Body

What The Study Did: Whether several recommended healthy eating patterns that combine various nutrients and foods are associated with long-term risk of cardiovascular disease, including heart disease and stroke, was the focus of this observational study that used data from three large study groups with up to 32 years of follow-up. Few studies have examined whether adherence to different dietary patterns could be associated with a lower risk of cardiovascular disease.

Authors: Frank B. Hu, M.D., Ph.D., of the Harvard T.H. Chan School of Public Health in Boston, 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.2020.2176)

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

What The Study Did: Researchers estimated the difference in overall life expectancy and years free from major chronic illnesses between individuals with HIV infection with access to care and similar uninfected adults from the same health care system from 2000 to 2016. Antiretroviral therapy has increased life expectancy for individuals with HIV, but recent data comparing life span between individuals with or without the disease are lacking.

Authors: Julia L. Marcus, Ph.D., M.P.H., of Harvard Medical School in Boston, 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.2020.7954)

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

What The Study Did: This randomized clinical trial assessed the effect of treating patients with relapsing multiple sclerosis with a therapeutic hookworm infection compared with placebo. Some studies have suggested that gut worms induce immune responses that can protect against multiple sclerosis.

Authors: Cris S. Constantinescu, M.D., Ph.D., and David I. Pritchard, Ph.D., of the University of Nottingham in Nottingham, England, are the corresponding authors.

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

(doi:10.1001/jamaneurol.2020.1118)

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

About 50,000 Danish diabetic patients are treated with GLP-1-based medicine. GLP-1 is a hormone that reduces the blood sugar and inhibits the appetite, and it is a frequent treatment for type 2 diabetes and obesity. A known side effect of this particular treatment is that it increases the patients' markers for pancreatitis.

Now, research from the Faculty of Health and Medical Sciences shows that the increased markers are not a sign of pancreatitis, but that the medicine is creating a new normal state, a so-called new steady state, in the patients. The new knowledge can contribute to the safety of GLP-1-based medicines worldwide.

'The increased biomarkers should not be interpreted as a sign of disease. Our study shows that GLP-1 treatment makes the pancreatic cells 'work' a bit more than they usually do. Instead of running around the soccer field once, they do it twice. And that in itself is not dangerous. It is something you also see in other contexts', explains Resident Medical Doctor and Assistant Professor Nicolai Albrechtsen from the Department of Biomedical Sciences and the Novo Nordisk Foundation Center for Protein Research at the Faculty of Health and Medical Sciences and Rigshospitalet.

New Steady State

Precisely because GLP-1-based treatment is a very frequently used treatment for diabetes and obesity, there has been international focus on detecting and understanding dangerous side effects - and thereby also on the increased markers of pancreatitis.

Since 2012, in collaboration with Rigshospitalet and Hvidovre Hospital, the researchers have conducted cell and animal studies and now also a human trial, supporting that GLP-1-based treatment does not increase pancreatitis, but rather increases the activity of the cells.

'We have recruited 17 overweight people who are suitable for receiving the maximum dose of GLP-1. Simultaneously with the treatment, we have monitored their possible development of pancreatitis by means of a particularly advanced imaging technique undertaken by Professor Andreas Kjær from the Department of Biomedical Sciences and Rigshospitalet. The patients did not develop inflammation, but their level of pancreatic enzymes, the biomarker of pancreatitis, increased. At the same time, we could see that the cell activity rose to a new normal level', says Nicolai Albrechtsen.

In the study, the test subjects were examined by means of blood samples and the special imaging technique PET-MRI before, during and after treatment with GLP-1. The PET-MR technology provides a special tracer that can show those cells in the body that are in a so-called active cell cycle. At the same time, inflammation in and around the cells can be seen.

The study was conducted by researchers from the Faculty of Health and Medical Sciences, Rigshospitalet and Hvidovre Hospital. The close cooperation made it possible for the research to move from mice to humans. This is the first time that the potential mechanism between GLP-1-based treatment and increased level of pancreatic enzyme has been shown in humans.

According to a survey by the Allensbach Institute, more than 6.1 million Germans stated last year that they were vegetarians, 400,000 more than two years earlier. A large-scale study at the Max Planck Institute for Human Cognitive and Brain Sciences (MPI CBS) in cooperation with the University Hospital of Leipzig has now examined in almost 9,000 people how this form of nutrition is related to the body and the psyche - regardless of age, gender and level of education.

It was found that the rarer the proportion of animal food in a person's diet, the lower their body mass index (BMI) on average and thus their body weight. One reason for this could be the lower proportion of heavily processed foods in the plant diet. "Products that are excessively rich in fat and sugar are particularly fattening. They stimulate the appetite and delay the feeling of satiety. If you avoid animal foods, you consume fewer such products on average," explains Evelyn Medawar, first author of the underlying publication, which has now been published in the journal Nutrients. In addition: Vegetarian food contains dietary fibres and has a positive effect on the microbiome in the intestine. This is another reason why they could fill you up earlier than those made from animal ingredients. "People who eat predominantly vegetable foods may therefore absorb less energy," Medawar adds. In addition to a changed feeling of satiety, lifestyle factors such as more sport and greater health awareness could also play a decisive role.

