaine addiction is a chronic disorder with a high rate of relapse for which no effective treatment is currently available. Scientists from the Institut Pasteur, the CNRS, Inserm and the Paris Public Hospital Network (AP-HP) recently demonstrated that two gene mutations involved in the conformation of nicotinic receptors in the brain appear to play a role in various aspects of cocaine addiction. The results of the study were published in Progress in Neurobiology.

There are approximately 18 million users worldwide, and cocaine is implicated in more than 50% of overdose deaths in the United States and 25% in France. It is also one of the only drugs for which there is no approved pharmacological treatment.

Cocaine acts primarily in the brain by blocking the dopamine transporter, thereby increasing the concentration of this "pleasure" molecule in the reward system. But cocaine can also act directly on the nicotinic receptors1 in the brain. Several human genetics studies have recently suggested that a mutation in the gene encoding the α5 subunit of nicotinic receptors, hereafter referred to as 'α5SNP', already known to increase the risk of tobacco dependence,2 may conversely also confer "protection" against cocaine addiction. This mutation is highly present in the general population (approximately 37% of Europeans and up to 43% of the Middle Eastern population carry it), so it is important to determine how it affects cocaine addiction and, more generally, to better understand the role of the α5 nicotinic subunit in the effects of cocaine.

Scientists of the Integrative Neurobiology of Cholinergic Systems Unit (Institut Pasteur/CNRS) began by evaluating the role of the α5 nicotinic subunit and the impact of the α5SNP mutation on various processes involved in the development of cocaine addiction in animal models. The results obtained were then used to characterize more specifically its impact on humans.

The scientists observed that the α5SNP mutation reduces the voluntary intake of cocaine upon first exposures. "These preclinical data suggest that the mutation protects against cocaine addiction by modulating an early phase in the addiction cycle," comments Morgane Besson, one of the lead authors of the study. Working in collaboration with the Paris Public Hospital Network (AP-HP) and Inserm, the scientists then confirmed this significant effect in approximately 350 patients with cocaine addiction: those with the mutation exhibited a slower transition from first cocaine use to the emergence of signs of addiction. At the same time, the authors showed that a total absence of the α5 nicotinic subunit increased the risk of relapse after withdrawal in preclinical models. This led the scientists to identify another mutation in another nicotinic subunit, β4, associated with a shorter time to relapse after withdrawal in addicted patients.

Taken together, these results elucidate the role played by both a highly frequent mutation in the α5 nicotinic subunit and the subunit itself in various stages of cocaine addiction. The research suggests that drugs modulating nicotinic receptors containing this α5 subunit could represent a novel therapeutic strategy for cocaine addiction.

Laboratory tests of surgical and N95 masks by researchers at the University of California, Davis, show that they do cut down the amount of aerosolized particles emitted during breathing, talking and coughing. Tests of homemade cloth face coverings, however, show that the fabric itself releases a large amount of fibers into the air, underscoring the importance of washing them. The work is published Sept. 24 in Scientific Reports.

As the COVID-19 pandemic continues, the use of masks and other face coverings has emerged as an important tool alongside contact tracing and isolation, hand-washing and social distancing to reduce the spread of coronavirus. The CDC and the World Health Organization endorse the use of face coverings, and masks or face coverings are required by many state and local governments, including the state of California.

The goal of wearing face coverings is to prevent people who are infected with COVID-19 but asymptomatic from transmitting the virus to others. But while evidence shows that face coverings generally reduce the spread of airborne particles, there is limited information on how well they compare with each other.

Sima Asadi, a graduate student working with Professor William Ristenpart in the UC Davis Department of Chemical Engineering, and colleagues at UC Davis and Icahn School of Medicine at Mount Sinai, New York, set up experiments to measure the flow of particles from volunteers wearing masks while they performed "expiratory activities" including breathing, talking, coughing and moving their jaw as if chewing gum.

Asadi and Ristenpart have previously studied how people emit small particles, or aerosols, during speech. These particles are small enough to float through the air over a considerable distance, but large enough to carry viruses such as influenza or coronavirus. They have found that a fraction of people are "superemitters" who give off many more particles than average.

