Culture

Study using electronic health records of 236,379 COVID-19 patients mostly from the USA estimates that one in three COVID-19 survivors (34%) were diagnosed with a neurological or psychiatric condition within six months of infection.

Anxiety (17%) and mood disorders (14%) were the most common. Neurological diagnoses such as stroke and dementia were rarer, but not uncommon in those who had been seriously ill during COVID-19 infection. For example, of those who had been admitted to intensive care, 7% had a stroke and almost 2% were diagnosed with dementia.

These diagnoses were more common in COVID-19 patients than in flu or respiratory tract infection patients over the same time period, suggesting a specific impact of COVID-19.

Authors say their findings should aid service planning and highlight need for ongoing research.

One in three COVID-19 survivors received a neurological or psychiatric diagnosis within six months of infection with the SARS-CoV-2 virus, an observational study of more than 230,000 patient health records published in The Lancet Psychiatry journal estimates. The study looked at 14 neurological and mental health disorders [1].

Professor Paul Harrison, lead author of the study, from the University of Oxford, UK, said: "These are real-world data from a large number of patients. They confirm the high rates of psychiatric diagnoses after COVID-19, and show that serious disorders affecting the nervous system (such as stroke and dementia) occur too. While the latter are much rarer, they are significant, especially in those who had severe COVID-19." [2]

"Although the individual risks for most disorders are small, the effect across the whole population may be substantial for health and social care systems due to the scale of the pandemic and that many of these conditions are chronic. As a result, health care systems need to be resourced to deal with the anticipated need, both within primary and secondary care services." [2]

Since the COVID-19 pandemic began, there has been growing concern that survivors might be at increased risk of neurological disorders. A previous observational study by the same research group reported that COVID-19 survivors are at increased risk of mood and anxiety disorders in the first three months after infection [3]. However, until now, there have been no large-scale data examining the risks of neurological as well as psychiatric diagnoses in the six months after COVID-19 infection.

This latest study analysed data from the electronic health records of 236,379 COVID-19 patients from the US-based TriNetX network, which includes more than 81 million people. Patients who were older than 10 years and who became infected with the SARS-CoV-2 virus after 20 January 2020, and were still alive on 13 December 2020, were included in the analysis. This group was compared with 105,579 patients diagnosed with influenza and 236,038 patients diagnosed with any respiratory tract infection (including influenza).

Overall, the estimated incidence of being diagnosed with a neurological or mental health disorder following COVID-19 infection was 34%. For 13% of these people it was their first recorded neurological or psychiatric diagnosis.

The most common diagnoses after COVID-19 were anxiety disorders (occurring in 17% of patients), mood disorders (14%), substance misuse disorders (7%), and insomnia (5%). The incidence of neurological outcomes was lower, including 0.6% for brain haemorrhage, 2.1% for ischaemic stroke, and 0.7% for dementia (see table 2).

Risks of a neurological or psychiatric diagnosis were greatest in, but not limited to, patients who had severe COVID-19. Compared to the overall 34% incidence, a neurological or psychiatric diagnosis occurred in 38% of those who had been admitted to hospital, 46% of those in intensive care, and 62% in those who had delirium (encephalopathy) during their COVID-19 infection. This gradient of risk applied to individual disorders too. For example, 2.7% of people needing intensive care and 3.6% of people with encephalopathy had a brain haemorrhage (compared to 0.3% in people without hospitalisation); 6.9% and 9.4% had ischaemic stroke (compared to 1.3% without hospitalisation); 1.7% and 4.7% developed dementia (0.4% without hospitalisation); and 2.8% and 7% were diagnosed with a psychotic disorder (0.9% without hospitalisation) (see table 2).

The authors also looked at people who experienced flu and other respiratory tract infections over the same time frame to help understand whether these neurological and mental health complications were linked specifically to COVID-19. After taking into account underlying health characteristics, such as age, sex, ethnicity, and existing health conditions, there was overall a 44% greater risk of neurological and mental health diagnoses after COVID-19 than after flu, and a 16% greater risk after COVID-19 than with respiratory tract infections. As a result, the authors say that COVID-19 does lead to a greater risk of neurological and psychiatric disorders than these other health conditions. However, this was not seen for all conditions; there was no clear evidence that COVID-19 led to an increased risk of parkinsonism or and Guillain-Barré syndrome.

Dr Max Taquet, a co-author of the study, from the University of Oxford, UK, said: "Our results indicate that brain diseases and psychiatric disorders are more common after COVID-19 than after flu or other respiratory infections, even when patients are matched for other risk factors. We now need to see what happens beyond six months. The study cannot reveal the mechanisms involved, but does point to the need for urgent research to identify these, with a view to preventing or treating them." [2]

The authors note several limitations to their study. Firstly, the completeness and accuracy of the electronic health records is not known. Secondly, many people with COVID-19 have mild or no symptoms and do not present for health care, therefore, the people studied here are likely to have been more severely affected than in the general population. Thirdly, the severity and course of the neurological and psychiatric disorders is not known.