For the BMI it also seems to make a difference which animal products a person feeds on. If it is predominantly so-called primary animal products, i.e. meat, sausage and fish, the person usually has a higher BMI than someone who eats primarily secondary animal products, i.e. eggs, milk, dairy products, cheese and butter. In the former case the correlation is statistically significant.

Medawar uses an example to illustrate what this could mean for nutrition: "A person with a 1.2 point lower BMI on average either completely avoids certain animal products, such as the primary ones, and is on a vegetarian diet. Or she continues to eat meat and fish, but less often. Whether nutrition is ultimately the cause of lower body weight or whether other factors are responsible for it cannot be determined from the data. A follow-up study in cooperation with the University Hospital Leipzig will now shed light on this.

Nutrition and personality

The researchers also found out that vegetarian or vegan nutrition is also related to personality. Especially with one of the five major personality factors, extroversion. It was shown that people with predominantly plant-based foods on their diet are more introverted than those who mainly fed on animal products. "It is difficult to say what the reason for this is," says Veronica Witte. "It could be because more introverted people tend to have more restrictive eating habits or because they are more socially segregated because of their eating habits." Here, again, further studies should follow on how people identify with the characteristics of their diet.

However, they could not confirm that a plant-based diet is associated with a tendency towards neurotic behaviour, as other studies suggested. "Earlier analyses had found that more neurotic people were generally more likely to avoid certain groups of foods and to behave more restrictively. We focused here solely on the avoidance of animal products and could not observe any correlation," explains study leader Veronica Witte.

In a third part, they finally concentrated on the question of whether a predominantly plant-based diet is more often associated with depressive moods. Here previous studies had also suggested a relationship between the two factors. "We could not detect this correlation," says Witte. "It is possible that in previous analyses other factors had blurred the results, including the BMI or conspicuous personality traits that are known to be associated with depression. We accounted for them," said Witte explaining a possible reason for the different results. In addition, the plant-based diet is now more common and more accepted and not anymore restricted to a certain group.

The scientists had investigated these connections within the so-called LIFE project, a broad-based study in cooperation with the University Hospital of Leipzig. They determined the personal diets by means of questionnaires in which the participants were asked to fill in how often they had eaten the individual animal products in the last 12 months - from "several times a day" to "never". The personality traits such as extroversion and neuroticism were assessed by means of a so-called personality inventory (NEOFFI), while depression was assessed by means of the so-called CESD test, a questionnaire that records various symptoms of depression.

HOW the police use extra powers they have received during Covid-19 will have a long-lasting effect on their relationship with the public, argues a university researcher who is also a senior police officer.

In a newly-published article, Dan Jones - an Inspector with the Edmonton Police Service in Canada who is completing a PhD at the University of Huddersfield in the UK - warns against police forces adopting an authoritarian or militarised approach.  That could mean they lose their legitimacy, especially with poor communities that have been hit hardest by the pandemic.

On the other hand, argues Mr Jones, "if the police respond with compassion and care when they are required to enforce public health laws due to the pandemic response of their respective nations, this could build police legitimacy in a time of crisis."

Now more than ever, the article concludes, "police leaders need to ensure that procedurally just practices are occurring between police and public". 

Drawing on data from around the world, the article states that "the over-policing of marginalized neighbourhoods and communities is particularly worrisome during the pandemic, when the police have to enforce new public health laws and ensure public safety while depending on the public's willingness to comply with social distancing or lockdowns in a way that they never had to before. 

"At the same time, police are tasked more than ever to prevent civil unrest.  Communities that already have strained relationships with the police might have a harder time complying with the new rules and regulations.  As police legitimacy is often lower in disadvantaged communities, there is the potential that the population does not see the laws as necessary.  As such, it becomes even more important for the police to be (and be perceived as) legitimate and procedurally just to gain compliance from community members."

Impacts of Pandemic Policing on Police Legitimacy

During his 23-year career with the Edmonton Police Service, Dan Jones has filled a wide variety of roles - from patrolling the inner city to investigating homicides and working undercover probing right-wing extremism.  He currently heads his department's research and community solutions accelerator and is also immersed in academic research. 

After completing a Master's degree in applied criminology at Cambridge University in the UK, he embarked on his doctoral project at Huddersfield, where he is supervised by the criminologist Professor Rachel Armitage.

For his PhD, he has been researching incarcerated women in the Canadian prison system, gauging their rates of reoffending and how they are often victims of crime themselves.

"The policing world and the justice world don't really understand who their clients are," states Mr Jones.  There are many interventions that are potential alternatives to jail and the authorities should try to address the root causes that lead to incarceration, he argues.

During his PhD, Mr Jones has paid regular visits to the University of Huddersfield, although coronavirus has meant that his successful progression viva had to take place via Skype.  He aims to complete his thesis during 2021 and after a lengthy career first in the prison service and then in the police, he hopes to make a full transition to academic work.