The 10 volunteers sat in front of a funnel in a laminar flow cabinet. The funnel drew air from in front of their faces into a device that measured the size and number of particles exhaled. They wore either no mask, a medical-grade surgical mask, two types of N95 mask (vented or not), a homemade paper mask or homemade one- or two-layer cloth mask made from a cotton T-shirt according to CDC directions.

Up to 90 percent of particles blocked

The tests only measured outward transmission -- whether the masks could block an infected person from giving off particles that might carry viruses.

Without a mask, talking (reading a passage of text) gave off about 10 times more particles than simple breathing. Forced coughing produced a variable amount of particles. One of the volunteers in the study was a superemitter who consistently produced nearly 100 times as many particles as the others when coughing.

In all the test scenarios, surgical and N95 masks blocked as much as 90 percent of particles, compared to not wearing a mask. Face coverings also reduced airborne particles from the superemitter.

Homemade cotton masks actually produced more particles than not wearing a mask. These appeared to be tiny fibers released from the fabric. Because the cotton masks produced particles themselves, it's difficult to tell if they also blocked exhaled particles. They did seem to at least reduce the number of larger particles.

The results confirm that masks and face coverings are effective in reducing the spread of airborne particles, Ristenpart said, and also the importance of regularly washing cloth masks.

WASHINGTON -- The anxiety, stress and worry brought on by COVID-19 is not limited to daytime hours. The pandemic is affecting our dreams as well, infusing more anxiety and negative emotions into dreams and spurring dreams about the virus itself, particularly among women, according to research published by the American Psychological Association.

In a special section in the journal Dreaming, researchers reported on the results of four studies from around the world about people's dreams during the pandemic. Previous research has suggested that our dreams often reflect what's happening in our waking lives and that other crises--including war, natural disasters and terrorist attacks--have led to an increase in anxious dreams. The four studies in this special section found that the same is true of COVID-19.

"All of these studies support the continuity hypothesis of dreaming: That dreams are consistent with our waking concerns rather than being some outlet for compensation, as some older psychoanalytic theories had hypothesized," said Deirdre Barrett, PhD, editor of Dreaming and an assistant professor of psychology in the Department of Psychiatry at Harvard Medical School. "The higher levels of anxiety, dreams about illness and death in general, and COVID-19 specifically, are in line with that."

Overall, the new studies also suggest that women's dreams have been more strongly affected by the pandemic than men's--possibly, Barrett suggested, because women are bearing more of the burden of caregiving, job loss and other hardships.

"Dreams can help us understand our emotional reactions to the pandemic," Barrett said. For example, one mother in a study by Barrett dreamed that her child's school contacted her to say that the child's whole class was being sent to her condominium to be home-schooled for the duration of the pandemic. "When mothers of young children hear that dream, there is a laughter but also usually a strong empathy at the overwhelmed feeling the dream dramatizes. Your dreams can make you more aware of just what about the pandemic is bothering you the most--and sharing them with trusted others is a good conversation-starter for talking about these shared feelings," Barrett said.

The four COVID-19 articles in the issue are:

"Dreaming and the COVID-19 pandemic: A survey in a U.S. American sample"

Michael Schredl, PhD, Zentralinstitut fu?r Seelische Gesundheit, and Kelly Bulkeley, PhD, The Sleep and Dream Database

This study of more than 3,000 U.S. adults surveyed in early May 2020 found that people who had been most strongly affected by the pandemic--such as those who had gotten sick or lost their job--also reported the strongest effects on their dream life (heightened dream recall, more negative dreams and more pandemic-related dreams). Women and people with more education also reported stronger effects of the pandemic on their dreams. The findings suggest that changes in the frequency, tone and content of dreams can help identify those at risk for mental health problems during the pandemic, according to the researchers.

