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With more than 140 SARS-CoV-2 vaccines in development, the race is on for a successful candidate to help prevent COVID-19. An effective and safe vaccine would be a major advance in the fight against COVID-19. However, there are challenges in evaluating the efficacy of these vaccines during the pandemic, as an analysis article outlines in CMAJ (Canadian Medical Association Journal).

Those evaluating vaccine efficacy must take into account the risk of infection in the population being studied, use of social distancing practices, rates of pre-existing immunity from earlier COVID-19 and factors that influence the likelihood of severe COVID-19.

"The dynamic and rapidly changing pattern of virus exposure and level of population immunity during the evolving pandemic are potentially important confounders in the assessment of the efficacy of SARS-CoV-2 vaccines," writes Dr. Bahaa Abu-Raya, BC Children's Hospital, Vancouver, British Columbia, with coauthors. "This should be considered in sample size calculations for efficacy trials."

Some considerations:

Adequate sample sizes are needed to demonstrate effect of a vaccine in reducing disease and may need to be revised based on rates of SAR-CoV-2 transmission in study populations.

Public health interventions such as social distancing may reduce transmission and affect ongoing assessment of SARS-CoV-2 vaccines.

The baseline level of immunity could influence a trial outcome. For example, the benefit of a highly efficacious vaccine may not be evident in a population with high levels of previous exposure later in the pandemic.

There is a possibility that COVID-19 might be more severe in some people who have been vaccinated (called antibody-dependent enhancement [ADE]). This should be monitored as vaccine-related ADE may be evident only after large numbers of vaccinated people have been exposed to the virus and followed for some time.

The authors emphasize the need to test vaccines in vulnerable populations such as seniors, health care workers, Black people and those with risk factors for severe disease and who may have a different response than younger, healthier trial participants.

"The changing dynamics of the COVID-19 pandemic present a unique challenge for evaluating vaccines for SARS-CoV-2," says author Dr. Manish Sadarangani, Director of the Vaccine Evaluation Center at BC Children's Hospital and Sauder Family Chair in Pediatric Infectious Diseases at the University of British Columbia. "Researchers need to understand the immune responses generated after infection with this virus and whether they are protective, as this will help to inform the development and evaluation of these vaccines."

Pasteurizing breast milk using a common technique inactivates severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) making it safe for use, according to new research in CMAJ (Canadian Medical Association Journal)

Current advice is for women with coronavirus disease 2019 (COVID-19) to continue to breastfeed their own infants. In Canada, it is standard care to provide pasteurized breast milk to very-low-birth-weight babies in hospital until their own mother's milk supply is adequate.

"In the event that a woman who is COVID-19-positive donates human milk that contains SARS-CoV-2, whether by transmission through the mammary gland or by contamination through respiratory droplets, skin, breast pumps and milk containers, this method of pasteurization renders milk safe for consumption," writes Dr. Sharon Unger, a neonatologist at Sinai Health and professor at the University of Toronto, who is medical director of the Rogers Hixon Ontario Human Milk Bank, with coauthors.

The Holder method, a technique used to pasteurize milk in all Canadian milk banks (62.5°C for 30 minutes), is effective at neutralizing viruses such as HIV, hepatitis and others that are known to be transmitted through human milk. In this study, researchers spiked human breast milk with a viral load of SARS-CoV-2 and tested samples that either sat at room temperature for 30 minutes or were warmed to 62.5°C for 30 minutes, and then measured for active virus. The virus in the pasteurized milk was inactivated after heating.

More than 650 human breast milk banks around the world use the Holder method to ensure a safe supply of milk for vulnerable infants.

The authors report that the impact of pasteurization on coronaviruses in human milk has not been previously reported in the scientific literature.

Amsterdam, NL, July 9, 2020 - Timely administration of anti-Parkinson drugs is a significant issue for hospitalized patients with Parkinson's disease (PD) with late or missed doses resulting in longer stays and worse outcomes. As part of a quality improvement project, a multidisciplinary team was able to change the culture at a US hospital by using a series of measures to ensure PD patients receive medications on time. Their findings are published in the Journal of Parkinson's Disease.

The proper administration of anti-Parkinson medications is a critical challenge for the hospitalized PD patient. Medication regimens for PD can be complex due to the use of multiple types of medications, the need for frequent dosing, or both. As the disease progresses, PD patients may require carbidopa-levodopa dosing as often as every one to two hours, with dramatic consequences on mobility and function when the medication benefits have worn off (OFF phase). Debilitating symptoms in an OFF phase can include freezing of gait, complete immobility, dysphagia, tremor, dystonia, shortness of breath, and anxiety.

"Previous studies have shown that neither patients with PD nor PD specialists are confident that PD medications are administered on time in the hospital setting, and up to 30% of carbidopa-levodopa doses are not given within an hour of the scheduled time," explained lead investigator Martha A. Nance, MD, Park Nicollet Struthers Parkinson's Center, Golden Valley, MN, USA, where the project took place. "Through a collaborative effort at our hospital that included contributions from PD specialists, hospitalist physicians, pharmacists, nurses, nursing administration, and information technology--and most importantly, patients and families--we were able to introduce strategies to substantially improve the timely administration of doses."

The primary goal of the quality improvement project was to improve the administration of carbidopa-levodopa to within 15 minutes of scheduled administration times at the Struthers Parkinson's Center, a Parkinson's Foundation-designated Center of Excellence treating about 2,000 individuals with Parkinson's disease and related conditions, and the 361-bed Park Nicollet Methodist Hospital. After two years of baseline data collection and planning, interventions were carried out.

Several interventions were used: three kinds of nursing alerts in the electronic medical record; staff in-service education; stocking of immediate-release carbidopa-levodopa products into automated medication dispensing machines on key hospital units; reports to nurse unit managers on timeliness of carbidopa-levodopa administration; and reconciliation of all initial inpatient and outpatient carbidopa-levodopa orders by the hospital pharmacist upon admission.

After the intervention, investigators report there has been a sustained improvement in the timing of administered carbidopa-levodopa doses, from a baseline of 42.3% given within 15 minutes of the scheduled time in 2012 to over 70% in 2018, and from less than 90% of doses given within an hour of the scheduled time in 2012 to 96.5% in 2018. The hospital administered nearly 6,000 carbidopa-levodopa doses in 2018.

"We believe that the measures we instituted can be implemented in other hospitals, and that they will improve the safety, wellbeing, and outcomes of hospitalized PD patients," commented Dr. Nance. "The measures are not overly burdensome to hospital staff responsible for delivering over 4,000 administrations each year, so should be feasible at other hospitals with a similar number of PD patients and levodopa administrations.