Writing in a linked Comment article, Dr Jonathan Rogers, who was not involved in the study, from University College London (UCL), UK, said: "[this] study points us towards the future, both in its methods and implications. Researchers need to be able to observe and anticipate the neurological and psychiatric outcomes of future emerging health threats by use of massive, international, real-world clinical data. Selection biases will remain an issue, not necessarily mitigated by sample size,10 and thus the onus should be on countries with public health-care systems to enable truly comprehensive national data to be available for research. Sadly, many of the disorders identified in this study tend to be chronic or recurrent, so we can anticipate that the impact of COVID-19 could be with us for many years."

CORVALLIS, Ore. - At a time when lumber prices are skyrocketing, an Oregon State University researcher has developed a new way to predict the future price of logs that uses readily accessible economic information.

"Log prices are really variable," said Jeff Reimer, a professor of applied economics at Oregon State. "That makes this a difficult business, whether you are land manager, mill owner, timberland investor or, as we are seeing now, a home builder."

The timber industry is critical to the economy of many regions of the world, including the Pacific Northwest. The health of the timber industry can be measured in various ways, including harvest levels, employment in timber harvesting and at mills, and lumber demand. Yet the prices of cut and delivered logs may be the most direct way to monitor the condition of timber markets, Reimer said.

Reimer's study, recently published in the journal Forest Policy and Economics, focused on Douglas-fir, the most commercially important timber species in the Pacific Northwest.

He found that simply knowing the number of housing permits issued in a month can explain about 46.8% of the variation in log prices over time. Adding additional information - including the monthly inventory of homes, mortgage rates, the exchange rate with Canada (also a big timber supplier) and the Case-Shiller home price index - explains about 74.3% of the price variation.

"These variables are readily observable and thus can be used by industry decision-makers to make better predictions about future values of logs and timberland," said Reimer, a professor in Oregon State's College of Agricultural Sciences.

In the paper, Reimer cites data that shows the average price of Douglas-fir logs between 2005 and 2020 was $631 per MBF (a forestry term for 1,000 board feet of lumber) of mill logs in southern Oregon. One board foot of lumber is 1 square foot and 1-inch thick.

Yet this average disguises a great deal of variation in price. From 2005 to 2020, the price ranged from $346 per MBF to $924 per MBF. The difference between the minimum and maximum was $578, nearly as large as the 15-year average price itself.

Since the paper was written, lumber prices have increased more, reaching the $1,000 per MBF range. The National Association of Home Builders recently released a report that said lumber prices have added an average of $24,000 to the cost of a new home.

"Right now log prices are phenomenally high," Reimer said. "It can feel like feast or famine in this industry but there is a logic that underlies the changes. The benefit of this paper is that we have identified a few pieces of readily observable information that allow people in the timber industry to make solid predictions about what will be happening in the next six months or so."

BOSTON - Men and women whose mothers experienced stressful events during pregnancy regulate stress differently in the brain 45 years later, results of a long-term study demonstrate.

In a unique sample of 40 men and 40 women followed from the womb into their mid-forties, the brain imaging study showed that exposure during fetal development to inflammation-promoting natural substances called cytokines, produced by mothers under negative stress, results in sex-associated differences in how the adult brain responds to negative stressful situations more than 45 years after birth, reports Jill M. Goldstein, PhD, founder and executive director of the Innovation Center on Sex Differences in Medicine (ICON) at Massachusetts General Hospital (MGH) and her co-authors.

The researchers found that abnormal levels of pro-inflammatory cytokines produced in mothers during pregnancy and the balance between pro-inflammatory and anti-inflammatory cytokines affect brain development differences by sex in their offspring that continue throughout life.

The findings are published in Proceedings of the National Academy of Sciences (PNAS).

"We know that there are developmental roots to major psychiatric disorders such as depression, schizophrenia and bipolar disorder, and we know that these roots begin in fetal development. We also know these disorders are associated with abnormalities in the brain circuitry that regulates stress--circuitry that is intimately tied to regulating our immune system," says Goldstein, a professor of Psychiatry and Medicine at Harvard Medical School. "Given that the stress circuitry consists of regions that develop differently in the male and female brain during particular periods of gestation and they function differently across our lifespans, we hypothesized that dysregulation of this circuitry in prenatal development would have lasting differential impact on the male and female brain in people with these disorders. We were particularly interested in the role of the immune system, in which some abnormalities are shared across these disorders."

Goldstein and colleagues used functional magnetic resonance imaging, which measures brain activity by showing differences in blood flow within and between different areas of the brain. The researchers found that exposure to pro-inflammatory cytokines in the womb was associated with sex differences in how areas of the brain are activated and communicate with one another under negative stressful conditions in midlife.