Contact: Michael Schredl

"Dreams about COVID-19 vs. Normative Dreams: Trends by Gender"

Deirdre Barrett, PhD, Harvard University

Women's dreams have been more negatively affected by COVID-19 than men's dreams, according to this international study of 2,888 participants. The researcher asked online survey respondents to recount their dreams about the pandemic and then compared the responses to a database of dreams from before the pandemic. Overall, women showed significantly lower rates of positive emotions and higher levels of anxiety, sadness, anger and references to biological processes, health and death in their pandemic dreams compared with the pre-pandemic dreams. Men's pandemic dreams showed slightly higher levels of negative emotions, anxiety and death than in pre-pandemic dreams, but the effects were less pronounced than they were for women.

Contact: Deirdre Barrett

"Dreaming in the Time of Covid-19: A Quali-Quantitative Italian Study"

Ilaria Iorio, PhD, Massimiliano Sommantico, PhD, and Santa Parrello, PhD, Universita degli Studi di Napoli Federico II

Researchers analyzed the dreams of 796 Italian participants, all of whom completed a dream
questionnaire in April and May 2020 and described their most recent dream in detail. Twenty percent of the dreams included an explicit reference to COVID-19, the researchers found. Overall, women reported higher emotional intensity and a more negative emotional tone in their dreams, as did participants who knew people affected by COVID-19.

Contact: Massimiliano Sommantico

"Pandemic Dreaming: The Effect of COVID-19 on Dream Imagery, a Pilot Study"

Cassidy MacKay, BSc, and Teresa L. DeCicco, PhD, Trent University

Pandemic-era dreams resemble the dreams of people with anxiety, suggests this study of Canadian college students. Researchers analyzed detailed dream journals from 19 Canadian college students recorded between mid-February and mid-March 2020, as the pandemic and pandemic-related physical distancing restrictions were taking hold in Canada. They found that the pandemic-era dreams contained more location changes, as well as animal, head, food and virus-related dream imagery compared with a control group of people who kept dream journals before the pandemic. This type of dream imagery is similar to previous findings of the dream imagery of people experiencing waking day anxiety, according to the researchers.

Contact: Teresa L. DeCicco

In her ongoing research about Americans' responses to the COVID-19 pandemic, Northern Arizona University anthropology professor Lisa Hardy and her collaborators have talked to dozens of people. A couple of them stand out to the researchers.

Hardy spoke to a man who had polio as a child and had to live in a home with an iron lung away from his family. He said he was not in good health but he was not afraid of COVID-19 because he has seen all of this. A woman told anthropology lecturer Leah Mundell that she was the only Spanish-speaking contact tracer in her county, and she took on the responsibility of helping clients with much more than their physical health, connecting them with services and translating for them as they struggled to access resources.

Hardy's research, to which Mundell contributed, was published this week in Medical Anthropology. "Connection, Contagion, and COVID-19" looks at how Americans' attitudes and responses have changed during the time of the pandemic and how to many people, the virus is not a biological agent but instead a malicious actor. This perception may play a role in the various responses Hardy's team heard, including comments about racism, social justice and mistrust of information.

"Social scientists have done an excellent job of exploring past pandemics with regard to xenophobia--the 'Spanish Flu,' for instance--and how people understand bodies and illness," Hardy said. "This work builds on that by examining the COVID-19 pandemic in the current political moment. The results of this and other research can help to inform areas where collaborative interventions could potentially help to slow the spread of the virus and support well-being for people living through this time."

The research project, which is a collaboration as part of the Social Science Community Engagement Lab, started six months ago, in the early days of the pandemic in the United States. Researchers, including Hardy, Mundell and two others, conducted semi-structured conversational phone interviews with 50 diverse participants. They asked open-ended questions about how people are dealing with the pandemic and their experiences of social and political responses. Then they transcribe the recorded interviews and apply codes to the transcripts to identify patterns. Hardy said this qualitative strategy is ideal for exploring a situation that is rapidly changing and unfolding over time.

As they've called more people, the researchers have seen the interview content change. In more recent interviews, people talked about social uprisings like Black Lives Matter. They're analyzing the relationship between these social movements and perceptions of COVID-19.