"This project was very rewarding for our team, because of its obvious, immediate, and important impact on patient care," continued Dr. Nance. "We have reason to think that timely administration of carbidopa-levodopa may be associated with shorter stays and better outcomes and satisfaction. Anecdotally, patients have reported being surprised and pleased that nurses were reminding them that medication doses were due soon, rather than the other way around!"

PD is a slowly progressive disorder that affects movement, muscle control, and balance. It is the second most common age-related neurodegenerative disorder affecting about 3% of the population by the age of 65 and up to 5% of individuals over 85 years of age.

Washington, July 8, 2020--As education researchers' ongoing work is interrupted by school closures, what can they do to support education and public health institutions dealing with the Covid-19 pandemic? An article published today in Educational Researcher aims to answer that question, providing recommendations based on conversations with public health officials, state and local policymakers, educational leaders, directors of national education organizations, and researchers across disciplines. Educational Researcher is a peer-reviewed journal of the American Educational Research Association.

Read the article "From the Field: Education Research During a Pandemic," Educational Researcher, July 8, 2020. https://www.aera.net/Newsroom/From-the-Field-Education-Research-During-a-Pandemic

Read the overview of the authors' recommendations. https://www.aera.net/Newsroom/From-the-Field-Education-Research-During-a-Pandemic-Overview-of-Authors-Recommendations

"The education research community has unique potential to provide immediate aid to public health researchers as well as state education agencies, districts, and schools faced with the urgent challenge of providing remote instruction and services," said article coauthor David DeMatthews, an associate professor of educational leadership and policy at the University of Texas at Austin. "This aid may require researchers to take the lead, work shoulder-to-shoulder with education organizations, or play a support role. They must also prepare for a future when schools reopen perhaps under significantly different conditions, and possibly for a short period before returning to remote learning."

DeMatthews's coauthors include David Knight (University of Washington), Pedro Reyes (University of Texas at Austin), Amber Benedict (Arizona State University), and Rebecca Callahan (University of Texas at Austin).

The authors' recommendations are grouped into the following categories.

Education researchers can provide research support to the medical and public health fields in their Covid-19 efforts.

Education researchers can support education leaders by synthesizing and translating research.

Education researchers can organize and develop timely professional development opportunities for educators, schools, and districts.

Education researchers are well positioned to partner with state education agencies, districts, and schools to evaluate new practices as schools move instruction online and make recommendations for improvement.

Education researchers can modify or adjust their research projects in the context of the pandemic.

For details on the recommendations, see the open access Educational Researcher article and the overview of the authors' recommendations.

The recommendations, which not intended to be exhaustive, were developed to encourage education researchers to consider how they can inform the knowledge base and support front-line educators and healthcare researchers during this crisis.

"While we grieve the loss of loved ones and colleagues and the freedoms we enjoyed prior to the pandemic, we need to remain steadfast and committed to our work, to research that can and will make a difference in our schools and communities," said DeMatthews. "Together, education researchers can work collaboratively with public health and educational organizations to make a profound impact, generating innovative ideas that make the world a better place for all, but especially for educators and students."

NANOPARTICLE-DELIVERED GENE THERAPY USED TO INHIBIT BLINDING EYE DISEASE IN RODENTS

Media Contact: Rachel Butch, rbutch1@jhmi.edu22

Johns Hopkins Medicine scientists report the successful use of nanoparticles to deliver gene therapy for blinding eye diseases in rats and mice.

The research, described in the July 3, 2020, issue of Science Advances, provides evidence of the potential value of nanoparticle-delivered gene therapy to treat wet age-related macular degeneration -- an eye disorder characterized by abnormal blood vessel growth that damages the light-sensitive tissue in the back of the eye -- as well as rarer inherited blinding diseases of the retina.

Many gene therapy approaches depend on viral vectors, which use a virus's natural ability to carry genetic material into cells. However, viruses create an immune response that prevents repeat dosing, and the most commonly used virus for ocular gene therapy cannot carry large genes.

"Some of the most prevalent inherited retinal degenerations are due to mutations in large genes that simply cannot fit into the most commonly used viral vector," says study senior author Peter Campochiaro, M.D., the George S. and Dolores D. Eccles Professor of Ophthalmology at the Johns Hopkins University School of Medicine, and a retina specialist at the Johns Hopkins Medicine Wilmer Eye Institute.

To overcome such limitations, Campochiaro and his colleagues developed a new approach involving a biodegradable polymer that surrounds and compacts long stretches of DNA, creating nanoparticles that can enter the cells. This technology allows the researchers to convert the cells of the eye into "minifactories" for a therapeutic protein.

In their rodent studies, the researchers showed that the genes delivered by nanoparticles stayed active within the cells for several months.

An estimated 1.6 million people in the United States with macular degeneration receive drug injections into the eye every four to six weeks to treat their disease. A gene therapy treatment could provide a way for the eye's tissue to prevent further vision deterioration with only a few initial treatments. Genetic diseases that cause blindness could be treated in a similar way, by introducing functional versions of genes that inherited mutations have disabled.

"These results are extremely promising," says study co-author Jordan Green, Ph.D., professor of biomedical engineering at the Johns Hopkins University School of Medicine. "We have the ability to reach the cells most significantly affected by degenerative eye disease with nonviral treatments that can allow the eye to create its own sustained therapies."

JOHNS HOPKINS RESEARCHERS SOLVE IMAGING SCAN PROBLEMS CAUSED BY METAL IMPLANTS

Media Contact: Vanessa Wasta, M.B.A., wasta@jhmi.edu

Engineers at Johns Hopkins Medicine have solved the problem of distorted imaging scans that plague surgeons who need to use them to assess the placement of metal implants. They have developed a simple and practical solution to "steer" a scanner and direct its imaging beam so that most of the distortion problem is remedied.

Metal implants are commonly used to stabilize bones and structures in the body. During an operation, surgeons use a C-arm X-ray or CT (computed tomography) scanner to see if an implant is correctly positioned, has caused hemorrhaging or is impinging on adjacent nerves.

Problems with the implant can necessitate second surgeries that are expensive and often have poor outcomes, say the Johns Hopkins engineers.

"Metal artifacts are a giant headache for surgeons," says Jeffrey Siewerdsen, Ph.D., professor of biomedical engineering at Johns Hopkins and leader of the team which published results of its proof-of-principle concept in the May 19, 2020, issue of the journal Physics in Medicine & Biology. "The beauty of the system we developed is that it has minimal change in the operating room workflow, time and cost."

Metal transmits X-rays differently than tissue or bone, often yielding distortions, or artifacts, which appear on imaging scans. Artifacts may make the implant appear larger than real and form streaks throughout the image, blocking the surgeon's ability to see potential problems.

Currently, scanners have built-in systems to analyze the X-ray signals and reduce the impact of metal artifacts. However, Siewerdsen says, these systems are not very effective, and the artifacts are worse with larger and denser implants.