For example, they found that in both sexes, lower maternal levels of tumor necrosis factor-alpha (TNFα) a pro-inflammatory cytokine, were significantly associated with higher activity in the hypothalamus, a region of the brain that, among other functions, coordinates brain activity that regulates the release of stress hormones, like cortisol.

In contrast, lower levels of TNFα were also associated with more active communication between the hypothalamus and the anterior cingulate in men only. The anterior cingulate is an area of the brain associated with impulse control and emotion.

In women only, higher prenatal exposure to interleukin-6, another inflammatory cytokine, was associated with higher levels of activity in the hippocampus, a brain region important for inhibitory control of arousal.

Lastly, they found that the ratio between TNFα and the anti-inflammatory cytokine interleukin-10 was associated with sex-dependent effects on activity in the hypothalamus and its communication with the hippocampus, which provides inhibitory control of arousal in the hypothalamus under stress.

"Given that these psychiatric disorders are developing differently in the male and female brain, we should be thinking about sex-dependent targets for early therapeutic intervention and prevention," says Goldstein.

UNIVERSITY PARK, Pa. -- Approximately 40,000 children in the United States may have lost a parent to COVID-19 since February 2020, according to a statistical model created by a team of researchers. The researchers anticipate that without immediate interventions, the trauma from losing a parent could cast a shadow of mental health and economic problems well into the future for this vulnerable population.

In the researchers' model, for approximately every 13th COVID-related death, a child loses one parent. Children who lose a parent are at higher risk of a range of problems, including traumatic prolonged grief and depression, lower educational attainment, economic insecurity and accidental death or suicide, said Ashton Verdery, associate professor of sociology, demography and social data analytics and Institute for Computational and Data Sciences co-hire, Penn State.

"When we think of COVID-19 mortality, much of the conversation focuses on the fact that older adults are the populations at greatest risk. About 81% of deaths have been among those ages 65 and older according to the CDC (Centers for Disease Control and Prevention)," said Verdery, who is also an affiliate of the Population Research Institute at Penn State. "However, that leaves 19% of deaths among those under 65 -- 15% of deaths are among those in their 50s and early 60s and 3% are among those in their 40s. In these younger age groups, substantial numbers of people have children, for whom the loss of a parent is a potentially devastating challenge."

Three-quarters of the children who lost a parent are adolescents, but one quarter are elementary-aged children, Verdery said.

The statistics of parental death are grimmer for Black families, which have been disproportionately impacted by the pandemic, according to the researchers, who report their findings in today's (April 5) issue of JAMA Pediatrics. The team estimated that 20% of the children who lost a parent are Black even though only 14% of children in the U.S. are Black.

The model also suggests that parental deaths due to COVID-19 will increase the country's total cases of parental bereavement by 18% to 20% over what happens in a typical year, further straining an already stretched system that does not connect all children who are eligible to adequate resources.

Historical comparison

As a historical comparison, the number of children who lost a parent to COVID-19 is about 13 times the approximate 3,000 children who lost a parent in attacks of Sept. 11, 2001. After those attacks, the federal government initiated several programs to support the families of the victims.

Parentally bereaved children in the pandemic may face unique challenges. The social isolation, institutional strain and economic struggles caused by the pandemic may strain access to potential sources of support for children. Further, with many children out of schools and less connected to other family and community supports, suffering children may be less likely to be recognized.

"Teachers are such a vital resource in terms of identifying and helping at-risk children, and it is harder for them to do that when schools are operating remotely and teachers are so overburdened, making it vital to resume in-person instruction safely and support worn-out educators," Verdery said.

The researchers added that as pandemic deaths increase, that shadow of mental health and economic ills may only grow longer for children.

They suggest that equal -- or greater -- national efforts are needed to help children who have lost parents in the pandemic.

"I think the first thing we need to do is to proactively connect all children to the available supports they are entitled to, like Social Security child survivor benefits -- research shows only about half of eligible children are connected to these programs in normal circumstances, but that those who do fare much better," said Verdery. "We should also consider expanding eligibility to these resources. Second, a national effort to identify and provide counseling and related resources to all children who lose a parent is vital."

Research suggests that brief, evidence-based interventions delivered widely could help prevent severe psychological problems, although some children may need longer-term support.

Using kinship networks of white and Black individuals, drawn from demographic simulations, the researchers estimate the expected number of children ages 0 to 17 who would lose a parent to COVID-19, called the parental bereavement multiplier. The model suggested that .078 children aged 0 to 17 years old would be parentally bereaved for each COVID-19 related death, or about one for each 13 deaths. The team then used the multiplier to estimate the scope of parental bereavement based on various scenarios of COVID-19 casualty figures.

PHILADELPHIA-- Approximately 6.5 million people are under correctional supervision in the United States on any given day. Justice-involved individuals (people currently or recently in prison or jail, on probation or parole, or arrested) experience higher rates of substance use disorders than the general population. In fact, among people with opioid use disorder (OUD), more than half have reported contact with the criminal justice system.