His article titled 'The Potential Impacts of Pandemic Policing on Police Legitimacy: Planning Past the COVID-19 Crisis' can be accessed via the journal Policing, published by the Oxford University Press by visiting: https://academic.oup.com/policing/advance-article/doi/10.1093/police/paaa026/5851658

A tuberculosis vaccine developed 100 years ago also makes vaccinated persons less susceptible to other infections. While this effect has been recognized for a long time, it is not known what causes it. Together with colleagues from Australia and Denmark, researchers from Radboud university medical center the universities of Nijmegen and Bonn have now presented a possible answer to this question. Their results are also interesting against the background of the Covid-19 pandemic: several studies are currently testing the use of the vaccine in preventing severe disease progression in populations at risk such as hospital staff and elderly individuals. The study is published in the journal "Cell Host & Microbe".

The BCG vaccine (the abbreviation stands for Bacillus Calmette-Guérin) is the only vaccine that provides effective protection against infections with the tuberculosis bacterium. Since its first medical application in 1921, it has been used billions of times. An unexpected side effect became apparent: vaccinated individuals not only contracted tuberculosis far less frequently, but also other infections. One example comes from Guinea-Bissau in West Africa: there, the mortality of vaccinated newborns was almost 40 percent lower than that of unvaccinated babies

A similar effect has now been observed with other vaccines, almost exclusively with those based on live pathogens. Experts also speak of "trained immunity": the capacity of innate immune response to become more efficient independently of the type of reinfection. However, it is still largely unknown why this training effect can persist for years, even long after the immune cells that were circulating in the blood at the time of vaccination have died. Detailed studies on this topic were lacking, especially in humans; the current study fills this gap to a certain extent: "We vaccinated 15 volunteers with the BCG vaccine and administered a placebo to five more people for comparison," explains Prof. Dr. Mihai Netea from the Radboud university medical center in Nijmegen, the Netherlands. "Three months later, we took both blood and bone marrow samples from these individuals."

Some striking differences were found between the two groups. For instance, the immune cells in the blood of vaccinated individuals released significantly more inflammatory messengers. These so-called cytokines strengthen the effectiveness of the immune defense; for example, they call on other immune cells for help and direct them to the site of infection. Moreover, the immune cells of vaccinated individuals showed activity of completely different genes than in the placebo group, especially those required for cytokine production.

Easier access to genes for infection defense

There are many different types of immune cells in the blood. All of them are produced in the bone marrow. This is where the so-called hematopoietic stem cells grow, the "mothers" of all immune cells. The BCG vaccination also causes long-term changes in their genetic program. "We have found that after vaccination, certain genetic material becomes more accessible, which means that it can be read by the cells more frequently," explains Prof. Dr. Andreas Schlitzer from LIMES Institute at the University of Bonn.

Metaphorically speaking, every human cell contains in its nucleus a huge library of tens of thousands of books, the genes. When the cell wants to produce a certain molecule, for example a cytokine, it looks up its assembly instructions in the corresponding book. But not all of the books can be taken out so easily: some are usually under lock and key. The BCG vaccination now makes some of these books available, probably for many months or years. These include those that are needed for increased cytokine production. "This explains why the vaccination results in an enhanced immune response in the long term," said Netea. "This may well be the basis for the lasting impact of the training effect."

Another aspect is also interesting: most of the released books, i.e. the genes that become more accessible after the vaccine has been administered, are additionally controlled by a molecule called HNF. This "hepatic nuclear factor" ensures that the immune cells use their newly acquired power prudently, meaning that they only release cytokines when there is actually a pathogen that needs to be attacked. "It may be possible to use this finding therapeutically to specifically manipulate the trained immunity," explains LIMES researcher Prof. Schlitzer.

The results are also of interest against the background of the current Covid-19 pandemic: the researchers hope that a BCG vaccination might have a positive effect on the disease. Although the trained immune system probably cannot prevent infection with the virus, it may reduce the risk of a severe course. This might benefit especially the particularly vulnerable medical staff. Several large-scale medical studies are currently investigating this question, among others two at Radboud university medical center Nijmegen, and another at the University of Melbourne, which is also a partner in the current project.

However, until the results are available, the WHO does not recommend mass vaccination with the BCG vaccine, also in order not to jeopardize the supply in tuberculosis regions. Tuberculosis claims more than one million victims every year, putting it at the top of the list of the world's deadliest infectious diseases.

Philadelphia, June 15, 2020--The number of patients visiting the emergency department (ED) for asthma treatment dropped by 76% in the first month of the COVID-19 pandemic, according to a new study by researchers at Children's Hospital of Philadelphia (CHOP). The proportion of ED visits that led to a patient being hospitalized also decreased over this period, suggesting the decrease in overall visits was not solely due to patients avoiding the hospital due to the pandemic or delays in care for less serious asthma events.

"We were surprised by the magnitude and extent of the reduced utilization of emergency services for asthma during the emergence of the COVID-19 pandemic," said Chén C. Kenyon, MD, MSHP, a pediatrician in CHOP's Division of General Pediatrics and first author of the study, which was published in JACI in Practice. "The trend was particularly striking given that the emergence of COVID-19 in the Northeastern United States occurred during the spring, when respiratory viruses and high-pollen counts can converge and exacerbate asthma symptoms."

