Body

Aspirin use may decrease ventilation, ICU admission and death in COVID-19 patients

George Washington University researchers found low dose aspirin may reduce the need for mechanical ventilation, ICU admission and in-hospital mortality in hospitalized COVID-19 patients. Final results indicating the lung protective effects of aspirin were published today in Anesthesia & Analgesia.

"As we learned about the connection between blood clots and COVID-19, we knew that aspirin - used to prevent stroke and heart attack - could be important for COVID-19 patients," Jonathan Chow, MD, assistant professor of anesthesiology and critical care medicine and director of the Critical Care Anesthesiology Fellowship at the GW School of Medicine and Health Sciences, said. "Our research found an association between low dose aspirin and decreased severity of COVID-19 and death."

Over 400 patients admitted from March to July 2020 to hospitals around the United States, including those at GW Hospital, the University of Maryland Medical Center, Wake Forest Baptist Medical Center and Northeast Georgia Health System, were included in the study. After adjusting for demographics and comorbidities, aspirin use was associated with a decreased risk of mechanical ventilation (44% reduction), ICU admission (43% reduction), and in-hospital mortality (47% reduction). There were no differences in major bleeding or overt thrombosis between aspirin users and non-aspirin users.

Preliminary findings were first published as a preprint in fall 2020. Since then, other studies have confirmed the impact aspirin can have on both preventing infection and reducing risk for severe COVID-19 and death. Chow hopes that this study leads to more research on whether a causal relationship exists between aspirin use and reduced lung injury in COVID-19 patients.

"Aspirin is low cost, easily accessible and millions are already using it to treat their health conditions," said Chow. "Finding this association is a huge win for those looking to reduce risk from some of the most devastating effects of COVID-19."

Credit: 
George Washington University

Racial/ethnic disparities in very preterm, preterm birth before, during COVID-19 pandemic

What The Study Did: Racial and ethnic disparities in very preterm birth and preterm birth among 8,026 women were similar during the first wave of the COVID-19 pandemic in New York City compared with the same period the year prior in this observational study.

Authors: Teresa Janevic, Ph.D., M.P.H., of the Icahn School of Medicine at Mount Sinai in 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/jamanetworkopen.2021.1816)

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

Credit: 
JAMA Network

Researchers provide complete clinical landscape for gene linked to epilepsy and autism

Philadelphia, March 17, 2021 - Researchers from Children's Hospital of Philadelphia (CHOP) affiliated with the CHOP Epilepsy Neurogenetics Initiative (ENGIN) have compiled a complete genetic and clinical analysis of more than 400 individuals with SCN2A-related disorder, which has been linked to a variety of neurodevelopmental disorders, including epilepsy and autism. By linking clinical features to genetic abnormalities in a standardized format, the researchers hope their findings lead to improved identification and clinical intervention.

The study was published online by the journal Genetics in Medicine.

Pathogenic variants in the SCN2A gene can lead to a wide range of clinical features - or phenotypes - associated with neurodevelopmental disorders. Several studies have described the genetic information collected on individuals with disease-causing changes in this gene. However, while genetic information is collected in a standardized manner, data on phenotypes is not standardized, and prior to this study, the available data on clinical features of these patients had not been thoroughly analyzed, meaning that many correlations between the genotypes and phenotypes of these patients were often anecdotal.

To properly link genetic and phenotypic data, researchers from CHOP utilized Human Phenotype Ontology (HPO), a method that standardizes a patient's clinical features and allows that data to be translated similar to genetic data.

"Based on our previous work with HPO, we knew we had the opportunity to provide the research and clinical community with the full phenotypic landscape of SCN2A-related disorders," said Ingo Helbig, MD, attending physician and director of the genomic and data science core of ENGIN and lead investigator of the study. "Individuals with variants of SCN2A present with a wide variety of clinical features, some of which have been difficult to easily categorize prior to our study."

The researchers extracted phenotypic information from SCN2A-related disorders published over the course of nearly two decades, encompassing every description of the disease in medical literature between 2001 and 2019, in addition to patients followed by ENGIN. Across 413 unrelated individuals, the study team derived a total of 10,860 clinical annotations in HPO terms, with a total of 562 terms unique terms. This allowed researchers to link clinical features with specific genetic variants.

For example, protein-truncating variants, which are genetic variants that shorten the coding sequence of genes, were associated with autism and behavioral abnormalities. Missense variants, or alterations of the genetic code that result in the production of a different amino acid than what would normally be expected, were associated with neonatal onset epileptic spasms and seizures. Using a principal component analysis to simplify the complexity of the data, the researchers found that three principal components accounted for one-third of the phenotypic variability in their dataset, emphasizing that despite the complexity of the data, informative clinical groups can be derived.

"The SCN2A-related disorders are the group of conditions where such a systematic mapping to computable phenotypes was performed. Our findings help define subclasses within SCN2A-related disorders that could pave the way for future precision medicine approaches to help these individuals," Helbig said. "This work, built upon our previous studies, now provides a framework on how HPO terminology can map complex clinical data in a variety of rare disorders to get to answers about clinical features, natural history, and outcomes that we do not have yet."

Credit: 
Children's Hospital of Philadelphia

AI method can detect precursors to cervical cancer

image: Johan Lundin, professor
Department of Global Public Health, Karolinska Institutet

Image: 
Ulf Sirborn

Using artificial intelligence and mobile digital microscopy, researchers hope to create screening tools that can detect precursors to cervical cancer in women in resource-limited settings. A study led by researchers at Karolinska Institutet in Sweden now shows that AI screenings of pap smears carried out with portable scanners were comparable to analyses done by pathologists. The results are published in the journal JAMA Network Open.

"Our method enables us to more effectively discover and treat precursors to cervical cancer, especially in low-income countries, where there is a serious lack of skilled pathologists and advanced laboratory equipment," says corresponding author Johan Lundin, professor at the Department of Global Public Health, Karolinska Institutet.