Numerous clinical studies have shown that medications for OUD -- specifically, methadone or buprenorphine -- lead to superior outcomes for retention in treatment, reduced illicit opioid use, and decreased opioid-related overdose rates and serious acute care compared with treatments that rely on psychosocial interventions alone. However, due to a number of barriers, including access to health insurance, access to medications for OUD for those on parole, formerly incarcerated, or recently arrested remain significantly lower than the general population.

A new study published today in Health Affairs reveals that Medicaid expansion is associated with substantial improvements in access to medications for OUD for individuals referred to substance use treatment by criminal justice agencies. However, the study, led by Utsha Khatri, MD, an emergency medicine physician and a research fellow in the National Clinician Scholars Program and Perelman School of Medicine at the University of Pennsylvania, also reveals that individuals referred for treatment by the criminal justice system were substantially less likely to receive medications for OUD as part of the treatment plan when compared with those referred through all other sources.

"The response to substance use disorders in the United States has historically been criminalization. As a result, many individuals with OUD are involved with the criminal justice system, and this may influence their treatment prospects," says Khatri. "Any policy or intervention that seeks to mitigate the harms of risky substance use must also consider the impact among populations with criminal justice involvement specifically."

The study evaluated 10 years of data from the Treatment Episode Data Set-Admissions (TEDS-A), a national survey of substance treatment facility admissions conducted by the Substance Abuse and Mental Health Services Administration (SAMHSA). Researchers reviewed the data for a flag indicating that medications for OUD were part of the treatment plan during the admission.

The data revealed a total of 3,209,691 adults with OUD between 2008 and 2017. Of these, 21% were referred by a criminal justice agency - such as police, probation officers, judges, or prosecutors. It also showed that the proportion of people with OUD receiving medications as a part of their treatment increased substantially between 2008 and 2017 across all referral sources. Overall, though, individuals referred by these agencies were less likely to receive medications for OUD (MOUD) than were those referred by other sources during the study period, although this disparity narrowed slightly after Medicaid expansion: among people with OUD referred by a criminal justice agency, the proportion of people receiving MOUD increased from 6.3% in 2008 to 16.5% in 2017.

"Our study shows that Medicaid expansion is an important tool for expanding access to evidence-based care for people involved in the criminal justice system," says senior author Tyler Winkelman, MD, MSc, Co-Director of the Health, Homelessness, and Criminal Justice lab at the Hennepin Healthcare Research Institute and a clinician-investigator in the Division of General Internal Medicine at Hennepin Healthcare. "However, Medicaid alone will not entirely close gaps in care between people with and without criminal justice involvement. Additional work is needed to understand key drivers of the persistent disparities we identified."

Researchers say that there is room for improvement in addressing OUD treatment, both for people with and without criminal justice involvement. There is an abundance of data that consistently shows the use of methadone or buprenorphine is associated with reduced risk for overdose and opioid-related morbidity and mortality when compared with other treatment modalities, such as abstinence-only approaches, or behavioral interventions. However, incarceration-related stigma and preferences of criminal justice agencies might also influence the treatment plans among individuals with criminal justice involvement.

"Medicaid expansion improves evidence-based treatment for individuals with criminal justice involvement and OUD, and should be prioritized by states that have not yet expanded Medicaid," concludes Khatri, "However, additional policy changes, like unobstructed access to medications for OUD, are likely needed to reduce persistent treatment disparities."

PHILADELPHIA-- While the emergency department (ED) functions as an integral part of the United States healthcare safety net by handling all medical complaints regardless of insurance status, ED visits are expensive, and many are for lower-acuity conditions that may be amenable to care in other settings. Previous research has suggested that greater availability of urgent care centers - freestanding facilities with extended hours that staff emergency physicians, primary care physicians, or nurse practitioners, and focus on a broad range of lower acuity complaints, like rash, muscle strain, bronchitis, and urinary tract infection - helps decrease ED visits, but whether the centers reduce or increase net spending for patients and insurers has yet to be determined.

A study published today in Health Affairs documents for the first time that urgent care centers are associated with increased spending for lower-acuity visits across EDs and urgent care centers. Urgent care centers increase the number of people seeking care. For every 37 urgent care visits, one fewer lower acuity ED visit occurs. Urgent care centers increase access, but pose risks for health insurers and patients who must pay these increased costs.

"Previous studies have used different approaches to show that urgent care centers reduce emergency department visits for lower acuity conditions," says senior author Ari Friedman, MD, PhD, an assistant professor of Emergency Medicine, Medical Ethics and Health Policy in the Perelman School of Medicine at the University of Pennsylvania. "Our findings confirm ED visits go down, but then show that total costs across both settings actually go up, not down."

Researchers conducted analyses using a claims database with more than twenty million patients per year covered by a national managed care plan from January 1, 2008, to December 31, 2019, spanning all fifty states. They assessed how the number of lower acuity ED visits changed when an urgent care center visit occurred within each ZIP code.