CHOP sees nearly 6,000 asthma patients in its ED every year, more than 2,000 of whom require hospitalization. To analyze the impact of the pandemic on ED use for asthma treatment, the researchers extracted data on visits to CHOP's ED for asthma care during the first four months of 2020. They compared that data to the average number of ED visits during the same four months of 2016 through 2019. They also compared the mean daily asthma ED visits from January 1 to March 18, 2020, before mandated social distancing measures went into effect, to the mean number of visits from March 19 to April 18, 2020.

The research team found that in the pre-pandemic period, an average of 24 patients visited the ED for asthma treatment each day, a number that was largely on par with the average daily number of visits for the prior four years. After March 19, when the City of Philadelphia implemented a stay-at-home order that included at-home learning and mandated social distancing, the average number of asthma-related ED visits dropped to less than 6 per day.

The dramatic decline played out across all presentations of the disease, from severe to mild cases. The researchers also found the percentage of children admitted to the hospital decreased from 31% to 22%, indicating the decline was not entirely driven by patients avoiding hospital settings or delaying care due to the stay-at-home order.

Given the dramatic decline in ED utilization during the pandemic period, the researchers suggest several areas for future investigation, including analyzing the impact on asthma symptoms of person-to-person transmission of respiratory viruses, outdoor seasonal vs. indoor allergens, and traffic and industrial pollution. Better understanding the reasons for the pandemic-related reduction in ED use for asthma care will help patients manage their disease once social distancing guidelines are relaxed.

"The COVID-19 pandemic and associated policies have had a dramatic impact on the number of patients we are seeing in the ED with asthma exacerbations," Dr. Kenyon said. "These results may offer new insights on where to best focus efforts to improve asthma outcomes outside of a pandemic scenario."

INDIANAPOLIS -- Disease tracking is an important area of focus for health departments in the midst of the COVID-19 pandemic. A new study from Regenstrief Institute and Indiana University shows that using electronic health information exchanges (HIE) to prepopulate forms for notifiable disease reports increases reporting and completeness of information.

Typically, health departments wait for hospital, laboratory or clinic staff members to initiate the report, and it is commonly done by fax. This process can be burdensome to those charged with filing the paperwork and the public health officials who analyze it, leading to delays or gaps in reporting.

"Surveillance is the cornerstone of public health," said Brian Dixon, PhD, MPA, study first author and director of public health informatics at Regenstrief Institute and Indiana University Richard M. Fairbanks School of Public Health at IUPUI. "The traditional way of reporting can potentially lead to delays in identifying outbreaks. This clinical decision tool leverages information that already exists in the HIE to simplify the process of reporting, ultimately helping to make surveillance more complete to inform public health decisions."

Using HIEs to facilitate reporting

The two-year controlled before-and-after trial analyzed reports submitted to a local health department for seven notifiable diseases. The research scientists compared "usual care," which is the use of paper and fax reports, with HIE-generated forms. They found that provider reporting rates for chlamydia and gonorrhea increased significantly in clinics using the HIE-generated forms, and completeness significantly improved for 4 of the 15 information fields on the reporting forms.

In addition, 75 percent of cases reported by intervention clinics contained a prepopulated form, which indicates that clinics are willing to use the tool.

To create the forms, the research team designed a clinical decision support tool that is triggered when an electronic laboratory message is examined by the Regenstrief Notifiable Condition Detector. The system extracts data from the Indiana Health Information Exchange and fills in the information fields on the official state reporting form. The form is delivered to an ambulatory care clinic using the HIE network, acting as a reminder for the clinician or staff member to review and submit the form to the local health department.

"We know that filling out forms can be challenging for providers and their staff for many reasons," said Shaun Grannis, M.D., M.S., senior author and vice president for data and analytics at Regenstrief. "Our solution facilitates public health reporting, which is crucial, while also allowing providers to do what they do best -- providing care for their patients." Dr. Grannis is also a professor of family medicine at Indiana University School of Medicine.

Benefits of HIEs and interoperability

The research team stressed the importance of continuing to build better integration between clinical and public health information systems.

"As demonstrated by the COVID-19 pandemic, timely and complete reporting is crucial to enable quick response to outbreaks that threaten the health of the public," said Dr. Dixon. "As we continue to track the spread of COVID-19 and other diseases, interoperability will play a key role in informing decisions. The healthcare field must continue to push forward in its effort to refine technical and workflow processes to make public health surveillance more efficient."

High percentages of Vermonters agree with the social distancing measures put in place by the state in response to the coronavirus pandemic and have complied with them, according to a new survey. But their attitudes and actions, while protecting their health, have come at a significant economic cost, especially for low income Vermonters, one of several ways in which poorer Vermonters have been disproportionately affected by the pandemic.

Vermonters overwhelmingly supported the state's social distancing guidelines, according to the survey, conducted by faculty in the University of Vermont's Larner College of Medicine between April 30 and May 13. Nearly 90% strongly agreed or agreed with the current approaches to social distancing, from closing schools (91%) to closing bars and restaurants (91%) to limiting mobility outside the home (93%) to forbidding mass gatherings (95.4%) to being required to wear a mask outside the home (85%).

While the positive attitudes translated to significantly fewer contacts overall, the survey showed, not all groups benefited equally.