In countries with national screening programmes designed to detect cell abnormalities and human papillomavirus (HPV) in cervical samples, the number of cases of cervical cancer has dropped dramatically. Despite this, the global case total is expected to increase in the coming decade, largely due to shortages of screening resources and HPV vaccines in low-income countries.

Innovative diagnostic solutions that take into account local conditions and constraints are needed if more women around the world are to be offered gynaecological screening.

For this study, the researchers trained an AI system to recognise cell abnormalities in the cervix, which when detected early can be successfully treated. Smears were taken from 740 women at a rural clinic in Kenya between September 2018 and September 2019. The samples were then digitalised using a portable scanner and uploaded via mobile networks to a cloud-based deep-learning system (DLS). Just under half of the smears were used to train the programme to recognise different precancerous lesions while the remainder were used to evaluate its accuracy.

The AI assessment was then compared with that made by two independent pathologists of the digital and physical samples. The study shows that the assessments were very similar. The DLS had a sensitivity of 96-100 percent as regards identifying patients with precancerous lesions. No patients with more serious high-grade lesions received a false-positive assessment. As regards identifying smears without lesions, the DLS made the same assessment as the pathologists in 78-85 percent of cases.

The researchers believe that the method can be used to exclude a majority of smears, which would free up time for local experts to examine the ones that stick out. Before this can happen, however, more research is needed on larger and more diverse patient groups, including more smears and different types of lesions as well as biopsies with confirmed precursors to cervical cancer.

"With the portable online microscope, the DLS can act as a 'virtual assistant' when screening for cervical cancer," Lundin explains. "The AI assistant can be accessed globally 24/7 and help local experts examine many more smears. This method will make it possible for countries with limited resources to provide their population with screening services much more efficiently and at a lower cost than is currently the case."

Credit: 
Karolinska Institutet

Trackable and guided 'nanomissiles' deliver cancer-fighting drug straight to the tumor

Researchers from Skoltech and their colleagues from Hadassah Medical Center have developed hybrid nanostructured particles that can be magnetically guided to the tumor, tracked by their fluorescence and pushed to release the drug on demand by ultrasound. This technology can help make cancer chemotherapy more targeted. The paper was published in the journal Colloids and Surfaces B: Biointerfaces.Current treatments for cancer include chemotherapy, immunotherapy, radiation, and surgery, but these are often not selective enough to target just the tumor and not the healthy tissues around it. They are also highly toxic for the whole organism, which makes therapy hard to tolerate for the patient. One solution to these problems is so-called focal therapy, and specifically delivering drugs to the tumor in nanoparticles, for which several biocompatible materials have been explored. That technology can also be used for diagnostic purposes, augmenting medical imaging.The Skoltech team, led by Professor Dmitry Gorin from the Center for Photonics and Quantum Materials and Professor Timofei Zatsepin from the Center for Life Sciences, developed multifunctional nanostructured particles containing magnetic nanoparticles, fluorescent Cy5 or Cy7 dyes, and the drug doxorubicin. MRI imaging was performed by Dr. Kirill Petrov from the Hadassah Medical Center. Dynamic light scattering, fluorescent tomography, and histology studies were performed using the equipment of the Bioimaging and Spectroscopy Core Facility of the Skolkovo Institute of Science and Technology. These tiny capsules can be magnetically guided to the specific sites of the tumor, provide good contrast in high-resolution MRI, optoacoustic, and fluorescent imaging, and can be triggered to release the drug with ultrasound. Multicomponent capsules allow multifuctionality of the capsules: multimodality for imaging (fluorescent, optoacoustic, MRI), remote release (focused ultrasound), and navigation (magnetic field gradient)."Drug delivery carriers were prepared by combination of two methods. The first one was suggested by the co-authors of this article earlier and is called freezing induced method (FIL). This method has been successfully applied for loading of vaterite submicron particles by inorganic nanoparticles, proteins, low molecular drugs etc. The vaterite particles served as templates for drug delivery carriers and were removed after formation of a polymeric shell. Second method is layer by layer assembly that has been used for polymer biodegradable shell formation," Gorin explains.The team used in vitro experiments and in vivo animal studies to show that the method is functional: they were able to show increased targeted delivery of doxorubicin in the liver after ultrasound-mediated release."This technology should pass preclinical studies using animal models to evaluate therapeutic efficiency and safety of such drug delivery system. It will be the next step of our research," Zatsepin notes. 

Credit: 
Skolkovo Institute of Science and Technology (Skoltech)

Simple blood test could replace surgery for some brain tumour patients

image: Fluorescent microscopic picture of 3D model meningioma

Image: 
University of Plymouth Brain Tumour research Centre of Excellence

A research breakthrough shows that a simple blood test could reduce, or in some cases replace, the need for intrusive surgery when determining the best course of treatment for patients with a specific type of brain tumour.

Researchers at the Brain Tumour Research Centre of Excellence at the University of Plymouth have discovered a biomarker which helps to distinguish whether meningioma - the most common form of adult primary brain tumour - is grade I or grade II.

The grading is significant because lower grade tumours can sometimes remain dormant for long periods, not requiring high risk surgery or harsh treatments such as radiotherapy and chemotherapy. Tumours classified as grade II can progress to become cancerous and more aggressive treatment may be needed in order to try to control their spread.

At the moment, meningioma patients are usually put on watch and wait, undergo radiotherapy or have surgery in an attempt to remove the tumour. Between 70 and 85% of meningioma cases are lower grade so, if the blood test - or liquid biopsy - is carried out these patients may well be spared surgery or radiotherapy.

The team at Plymouth, led by Professor Oliver Hanemann, has published its work on this novel biomarker known as the protein Fibulin-2 (FBLN2) in the International Journal of Molecular Sciences. FBLN2 has not previously been shown to play a role in meningioma development, although it has been linked to other types of cancer such as forms in the lung, liver, breast and pancreas. The team therefore believes that this study is the first to link the FBLN2 protein as a biomarker for meningioma.