Across the twelve years of the study period, researchers found that by 2019, the opening of an urgent care center led to a decline in the number of lower acuity ED visits, and that these ED visits were approximately ten times more expensive than urgent care center visits. Researchers found that the substitution ratio (the number of urgent care visits needed to deter a single ED visit) was high: an increase of 37 urgent care center visits was associated with the substitution of a single lower-acuity ED visit. While urgent care center visits are less expensive than ED visits, it's not enough to offset this difference. Each $1,646 lower-acuity ED visit prevented was offset by a $6,327 increase in urgent care center costs.

First author Bill Wang notes, "We expected urgent care centers to increase access and decrease emergency department visits, but we were surprised by just how many urgent care visits it took to substitute for a lower acuity ED visit."

Friedman points out that cost saving shouldn't be the only factor considered when determining where and how to access care. "We should evaluate new care models and interventions on the same standard as we evaluate new drugs - do they improve lives more than they increase costs? That's the important metric. But the cost increases here are so large that the value side of the equation would have to do a lot of work to make it pay off."

The authors note that the possibility remains that the availability of urgent care centers in a market, when combined with other interventions - like telemedicine, primary care, or changes to benefits - could be effective in augmenting the substitution ratio.

Beyond access, the clinical benefit of these additional visits to unscheduled care requires further research, as does the impact and role of telemedicine, says Friedman. "We're watching the field with interest."

What The Study Did: Researchers estimated and projected the number of children in the United States affected by the death of a parent from COVID-19.

Authors: Rachel Kidman, Ph.D., of Stony Brook University in Stony Brook, New York, is the corresponding author.

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

(doi:10.1001/jamapediatrics.2021.0161)

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

An interdisciplinary team led by KU Leuven and Stanford has identified 76 overlapping genetic locations that shape both our face and our brain. What the researchers didn't find is evidence that this genetic overlap also predicts someone's behavioural-cognitive traits or risk of conditions such as Alzheimer's disease. This means that the findings help to debunk several persistent pseudoscientific claims about what our face reveals about us.

There were already indications of a genetic link between the shape of our face and that of our brain, says Professor Peter Claes from the Laboratory for Imaging Genetics at KU Leuven, who is the joint senior author of the study with Professor Joanna Wysocka from the Stanford University School of Medicine. "But our knowledge on this link was based on model organism research and clinical knowledge of extremely rare conditions," Claes continues. "We set out to map the genetic link between individuals' face and brain shape much more broadly, and for commonly occurring genetic variation in the larger, non-clinical population."

Brain scans and DNA from the UK Biobank

To study genetic underpinnings of brain shape, the team applied a methodology that Peter Claes and his colleagues had already used in the past to identify genes that determine the shape of our face. Claes: "In these previous studies, we analysed 3D images of faces and linked several data points on these faces to genetic information to find correlations." This way, the researchers were able to identify various genes that shape our face.

For the current study, the team relied on these previously acquired insights as well as the data available in the UK Biobank, a database from which they used the MRI brain scans and genetic information of 20,000 individuals. Claes: "To be able to analyse the MRI scans, we had to measure the brains shown on the scans. Our specific focus was on variations in the folded external surface of the brain - the typical 'walnut shape'. We then went on to link the data from the image analyses to the available genetic information. This way, we identified 472 genomic locations that have an impact on the shape of our brain. 351 of these locations have never been reported before. To our surprise, we found that as many as 76 genomic locations predictive of the brain shape had previously already been found to be linked to the face shape. This makes the genetic link between face and brain shape a convincing one."

The team also found evidence that genetic signals that influence both brain and face shape are enriched in the regions of the genome that regulate gene activity during embryogenesis, either in facial progenitor cells or in the developing brain. This makes sense, Wysocka explains, as the development of the brain and the face are coordinated. "But we did not expect that this developmental cross-talk would be so genetically complex and would have such a broad impact on human variation."

No genetic link with behaviour or neuropsychiatric disorders

At least as important is what the researchers did not find, says Dr Sahin Naqvi from the Stanford University School of Medicine, who is the first author of this study. "We found a clear genetic link between someone's face and their brain shape, but this overlap is almost completely unrelated to that individual's behavioural-cognitive traits."

Concretely: even with advanced technologies, it is impossible to predict someone's behaviour based on their facial features. Peter Claes continues: "Our results confirm that there is no genetic evidence for a link between someone's face and that individual's behaviour. Therefore, we explicitly dissociate ourselves from pseudoscientific claims to the contrary. For instance, some people claim that they can detect aggressive tendencies in faces by means of artificial intelligence. Not only are such projects completely unethical, they also lack a scientific foundation."