"We steer the C-arm scan to give data that contain the fewest errors that could cause image artifacts," says Siewerdsen. "In some cases, the solution is as simple as tilting the C-arm."

Using cadavers, torso models and surgery simulations, Siewerdsen's team developed a computer algorithm that assesses the location of a metal implant and determines the best position of the CT scanner to avoid artifacts. They dubbed the method "metal artifact avoidance," since it avoids errors in the original data, unlike other techniques that try to correct them later.

The researchers found that their tests of the algorithm and tilting of the C-arm reduced the magnitude of errors in the X-ray data and resulting artifacts in the image. In one example, a 5-millimeter-diameter metal screw was implanted into the spine of a cadaver. Without the metal artifact avoidance algorithm, the image of the screw was distorted so that it appeared to be 8-12 millimeters in diameter. With the algorithm, the screw appeared as its real size.

"The key is to compute a scan orbit in a simple way that can be easily run by the C-arm," says Siewerdsen. "We were surprised at how well it works."

To enable the computer algorithm to work on most C-arms, manufacturers would need to calibrate their scanners to be tilted in the operating room, notes Siewerdsen. He adds that the metal artifact avoidance method can be paired with different algorithms that correct other kinds of artifacts.

STUDY SHOWS MOBILE HEALTH, VIDEO TECHNOLOGY INFLUENCE BEHAVIOR OF AFFECTED POPULATIONS

Media Contact: Danny Jacobs, djacob41@jhmi.edu

Ensuring patients follow prescribed methods of care is a challenge for health care providers around the globe. In India, for example, 97% of HIV-infected pregnant women and their babies receive antiretroviral therapy (ART) for prevention of mother-to-child transmission (PMTCT). Poor outcomes persist, however, due to personal and socioeconomic factors -- current estimates indicate that mother-to-infant transmission of HIV drops from 25% to less than 2% if HIV-infected women begin ART early in their pregnancy and maintain exclusive breastfeeding.

Researchers with the Johns Hopkins Center for Clinical Global Health Education (CCGHE) wanted to see if technology could assist uptake of PMTCT services. They supplied a group of HIV outreach workers (ORWs), who visited the homes of pregnant or breastfeeding women with specially designed videos -- in the native language of the mothers -- that were focused on (1) exclusive breastfeeding, (2) how to take ART medicines, (3) issues related to disclosure of HIV status and (4) ensuring HIV testing of babies. ORWs also collected information using smart forms on emocha Mobile Health's platform and sent text alerts for upcoming and missed visits to mothers with HIV.

After two years, mothers and mothers-to-be who used technological aids showed significantly increased uptake of exclusive breastfeeding at two months as well as early infant diagnosis at six weeks compared to a control group, according to results published July 3, 2020, in the Journal of the International AIDS Society.

"Information given through videos in the local language to mothers with low health literacy in a standardized manner is a more effective way of communicating. Women in our study could relate to the women in the video stories," says Nishi Suryavanshi, Ph.D., a CCGHE faculty member based in Pune, India, and the study's lead author. "This kind of communication delivery is an easy and cost-effective method to encourage a positive change and improvement in patient behaviors, and to ensure consistent messaging is being delivered."

While speaking with ORWs and their patients, the researchers found that the mobile health platform helped ORWs do their job more effectively, and that both ORWs and patients felt more confident and empowered to make decisions. The use of technology also can be scaled and optimized for all of India -- or anywhere in the world -- to change health-related behavior, according to Suryavanshi.

"An intervention could be adapted as per the cultural context of the setting," she says. "For the United States, I think it could be adapted for lifestyle changes to reduce the risk of cardiovascular diseases, for example."

The Johns Hopkins University has a financial interest in emocha, which was invented at the university. This financial interest includes equity in the company and entitlement to royalties. CCGHE founder Robert Bollinger Jr., M.D., M.P.H., a co-author of the paper, is an inventor of the technology who has equity and a royalty interest in emocha. He is a member of the emocha board of directors and a consultant for the company. These conflicts of interest are being managed by the university in accordance with its policies.

ONE FORM OF PROTEIN KEY TO LEARNING AND MEMORY IS BEST BET FOR THERAPY DEVELOPMENT

Media Contact: Vanessa Wasta, M.B.A., wasta@jhmi.edu

Johns Hopkins Medicine scientists have analyzed four versions of a protein made by the gene SYNGAP to find that one of the versions is the most promising target for developing therapies to correct the gene when it is mutated. The mutated form of the SYNGAP gene contributes to conditions including intellectual disability, autism and schizophrenia.

Among DNA in human cells, a portion of about 20,000 genes churn through the process of making proteins, the tiny molecules that keep cells in working order. Each gene is coded to produce a certain protein, but depending on the cell's stage of development, environmental stress and other factors, a gene can produce different versions of its protein, called an isoform.

The function of one isoform compared with another could be as different as night and day, and scientists have long studied these variations. However, says Richard Huganir, Ph.D., professor of neuroscience and director of the Department of Neuroscience at the Johns Hopkins University School of Medicine, the functions of SYNGAP isoforms had not been well characterized, so he and his colleagues performed the analysis and published their results in the June 24, 2020, issue of eLife.

Huganir has been studying SYNGAP since he and his research team first isolated the gene in 1998. Studying the gene has been interesting, he says, because the protein it produces is a critical part of a neuron's communications center.

SYNGAP is a protein that regulates the structure of the contact point between two neurons, called a synapse, where brain cells trade messages. Without SYNGAP, learning and memory are impaired. According to Huganir, mutations in the gene underlie 1% of intellectual disability, and SYNGAP is among the top five genes implicated in autism. He says that it also is genetically associated with schizophrenia.

To restore SYNGAP proteins, Huganir has been working with biotechnology companies on gene therapies that can boost their production. A key step is determining which of the protein's four isoforms researchers should target.

Huganir's team used mouse models to show that the SYNGAP alpha 1 isoform has the most potential for creating a gene therapy that increases SYNGAP protein production in a cell. The researchers found that SYNGAP alpha 1 has the strongest presence in the synapse in a state called liquid phase transition, during which the proteins are very well organized and defined. The other isoforms of SYNGAP, the researchers report, were not as potent as the alpha 1 version.

SYNGAP alpha 1 is typically produced in larger quantities shortly after birth, when synapses are forming and maturing in the brain. It's a critical time for learning, says Huganir.

The need to cover an open wound on cycad stem cuttings has been confirmed by the Western Pacific Tropical Research Center at the University of Guam in a study published in the Tropical Conservation Science journal on April 27. And the scientists have shown that the list of products that effectively fulfill this purpose is not restrictive.

Guam is home to Cycas micronesica, an arborescent cycad species that is facing threats from several invasive insect pests. The once widespread tree has been decimated from the forests on Guam and the nearby island of Rota, leading the International Union for Conservation of Nature to list the gymnosperm tree species as endangered.