The results build on the important work of the Plymouth centre to identify non-invasive biomarkers of different grades of meningioma tumours. More information on an earlier paper, "GATA-4, a potential novel therapeutic target for high-grade meningioma, regulates miR-497, a potential novel circulating biomarker for high-grade meningioma" can be found here https://www.braintumourresearch.org/media/news/news-item/2020/08/19/news-on-meningioma-research-from-our-plymouth-centre.

Using tumour samples, cancer cells grown in the laboratory and liquid biopsies from patients, the scientists were able to distinguish grade I from grade II tumours. In a smaller sub-study, the researchers have shown that levels of the biomarker could differentiate between good (slower growing) and bad (faster growing) grade tumours as defined by genetic make-up.

Prof Hanemann said: "In this study, we identified FBLN2 as a novel biomarker that can distinguish grade II from grade I meningiomas. Higher levels of this biomarker were found in tumour samples from grade II meningioma compared with the grade I form. We also showed that higher levels of FBLN2 can be detected in blood samples from grade II meningioma patients, compared to those from grade I meningioma patients. The identification of FBLN2 as a biomarker for meningioma has significant potential to improve the diagnosis, treatment, prognosis and follow-up of meningiomas."

Hugh Adams, spokesman for Brain Tumour Research, which funded the study said: "This is an exciting breakthrough which could see patients spared the ordeal of neurosurgery at what is already likely to be one of the most difficult times of their life. In the UK, 16,000 people are diagnosed with a brain tumour each year and more children and adults under the age of 40 are lost to brain tumours than any other cancer."

Victoria Bradley, aged 50, from Plymouth, was diagnosed with a meningioma in 2017 and underwent surgery at Derriford Hospital six weeks later. She has lifelong side effects including debilitating seizures. No longer able to work as an overseas holiday representative, Victoria is now developing a mindfulness and meditation app to help others with brain tumours and epilepsy.

"My diagnosis and operation has changed everything about my life," she said. "Going through neurosurgery is a massive thing. I live in constant fear, no longer feel comfortable going out on my own and always, always, have an emergency alarm with me to call help in case I have a seizure.

"It is absolutely wonderful and incredible to think that, one day, patients like me might not have to go through surgery."

It is hoped the findings will contribute to the development of more personalised treatment options for patients with meningioma. Indeed, there exists a lack of consensus currently on the best management for grade II meningioma. FBLN2 could become a valuable tool for identifying and treating meningioma, accessible through a non-invasive blood test. Further research is required to assess the accuracy of diagnosing meningioma using a liquid biopsy for FBLN2 in comparison to current methods.

Credit: 
University of Plymouth

Health promotion, prevention, and psychosocial health

The promotion of psychosocial health among individuals, groups, and society is an increasingly important subject in the field of public health. Psychosocial health is a complex interaction between the psyche of an individual and the social environment in which that individual lives. Promoting psychosocial health is often challenging and complex for health care professionals. Therefore, an important question of public health significance is: "how can we address and improve the psychosocial health of individuals, groups, as well as society in general?"

An interdisciplinary team of specialists at the Department of Health Professions at the Bern University of Applied Sciences, Switzerland, have proposed action models based on the relationships between health promotion, prevention, and psychosocial health. The swiss team, led by Tannys Helfer have defined these concepts in relation to how they could be synergistically combined to promote psychosocial health. Understanding the terms helps to construct an action model. The researchers have depicted the model in a graphical manner.

Their proposed action model is based upon already well-established concepts, models, frameworks in health promotion, and prevention practice. "We have tried to depict them in a way that clearly integrates and combines their core concepts for their practical application in promoting psychosocial health" says Heifer. As these topics are overlapping, their clear illustration is important in promoting their systematic and planned usage.

The action model has five elements: 1. psychosocial health (the combination of an individual's experience, perception, psychological/mental processes, behaviour, and lifestyle as a continuum of healthy function), 2. health promotion (supporting processes that enable and increases peoples' self-determination and control over their health, 3. disease prevention (steps taken to prevent the development and spread of disease symptoms and control risk factors, 4. the relationship between health promotion and disease prevention, 5. and The relationship between Psychosocial Health, Health Promotion and Prevention

This new suggested action model encourages the systematic usage of health promotion and prevention for the promotion of psychosocial health. The researchers acknowledge that there is a need to evaluate how the model performs in a practical setting.

Credit: 
Bentham Science Publishers

Story tips from Johns Hopkins experts on Covid-19

image: Illustration for Research Story Tips from Johns Hopkins Medicine

Image: 
Johns Hopkins Medicine

MAN'S BEST FRIEND COULD HELP SAVE HIM FROM PROSTATE CANCER

Media Contact: Brian H. Waters, bwaters3@jhmi.edu

Dogs have been called man's best friend because of their loyalty and protection, but now, thanks to Johns Hopkins Medicine researchers and an international team of collaborators, canines may provide an even greater service for their human male companions: prostate cancer screening.

Prostate cancer is the second leading cause of cancer death in men in the developed world. Clinicians have been seeking accurate and reliable noninvasive diagnostic tools to differentiate early stage, less dangerous and more treatable stages of the disease from the aggressive, high-grade and likely-to-spread forms. Standard blood tests for early detection, such as the prostate specific antigen (PSA) test, often miss cancers in men whose PSA levels are within normal levels or overdiagnose men with clinically insignificant tumors or no cancer at all.

Recently, Alan Partin, M.D., Ph.D., urologist-in-chief at The Johns Hopkins Hospital and colleagues, along with collaborators from the United Kingdom, the Prostate Cancer Foundation and the Massachusetts Institute of Technology, have been researching a dog's extremely sensitive sense of smell as a novel way to improve testing for prostate cancer.