Those living in apartments and mobile homes and at the lower end of the income scale had more contact with other adults, seniors and children after the lockdown than those living in single family homes and condos and higher income Vermonters, who could often work from home.

"For the less well-off and especially those on the margins, the pandemic presented much more of a health risk than for more affluent Vermonters," said Eline van den Broek-Altenburg, an assistant professor and vice chair for Population Health Science in the Department of Radiology at the Larner College of Medicine's and the survey's principal investigator.

Heavy Economic Toll

The social distancing measures played a role Vermont's comparatively low infection rate but took a heavy economic toll, the survey found. Ten percent of Vermonters lost their jobs, and 28% saw their income reduced after social distancing guidelines were put in place. Sixteen percent of respondents were concerned about their ability to pay for basic necessities like food and rent, 19% used savings to cover monthly spending, and 10% said they had reduced ability to buy fresh fruit and vegetables.

As with social distancing, the economic impact was not felt equally, van den Broek-Altenburg said.

"Lower income Vermonters are being hit disproportionately," she said. "That's largely because those in higher income groups tend to have jobs where they can tele-work from home. That's not an option for most low-income workers, so many lost their jobs and their income."

Lower Income Vermonters More Likely to Defer Medical Care

The survey also asked respondents if they deferred medical care during the pandemic.

Nearly half the population deferred care, according the survey, and nearly one-third were concerned about the consequent health impacts. The mostly commonly deferred areas of care were dental services (27%) and primary care (23%).

Reasons given for deferring care included having a newly developed problem that could be treated later to the care being preventative to the health issue being ongoing. But income level and job loss were also strongly correlated with those deferring all kinds of care, said van den Broek-Altenburg.

"Those in disadvantaged populations are also being hit harder when it comes to necessarily healthcare needs or chronic conditions," she said.

Telemedicine may provide a solution for some.

The survey found that, while those who were deferring care were less likely to use telemedicine than those who were not, older respondents were more likely to use the service, as were those with chronic conditions. Those who deferred mental health services were also significantly more likely to use telemedicine.

Light Impact in Vermont Largely Due to Population Density

The Vermont survey was done in conjunction with similar surveys in Italy, the United Kingdom, France and China, and in other states.

The comparative data make clear that the pandemic's relatively light impact in Vermont has less to do with state residents' compliance with social distancing guidelines, although their behaviors helped, than with population density.

China's Hubei Province, where the pandemic's epicenter, Wuhan, is located, has 310 people per square mile; Italy has an average of 201 people per square; Vermont has just 26 and Burlington 98.

The key takeaway from the survey, van den Broek-Altenburg said, is that Vermonters have been affected disproportionately the pandemic across the board.

"In the future we need policies that are differentiated and much more targeted towards particular age groups, particularly income groups and particular professions," she said. "There is no one-size-fits-all solution."

The survey sample is a representative group drawn from primary care patients in the University of Vermont Medical Center's Vermont hospital service area. Researchers used census data to weight the sample so it was representative of the Vermont population.

Many serious diseases, including autism, schizophrenia and numerous cardiac disorders, are believed to result from mutation of an individual's DNA. But some large mutations, which still make up only a small fraction of the total human genome, have been surprisingly challenging to detect.

Now, researchers at the National Institute of Standards and Technology (NIST) have developed a way for laboratories to determine how accurately they can detect these mutations, which take the form of large insertions and deletions in the human genome. The new method and the benchmark material enable researchers, clinical labs and commercial technology developers to better identify large genome changes they now miss and will help them reduce false detections of genome changes.

The researchers present their new benchmark in Nature Biotechnology.

Scientists in the Human Genome Project generated the first reference genome in the late 1990s, pieced together from a collection of genome sequences from different individuals. When scientists sequence DNA, they are essentially randomly chopping up the DNA into smaller pieces, which then need to be pieced back together like a puzzle.

The building blocks of DNA include four types of bases: adenine (A), cytosine (C), guanine (G) and thymine (T), strung together to form 23 chromosomes in human cells. These genetic codes contain all the information of life. To understand the genetic basis for a given disease, scientists sequence a person's DNA and compare it against a reference genome. Differences between the individual's DNA sequence and the reference genome are called variants. Some of these variants, which can range from insertions and deletions of 50 to tens of thousands of letters (or bases) of the roughly 6.4 billion bases that make up the human genome, are found to be linked to a disease.

Over the last eight years, the NIST-led Genome in a Bottle consortium (GIAB), which includes members from the federal government, academia and industry, developed whole human genome benchmarks for small variants for seven individuals. For this new paper, NIST worked with GIAB to develop a new benchmark for large insertions and deletions. To form this benchmark, NIST integrated results from 19 different analysis approaches by GIAB members, using GIAB's public data from a well-characterized set of human DNA from a family of Eastern European Ashkenazi Jewish ancestry (NIST Reference Material 8392).

The NIST Genome in a Bottle Consortium is a public-private-academic consortium hosted by NIST to develop the technical infrastructure (reference standards, reference methods, and reference data) to enable translation of whole human genome sequencing to clinical practice. In this animation, learn more about the genome sequencing process and why standards are such an important part of this process.