Additionally, large expanses of forests are being bulldozed on Guam for construction activities, according to Benjamin Deloso, one of the authors of the study.

"Many of these forests contain populations of our endangered cycad, and rescue activities have included the use of stem cuttings to propagate the trees in an effort to conserve the genetic diversity within the construction sites."

This has driven the Guam authors to, for the past decade, look into various issues that enable success of asexual propagation of cycad plants.

In their seven-month study, 100% of the cuttings that were left untreated died prior to adventitious root formation. In contrast, all of the cuttings that received wound sealants from various products exhibited 100% survival at the end.

When cycad stem cuttings are removed for propagation purposes, the exposed parenchyma tissues of the wound are highly vulnerable to desiccation and pathogens. Cycad horticulturists treat the open wounds with sealants to sustain hydration within the cuttings and exclude pathogens.

The authors employed an innovative approach to the study by comparing various common products that are not normally exploited for horticultural use. Petroleum jelly, lanolin paste, honeycomb wax, and even modelling clay were shown to be fully capable of enabling success in the nursery study. The findings indicate almost any malleable, clean product that effectively formed a seal over the wound and retained hydration throughout the propagation phase was effective.

The team's past research has shown that carbohydrate depletion following chronic infestations of the invasive insect pests reduces the ability of stem cuttings to produce adventitious roots.

"Using this prior information, we designed nursery studies to determine which protocols that reside in cycad propagation folklore are required and which can be ignored," Deloso said. "When one is working with an endangered tree species, the stakes are raised. The results from replicated studies should support nursery management decisions if possible."

Cycad plants construct unique stems that are mostly comprised of soft parenchyma tissue. The innovative engineering of cylindrical vascular tissues and tough exterior layers allow heights of 18 meters or more to be obtained despite the copious amounts of soft internal tissue.

The Guam-based research that informs the ongoing propagation studies began in 2009 when anatomy methods were used to determine how the tissues within a cycad stem respond to a wound. The external tissues of an intact cycad stem include a protective layer called periderm, which retains moisture on the inside and excludes pests and pathogens from the outside. Secondary tissue degradation ensues if the integrity of the periderm is challenged by an open wound. Intact cycad stems eventually seal off the problematic areas with a corky layer called phellem.

"This informative research means that cycad horticulturists have known for more than a decade that some kind of protective sealant is needed to cover an open wound on a cycad stem cutting," Deloso said. "The sealant acts as an artificial phellem."

Move over, murder hornets. There's a new bee killer in town.

CU Boulder researchers have found there is growing evidence that another "pandemic," as they call it, has been infecting bees around the world for the past two decades and is spreading: a fungal pathogen known as Nosema.

Yet while it's been documented across Europe, Canada and even in Kenya, this infection has almost exclusively been recorded in the European honeybee, the recognizable commercial pollinator. Their findings, published in Plos Pathogens, reveal that almost nothing is known about the impact of this pathogen on native, solitary bees, which make up the majority of the approximately 20,000 bee species on the planet.

"More work needs to be done to understand Nosema infections in native bee species and the potential consequences to native ecosystems, if native bees suffer a similar fate as honeybees when infected," said Arthur Grupe II, lead author and postdoctoral researcher in the Department of Ecology and Evolutionary Biology.

Not only are native bees incredibly important as pollinators in their local ecosystems, as honeybees are not generally found in these places, but they also contribute to pollination of agricultural crops.

"One out of every three bites of the food we eat is due to a pollinator," said Grupe.

Bee populations, and specifically honeybee hives, around the world have been declining in the past two decades due to colony collapse disorder. While there is no singular cause behind this phenomenon, bees and their colonies' health are affected by what's known as the four P's: pests, pathogens, poor nutrition and pesticides.

Nosema is a fungal pathogen, a type of Microsporidia, or spore-forming single-celled parasite.

It survives by infecting the guts of bees, where it germinates, infects the host's cell, reproduces, and ruptures the host cell to release its spores. While being passed through the digestive tract, these spores can infect other cells in the bee's body, sickening the bee and contaminating flowers, pollen, and hives along the way. Some strains of Nosema even lower sperm count and mutilate the male genitalia of bumblebees, reducing their reproductive success.

Different strains, mainly Nosema apis and Nosema ceranae, are now also appearing in new places, with some strains, specifically N. ceranae, causing year-round infections in hives where previously the bees could fight it off seasonally.

So far only Nosema bombi, which infects bumblebees, has been documented in Colorado. However, the more detrimental N. ceranae is probably not far behind, according to Grupe.

A few treatments exist, including plant extracts, breeding methods for resistance and microbial supplements. But most research in native bee populations has been limited to DNA-based methods which test for the pathogen in a bee, rather than looking more holistically at how it effects the bee and the broader population.

The study authors say it's crucial for scientists to better understand how these Nosema strains are traveling the globe and affecting native, solitary bees, as they could lead to further bee pandemics and contribute to colony collapse.

A cascade of effects

Some flowers, like the snapdragon (Penstemon), can only be pollinated by a bee or insect with the right size and weight, triggering the flower to open as the bee lands on it. If that type of bee is wiped out by an infection, that plant could also disappear--and with it, other animals that ate its fruit or leaves.

Flowers are also almost exclusively where solitary bees--the majority of all bee species--meet their mates, since otherwise females nest alone in the ground or in structures built from plant materials. If these flowers die off, so too do the places where bees find their reproductive partners.

Another major threat for native bees is pathogen spillover, when infected bees from commercial hives leave the fungus on flowers and native bees pick it up. These native bees, having never encountered this pathogen before, could be much more susceptible to its negative effects.

The same thing could happen in reverse: If a novel strain of Nosema develops in native bees, that more aggressive strain could then find its way back into commercial honeybee populations--who wouldn't have resistance to that particular version of it.

Without knowing how Nosema is affecting native, solitary bees, a whole pandemic and its ecological consequences could be going on unnoticed.

"We know so little about the biology of what's happening," said Alisha Quandt, co-author and assistant professor of ecology and evolutionary biology. "That's one of the reasons why we think it's so important for people to start doing this kind of surveillance work, going out there and sampling more native bees."

Several essays look specifically at how racial inequality is embodied in health inequities.

Black Lives in a Pandemic: Implications of Systemic Injustice for End-of-Life Care

Alan Elbaum

In recent months, Covid-19 has devastated African American communities across the nation, and a Minneapolis police officer murdered George Floyd. The agents of death may be novel, but the phenomena of long-standing epidemics of premature black death and of police violence are not. This essay argues that racial health and health care disparities, rooted as they are in systemic injustice, ought to carry far more weight in clinical ethics than they generally do. In particular, this essay examines palliative and end-of-life care for African Americans, highlighting the ways in which American medicine, like American society, has breached trust. Is there such a thing as a "good" or "dignified" death when African Americans are dying not merely of Covid-19 but of structural racism? Elbaum is a medical student in the UC Berkeley-UCSF Joint Medical Program.