In a small study published Feb. 17, 2021, in the journal PLOS ONE, the researchers had two dogs sniff samples of urine from men diagnosed with high-grade prostate cancer and from men without cancer. The animals, Florin, a 4-year-old female Labrador, and Midas, a 7-year-old female wirehaired Hungarian vizsla, had been trained to respond to cancer-related chemicals -- known as volatile organic compounds (VOCs) -- added to urine samples and not respond to ones without them.

"Besides PSA, other methods to detect prostate cancer make use of a molecular analyzer called a gas chromatography-mass spectrometer [GC-MS] to find specific VOCs or profiling bacterial population in a urine sample looking for species associated with cancer, but these have limitations," says Partin. "We wondered if having the dogs detect the chemicals, combined with analysis by GC-MS, bacterial profiling and an artificial intelligence [AI] neural network trained to emulate the canine cancer detection ability, could significantly improve the diagnosis of high-grade prostate cancer."

Adding the AI analysis, says Partin, helped the researchers filter the more than 1,000 VOCs present in a typical urine sample down to those most beneficial for cancer diagnosis.

The dogs, says Partin, performed their cancer detection roles well. Both Florin and Midas identified five of seven urine samples from men with cancer, or 71.4% accuracy. Florin was able to correctly identify 16 of the 21 non-aggressive or no cancer samples (76.2%), while Midas was able to pick out 14 (66.7%).

When the canine olfactory (smell) results were combined with GC-MS, bacterial profiling and AI analysis, the multisystem approach proved a more sensitive and more specific means of detecting lethal prostate cancer than any of the methods alone.

Partin says that this recent study, and other prostate cancer research at Johns Hopkins Medicine, is only possible because of a long history of "biobanking" valuable patient samples. He says that "larger sample pools will be the key enabler of statistically powered, multi-institutional future studies seeking to fully integrate VOC and microbiota profiling."

Partin is available for interviews.

CHANGES IN THE EYE MAY OFFER EARLY WARNING FOR ALZHEIMER'S DISEASE

Media Contact: Ayanna Tucker, atucke25@jhmi.edu

Some say the eyes are the windows to the soul, but new findings from researchers at the Johns Hopkins Wilmer Eye Institute suggest they may offer insight into the mind as well. Their new proof-of-principle study shows how an imaging technique that measures blood flow in the back of the eye may offer a noninvasive way to detect early-onset Alzheimer's disease.

Results of the small study are published as the cover article in the March 4, 2021, issue of the journal Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring.

"We set out to investigate the idea that changes in the retinal capillaries at the back of the eye can reveal changes in the brain that are otherwise undetectable and that occur before the disease is diagnosed ," says lead study author Amir Kashani, M.D., Ph.D., associate professor of ophthalmology at the Johns Hopkins University School of Medicine.

The study involved 13 people with a rare, genetically inherited form of early-onset Alzheimer's disease marked by mutations identified in three genes. This form of familial Alzheimer's disease affects approximately 1% of all patients with the condition.

Using an imaging technology called optical coherence tomography angiography (OCTA), the researchers took images of blood vessels in the back of the eyes of study participants with and without the mutation leading to the familial form of Alzheimer's disease. They also cataloged the disease stage for the people with Alzheimer's and the cognitive abilities of both groups.

Kashani and his team found that abnormal blood flow through the smallest vessels at the back of the eye correlated with the mutation status of subjects at risk for the familial form of Alzheimer's disease. Patients with the Alzheimer's-causing mutations who had no signs of disease had abnormally high and heterogeneous blood flow in their retinal capillaries. The researchers believe this may be a sign of the early inflammatory changes involved in the pathogenesis of Alzheimer's disease.

The researchers say these data support the belief that changes in the eye can demonstrate the earliest signs of brain disease before symptoms are present. With further evidence from larger studies over time, they believe that the method could offer clinicians a tool for earlier diagnosis and enable intervention to slow cognitive decline in patients.

Kashani is available for interviews.

ADDICTION TREATMENT CENTERS USING ELECTRONIC HEALTH RECORDS LESS AND MAY HINDER CARE

Media Contact: Marisol Martinez, mmart150@jhmi.edu

Despite their existence for decades, electronic health records -- digitized patient information and medical histories available instantly and securely to authorized users -- are not commonly used by many addiction and substance use disorder treatment facilities in the United States. Now, a recent study by Johns Hopkins Medicine researchers suggests why this is happening. It also describes how not using this technology may hinder coordination between treatment programs and health care providers, leaving patients to flounder through the system on their own.

In their findings, published online on Jan. 9, 2021, in the journal Drug and Alcohol Dependence, the researchers conclude that electronic health records are less commonly used by substance use disorder programs compared with other mental health treatment facilities, and that this difference is significant. Overall, only 9.6% of substance use disorder treatment programs and 15% of mental health centers report exclusively using electronic health records. Even more troubling, they say, is that fewer than 25% of both these facility types are using electronic health records for core clinical activities, such as progress notes, laboratory monitoring and medication prescriptions.

Since their general acceptance by the medical community, electronic health records have provided a number of benefits, including increased storage capability and faster access to a patient's health information. They also enable the secure exchange of a patient's records between facilities and providers.

"This is key, because without electronic health records, patients may experience disjointedness in their care, and for the most part, these records have to be the link between the treatment facilities and care providers," says Stanislav Spivak, M.D., assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine.

Compared with other settings, the researchers say that implementing electronic health records can be more difficult in addiction treatment facilities because these centers often face unique regulatory and funding challenges. The researchers also found that mental health facilities had more diverse sources of funding from insurance than addiction treatment centers.

"Traditionally, substance use disorder programs are smaller and may lack the resources and funding that other mental health treatment facilities might have," says Spivak.

According to Spivak, the initial hurdle to substance use disorder programs adopting electronic health records may be cost and technology.