Researchers also are talking to more people who have had COVID-19 or had loved ones who got sick. Recent data includes how people reflect on medical care and contact tracing; that information will be useful for pandemic response. They also will continue interviewing after the Nov. 3 election, which will offer insight into the politicization of the pandemics and its effects.

Tracing the logic of different groups also is important for the group's research. Hardy said they've seen an increase in conspiracy theories in more recent interviews, as people across the political spectrum develop unfounded theories about the virus and its reach.

"We want to understand where these ideas are coming from and see how they influence behavior like vaccine uptake, health practices and voting patterns," she said.

The article includes specific responses researchers have collected as they describe their experiences. They run the gamut; interviewees shared fears, concerns and conspiracy theories. Other interviewees talked at length about new connections and circles of care they have formed to help others and to accept help when needed.

"The strength of some of the people who are having to live through hardships is really heartwarming to us," Hardy said. "It gives us hope in this time of tragic loss and tension in the United States."

While the long-term effects of the pandemic are impossible to predict at this point, Hardy anticipates ongoing effects from the loss of loved ones and inability to grieve together as well as long-term health effects in people who survive COVID-19 but continue to have symptoms. But, she added, the country is seeing the development of creative and dynamic strategies for connection and resilience that will hopefully persist through generations.

Researchers have identified two antibodies that protect mice against lethal infections of influenza B virus, report scientists at Washington University School of Medicine in St. Louis and Icahn School of Medicine at Mount Sinai. Together with an antibody that targets the other major kind of influenza viruses that infect people -- influenza A -- these antibodies potentially could form the basis of a broad-spectrum flu drug that could treat almost all flu cases.

The findings are published Sep. 24 in the journal Immunity.

"People forget that before COVID-19 hit last winter, we were already in the midst of a really bad influenza season, especially for children," said co-senior author Ali Ellebedy, PhD, an assistant professor of pathology and immunology at Washington University. "Last year, influenza B viruses attacked much earlier in the season than usual and resulted in significant illness and death among children. We really need better treatments for influenza B. I'm hopeful that these antibodies, which neutralized every strain of influenza B that we tested, could be developed into drugs to treat patients with severe influenza B infection."

Nearly all influenza viruses that sicken people can be classified into one of two groups: A and B. The most widely used flu medication -- Tamiflu -- is approved to treat both kinds, but the drug is less effective for influenza B.

Influenza B is the less common of the two and tends to show up late in the flu season, but, for unclear reasons, children are particularly vulnerable to it. During the 2019-20 flu season, 187 children in the U.S. died of influenza, nearly two-thirds from influenza B, making it the worst flu season for children in a decade. In comparison, between 24,000 and 62,000 adults also died of flu during the 2019-20 season, but about a quarter of the adult deaths were due to influenza B.

Last year, Ellebedy's group identified an antibody called 1G01 that protects mice from the flu by jamming up a critical viral enzyme known as neuraminidase. Both influenza A and influenza B viruses use the enzyme to cut themselves free from cells so they can go on and infect more cells. When neuraminidase is out of order, viral reproduction grinds to a halt. The antibody they found last year inactivated neuraminidases from a wide range of influenza A viruses and some influenza B viruses.

"That antibody recognized neuraminidases from the older influenza B strains, but it didn't recognize the enzyme from the influenza B strains that are circulating now," Ellebedy said. "If we tried to make a drug based on that antibody alone, it wouldn't work for most people with influenza caused by influenza B viruses. So we decided to look for antibodies that are broadly protective against influenza B viruses with the idea that we would combine them with the earlier antibody that protects against influenza A to get a broad-spectrum antiviral for influenza."

Co-author Philip A. Mudd, MD, PhD, an assistant professor of emergency medicine, and the clinical sample collection team in the Washington University Emergency Care and Research Core obtained consent to take blood samples from a patient hospitalized with influenza B virus infection. Ellebedy and colleagues separated out antibody-producing cells from the patient's blood. The research team included co-senior authors Florian Krammer, PhD, a microbiology professor at Icahn School of Medicine at Mount Sinai, and Daved Fremont, PhD, a professor of pathology and immunology at Washington University; and co-first authors Anders Madsen, PhD, of the University of Bergen in Norway; Ya-Nan Dai, PhD, a postdoctoral researcher in Fremont's lab at Washington University; and Meagan McMahon, PhD, a research assistant professor at Mount Sinai.