"Just like a company making rulers could compare their ruler to a standard measuring stick to make sure it is measuring the correct distance, clinical laboratories doing DNA sequencing can measure NIST reference material DNA and compare their answer to this new benchmark to help make sure they measure large insertions and deletions well," said NIST biomedical engineer Justin Zook.

Laboratories have accurately detected many small insertions and deletions in the genome for years. One would think detecting larger insertions and deletions would be easier, but it's actually harder because "the most widely used sequencing technologies output relatively short strings of genetic code, making it hard to reconstruct what's happening," says Zook. With new DNA sequencing technologies, it is now possible to detect many more large insertions and deletions.

Imagine the genome as a book. The benchmark helps scientists detect large chapters that are missing (deleted chapters) or not in the original (inserted chapters).

"DNA sequencing is like shredding the book into smaller pieces and then trying to find any differences between the book that was shredded and a similar book, perhaps the same book before it went through editorial revisions," said Zook. Even though the DNA is broken into smaller pieces, the new DNA sequencing technologies make it possible to read the larger pieces, making it easier to find these larger insertions and deletions.

The NIST Genome in a Bottle Consortium is a public-private-academic consortium hosted by NIST to develop the technical infrastructure (reference standards, reference methods, and reference data) to enable translation of whole human genome sequencing to clinical practice. In this animation, learn more about why developing these reference materials is so important.

This benchmark for large insertions and deletions will improve the accuracy of DNA sequencing technologies and analysis methods, reducing the likelihood of errors such as false positives and negatives. A false positive means detecting an insertion or deletion in the genome that's not real, while a false negative means not detecting a change in the genome when it's actually there.

Reducing false positive and negative numbers is critical, especially in clinical settings where many diseases such as autism, schizophrenia and cardiovascular disease have been linked to structural variants. For example, if a clinical laboratory is sequencing a patient's DNA, a false negative can result in missing the change in the genome that is causing the disease, leading to incorrect treatments.

Down the road, applications of the benchmark will help labs detect disease-associated structural variants by validating their methods.

For NIST researchers, next steps include characterizing difficult regions of the genome that contain repetitive sequences. DNA sequence technologies and methods continue to improve, enabling researchers to push into more challenging regions of the genome and identify structural variants that are harder to detect.

But according to Zook, this is precisely why this area is fun to work in, as technologies have changed and improved in the past 30 years. He credits the collaboration with GIAB as being key to these efforts: "All of this work wouldn't be possible if we weren't able to collaborate with a group of diverse people with different areas of expertise."

Universal testing of pregnant women admitted to labor and delivery units is part of a multipronged approach to reducing transmission of the virus that causes COVID-19 in hospitals and clinics.

A team led by investigators at Massachusetts General Hospital has now provided a report on the prevalence of infections with the virus in women admitted to such units in several Boston hospitals. The findings are published in Infection Control & Hospital Epidemiology.

Universal testing in the labor and delivery units began more than 30 days after physical distancing orders were placed in Massachusetts.

Over 18 days of universal testing in units at the four major hospitals affiliated with Mass General Brigham Health (which provides maternity care to approximately 14,750 women per year), 757 women were tested. Of those tested, 139 had symptoms possibly consistent with COVID-19.

Among symptomatic women, 7.9% tested positive (11 women) for SARS-CoV-2, the virus that causes COVID-19. Among asymptomatic women, 1.5% tested positive (9 women).

Thus, 9 of the 20 women--or 45%--who tested positive at admission had no symptoms of COVID-19. Across the four hospitals, none of the positive asymptomatic women developed COVID-19 symptoms during their hospitalization, and all 9 newborns tested negative for the SARS-CoV-2.

"Although our results indicate a low prevalence of SARS Cov-2 in an asymptomatic pregnant population, my coauthors and I believe that universal testing of this population can provide a window into the community prevalence of infection, which can in turn help guide decision-making about moving between mitigation versus containment measures in the hospital and in the community," said lead author Ilona Telefus Goldfarb, MD, MPH, a Maternal-Fetal Medicine Specialist at Mass General and Harvard Medical School.

The researchers noted that universal testing in this specific patient population is an especially important public health priority given the potential dangers of COVID-19 for maternal and newborn care during and after birth.

"Our findings underscore the importance of understanding the local prevalence of disease, which varies across geographical areas and will change over time due to many factors. Tracking prevalence prospectively can inform public health interventions and our approaches to testing," said co-senior author Erica Shenoy, MD, PhD, Associate Chief of Mass General's Infection Control Unit and an Assistant Professor of Medicine at Harvard Medical School.

LA JOLLA, CA--Scientists at Scripps Research have developed molecules that can remodel the bacterial population of intestines to a healthier state and they have shown--through experiments in mice--that this reduces cholesterol levels and strongly inhibits the thickened-artery condition known as atherosclerosis.

The scientists, who report their findings in Nature Biotechnology, created a set of molecules called peptides that can slow the growth of less-desirable species of gut bacteria. In mice that develop high cholesterol and atherosclerosis from a high-fat diet, the peptides beneficially shifted the balance of species in the gut microbiome, which refers to the trillions of bacteria that live inside the digestive system. This shift reduced cholesterol levels and dramatically slowed the buildup of fatty deposits in arteries--symptoms that are the hallmarks of atherosclerosis.