"For example," Spivak explains, "if you need computers powerful enough to encrypt the data or special printers to access the information, the cost of electronic health records may be prohibitive to a low-funded substance use disorder facility."

Spivak is available for interviews.

STEWARDSHIP PROGRAM HELPS HOSPITALS REDUCE ANTIBIOTIC USE AND PREVENT BACTERIAL INFECTIONS

Media Contact: Michael E. Newman, mnewma25@jhmi.edu

The overuse of antibiotics in hospitals can lead to the emergence of drug-resistant strains of bacteria or outbreaks of infections by bacteria such as Clostridioides difficile. Over the past decade, efforts to combat the overuse problem have included antibiotic stewardship programs (ASPs) that ensure patients only receive antibiotics when needed, and then, only in the correct amounts and for the prescribed dosage period. However, ASPs have not been established in all medical facilities, particularly smaller and rural hospitals where access to experts in the use of antibiotics may not be available.

Researchers at Johns Hopkins Medicine and NORC at the University of Chicago developed a comprehensive stewardship intervention, the Safety Program for Improving Antibiotic Use, which is applicable for all types of hospitals and enables frontline clinicians to make informed and responsible decisions about prescribing antibiotics. In a recent study, the researchers evaluated the effectiveness of the program over a year's time at 402 hospitals across the nation -- the largest project of its kind to date. As a measure of success, they looked at overall antibiotic use and C. difficile infection rates in the hospitals during the study period.

Their findings were published Feb. 26, 2021, in JAMA Network Open.

According to the U.S. Centers for Disease Control and Prevention, C. difficile is a bacterium that causes severe diarrhea and colitis (an inflammation of the colon), and is estimated to cause nearly 500,000 infections in the United States each year. Most cases occur in people taking antibiotics during or just after hospitalization. This is because antibiotics may destroy some of the intestinal bacteria that normally keep C. difficile at bay.

"The Safety Program for Improving Antibiotic Use was designed to reduce the harm associated with antibiotic overuse by making stewardship part of the decision-making process for clinicians," says study lead author Pranita Tamma, M.D., M.H.S., director of the Pediatric Antimicrobial Stewardship Program at Johns Hopkins Children's Center and associate professor of pediatrics at the Johns Hopkins University School of Medicine. "We wanted to see how much of a difference an ASP could make in a one-year period," she says.

The ASP used in the study consisted of 17 webinars -- each repeated three times, as well as recorded for online viewing -- over a 12-month timespan (January to December 2018). Conducted by Tamma and her colleague, Sara Cosgrove, M.D., M.S., professor of medicine at the Johns Hopkins University School of Medicine, the webinars focused on how to establish and maintain an ASP at a hospital, methods for improving teamwork and communication, and best practices for diagnosing and managing infections without overusing antibiotics.

Participants in the program received additional coaching and tools to enhance their ASP activities.

The 402 hospitals that completed the one-year study program included 28 academic medical centers, 122 mid-level teaching hospitals, 167 community hospitals and 85 critical access hospitals. Compliance with the four key components of antibiotic stewardship (interventions before and after prescribing of antibiotics, availability of local antibiotic guidelines, ASP leads with dedicated salary support, and quarterly reporting of antibiotic use) improved from 8% to 74% overall during the 12 months. Antibiotic use (measured by days of antibiotic therapy per 1,000 patient days) decreased 30% and C. difficile infections decreased 20%.

"These results are particularly remarkable as a large proportion of the hospitals in the study were under-resourced and did not have access to infectious disease specialists," says Cosgrove. "They show that no matter their size, all hospitals can develop, establish and conduct good stewardship practices with the proper resources -- and remind us of the importance of organized strategies to assist hospitals and clinicians in implementing medical care best practices."

Hospitals wanting more information can access the "Toolkit Implementation Guide for Acute Care Antibiotic Stewardship Programs."

Tamma and Cosgrove are available for interviews.

Credit: 
Johns Hopkins Medicine

Astronauts in crewed missions to Mars could misread vital emotional cues

image: Head-down bed rest at a slight 6-degree angle is the standard way of simulating the effects of microgravity on Earth.

Image: 
DLR

Living for nearly 2 months in simulated weightlessness has a modest but widespread negative effect on cognitive performance that may not be counteracted by short periods of artificial gravity, finds a new study published in Frontiers in Physiology. While cognitive speed on most tests initially declined but then remained unchanged over time in simulated microgravity, emotion recognition speed continued to worsen. In testing, research participants were more likely to identify facial expressions as angry and less likely as happy or neutral.

“Astronauts on long space missions, very much like our research participants, will spend extended durations in microgravity, confined to a small space with few other astronauts,” reports Mathias Basner, professor in the Department of Psychiatry at the University of Pennsylvania Perelman School of Medicine.

“The astronauts’ ability to correctly ‘read’ each other’s emotional expressions will be of paramount importance for effective teamwork and mission success. Our findings suggest that their ability to do this may be impaired over time.”

2 months in bed

Previous studies have shown microgravity causes structural changes in the brain, but it’s not fully understood how this translates to changes in behavior. Head-down bed rest at a slight 6-degree angle is the standard way of simulating the effects of microgravity on Earth. Participants for this research were kept in that position for nearly 2 months, and this is one of the first studies to strictly enforce the tilted head position.

“Participants regularly completed 10 cognitive tests relevant to spaceflight that were specifically designed for astronauts, such as spatial orientation, memory, risk taking and emotion recognition,” explains Basner. “The main goal was to find out whether artificial gravity for 30 minutes each day – either continuously or in six 5-minute bouts – could prevent the negative consequences caused by decreased mobility and head-ward movement of body fluids that are inherent to microgravity experienced in spaceflight.”

Artificial gravity countermeasures consisted of spinning participants on a centrifuge. Positioned like an arm on a clock with their head in the middle, the participants were spun round at the speed of 1 revolution around the ‘clock’ every 2 seconds.