The Future of Bioethics: It Shouldn't Take a Pandemic

Larry R. Churchhill, Nancy M.P. King, and Gail E. Henderson

This essay looks at how a focus on "lifeboat" issues in the pandemic, such as rationing and fair allocation of scarce medical resources, has diverted attention from the structural racism that magnifies the burden of disease for people of color. "The Centers for Disease Control and others are now posting race-linked data showing that Covid-19 is fast becoming what Keeanga-Yamahtta Taylor has called 'the Black Plague,'" the authors write. They argue that it is time to broaden our teaching, research, and practice to match the breadth of the field in order to help address these significant societal inequities and unmet health needs. Churchill is a professor of medical ethics emeritus at Vanderbilt University. King is a professor at Wake Forest University. Henderson is a professor at University of North Carolina School of Medicine.

Other essays include:

Disability Rights as a Necessary Framework for Crisis Standards of Care and the Future of Health Care

What Could "Fair Allocation" during the Covid-19 Crisis Possibly Mean in Sub-Saharan Africa?

Rethinking "Elective" Procedures for Women's Reproduction during Covid-19

Employment-Based, For-Profit Health Care in a Pandemic

Digital Contact Tracing, Privacy, and Public Health

AI Surveillance during Pandemics: Ethical Implementation Imperatives

Pandemics, Protocols, and the Plague of Athens: Insights from Thucydides

Interdependent Citizens: The Ethics of Care in Pandemic Recovery

Older Adults and Covid-19: The Most Vulnerable, the Hardest Hit

Communities Matter

Global Disparity and Solidarity in a Pandemic

Duties toward Patients with Psychiatric Illness

Vulnerable Children in a Dual Epidemic

Covid-19: Exposing the Lack of Evidence-Based Practice in Medicine

Our Next Pandemic Ethics Challenge? Allocating "Normal" Health Care Services

A new study published in the American Journal of Obstetrics & Gynecology shows that a University of Rochester Medical Center (URMC) community outreach initiative has helped adolescents in Rochester adopt long-acting reversible contraception (LARC) at a rate far higher than the U.S. overall.

The study, "Impact of the Rochester LARC Initiative on Adolescents' Utilization of Long-Acting Reversible Contraception," used Youth Risk Behavior Surveillance System data from the years 2013, 2015, and 2017 for Rochester, New York City, New York State, and the U.S. overall. These years cover the time before and after the Initiative began in 2014.

The study found that usage of LARC among sexually active high school females in Rochester increased from 4 to 24 percent from 2013-2017, compared to an increase from 2.7 to 5.3 percent in New York City, 1.5 to 4.8 percent in New York State, and 1.8 to 5.3 percent in the U.S. overall.

The Greater Rochester LARC Initiative was started six years ago by the Hoekelman Center for Health Beyond Medicine, a unit of the URMC Department of Pediatrics that connects doctors with non-profits to benefit kids and adults by making communities healthier places to live. Primarily funded by the Greater Rochester Health Foundation, the Initiative aims to increase access to highly effective methods of birth control, including intrauterine devices and contraceptive implants (LARCs) for adolescents in Rochester.

Andrew Aligne, M.D., M.P.H., director of the Hoekelman Center, and his team have led the community effort to promote LARC by conducting outreach to local organizations that work with youth. They employ a simple "lunch-and-learn" approach to disseminate accurate information that forms the backbone of the Hoekelman Center's advocacy work.

"An interesting aspect of the LARC project is that we talk to adults, not to teens. We work with our community partners to teach adults about birth control. This way, they can help teens to make well-informed choices about preventing unintended pregnancy," says Jessica VanScott, M.P.H., the LARC Initiative's health project coordinator.

Through their research with area teens, the LARC project team found that many were interested in learning about birth control, and that they often asked their most trusted peers and adults for advice.

"If teens are learning outside the medical setting from trusted youths and adults, then how do we increase the likelihood that anyone they talk to will share accurate information? We thought it could help if we gave resources with useful information to adults who work with teens in the community," said Aligne, associate professor of Pediatrics at URMC.

So far, the team has presented to more than 2,700 adults in health care settings, as well as those in community settings such as staff of after-school programs. The talks provide information about the safety, efficacy, and availability of LARC, with the goal of improving knowledge and access at the community level.

This approach is different from previous attempts to disseminate information about LARC. Typically, past outreach efforts have focused on targeting primary care providers or utilizing advertising resources to raise awareness. The Hoekelman Center's community-based approach achieved strong results because few of these community organizations had ground-level information available about LARC, according to Aligne.

"Almost nobody knew that the LARC program was free and covered by Medicaid," said Aligne. 26 states offer reimbursement for LARC under the Medicaid Family-Planning Benefit - included as part of the Medicaid expansion in the Affordable Care Act (ACA) - and Aligne believes these states could scale-up the Hoekelman Center's model to raise awareness as well.

Studies have shown that unintended teen pregnancy can lead to a number of critical health and social problems for young parents and their children: low birth weight, unemployment, school failure, and many other serious issues. Because of these risks, the Centers for Disease Control and Prevention (CDC) has declared teen pregnancy a national public health priority, and the CDC -- along with the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists -- recommends LARC as a safe and highly effective method of pregnancy prevention for adolescents seeking contraception.

"LARCs are more effective than pills, patches, and other contraceptives because they remain in place all the time," said Katherine Greenberg, M.D., an adolescent medicine specialist at UR Medicine's Golisano Children's Hospital. "Today's LARCs are safe, effective, invisible, and can be easily removed with no lingering effects when you decide to become pregnant." LARC methods protect against pregnancy for up to three to 12 years, can be removed at any time, and are 40 times more effective for teens than the traditional birth control pill.

The Hoekelman Center's efforts are bolstered by an extensive network of local agencies, including the Initiative's core partners: the Metro Council for Teen Potential, Healthy Baby Network, Highland Family Planning, and Planned Parenthood of Central and Western New York.

"As we strive to fulfill our mission to pursue and invest in solutions that build a healthier region where all people can thrive, we are proud to support the LARC Initiative at URMC, and celebrate its successes," said Matthew Kuhlenbeck, president and CEO of the Greater Rochester Health Foundation.

"The LARC project team takes a proactive, practical approach in its efforts to help reduce teen pregnancy by sharing information and increasing awareness of options, and we are especially grateful for the collaboration among URMC and community partners who are working together to address this challenge."