In their study, the authors also briefly address conditions such as Alzheimer's, schizophrenia, and bipolar disorder. Claes: "As a starting point, we used the results that were previously published by other teams about the genetic basis of such neuropsychiatric disorders. The possible link with the genes that determine the shape of our face had never been examined before. If you compare existing findings with our new ones, you see a relatively large overlap between the genetic variants that contribute to specific neuropsychiatric disorders and those that play a role in the shape of our brain, but not for those that contribute to our face." In other words: our risk of developing a neuropsychiatric disorder is not written on our face either.

Journal Name: Nature Methods

Title of the Article: Discovering multiple types of DNA methylation from individual bacteria and microbiome using nanopore sequencing

Corresponding Author: Gang Fang, PhD

Bottom Line:

Bacterial DNA methylation occurs at diverse sequence contexts and plays important functional roles in cellular defense and gene regulation. An increasing number of studies have reported that bacterial DNA methylation has important roles affecting clinically relevant phenotypes such as virulence, host colonization, sporulation, biofilm formation, among others.

Bacterial methylomes contain three primary forms of DNA methylation: N6-methyladenine (6 mA), N4-methylcytosine (4mC) and 5-methylcytosine (5mC). The widely used bisulfite sequencing for DNA methylation mapping in mammalian genomes are not effective at resolving bacterial methylomes. Single molecule real-time (SMRT) can effectively map 6mA and 4mC events, and have empowered the study of >4,000 bacterial methylomes in the past ten years. However, SMRT sequencing cannot effectively detect 5mC methylation.

Results: In this work, we developed a new method that enables nanopore sequencing for broadly applicable methylation discovery. We applied it to individual bacteria and the gut microbiome for reliable methylation discovery. In addition, we demonstrated the use of DNA methylation for high resolution microbiome analysis, mapping mobile genetic elements with their host genomes directly from microbiome samples.

Why the Research Is Interesting:

To battle with bacterial pathogens. Antibiotics resistance poses great risk to public health. To best battle with bacterial pathogens, it is important to discover novel drug targets. Increasing evidence suggests that bacterial DNA methylation plays important roles in regulating bacterial physiology such as virulence, sporulation, biofilm formation, pathogen-host interaction etc. The new method in this work allows researchers to more effectively discover novel DNA methylation from bacterial pathogens, opening new opportunities to discovery novel targets to design new inhibitors.

To better understand microbiome. Despite growing appreciation for the role of microbiome in human health, comprehensive characterization of microbiomes remains difficult. To effectively harness the therapeutic power of microbiome, it is important to understand the specific bacteria species and particular strains in human microbiome. Our new method combines the power of long read sequencing and bacterial DNA methylation to resolve complex microbiome samples into individual species and strains. So, it will also empower higher resolution characterization of human microbiome for medical applications.

The power of methylation based mapping of mobile genetic elements (often encoding antibiotics resistance genes) to their host genomes also helps tracking the transmission of antibiotic resistance genes.

How: By examining three types of DNA methylation in a large diversity of sequence contexts, we observed that nanopore sequencing signal displays complex heterogeneity across methylation events of the same type. To capture this complexity and enable nanopore sequencing for broadly applicable methylation discovery, we generated a training dataset from an assortment of bacterial species and developed a novel method that couples the identification and fine mapping of the three forms of DNA methylation into a multi-label classification design. We evaluated the method and then applied it to individual bacteria and mouse gut microbiome for reliable methylation discovery. In addition, we demonstrated in the microbiome analysis the use of DNA methylation for binning metagenomic contigs, associating mobile genetic elements with their host genomes, and for the first time, identifying misassembled metagenomic contigs.

Said Mount Sinai's Gang Fang of the work:

DNA methylation plays important roles in the human genome, and is widely studied in health and various diseases. DNA methylation is also prevalent in bacteria, but our current understanding is still at a relatively early stage.

An increasing number of studies have reported that bacterial DNA methylation plays important roles in regulating medically relevant phenotypes of pathogenic bacteria, such as virulence, biofilm formation, virulence, sporulation, among others.

Broader and deeper study of bacterial DNA methylation requires reliable technologies, and our new method fills an important gap in that it now enables the use of Nanopore sequencing to make new discoveries from bacterial genomes.

This novel method has broad utility for discovering different forms of DNA methylation from bacteria, assisting functional studies of epigenetic regulation in bacteria, and exploiting bacterial epigenomes for more effective metagenomic analyses.

What The Study Did: A clinical risk assessment tool developed in China was tested with a group of patients in Spain to evaluate its ability to predict critical illness among patients hospitalized with COVID-19 in Europe.

Authors: Oscar Moreno-Perez, M.D., Ph.D., of the Alicante General University Hospital-Alicante Institute of Sanitary and Biomedical Research in Alicante, Spain, is the corresponding author.

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

(doi:10.1001/jamainternmed.2021.0491)

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

What The Study Did: Researchers investigated the association of sociodemographic factors and blood group type with the risk of SARS-CoV-2 infection and severity of COVID-19.

Authors: Jeffrey L. Anderson, M.D., of the Intermountain Medical Center Heart Institute in Salt Lake City, is the corresponding author.