Future disentanglement needed

“There are 2 ways to produce gravity in spaceflight: rotate the whole spacecraft/station, which is expensive, or just rotate the astronaut. The centrifuge could be self-powered, doubling up as an opportunity for exercise,” says Alexander Stahn, study co-author and research assistant professor at the University of Pennsylvania’s Perelman School of Medicine. “Unfortunately, we found that the artificial gravity countermeasures in our study did not have the desired benefits. We are currently performing additional analyses using functional brain imaging to identify the neural basis of the effects observed in the present study.”

In the future, the team plans to test longer duration artificial gravity countermeasures and to vary the degree of social isolation.

“We cannot say whether the effects observed on the emotion recognition test were induced by simulated microgravity or by the confinement and isolation inherent to the study, with separate bedrooms and sporadic contact to the study team. Future studies will need to disentangle these effects.”

Current and planned research efforts are seeking to mitigate potential decrements in social cohesion, including tasks looking at team problem solving and providing psychological support for crews under conditions of communication delays.

Credit: 
Frontiers

Researchers reveal UK trends in inflammatory eye disease

Scleritis is a vision-threatening inflammatory condition of the white portion of the eye, or the sclera, that is thought to be the result of an over-reaction of the body's immune system. A new study published in Arthritis & Rheumatology provides estimates of the incidence and prevalence of scleritis between 1997 and 2018 in the U.K.

Investigators found that the U.K. incidence of new cases appears to have fallen by about one-third over the past 22 years, to 2.8 new cases per 100,000 people per year. This trend is likely due to improvements in the management of immune-related diseases. Individuals who developed scleritis often had immune-related diseases before or after being diagnosed with scleritis.

"This study highlights how the use of routinely collected large-scale data offers unprecedented opportunity to advance understanding of the epidemiology of rare conditions and their associations," the authors wrote.

Credit: 
Wiley

UCSF study finds evidence of 55 new chemicals in people

Scientists at UC San Francisco have detected 109 chemicals in a study of pregnant women, including 55 chemicals never before reported in people and 42 "mystery chemicals," whose sources and uses are unknown.

The chemicals most likely come from consumer products or other industrial sources. They were found both in the blood of pregnant women, as well as their newborn children, suggesting they are traveling through the mother's placenta.

The study will be published March 17, 2021, in Environmental Science & Technology.

"These chemicals have probably been in people for quite some time, but our technology is now helping us to identify more of them," said Tracey J. Woodruff, PhD, a professor of obstetrics, gynecology and reproductive sciences at UCSF.

A former EPA scientist, Woodruff directs the Program on Reproductive Health and the Environment (PRHE) and the Environmental Research and Translation for Health (EaRTH) Center, both at UCSF.

"It is alarming that we keep seeing certain chemicals travel from pregnant women to their children, which means these chemicals can be with us for generations," she said.

The scientific team used high-resolution mass spectrometry (HRMS) to identify man-made chemicals in people.

But, while these chemicals can be tentatively identified using chemical libraries, they need to be confirmed by comparing them to the pure chemicals produced by manufacturers that are known as "analytical standards." And manufacturers do not always make these available.

Recently, for example, chemical manufacturer Solvay stopped providing access to a chemical standard for one perfluorooctanoic acid (PFAS) compound that has emerged as a replacement for phased-out PFAS compounds. The researchers have been using this chemical standard to evaluate the presence and the toxicity of the replacement PFAS.

"These new technologies are promising in enabling us to identify more chemicals in people, but our study findings also make clear that chemical manufacturers need to provide analytical standards so that we can confirm the presence of chemicals and evaluate their toxicity," said co-lead author Dimitri Panagopoulos Abrahamsson, PhD, a postdoctoral fellow with UCSF's PRHE.

The 109 chemicals researchers found in the blood samples from pregnant women and their newborns are found in many different types of products. For example, 40 are used as plasticizers, 28 in cosmetics, 25 in consumer products, 29 as pharmaceuticals, 23 as pesticides, 3 as flame retardants, and 7 are PFAS compounds, which are used in carpeting, upholstery, and other applications. The researchers say it's possible there are also other uses for all of these chemicals.

The researchers report that 55 of the 109 chemicals they tentatively identified appear not to have been previously reported in people:

1 is used as a pesticide (bis(2,2,6,6-tetramethylpiperidini-4-y) decanedioate)

2 are PFASs (methyl perfluoroundecanoate, most likely used in the manufacturing of non-stick cookware and waterproof fabrics; 2-perfluorodecyl ethanoic acid)

10 are used as plasticizers (e.g. Sumilizer GA 80 - used in food packaging, paper plates, small appliances)

2 are used in cosmetics

4 are high production volume (HPV) chemicals

37 have little to no information about their sources or uses (e.g., 1-(1-Acetyl-2,2,6,6-tetramethylpiperidin-4-yl)-3-dodecylpyrrolidine-2,5-dione, used in manufacturing fragrances and paints--this chemical is so little known that there is currently no acronym--and (2R0-7-hydroxy-8-(2-hydroxyethyl)-5-methoxy-2-,3-dihydrochromen-4-one (Acronym: LL-D-253alpha), for which there is limited to no information about its uses or sources

"It's very concerning that we are unable to identify the uses or sources of so many of these chemicals," Woodruff said. "EPA must do a better job of requiring the chemical industry to standardize its reporting of chemical compounds and uses. And they need to use their authority to ensure that we have adequate information to evaluate potential health harms and remove chemicals from the market that pose a risk."

Credit: 
University of California - San Francisco

Researchers identify head impact rates in four major high school sports

Philadelphia, March 17, 2021 - As high school athletes return to practice and games for a variety of sports, the threat of concussions remains. A new study from researchers at Children's Hospital of Philadelphia (CHOP) used head impact sensors in four different sports and studied male and female athletes to determine which of these sports put students at the highest risk for head impacts that could lead to concussions. The findings were published online by the Orthopaedic Journal of Sports Medicine.