Atherosclerosis is the condition that leads to heart attacks and strokes, the two leading causes of death among humans.

"It was surprising to us that simply remodeling the gut microbiome can have such an extensive effect," says study co-senior author Reza Ghadiri, PhD, professor in the Department of Chemistry at Scripps Research.

Gut microbes shape our health

The gut microbiome, which includes hundreds of bacterial species, evolved long ago as part of a fundamental symbiosis: The bacteria get a place to live and plenty to eat, and in return they assist their animal hosts, largely by helping them digest food.

In the past two decades, these symbiotic bacteria have become a focus of intense study around the world, as scientists have discovered that the microbes--in part by their production of molecules called metabolites--not only help digest food, but play a role in metabolism, immunity and other important functions.

Scientists also have learned that this symbiosis can have a downside for the bacteria's human hosts. When people overuse antibiotics or consume "Western" diets rich in carbs, fats and sugar, the gut microbiome can be altered in ways that promote disease.

Indeed, it now appears that the increased risks of obesity, diabetes, hypertension and atherosclerosis that are conferred by the Western diet are due in part to adverse changes in the microbiome.

That recognition has led researchers to look for ways to remodel the microbiome, with the goal of rolling back those adverse changes to restore good health. Ghadiri and his team have been working on a method that involves delivering small molecules to kill or slow the growth of bad gut bacteria without affecting good gut bacteria.

"Our approach, using small molecules called cyclic peptides, is inspired by nature," says co-senior author Luke Leman, PhD, an assistant professor in the Department of Chemistry at Scripps Research. "Our cells naturally use a diverse collection of molecules including antimicrobial peptides to regulate our gut microbe populations."

A screening system to identify microbiome remodelers

Prior to the experiments, the team already had a small collection of cyclic peptides that had been made using chemistry techniques. For the study, they set up a screening system to determine if any of those peptides could beneficially remodel the mammalian gut microbiome by suppressing undesirable gut bacterial species.

Using mice that are genetically susceptible to high cholesterol, they fed the animals a Western-type diet that swiftly and reliably produces high blood cholesterol and atherosclerosis, as well as adverse shifts in the gut microbiome. The researchers then sampled the animals' gut contents and applied a different cyclic peptide to each sample. A day later, they sequenced the bacterial DNA in the samples to determine which peptides had shifted the gut bacteriome in the desired direction.

The scientists soon identified two peptides that had significantly slowed the growth of undesirable gut bacteria, shifting the species balance closer to what is seen in mice that are fed a healthier diet. Using these peptides to treat atherosclerosis-prone mice that were eating a high-fat Western diet, they found striking reductions in the animals' blood levels of cholesterol compared to untreated mice--about 36 percent after two weeks of treatment. They also found that after 10 weeks, the atherosclerotic plaques in the arteries of the treated mice were about 40 percent reduced in area, compared to those in untreated mice.

"These were really remarkable effects," Ghadiri says.

The cyclic peptides used in the study apparently interact with the outer membranes of certain bacterial cells in ways that slow or stop the cells' growth. Ghadiri and his team have been researching these peptides for years and have put together a set of dozens that show no toxicity to the cells of mammals. The molecules also transit through the gut without entering the bloodstream. In the study, the peptides were delivered to the mice in drinking water and were not associated with any adverse side effects.

Cheered by the proof-of-principle demonstration, the researchers are now testing their peptides in mice that model diabetes, another common condition that has been linked to an unhealthy microbiome.

ANN ARBOR, Mich. -- Not all bloodsuckers are created equal in parents' eyes.

When it comes to bug bites, parents are twice as likely to be concerned about ticks as they are about mosquitoes transmitting disease, a new national poll finds.

But as children spend more time outside, families may not always know the best way to protect them from both of these pesky insects.

Among parents who use bug repellent, just one in three use ones containing N,N-Diethyl-meta-Toluamide (DEET) - which is most effective against mosquitoes - according to the C.S. Mott Children's Hospital National Poll on Children's Health at Michigan Medicine. DEET has been tested and approved for children ages two months and older when used as directed.

"Many bug bites from mosquitoes and ticks will cause irritation or discomfort for children. But in some less common instances, they may also potentially transmit disease," says poll co-director Gary L. Freed, M.D., M.P.H.

"Choosing the appropriate bug repellent can be confusing for parents," he adds. "Some may protect against mosquitos but not ticks, for example. Parents should research the options and recommendations before deciding what to use based on their child's age and their outdoor plans."

Although it is uncommon, mosquitos may carry and transmit viruses like Zika, West Nile and Eastern Equine Encephalitis (EEE), which can all potentially cause disability or death in humans and animals.

In the summer of 2019, EEE made a comeback in the U.S., with a significantly higher number of cases reported than the typical average of eight cases a year. The virus can cause mild, flu-like illness but 20% of people infected get much sicker. A third of those who develop a condition called encephalitis - when the virus inflames the brain - die.