LARC services have continued during COVID-19, and access expanded at an increasing number of primary care practices serving teens and young adults throughout the Finger Lakes region during the last year, thanks to Accountable Health Partners (AHP), URMC's clinically integrated network of hospitals and physicians. In partnership with the Hoekelman Center team, and funded by a grant from the Finger Lakes Performing Provider System (FLPPS), AHP has promoted training in both reproductive counseling and LARC placement for primary care providers in order to further reduce access barriers for patients.

"The LARC Initiative demonstrates true collaboration between health care and community and is a significant population health success for our region," said Laura Jean Shipley, M.D., professor of clinical pediatrics, vice chair for Population and Behavioral Health at URMC and associate medical director at AHP.

BIRMINGHAM, Ala. - The lab of Jeremy Day, Ph.D., at the University of Alabama at Birmingham, has used single-nucleus RNA sequencing approaches to compare transcriptional responses to acute cocaine in 16 unique cell populations from a portion of the brain called the nucleus accumbens, or NAc. This molecular atlas is "a previously unachieved level of cellular resolution for cocaine-mediated gene regulation in this region," said Day, an associate professor in the UAB Department of Neurobiology.

The atlas was just the beginning of a major study, published in the journal Science Advances, that used multiple cutting-edge technologies to describe a dopamine-induced gene expression signature that regulates the brain's response to cocaine.

"These results mark a substantial advance in our understanding of the neurobiological processes that control drug-related adaptations," Day said. "They also reveal new information about how transcriptional mechanisms regulate activity-dependent processes within the central nervous system."

The approaches used in this study, Day says, may also help dissect the role of similar gene programs that mediate other types of behavior, memory formation or neuropsychiatric disorders.

The NAc is deeply involved in drug addiction, and detailed understanding of how drugs alter its neural circuitry to initiate addictive behavior can suggest new therapeutic interventions. The NAc is a central integrator of the brain's reward circuit, and all addictive drugs acutely raise the level of the neurotransmitter dopamine in the NAc. Dopamine signaling during repeated drug use leads to widespread changes in gene expression, initiating alterations in neural synaptic circuitry and changes in behavior associated with drug addiction.

Previous studies of changes in NAc gene expression were only able to look at bulk tissue -- a mix of many different cell types. When the Day lab looked at single cell changes by RNA-sequencing 15,631 individual rat NAc nuclei, they found a surprise. Only a small fraction of neurons in the NAc were transcriptionally responsive to cocaine administration -- mainly a specific subcluster of medium spiny neurons that express the Drd1 dopamine receptor.

The researchers next comprehensively defined the core gene structure that is activated when dopamine is added to a striatal neuron culture system. Similar to the responses in the rat NAc after cocaine administration, transcriptional activation predominantly occurred in Drd1-receptor-medium spiny neurons. Day and colleagues identified a core set of around 100 genes altered by dopamine, which also correlated with key genes activated in the NAc of rats given cocaine.

It has been hypothesized that gene expression programs in the brain work in concert to produce downstream effects on neuronal function and behavior. However, until recently researchers have lacked a way to test key gene expression programs, which requires inducing multiple genes at the same time.

Day and colleagues engineered a multiplexed CRISPR guide-RNA array to target 16 of the top candidate genes altered by dopamine. When paired with a neuron-optimized CRISPR/dead-Cas9 activation system, they were able to simultaneously upregulate the 16 genes in neuronal cultures or in the NAc of live rats. They then explored the transcriptional, physiological and behavioral consequences.

In primary neuronal culture, induction of this gene signature produced large-scale transcriptional changes that were enriched for genes involved in synaptic plasticity, neuronal morphogenesis and ion channel function. This program also significantly increased neuron burst firing frequency. In live rats, induction of the gene signature produced sensitization to repeated cocaine administration. These changes seen in the neuronal culture and live rats are similar to the neuronal and behavioral changes initiated by drugs of abuse.

Day says his group's study is the first proof-of-principle evidence that CRISPR activation can be used for simultaneous and selective regulation of a gene expression signature in vivo.

"Critically," Day said, "these results represent the first demonstration -- to our knowledge -- of multiplexed gene regulation in any neuropsychiatric model, providing a roadmap for future studies to investigate the relationship between altered gene programs and neuronal disease states.

"While the present work provides insight into how cellular diversity contributes to transcriptional responses after an initial cocaine experience," Day said, "repeated exposure to drugs of abuse promotes neurophysiological adaptations that are thought to drive compulsive drug-seeking long after cessation of use. Hence, it will be critical for future studies to expand on this work by examining the transcriptional consequence of repeated or self-administered drug use at the single-cell level, as well as understanding how these changes are maintained within different cell populations over longer periods of time and as a result of volitional drug experience."

Scientists are ready to trial a new cancer vaccine in humans following the successful outcome of their preclinical studies.

The new vaccine was developed by a Mater Research team based at The Translational Research Institute in collaboration with The University of Queensland.

Lead Researcher Associate Professor Kristen Radford says the vaccine has the potential to treat a variety of blood cancers and malignancies and is a major breakthrough for cancer vaccinations.

"We are hoping this vaccine could be used to treat blood cancers, such as myeloid leukaemia, non-Hodgkin's lymphoma, multiple myeloma, and paediatric leukaemias, plus solid malignancies including breast, lung, renal, ovarian, and pancreatic cancers, and glioblastoma," she said.

"Our new vaccine is comprised of human antibodies fused with tumour-specific protein, and we are investigating its capacity to target human cells while activating the memory of the tumour cells."

Associate Professor Radford says the vaccine offers several key advantages over existing cancer vaccines, which have already shown promise in early clinical trials.

"First, it can be produced as an 'off the shelf' clinical grade formulation, which circumvents the ?nancial and logistical issues associated with patient-specific vaccines," she said.

"Secondly, this prototype vaccine targets the key tumour cells required for the initiation of tumour-specific immune responses, thereby maximising potential effectiveness of treatment, while minimising potential side effects.

"We are very happy to see our research published in a prestigious journal, and we hope our continued work towards finding a safe and effective cancer vaccine will benefit cancer patients in the future."

Researchers at Kumamoto University, Japan have revealed that DNA methylation occurs in the gene that codes serotonin transporter (SERT), a protein that regulates neurotransmitter transmission, in schizophrenia and bipolar patients. Particularly prominent in males and patients with certain genetic polymorphisms, this methylation is inversely correlated with volume of the amygdala in the brain. This work is expected to lead to a better understanding of the pathophysiology of schizophrenia and bipolar disorder. It may also help to develop therapeutic agents and diagnostic/therapeutic markers that target epigenetic conditions.

Schizophrenia and bipolar disorder are serious mental illnesses that affect approximately 1% of the population and require long-term treatment. Past epidemiological studies suggest that onset involves a complex interplay of genetic and environmental factors, but no definitive genetic factors have been identified yet.