"Adolescents are particularly vulnerable to concussion because they frequently participate in sporting and recreational activities and have slower recovery periods compared to adults," said Kristy Arbogast, PhD, senior author and co-lead of the Minds Matter Concussion Program at CHOP. "Providing reliable data on head impact exposure and sport-specific mechanisms may help sports organizations identify strategies to reduce impact exposure and lower the risk of acute injury."

Building upon previous research that determined how to derive accurate data from headband-mounted head impact sensors through video confirmation, CHOP researchers sought to quantify sport and gender differences in head impact rates and mechanisms in male and female high school soccer, basketball, lacrosse, and female field hockey.

This is the first study to provide head impact analysis for basketball and field hockey and is one of the largest studies of its kind because of its inclusion of multiple sports and both genders. Data was collected from 124 athletes (56 girls, 68 boys) over the course of 104 games and more than 1,600 head impacts across the four sports.

Soccer had the highest head impact rate for both boys and girls across the sports that were analyzed. This was attributed to the role of intentional headers, which accounted for 80% of the head impacts in that sport. High school male sports consistently had higher head impact rates than female sports in soccer, basketball, and lacrosse.

Basketball had a higher head impact rate than lacrosse and field hockey for females and a similar impact rate to lacrosse for males. The similarity in impact rate between male basketball and lacrosse was unexpected considering male lacrosse is classified as a collision sport permitting intentional checking and body contact and requires the use of a helmet.

Impact mechanisms varied by sport, creating sport-specific targets for prevention efforts aimed at reducing head impact exposure. For example, lacrosse had a higher proportion of equipment-to-head impacts than the other sports due to the role of the stick in lacrosse. However, most of the head impacts in basketball were due to player-to-player contact. These findings point to potential sport- and gender-specific rule and equipment strategies to minimize head impact exposure.

"It's important to recognize that all head impacts are not created equal, so future studies need to explore the magnitude of these impacts," Arbogast said. "For example, lacrosse and basketball may have similar impact rates, but the severity of impacts in lacrosse may be higher."

Credit: 
Children's Hospital of Philadelphia

Helping stevia plants brave the cold

image: Making cuttings for propagation of stevia at North Carolina State University.

Image: 
Todd Wehner

It's a fact - humans love sugar. For those of us who also like to watch our calories, sugar substitutes can help.

Some zero-calorie or low-calorie sweeteners have attracted bad reputations for containing unnatural ingredients. But there are also natural sweeteners derived from plants, like stevia.

Stevia is hundreds of times sweeter than sugar, and it has no calories. The global stevia market is now worth hundreds of millions of dollars.

The sweetener is derived from the leaves of the plant Stevia rebaudiana, a native of Paraguay and Brazil. The leaves make chemicals similar enough to sugar to trick the tongue. But our body doesn't burn these chemicals as fuel.

Todd Wehner is a plant breeder who aims to develop stronger varieties of stevia. These better varieties can help farmers and consumers alike.

His research was published in Agrosystems, Geosciences & Environment, a journal of the American Society of Agronomy and Crop Science Society of America.

"The market is growing rapidly as companies and consumers move away from sugar in their diet," says Wehner.

Although this tropical plant is grown around the world, it faces hurdles growing in cold climates. Freezing temperatures can dramatically injure or even kill stevia plants in short order. That makes it harder for farmers in countries like the U.S. to grow the sweet crop.

So, plant breeders like Wehner are interested in finding the hardiest stevia plants out there to help crops brave the cold.

"As we continue to select varieties that are cold tolerant in our area, new releases will have adaptation to a wider production region," says Wehner.

With his teammates, Wehner recently shared findings about the cold tolerance of different stevia varieties. Their results can help scientists breed cold-hardy stevia plants better adapted to the U.S. and other temperate climates.

To find the strongest plants, the research team subjected 14 varieties of stevia to different cold stress tests. The tests ranged from just below to just above freezing. Plants were exposed to cold for anywhere from 2 to 10 days. After the stress tests, the scientists assessed how much damage the plants sustained.

A couple varieties were clear standouts in their ability to resist the cold. These varieties might be useful for breeders who want to make cold tolerant stevia crops.

The plants grew normally after being moved to warmer conditions. This allowed researchers to harvest seeds for the next generation.

The temperature of the test really mattered for measuring hardiness. Somewhat surprisingly, some varieties that were resistant to temperatures just above freezing were some of the most susceptible to temperatures just below freezing. That finding provides useful information for how breeders should test for cold tolerance in the future.

"It appears that we will need to select for cold tolerance using a range of temperatures, so that we avoid the problems where a selection is resistant to only one temperature," says Wehner. "Tests will become a standard part of the breeding program."

Wehner and his team are now providing the seeds of the most cold-tolerant varieties to any other interested researchers. Recruiting other scientists to contribute can increase the pace of improvements to stevia.

The team is also studying other types of improvements to the crop. These include increasing the germination of seeds, beefing up resistance to diseases, and improving the production of leaves and sweetener chemicals.

"We are continuing to develop new varieties that will be higher yielding and better tasting. New varieties will be less expensive to produce as the genetics are improved for the environments of interest," says Wehner.

"For the 95% of humans who like stevia, we are continuing to make these products taste better," he adds.

Credit: 
American Society of Agronomy

Pandemic has increased pregnancy stress for US women

SPOKANE, Wash. - COVID-19 has created new problems for pregnant women in the United States, a group that already faced the highest maternal mortality rate in the developed world even before the pandemic.

One of their biggest concerns is their baby contracting the disease, according to a Washington State University study published recently in the journal BMC Pregnancy and Childbirth. Some women expressed fears that simply going to the hospital to deliver would cause them to get the virus and then be forced to isolate from their newborn.