Some summers, ticks have also been more rampant in certain parts of the country than others. Among diseases they may carry is Lyme Disease, a potentially serious bacterial infection that can cause flu-like symptoms and joint pain and weakness in the limbs.

The nationally-representative Mott Poll report is based on responses from 1,120 parents who had at least one child age 5-12 years.

Most parents say they usually use bug spray for their children, but they are more likely to do so in wooded and swampy areas than at a local park or in their yard or neighborhood.

While DEET protects against mosquitoes, it is less effective in repelling ticks. Repellents containing picaridin, which provides better protection against ticks, are also a safe option for children two months and older . But parents should be conscious of keeping young children from getting repellent on their hands or faces to prevent irritation on the eyes and mouth, Freed notes. The best repellant for ticks is permethrin, but it should only be sprayed on clothing and never directly on skin.

Nearly half of parents polled choose a repellent specifically advertised for children while 30% use "natural" or homemade products. Oil of lemon eucalyptus is among recommended alternatives for those who prefer a chemical-free repellent but should only be used for children over three years.

Other parent strategies to prevent bites center around clothing, according to the report. Parents say they often have their child wear long pants and sleeves (34%), light colored clothing (21%) or always wear shoes (73%). About one in five parents have their child avoid soaps or shampoos with a floral scent.

Nearly half of parents also give their children oral antihistamines to provide relief from bites while 40 % prefer calamine lotion and 27 % use rubbing alcohol. Many parents also use home remedies, including an ice cold rag, oatmeal baths and baking soda.

Signs to watch for

Most parents polled would appropriately respond to concerning symptoms after a bug bite. The majority say they would definitely seek medical care for their child if they had a fever (82 %) or rash (73%). More than half would seek care if they couldn't tell if a tick was still attached (62%) or if there was a dark spot in the bite area (58%).

"Because some mosquitoes and ticks may carry certain diseases, parents should contact their child's health care provider if their child develops fever, headache, or body aches within 3-14 days of a bite," Freed says.

The most common strategies among parents to remove a tick from their child included pulling it off with tweezers (72%), applying rubbing alcohol (23%), using a fingernail or credit card to scrape it off (19%) or covering it with Vaseline (13%).

Experts recommend using tweezers as a first choice, grasping the tick close to where it's attached and pulling straight up without twisting or crushing the insect.

Although ticks will burrow into the skin in order to suck blood, their bite is painless. An infected tick usually has to stay attached for 24 hours or more before transmitting the organism that causes Lyme disease. These are reasons why "tick checks" are important before and after outdoor outings, Freed says.

"After hiking in the woods or high grassy areas, parents should always check their kids for ticks, especially looking on the back, neck, hairline and around the groin areas," Freed says. "It's important to find and remove them quickly to reduce the risk of disease transmission."

FAIRFAX, Va. (June 15, 2020)-- Interventional radiologists participating in a collaborative house call model in rural Indiana helped reduce emergency department use by 77 percent and hospital readmissions by 50 percent for nearly 1,000 elderly homebound patients with chronic illnesses, according to a research abstract presented during a virtual session of the Society of Interventional Radiology's 2020 Annual Scientific Meeting on June 13. The novel care model brings interventional radiology treatments into patients' homes to provide more value through in-home advanced specialty care, prevent common complications of chronic diseases, and avoid unnecessary emergency department visits and hospital admissions.

"Older homebound patients, including those in nursing home settings, have few resources available to receive specialty care and often delay care until preventable issues become urgent and acute," said Nazar Golewale, MD, lead author of the study and an interventional radiologist with Modern Vascular & Vein Center in Valparaiso, Indiana and the northwest Indiana area. "By providing image-guided treatments in a patient's home, we are improving access to care that otherwise would need to be delivered in the hospital."

Dr. Golewale sees more than 900 of the practice's patients to diagnose and manage their conditions. Through varieties of portable technology, he brings interventional radiology care into patients' homes that would normally be delivered in clinics, such as ultrasound-guided needle biopsy, paracentesis and thoracentesis, ultrasound-guided joint injections for pain, wound care, and drug infusions. Payments for care are covered by Medicare reimbursement for homebound patients.

The care partnership was formed to overcome the difficulty of providing specialty care for chronically ill, homebound patients in Dr. Golewale's rural community. As a result of the program, patient satisfaction scores increased from 17 percent to 84 percent from before and after implementation of the program. Primary care providers, including internists and nurse practitioners, recruited specialists based on the needs of the patients they serve. In addition to interventional radiology, the house call practice includes providers in internal medicine, podiatry, laboratory services, and wound care.

"Some specialty services are available at our local hospitals, but cost-effective ways of coordinating patients' transportation and visits remained a significant barrier to care," said Golewale. "By bringing the hospital care to the patient, we're eliminating these hurdles and providing timely, personalized care."

Abstract 117: A Novel Health Care Delivery Model-House Call Docs. N. Golewale, Modern Vascular & Vein Center, Valparaiso, IN, S. Sinha, House Call Doc, PC, Highland, IN.

The research was originally scheduled to be presented in person at SIR's Annual Scientific Meeting, March 28-April 2, in Seattle before the meeting was canceled due to COVID-19 concerns. Visit sirmeeting.org for the latest information.