The researchers then generated antibodies from the cells and analyzed them. They found seven different antibodies that targeted neuraminidase. Two of the antibodies -- 1G05 and 2E01 -- potently inhibited all neuraminidases from a diverse set of nine influenza B viruses.

Further, the two antibodies protected mice against a lethal dose of influenza B virus. The researchers infected groups of five mice with influenza B virus, and then treated them three days later with one of the two antibodies or a placebo antibody. The animals became sick and lost weight, but all of the mice treated with 2E01 and four of the five mice treated with 1G05 survived. In comparison, all the mice that received a placebo antibody died.

"Given their potency, I think these antibodies against influenza B - especially when combined with the antibody against influenza A - could form the basis for a new and more effective treatment for influenza virus infections, especially in children," Krammer said.

Further experiments conducted by Dai showed that, like the influenza A antibody previously identified, the two influenza B antibodies neutralized neuraminidase by clogging up the part of the enzyme that cuts the virus loose from cells. Structural analysis of the interactions between the antibodies and the neuraminidases, though, showed that each antibody interfered in a slightly different way, meaning that it would be especially hard for the virus to evolve drug resistance to both of them at once.

"There's a piece of the antibodies that gets down deep into the enzyme's active site and prevents it from cutting by interfering at multiple spots," Fremont said. "It is hard to see how you could mutate this site in such a way that the antibodies no longer interfere but the site still functions. It's really a no-win situation for the virus, which is good for us."

Dai added: "There are some strains of influenza virus that have mutations that make them resistant to Tamiflu. We tested two of those resistant strains, and our antibodies inhibited both of them, so we think that these antibodies might be even more broadly protective than Tamiflu."

The researchers are in discussions with potential partners to begin the process of developing the antibodies into a drug for influenza. They also have begun experiments using 1G05 and 2E01 antibodies as templates, with a goal of developing a universal flu vaccine that reliably elicits broadly protective antibodies.

Philadelphia, September 24, 2020 - Building upon years of research, a new study from Children's Hospital of Philadelphia (CHOP) has demonstrated how a specific assessment of the eye could someday help properly diagnosis and monitor concussions. The findings were published today in JAMA Ophthalmology.

In the first study of its kind, the research team demonstrated that quantitative pupillary light reflex (PLR) metrics, which determine how the pupil responds to light and are obtained by using a hand-held dynamic infrared pupillometer (DIP), and can be used to differentiate concussed adolescent athletes from healthy adolescents.

"We know the visual system is affected after a sports-related concussion, and this is something that patients can't intentionally control or hide. The pupil's response to light is an autonomic function with metrics easily captured via automated dynamic infrared pupillometry," said lead author Christina L. Master, MD, co-lead of the Minds Matter Concussion Research Program and a pediatric primary care sports medicine specialist at CHOP. "We thought if PLR could distinguish between concussed and non-concussed adolescent athletes, we may have an opportunity for objective assessment where data is easily obtained via a hand-held device in clinical and sports settings."

Today, properly diagnosing a concussion is a challenge due to a lack of objective diagnostic tests for adolescents. In recent years, researchers at CHOP have studied the body's visio-vestibular system - the sensory system that processes spatial motion and visual information - to seek objective biomarkers for concussion that can support diagnosis and guide individualized treatment and recovery plans.

Previous studies have shown concussion leads to difficulty adjusting visual focus and impairments in the autonomic nervous system, making the PLR a promising potential physiological biomarker for concussion. This prospective observational study sought to quantify these differences in PLR via DIP to provide clinicians with a future objective diagnostic tool.

The study, which took place at a specialty concussion program and private suburban high school, enrolled a cohort of adolescent athletes between 12 and 18 years old and included both healthy athletes (n = 134) and athletes with a diagnosis of sport-related concussion (SRC; n = 98). Researchers were interested in nine specific PLR metrics that objectively assess autonomic function, which occurs automatically, without a person's conscious effort.