SERT regulates the concentration of the neurotransmitter serotonin within the gap between neurons where neurotransmitters are exchanged (the synaptic cleft). It is considered to be deeply involved with mental illnesses, and drugs targeting the protein are widely used as treatments for depression and anxiety disorders. In particular, a polymorphism called 5-HTTLPR in the gene that encodes SERT has been a target for many mental disorder studies. When the polymorphism is the L (long) type, more SERT is produced, and when it is the S (short) type, less is produced. People generally have one combination of these types, L/L, S/L, or S/S. In 2003, an analysis (Capsi et al., 2003) became highly regarded for reporting that people with the S-type polymorphism had a stronger tendency for anxiety and were more susceptible to depression. However, recent large-scale studies scrutinized that work and clearly denied the simple association between the 5-HTTLPR polymorphism and mental illness.

Expression of genes in DNA is controlled by chemical modifications like methylation. A collaborative research group between Kumamoto University and the University of Tokyo used DNA methylation analysis in patients with bipolar disorder (Sugawara et al., 2011) to show that two specific sites (CpG3 and CpG4) in the SERT gene show high methylation status. Here, they conducted a large-scale follow-up study on those CpG sites, a new study with patients having schizophrenia, and a comprehensive study on the pathology of SERT DNA methylation.

They measured the DNA methylation status of the SERT gene using genomic DNA extracted from the blood of 450 patients with bipolar disorder, 440 patients with schizophrenia, and 460 healthy subjects. They found that the SERT CpG3 site in patients with bipolar disorder and schizophrenia is hypermethylated in male patients. Additionally, after administration of an antipsychotic drug over four weeks, no change in methylation was detected in animal test subjects (marmoset, n=3) compared to control (n=3), which suggests that methylation in bipolar and schizophrenic patients is not affect by medication.

Furthermore, a detailed analysis of the SERT gene polymorphism 5-HTTLPR revealed that the methylation rate was high in patients with bipolar disorder and schizophrenia when 5-HTTLPR was hypoactive type (S/S or S/L). When the CpG3 site of the SERT gene was artificially methylated, researchers found that the transcriptional activation ability and production of the SERT protein were both markedly suppressed.

Researchers also investigated the volume of the amygdala with MRI images from 41 healthy subjects and 57 schizophrenia age- and gender-matched patients. The amygdala is a part of the brain that, among other functions, plays a major role in emotional responses. SERT actions are strong there and its association with DNA methylation has been reported in the past. The volume of the left amygdala of male patients with hypoactive type 5-HTTLPR polymorphism was found to have an inverse correlation with the DNA methylation rate of CpG3. This suggests that male schizophrenia patients of this polymorphism type may have a hypermethylated SERT gene that leads to decreased amygdala volume through decreased SERT protein levels.

"Our research shows that a specific site in the SERT gene is hypermethylated in male patients with schizophrenia and bipolar disorder, and is associated with volume changes in the amygdala," said study leader, Dr. Kazuya Iwamoto. "In the future, we believe that this can be used as a biomarker for onset prediction, diagnosis, and to assess therapeutic effects. It could even be a clue for the molecular pathologies of these disorders."

WHAT

Findings reported online today in the New England Journal of Medicine suggest that a nurse-managed, individually tailored falls prevention plan administered for at least 20 months did not significantly reduce risk of serious fall injuries in older adults aged 70 and over who were at high risk for falls. Each year in the United States, about 3 million adults 65 and older are treated in the emergency department for serious injuries from a fall. To promote the development of effective approaches to prevent these injuries, the Patient-Centered Outcomes Research Institute (PCORI) and National Institutes of Health supported the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial.

STRIDE was a multisite, randomized pragmatic trial, meaning it was conducted in a real-world primary care setting. All participants in the study were screened for seven risk factors for fall injuries: walking and balance impairment; hazards for falling in the home environment; troubles with feet or shoes; vision problems; medications that increased fall risk; experiencing low blood pressure when standing up; and having weak bones from osteoporosis and low levels of vitamin D. The Falls Care Managers helped participants in the intervention group identify their risk factors and select which risks to modify. Control group participants received their usual care plus a falls information pamphlet, and were encouraged to discuss fall prevention with their primary care doctors, who also received the risk factor screening results.

The primary outcome of this large-scale trial was the length of time to the first serious fall injury. After a participant reported a serious injury, it was verified by trial sites or health records. The rates of verified serious fall injuries did not differ significantly between the intervention and control groups. For both intervention and control groups, the number of verified first serious fall injuries was lower than expected based on rates previously reported by older persons who matched the trial's requirements for inclusion.

Spokespeople from NIH's National Institute on Aging (NIA) can provide important context about this study, including:

Explaining the design of the STRIDE study, including the study's strengths and limitations

Sharing background about previous smaller studies on falls prevention

Providing context for NIA-funded falls prevention research

WHEN AND WHO

The following NIA spokespeople are available for interviews by phone or email. The embargo lifts on Wednesday, July 8, at 5 p.m. ET.

Evan Hadley, M.D., director of NIA's Division of Geriatrics and Clinical Gerontology (DGCG)

Rosaly Correa-de-Araujo, M.D., M.Sc., Ph.D., a coauthor of the paper and DGCG senior scientific advisor

Sergei Romashkan, M.D., Ph.D., chief of DGCG Clinical Trials Branch and program official for STRIDE

ADDITIONAL BACKGROUND

STRIDE assessed the benefit of an evidence-based, multipronged, individually tailored falls prevention intervention implemented by nurses who were trained to be Falls Care Managers. Led by investigators at Brigham and Women's Hospital, Harvard Medical School, Boston; Yale School of Medicine, New Haven, Connecticut; and David Geffen School of Medicine, University of California, Los Angeles, the study was conducted at 86 primary care practices in 10 U.S. healthcare systems. The large trial enrolled more than 5,000 people who were at least 70 years old and had been injured from a fall, had fallen at least two times in the previous year, or were afraid of falling because of difficulty walking or balancing.

STRIDE was designed after small-scale trials showed that risk factor reduction interventions reduced the rate of falls and fall injuries. STRIDE participants were asked to diminish one to three of seven risk factors. In some cases, important risk factors were not diminished; therefore, a participant's risk reduction may not have been optimal. Other strategies to achieve risk reduction in health care systems might be more effective, and lessons learned from STRIDE can help inform the design and implementation of future clinical trials in various health care delivery settings.

An experimental drug for a rare, inherited form of amyotrophic lateral sclerosis (ALS) has shown promise in a phase 1/phase 2 clinical trial conducted at Washington University School of Medicine in St. Louis, Massachusetts General Hospital in Boston and other sites around the world and sponsored by the pharmaceutical company Biogen Inc. The trial indicated that the experimental drug, known as tofersen, shows evidence of safety that warrants further investigation and lowers levels of a disease-causing protein in people with a type of amyotrophic lateral sclerosis, or ALS, caused by mutations in the gene SOD1.