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

(doi:10.1001/jamanetworkopen.2021.7429)

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

Public trust in the federal Centers for Disease Control and Prevention has fallen during the coronavirus pandemic, with the decline bringing overall population-level trust in the agency to the same lower level of trust long held by Black Americans about the agency, according to a new RAND Corporation study.

Surveys done among a representative group of Americans in May and October of 2020 show about a 10% decline in trust of the CDC over that period.

In contrast, the same research found that public trust in the U.S. Postal Service and the Federal Emergency Management Agency increased significantly over the period, despite those agencies facing their own challenges.

"The Biden administration will have an uphill battle in rehabilitating trust in the CDC at this critical junction in the coronavirus pandemic," said Michael Pollard, lead author of the study and a senior social scientist at RAND, a nonprofit research organization. "A key challenge in the months ahead will be to identify who will be viewed as trusted messengers regarding vaccines and public health policies."

The study found that non-Hispanic white and Hispanic respondents reported significant declines in trust in the CDC, while the changes were not statistically significant for non-Hispanic Black or "other race" respondents.

"There is remarkable consistency and convergence in reported levels of trust in the CDC across these subgroups after the declines," Pollard said. "Lack of trust among Black Americans has been a well-publicized concern regarding the COVID-19 vaccine rollout, and the convergence in lower levels of trust across race/ethnicity highlights a key challenge that the CDC now faces."

Black Americans have historically held a low level of trust in the CDC and other health institutions, widely seen as a legacy of past racism in the nation's health system.

RAND researchers surveyed a representative sample of more than 2,000 Americans in May 2020, asking to rate their trust of the CDC, the USPS and FEMA on a scale of 0 to 10. Most of the participants were surveyed again in October 2020. All participants were part of the RAND American Life Panel, a nationally representative internet panel.

The survey found that trust in the CDC fell from 7.6 in May to 7 in October. Meanwhile, trust in the Postal Service rose from 6.9 in May to 7.7 in October; trust in FEMA rose from 6.4 in May to 6.7 in October.

Drop in trust of the CDC was particularly significant among people who intended to vote for a candidate other than Joe Biden in the 2020 presidential election or did not intend to vote at all, suggesting that views of the CDC are now strongly politicized. Similar politicization was not observed for FEMA or the USPS.

"The public trust in federal government agencies has never been as important as during the current COVID-19 pandemic, yet public suspicions of scientific experts and distrust of government institutions are increasing for a variety of reasons," said Lois Davis, co-author of the report and a senior policy researcher at RAND. "Reasons for this include a blurring of the line between opinion and fact, and access to more sources of conflicting information."

Researchers say one strategy that may help the CDC rebuild trust and depoliticize the public's views of the agency is to ensure that the public understands the scientific rationale for policy changes and guidance during the COVID-19 pandemic.

New research suggests anxiety among men transitioning into parenthood is significantly higher than reported by the global World Health Organization (WHO) regional prevalence rates.

In a new study published in The Journal of Psychosomatic Obstetrics & Gynecology, researchers from the Colorado School of Public Health on the University of Colorado Anschutz Medical Campus studied the prevalence of anxiety among fathers during the perinatal period, which includes pregnancy through the first year of postpartum.

"The transition to parenthood is a major life event that's often accompanied with new challenges related to financial, relationship, and work-life balance concerns. Despite those changes happening for both men and women, not much is known about the prevalence of anxiety among new fathers," said Jenn Leiferman, PhD, professor at the Colorado School of Public Health. "To our knowledge, our study is the first meta-analysis to explore the prevalence rates of anxiety among both fathers and mothers during the perinatal period."

The researchers reviewed eligible studies representing more than 40,000 participants that have published between 1995-2020. The researchers found that the overall estimate of anxiety among men during the perinatal period was nearly 11 percent, with rates being lower during pregnancy (9.9 percent) than during the first year postpartum (11.7 percent).

These rates are considerably higher than the global WHO regional prevalence rates for anxiety among men that range between 2.2 to 3.8 percent, suggesting the transition into parenthood may increase risk for anxiety in men.

In terms of anxiety among mothers, the researchers found an estimated 17.6 percent of women experience it during the perinatal period. This is also substantially higher than global WHO regional preferences for anxiety among women, but in line with estimates for maternal anxiety from other meta-analyses.

"The prevalence of anxiety and depression among men is talked about less as a society, even though research shows men are more likely to commit suicide or abuse alcohol than women. It's important that we create more transparency around men's mental health issues. Our hope is by creating awareness, we can help people get help earlier when needed," said Leiferman.

The researchers suggest that many men suffer anxiety during the transition to parenthood, starting as soon as the first trimester throughout the first year postpartum. Given this, identifying appropriate support for new fathers as well as early identification and treatment efforts for paternal anxiety are needed.

ORLANDO, April 5, 2021 - A new study from the University of Central Florida suggests that masks and a good ventilation system are more important than social distancing for reducing the airborne spread of COVID-19 in classrooms.