The study found significant differences between concussed athletes and healthy adolescents for all PLR metrics except latency, or the time it takes for the pupil to respond to the light. Athletes with concussion had larger maximum and minimum pupil diameter, greater percentage constriction, and greater peak and average constriction and dilation velocity compared with healthy athletes. When the data were restricted to only concussions assessed within seven days of injury, seven out of the nine PLR metrics remained sensitive to identifying concussion as compared with healthy individuals.

The researchers also examined sex differences in the data. No sex differences were found in the healthy control group for any pupillary metric, confirming previously published research. However, there were differences observed for females with a concussion, who exhibited longer time to 75% pupillary re-dilation than males, which warrants further investigation to better characterize any sex differences in concussion.

Researchers hope these findings may lead to a future objective assessment tool for use in sports or urgent care settings, ultimately leading to more timely and accurate concussion diagnosis and treatment.

Ka-thump. Ka-thump. Ka-thump. Though we barely notice it most of the time, the steady beating of a human heart is an amazingly complex performance. Like an orchestra, thousands of cells have to master their individual performances as well as work together.

Now a team of scientists has created the first atlas of human heart cells, a collection of maps showing nearly half a million heart cells and identifying the role of each in the heart's symphony. The researchers examined six regions in 14 healthy donor hearts, creating a detailed database that provides a new basis of comparison for studying heart disease, the leading cause of death worldwide.

To understand what's going wrong in various forms of heart disease, "first we need to know what is normal," says Howard Hughes Medical Institute Investigator Christine Seidman, a cardiovascular geneticist at Harvard University and director of the Cardiovascular Genetics Center at Brigham and Women's Hospital. Seidman and colleagues describe the new heart atlas September 24, 2020, in the journal Nature.

"I can summarize my thoughts in one word: monumental," says cardiologist Douglas Mann of Washington University School of Medicine in St. Louis, who was not involved in the study. "I think it's a really big accomplishment and will be a tremendous source of reference for the field."

Heart cells have proven particularly difficult to study. Unlike some cancer cells and other tissues, there are no heart cells that can be grown indefinitely in the laboratory and studied. Instead, much cardiac research is done using mice, whose hearts have important differences from human hearts.

And healthy human hearts can be hard to find (most are used in transplants). Seidman's team relied on those unusual instances in which healthy hearts were rejected for transplantation and could be frozen for use in research. First, the researchers used a high-throughput sequencing method to define individual characteristics of every heart cell. They then mapped those cells in six regions of 14 human hearts, seven from men and seven from women. "For the first time, we have a zip code for each cell to know what population it belongs to," Seidman says.

The team also analyzed heart cells' RNA levels using fluorescent markers to glean molecular details of their function. Identifying not only where cells are, but which proteins they're producing, will be a particular boon for research, Mann says. For instance, by comparing cells in diseased hearts to those in healthy hearts using the atlas, researchers might pinpoint differences and target new therapies for heart disease.

Though the researchers studied a relatively small group of hearts ("fourteen people cannot replicate the world's population," Seidman says), the new atlas revealed some biological surprises. The team found previously unknown cell diversity in various parts of the heart. They also uncovered differences between the healthy hearts of males and females; females had a greater proportion of heart muscle cells, called cardiomyocytes, than males. That warrants more research, Seidman says, as those cells might hold clues to differences in heart disease between the sexes.

Still, "what we see is striking heterogeneity -- in terms of the diverse cell types that we now know make up the tissue of the human heart, and in terms of the regional differences within the heart," says cardiologist Hugh Watkins of Oxford University in England, who was not part of the study team. "It's certainly a much more complicated organ than many might have imagined!"

The atlas is part of the Human Cell Atlas initiative, an effort funded by the Chan Zuckerberg Initiative to map all the cell types in the human body. "It takes a big village to do this," Seidman says. Her group worked with an international team of experts on everything from heart surgery to computational biology in order to create the database atlas. All of the data are available at http://www.heartcellatlas.org.