The results of the study, published July 9 in the New England Journal of Medicine, have led to the launch of a phase 3 clinical trial to further evaluate the safety and efficacy of tofersen.

"ALS is a devastating, incurable illness," said principal investigator Timothy M. Miller, MD, PhD, the David Clayson Professor of Neurology at Washington University and director of the ALS Center at the School of Medicine. "While this investigational drug is aimed at only a small percentage of people with ALS, the same approach - blocking the production of specific proteins at the root of the illness - may help people with other forms of the illness.

"This trial indicated that tofersen shows evidence of safety that warrants further investigation and that the dose we used lowers clinical markers of disease. There are even some signs that it slowed clinical progression of ALS, although the study was not designed to evaluate effectiveness at treating the disease, so we can't say anything definitive. Overall, the results are just what we hoped for, and a phase 3 trial is currently underway."

About 20,000 people in the United States are living with ALS. The disease kills the nerve cells that control walking, eating and breathing. Few people survive more than five years after diagnosis, and existing treatments are only modestly effective at slowing the pace of the disease.

About 10% of ALS cases are inherited, and one-fifth of those are caused by mutations in SOD1. Such mutations cause the SOD1 protein to be overly active, so reducing protein levels might help ALS patients with one of these specific mutations.

Tofersen is an antisense oligonucleotide, which is a DNA-based molecule that interferes with the genetic instructions for building proteins. The molecule is designed to block production of the SOD1 protein. In earlier studies in mice and rats with SOD1 mutations, the animals lived longer and showed fewer signs of neuromuscular damage when they were treated with the oligonucleotide.

To assess the oligonucleotide's safety and whether it is biologically active in people, Biogen and the participating sites recruited 50 people with SOD1 ALS for a phase 1/phase 2 clinical trial. Participants were randomly selected to receive the experimental drug or a placebo injected into the fluid surrounding their spinal cords. For every three participants selected to receive tofersen, one was selected to receive a placebo. Each participant received five doses over a 12-week period. The participants were divided into four groups and received 20 mg, 40 mg, 60 mg or 100 mg of the drug per dose.

The researchers found that the drug was generally well-tolerated. Most of the adverse events patients experienced - such as headache, and pain during the procedure and at the site of injection - were linked to the drug being administered via spinal tap. Five patients who received tofersen and two who received placebo experienced serious adverse events, including two deaths in the tofersen group and one in the placebo group.

In addition, the study provided evidence that the drug lowered SOD1 protein levels in the cerebrospinal fluid that surrounds the brain and spinal cord. Protein concentrations dropped by an average of 2% in the low-dose group and 33% in the high-dose group.

Biogen is continuing to provide tofersen to participants in the phase 1/phase 2 trial under an open-label extension, until further evaluation of the drug is complete. Additional participants are being enrolled in a separate phase 3 trial to further assess safety and whether the drug helps patients preserve muscle strength and function, and lengthens survival.

If tofersen proves effective in the phase 3 trial at treating SOD1 ALS, it would directly benefit only a tiny fraction of ALS patients. But this approach could pave the way for other experimental oligonucleotide-based drugs. The Muscular Dystrophy Association, the ALS Association, and the National Institute of Neurological Disease and Stroke at the National Institutes of Health (NIH) helped support the early work on oligonucleotides because of the potential such compounds hold for treating neurodegenerative conditions, many of which are linked to misshapen or abnormally high levels of proteins.

"Sometimes patients say, 'Why is all this work being done in the 2% who have SOD1 ALS? What about the 98%?'," said co-principal investigator Merit Cudkowicz, MD, director of the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital. "But the same technology that can turn off the SOD1 gene can be used to turn off other targets, and in fact, there are many companies working on other targets. Everything we have learned with SOD1 ALS could end up aiding new approaches to fighting other forms of ALS or other neurological conditions."

MINNEAPOLIS - A blood biomarker in people who have had concussions may be just as accurate at predicting the severity of the injury and how long it will last as biomarkers that are obtained through more expensive and invasive tests, according to a study published in the July 8, 2020, online issue of Neurology®, the medical journal of the American Academy of Neurology.

The study looked at a biomarker called neurofilament light chain, a nerve protein that can be detected in the blood and cerebrospinal fluid when nerve cells are injured or die.

"When your brain is injured, neurofilament light chain levels are higher in both your blood and your spinal fluid," said study author Pashtun Shahim, M.D., Ph.D., of the National Institutes of Health in Bethesda, Md. "Measuring this biomarker in your blood with a simple blood draw is faster and easier than measuring it your spinal fluid, which requires a more invasive spinal tap. Our findings are exciting because they show that the simple test may also be just as accurate for determining how severe the injury is and predicting how you might do long term."

The study involved two groups of people with head injuries.

The first group consisted of 104 professional Swedish hockey players. This group's average age was 27 and included 45 athletes who had a concussion within the past week, 31 athletes with who had multiple concussions, 28 athletes with no recent concussion or symptoms and 14 healthy people who weren't athletes. All of the participants had the biomarker levels in their blood tested. The 31 athletes with multiple concussions and the 14 healthy controls also had the biomarkers in their spinal fluid tested through spinal taps.

Researchers found that the amount of the biomarker in the athletes' blood was similar to the level in their spinal fluid. Researchers were also able to accurately predict based on the participants' biomarker levels whether they had no concussions, concussions less than a year before or concussions more than a year before.

The athletes with multiple concussions had an average of 18 picograms/milliliter (pg/mL) of the protein biomarker their blood, those with recent concussions had 12 pg/mL, the athletes with no recent concussions or symptoms had 10 pg/nL and the healthy non-athletes had 9 pg/mL. These levels correlated well with the levels researchers found in their spinal fluid.

Further, the biomarker levels in the hockey players' blood correlated strongly with more concussions and more severe concussions, even a year after the injury.

The second group, based at a Maryland clinic, had an average age of 43 and included 162 people with brain injuries and 68 healthy people. Researchers examined the role of the biomarker in distinguishing between mild, moderate and severe concussions.

In the clinic-based study, the group with head injuries had 12.8 pg/mL of the biomarker in their blood, while the healthy control group had 6.3 pg/mL. Again, those levels correlated closely with levels detected by more sophisticated tests like brain imaging. The level of biomarker in the blood accurately let researchers distinguish between mild, moderate and severe concussions. The difference in biomarker levels between people with concussions and the healthy controls was found up to five years after the concussion.

"In both of our studies, the same idea came through: Neurofilament light chain shows great promise as a biomarker in the blood," Shahim said. "This is notable because the test may help us identify people whose concussions might give them debilitating symptoms for years after the injury. And that may help doctors treat their patients more specifically for the type of concussion they have."

Shahim said one limitation of the study is the need for a longer follow-up study to determine the relationship between the blood biomarker and progressive neurodegeneration.