The research, published recently in the journal Physics of Fluids, comes at a critical time when schools and universities are considering returning to more in-person classes in the fall.

"The research is important as it provides guidance on how we are understanding safety in indoor environments," says Michael Kinzel, an assistant professor in UCF's Department of Mechanical and Aerospace Engineering and study co-author.

"The study finds that aerosol transmission routes do not display a need for six feet social distancing when masks are mandated," he says. "These results highlight that with masks, transmission probability does not decrease with increased physical distancing, which emphasizes how mask mandates may be key to increasing capacity in schools and other places."

In the study, the researchers created a computer model of a classroom with students and a teacher, then modeled airflow and disease transmission, and calculated airborne-driven transmission risk.

The classroom model was 709 square feet with 9-foot-tall ceilings, similar to a smaller-size, university classroom, Kinzel says. The model had masked students -- any one of whom could be infected-- and a masked teacher at the front of the classroom.

The researchers examined the classroom using two scenarios -- a ventilated classroom and an unventilated one -- and using two models, Wells-Riley and Computational Fluid Dynamics. Wells-Riley is commonly used to assess indoor transmission probability and Computational Fluid Dynamics is often used to understand the aerodynamics of cars, aircraft and the underwater movement of submarines.

Masks were shown to be beneficial by preventing direct exposure of aerosols, as the masks provide a weak puff of warm air that causes aerosols to move vertically, thus preventing them from reaching adjacent students, Kinzel says.

Additionally, a ventilation system in combination with a good air filter reduced the infection risk by 40 to 50% compared to a classroom with no ventilation. This is because the ventilation system creates a steady current of air flow that circulates many of the aerosols into a filter that removes a portion of the aerosols compared to the no-ventilation scenario where the aerosols congregate above the people in the room.

These results corroborate recent guidelines from the U.S. Centers for Disease Control and Prevention that recommend reducing social distancing in elementary schools from six to three feet when mask use is universal, Kinzel says.

"If we compare infection probabilities when wearing masks, three feet of social distancing did not indicate an increase in infection probability with respect to six feet, which may provide evidence for schools and other businesses to safely operate through the rest of the pandemic," Kinzel says.

"The results suggest exactly what the CDC is doing, that ventilation systems and mask usage are most important for preventing transmission and that social distancing would be the first thing to relax," the researcher says.

When comparing the two models, the researchers found that Wells-Riley and Computational Fluid Dynamics generated similar results, especially in the non-ventilated scenario, but that Wells-Riley underpredicted infection probability by about 29 percent in the ventilated scenario.

As a result, they recommend some of the additional complex effects captured in Computational Fluid Dynamics be applied to Wells-Riley to develop a more complete understanding of risk of infection in a space, says Aaron Foster, a doctoral student in UCF's Department of Mechanical and Aerospace Engineering and the study's lead author.

"While the detailed Computational Fluid Dynamics results provided new insights into the risk variation and distance relationships, they also validated the more commonly used Wells-Riley models as capturing the majority of the benefit of ventilation with reasonable accuracy," Foster says. "This is important since these are publicly available tools that anyone can use to reduce risk."

WINSTON-SALEM, N.C. - April 5, 2021 - According to the American Cancer Society, a noninvasive breast cancer called ductal carcinoma in situ (DCIS) accounts for approximately one of every four new breast cancer cases in the United States. If left untreated, DCIS has the potential to evolve into invasive cancer, so many patients choose to have breast-conserving surgery or mastectomy after a diagnosis.

However, obtaining clear or negative margins -- no cancer cells in the outer edge of removed tissue -- is critical to mastectomy success as positive margins are associated with higher rates of recurrence.

A new study from Wake Forest School of Medicine suggests removing additional tissue around the tumor cavity, a technique known as cavity shave margin resection, reduces the rate of positive margins in patients with DCIS. The findings are published online in the April 2021 issue of the Journal of the American College of Surgeons.

"Our previous clinical trial showed that this technique can reduce positive-margin rates in invasive disease by at least 50%, but to my knowledge, this is the first analysis involving pure DCIS," said Marissa Howard-McNatt, M.D., director of the Breast Cancer Center at Wake Forest Baptist Health and associate professor of surgical oncology at Wake Forest School of Medicine, part of Wake Forest Baptist.

Researchers randomized 109 patients with pure DCIS (no invasive cancer) from 10 centers across the U.S., and 58 (53.2%) of these patients were randomized for cavity shave margin resection. In this group, researchers noted a nearly 65% reduction in the positive-margin rate.

According to Howard-McNatt, achieving clear margins in patients with DCIS can be difficult due to the continuous and branching nature of the spread of this disease. Clear margins free of cancer are vital in decreasing the chance of recurrence of cancer in the breast.

"Our study shows a significant reduction in positive margins," Howard-McNatt said. "This technique should be considered for DCIS patients."