Next, Seidman and her colleagues hope to expand the atlas to a more diverse population (the initial hearts were all from white donors). They are also beginning to compare the proteins made in healthy heart cells to those affected by heart disease.

"In due course, what we really want to know is how the different cell types fit together at the microscopic and functional level," Watkins says. "That's another ambitious goal, but the atlas provided here is an exciting start."

Scientists have created a detailed cellular and molecular map of the healthy human heart to understand how this vital organ functions and to shed light on what goes awry in cardiovascular disease.

The work, published in Nature Sept. 24 was led by investigators at Harvard Medical School, Brigham and Women's Hospital, the Wellcome Sanger Institute, Max Delbrück Center for Molecular Medicine (MDC) in Germany, Imperial College London and their global collaborators.

The team analyzed almost a half million individual cells to build the most extensive cell atlas of the human heart to date. The atlas shows the huge diversity of cells and reveals heart muscle cell types, cardiac protective immune cells and an intricate network of blood vessels. It also predicts how the cells communicate to keep the heart working.

The research is part of the Human Cell Atlas initiative to map every cell type in the human body. The new molecular and cellular knowledge of the heart promises to enable better understanding of heart disease and guide the development of highly individualized treatments.

The work also sets the stage for therapies based on regenerative medicine in the future, the researchers said.

Over a lifetime, the average human heart delivers more than 2 billion life-sustaining beats to the body. In doing so, it helps deliver oxygen and nutrients to cells, tissues and organs and enables the removal of carbon dioxide and waste products. Each day, the heart beats around 100,000 times with a one-way flow through four different chambers, varying speed with rest, exercise and stress. Every beat requires an exquisitely complex but perfect synchronization across various cells in different parts of heart. When this complex coordination goes bad, it can result in cardiovascular disease, the leading cause of death worldwide, killing an estimated 17.9 million people each year.

Detailing the molecular processes inside the cells of a healthy heart is critical to understanding how things go awry in heart disease. Such knowledge can lead to more precise, better treatment strategies for various forms of cardiovascular illness.

"Millions of people are undergoing treatments for cardiovascular diseases. Understanding the healthy heart will help us understand interactions between cell types and cell states that can allow lifelong function and how these differ in diseases," said study co-senior author Christine Seidman, professor of medicine in the Blavatnik Institute at Harvard Medical School and a cardiovascular geneticist at Brigham and Women's.

"Ultimately, these fundamental insights may suggest specific targets that can lead to individualized therapies in the future, creating personalized medicines for heart disease and improving the effectiveness of treatments for each patient," Seidman said.

This is what researchers set out to do in the new study.

The team studied nearly 500,000 individual cells and cell nuclei from six different regions of the heart obtained from 14 organ donors whose hearts were healthy but unsuitable for transplantation.

Using a combination of single-cell analysis, machine learning and imaging techniques, the team could see exactly which genes were switched on and off in each cell.

The researchers discovered major differences in the cells in different areas of the heart. They also observed that each area of the heart had specific subsets of cells--a finding that points to different developmental origins and suggests that these cells would respond differently to treatments.

"This project marks the beginning of new understandings into how the heart is built from single cells, many with different cell states," said study co-first author Daniel Reichart, research fellow in genetics at Harvard Medical School. "With knowledge of the regional differences throughout the heart, we can begin to consider the effects of age, exercise and disease and help push the field of cardiology toward the era of precision medicine."

"This is the first time anyone has looked at the single cells of the human heart at this scale, which has only become possible with large-scale single-cell sequencing," said Norbert Hübner, co-senior author and professor at Max Delbrück Center for Molecular Medicine. "This study shows the power of single-cell genomics and international collaboration," he added. "Knowledge of the full range of cardiac cells and their gene activity is a fundamental necessity to understand how the heart functions and to start to unravel how it responds to stress and disease."

As part of this study, the researchers also looked at blood vessels running through the heart in unprecedented detail. The atlas showed how the cells in these veins and arteries are adapted to the different pressures and locations and how this could help researchers understand what goes wrong in blood vessels during coronary heart disease.