"Pregnant women are really stressed about contracting COVID-19," said lead author Celestina Barbosa-Leiker, vice chancellor for research at WSU Health Sciences Spokane. "They have a lot of questions for their health care providers. There's a lot of we don't know yet, which is understandable, but it's especially stressful for the moms."

Researchers also found that the pandemic increased pregnant women's financial worries, made finding healthy food difficult and caused them to miss prenatal appointments. The study revealed even greater levels of stress and lack of social support among women of color and low-income pregnant women, highlighting an increase in health disparities that already existed prior to the pandemic.

"We know that prenatal stress impacts fetal development, so these are really big concerns," Barbosa-Leiker said.

For the study, the WSU research team analyzed survey responses from more than 160 pregnant and post-partum women from April 28 to June 30, 2020. They collected both quantitative survey responses from the whole group and more in-depth qualitative responses from a sub-set of women.

In the study, 52% of pregnant women and 49% of postpartum women worried about their babies contracting COVID-19, and 46% had sought extra information about COVID-19 protocols from the hospital where they had planned to deliver, or had delivered, their babies.

In the qualitative portion of the survey, women reported many serious concerns. For example, a participant noted that their main concern during the pandemic was contracting COVID-19 and dying. Others worried about contracting the virus in the hospital when they delivered and that COVID-19 policies would force them to isolate from their newborn or keep their partners out of the birthing room. Barbosa-Leiker said hospitals had varying policies especially at the beginning of stay at home measures though the recommendation now is to keep babies and mothers together.

During the survey period, 27% of pregnant women reported an inability to obtain healthy food and 25% had missed prenatal appointments. Finances also emerged as a substantial issue: 19% reported having their income reduced; 9% had been laid off and another 10% reported that someone in their household had lost their job.

Within the survey sample, the pregnant women appeared to be more stressed than post-partum women who had already delivered, as they were less likely to engage in healthy stress-coping behaviors, such as exercising, taking breaks from the news and making time to relax.

U.S. pregnant women already face more stressors than many of their peers in industrialized countries. According to a report from nine maternal mortality review committees, they have the highest maternal mortality rate in the developed world, and social and environmental stressors contribute to a U.S women's risk of dying within the first year of pregnancy. Previous studies have also showed U.S. pregnant women have higher levels of anxiety and depression compared to Dutch women, and higher levels of psychological stress than British women - and this was before COVID-19.

The results of the recent WSU study reinforce the need for more resources and support for pregnant women, especially during the pandemic, Barbosa-Leiker said.

"Health care providers should continue to talk with moms about all their stressors as their mental health and emotional well-being is key during this time," she said. "Providers can keep resources on hand. For instance, if they learn there is job loss in the family, they could quickly refer them to wraparound services."

Other people can also provide more support but in a physically distanced way, Barbosa-Leiker said, as pregnant women and new mothers expressed a lot of guilt for keeping relatives, especially grandparents, away from the newborn.

"We heard a lot from our participants that they were stressed because they were afraid of offending family members," she said. "Keeping in mind that new parents are doing everything they can to keep their baby and themselves safe and healthy, we should really try to support the parents' wishes about how they want to deal with visitors during the pandemic."

Credit: 
Washington State University

Multidrug-resistant candida auris discovered in a natural environment

Washington, D.C. - March 16, 2021 - For the first time, researchers have isolated the fungus Candida auris from a sandy beach and tidal swamp in a remote coastal wetland ecosystem. The discovery, reported this week in mBio, an open-access journal of the American Society for Microbiology, represents the first evidence that the pathogen thrives in a natural environment and is not limited to mammalian hosts. C. auris can cause infections resistant to major antifungal drugs, and since its identification in clinical patients 10 years ago scientists have sought to understand its origins.  
 

A commentary accompanying the study, published concurrently in the journal, hailed the work as a "landmark discovery."  
 

Medical mycologist Anuradha Chowdhary, Ph.D, at the University of Delhi, in India, led the new study. She and her colleagues analyzed 48 samples of soil and water collected from 8 sites including rocky shores, sandy beaches, tidal marshes, and mangrove swamps around the Andaman Islands, an isolated archipelago with a tropical climate in the Bay of Bengal. They isolated C. auris in the samples from two sites, a bay tidal salt marsh wetland and a beach.  
 

In samples from the salt marsh, which was rich in seagrass and low in human activity, the researchers found 2 isolates, one of which proved to be multidrug susceptible when tested against antifungals. In samples from the beach, which was high in human activity, the team identified 22 isolates, all of which were multidrug resistant. Whole genome sequencing of the isolates revealed that they were closely related to pathogenic strains found in Southeast Asia. 
 

"The isolates?found in the area where there was human activity were more related to strains we see in the clinical setting," Chowdhary said. Future studies, she said, may be able to explain that connection. "It might be coming from plants, or might be shed from human skin, which we know C. auris can colonize. We need to explore more environmental niches for the pathogen."  
 

Although cases of C. auris trace to the mid-1990s, the fungus wasn't named until 2009.  
The new work also provides evidence for a hypothesis recently introduced by the microbiologists who authored the new commentary, including Arturo Casadevall, Ph.D, of the Johns Hopkins Bloomberg School of Public Health in Baltimore; Dimitrios Kontoyiannis, Ph.D, of the The University of Texas MD Anderson Cancer Center in Houston; and Vincent Robert, Ph.D, Westerdijk Fungal Biodiversity Institute, in Utrecht, Netherlands.  
 

The trio proposed that C. auris, which is tolerant to a range of temperatures and salinity, is native to wetlands, and its emergence as a pathogen in humans has resulted from global warming effects on those environments. Chowdhary, who has been studying C. auris for nearly a decade, said that hypothesis inspired her to explore ecological niches where the fungus might live. 
 

"This study takes the first step in toward understanding how pathogen survives in the wetland," Chowdhary said, "but this is just one niche." Future studies, she said, could reveal more about how the fungus thrives in the wild--and better explain why it's such a menace to humans. 

Credit: 
American Society for Microbiology