"Our international effort provides an invaluable set of information to the scientific community by illuminating the cellular and molecular details of cardiac cells that work together to pump blood around the body," said co-senior author Michela Noseda of Imperial College, London. "We mapped the cardiac cells that can be potentially infected by SARS-CoV-2 and found that specialized cells of the small blood vessels are also virus targets," she said. "Our datasets are a goldmine of information to understand subtleties of heart disease."

The researchers also focused on understanding cardiac repair, looking at how the immune cells interact and communicate with other cells in the healthy heart and how this differs from skeletal muscle.

Further research will include investigating whether any heart cells could be induced to repair themselves.

"This great collaborative effort is part of the global Human Cell Atlas initiative to create a 'Google map' of the human body," said Sarah Teichmann of the Wellcome Sanger Institute, co-senior author of the study and co-chair of the Human Cell Atlas Organising Committee.

"Openly available to researchers worldwide, the Heart Cell Atlas is a fantastic resource, which will lead to new understanding of heart health and disease, new treatments and potentially even finding ways of regenerating damaged heart tissue," she said.

Being held by a parent with skin-to-skin contact reduces how strongly a newborn baby's brain responds to a painful medical jab, finds a new study led by researchers at UCL and York University, Canada.

The scientists report in the European Journal of Pain that there was more activity in the brains of newborn babies in reaction to the pain when a parent was holding them through clothing, than without clothing.

Joint senior author, Dr Lorenzo Fabrizi (UCL Neuroscience, Physiology & Pharmacology) said: "We have found when a baby is held by their parent, with skin-on-skin contact, the higher-level brain processing in response to pain is somewhat dampened. The baby's brain is also using a different pathway to process its response to pain.

"While we cannot confirm whether the baby actually feels less pain, our findings reinforce the important role of touch between parents and their newborn babies."

The study involved 27 infants, 0-96 days old and born premature or at term age, at University College London Hospitals. The researchers were measuring their response to a painful but clinically required heel lance (blood test). Brain activity was recorded with EEG (electroencephalography) electrodes placed on the scalp.

The babies were either held by their mother skin-to-skin (wearing a diaper, against their mother's chest), or held by their mother with clothing, or else lying in a cot or incubator (most of these babies were swaddled).

The researchers found that the initial brain response to the pain was the same, but as the heel lance elicited a series of four to five waves of brain activity, the later waves of activity were impacted by whether the baby was held skin-to-skin or with clothing.

Joint senior author, Professor Rebecca Pillai Riddell (Department of Psychology, York University, Canada) said: "The slightly delayed response was dampened if there was skin contact with their mother, which suggests that parental touch impacts the brain's higher level processing. The pain might be the same, but how the baby's brain processes and reacts to that pain depends on their contact with a parent.

"Our findings support the notion that holding a newborn baby against your skin is important to their development."

The brains of the babies that remained in the cot or incubator also reacted less strongly to the pain than those held in clothing, but the researchers say that may be because the babies were not disrupted by being picked up before the procedure, or else due to the success of the sensitive, individualised care they were provided.

The babies' behaviour was not significantly different between the groups, although the skin-to-skin group did exhibit slightly reduced responses in terms of facial expression and heart rate. Other studies have found that skin-to-skin contact with a parent does affect baby behaviour, and may reduce how strongly they react to pain, but those studies did not investigate the brain response.

In the current study, the babies' brain responses were not only dampened in the skin-to-skin group, but also followed a different neural pathway.

First author, Dr Laura Jones (UCL Neuroscience, Physiology & Pharmacology) said: "Newborn babies' brains have a high degree of plasticity, particularly those born preterm, and their development is highly dependent on interactions with their parents. Our findings may lend new insights into how babies learn to process threats, as they are particularly sensitive to maternal cues."

Co-author Dr Judith Meek (University College London Hospitals) said: "Parents and clinicians have known for many years how important skin to skin care is for babies in NICU. Now we have been able to demonstrate that this has a solid neurophysiological basis, which is an exciting discovery."